Sample records for r7t7 etude du

  1. Inhibition of IGF1-R overcomes IGFBP7-induced chemotherapy resistance in T-ALL.

    PubMed

    Bartram, Isabelle; Erben, Ulrike; Ortiz-Tanchez, Jutta; Blunert, Katja; Schlee, Cornelia; Neumann, Martin; Heesch, Sandra; Baldus, Claudia D

    2015-10-08

    T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease with the need for treatment optimization. Previously, high expression of Insulin-like growth factor binding protein 7 (IGFBP7), a member of the IGF system, was identified as negative prognostic factor in adult T-ALL patients. Since aberrant IGFBP7 expression was observed in a variety of neoplasia and was relevant for prognosis in T-ALL, we investigated the functional role of IGFBP7 in Jurkat and Molt-4 cells as in vitro models for T-ALL. Jurkat and Molt-4 cells were stably transfected with an IGFBP7 over-expression vector or the empty vector as control. Proliferation of the cells was assessed by WST-1 assays and cell cycle status was measured by flow-cytometry after BrDU/7-AAD staining. The effect of IGFBP7 over-expression on sensitivity to cytostatic drugs was determined in AnnexinV/7-AAD assays. IGF1-R protein expression was measured by Western Blot and flow-cytometric analysis. IGF1-R associated gene expression profiles were generated from microarray gene expression data of 86 T-ALL patients from the Microarrays Innovations in Leukemia (MILE) multicenter study. IGFBP7-transfected Jurkat cells proliferated less, leading to a longer survival in a nutrient-limited environment. Both IGFBP7-transfected Jurkat and Molt-4 cells showed an arrest in the G0/G1 cell cycle phase. Furthermore, Jurkat IGFBP7-transfected cells were resistant to vincristine and asparaginase treatment. Surface expression and whole protein measurement of IGF1-R protein expression showed a reduced abundance of the receptor after IGFBP7 transfection in Jurkat cells. Interestingly, combination of the IGF1-R inhibitor NPV-AEW541 restored sensitivity to vincristine in IGFBP7-transfected cells. Additionally, IGF1-R associated GEP revealed an up-regulation of important drivers of T-ALL pathogenesis and regulators of chemo-resistance and apoptosis such as NOTCH1, BCL-2, PRKCI, and TP53. This study revealed a proliferation

  2. Stratégie transfusionnelle des hémorragies graves du post-partum: étude rétrospective à propos de 47 cas

    PubMed Central

    Khouadja, Hosni; Rouissi, Wissem; Mahjoub, Mohamed; Sakhri, Jaballah; Beletaifa, Dhafer; Jazia, Khaled Ben

    2016-01-01

    Introduction L’hémorragie du post-partum est la principale cause de morbi-mortalité maternelle dans le monde. La prise en charge est multidisciplinaire. La stratégie transfusionnelle est capitale jouant un rôle majeur dans le pronostic maternel. L’objectif de ce travail a été de déterminer le rapport PFC/CGR lors de la prise en charge des hémorragies graves du post-partum. Méthodes Une étude Etude rétrospective sur une période de 4 ans (2009-2012) a été réalisée dans un centre de maternité de référence de niveau III du centre-Est tunisien. Elle a inclut les parturientes admises pour une hémorragie sévère du post-partum définit par la nécessité d’une transfusion de plus de 04 CGR durant les 3 premières heures ou de plus de 10 CGR durant les 24 premières heures de prise en charge. Résultats Notre étude a inclut 47 parturientes. Le diagnostic de l’HPP a été fait devant un saignement vaginal dans 28 cas et suite à une césarienne dans 19 cas. En préopératoire le taux d’Hb a été de 6.3 g/dl. Le rapport transfusionnel (PFC/CGR) a été de 1/0.7. Conclusion Au cours de notre prise en charge, le rapport transfusionnel a été plus élevé que les recommandations récentes de la littérature stipulant une administration précoce et massive de PFC avec un ratio PFC/CGR compris entre 1/2 et 1/1. L’administration du fibrinogène (Fbg) et de l’acide tranexamique doit être précoce. L’emploi du facteur VII activé recombinant (rFVIIa) doit rester une solution ultime de prise en charge. PMID:28292131

  3. Overexpression of IL-7R alpha provides a competitive advantage during early T-cell development.

    PubMed

    Laouar, Yasmina; Crispe, I Nicholas; Flavell, Richard A

    2004-03-15

    Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre-T-cell antigen receptor. Although alpha beta T-cell development is observed in IL-7- and IL-7R alpha-deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7R alpha that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7R alpha was revealed by surface staining, and increased IL-7R alpha mRNA was documented by using reverse transcriptase-polymerase chain reaction (RT-PCR). This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL(+) (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate [dUTP]-fluorescein nick end labeling) cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over healthy thymocytes. This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy.

  4. α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow–Derived Non–T Cells Is Required for the Inflammatory Reflex

    PubMed Central

    Olofsson, Peder S; Katz, David A; Rosas-Ballina, Mauricio; Levine, Yaakov A; Ochani, Mahendar; Valdés-Ferrer, Sergio I; Pavlov, Valentin A; Tracey, Kevin J; Chavan, Sangeeta S

    2012-01-01

    The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease. This mechanism, the inflammatory reflex, requires the α7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel expressed on macrophages, lymphocytes, neurons and other cells. To investigate cell-specific function of α7nAChR in the inflammatory reflex, we created chimeric mice by cross-transferring bone marrow between wild-type (WT) and α7nAChR-deficient mice. Deficiency of α7nAChR in bone marrow–derived cells significantly impaired vagus nerve–mediated regulation of tumor necrosis factor (TNF), whereas α7nAChR deficiency in neurons and other cells had no significant effect. In agreement with recent work, the inflammatory reflex was not functional in nude mice, because functional T cells are required for the integrity of the pathway. To investigate the role of T-cell α7nAChR, we adoptively transferred α7nAChR-deficient or WT T cells to nude mice. Transfer of WT and α7nAChR-deficient T cells restored function, indicating that α7nAChR expression on T cells is not necessary for this pathway. Together, these results indicate that α7nAChR expression in bone marrow–derived non–T cells is required for the integrity of the inflammatory reflex. PMID:22183893

  5. Reclassification of strains MAFF 303099T and R7A into Mesorhizobiumjaponicum sp. nov.

    PubMed

    Martínez-Hidalgo, Pilar; Ramírez-Bahena, Martha Helena; Flores-Félix, José David; Igual, José M; Sanjuán, Juan; León-Barrios, Milagros; Peix, Alvaro; Velázquez, Encarna

    2016-12-01

    In this work we revise the taxonomic status of the Lotus-nodulating strains MAFF 303099T and R7A isolated in Japan and New Zealand, respectively. Their 16S rRNA gene sequences are identical and show 98.0, 99.7, 99.8 and 99.9 % similarity values with respect to Mesorhizobium loti NZP 2213T, M. jarvisii ATCC 33669T, M. huakuii USDA 4779T (=CCBAU 2609T) and M. erdmanii USDA 3471T, respectively. The analysis of recA and glnII gene sequeces showed that M. jarvisii ATCC 33669T and M. huakuii USDA 4779T (=CCBAU 2609T) are the most closely related strains to MAFF 303099T and R7A, with similarity values suggesting that these two strains belong to a different species for which MAFF 303099T is selected as the type strain. The DNA-DNA relatedness values between strain MAFF 303099T and its closest phylogenetic relatives ranged from 53 to 60 % in average. Strains MAFF 303099T and R7A presented slight differences in the proportions of C18 : 1ω7c 11-methyl and C19 : 0 cyclo ω8c fatty acids with respect to M. jarvisii ATCC 33669T and M. huakuii USDA 4779T, and also in several phenotypic characteristics. Therefore, we propose the reclassification of these two strains into a novel species named Mesorhizobium japonicum sp. nov., with the type strain being MAFF 303099T (=LMG 29417T=CECT 9101T).

  6. Etude de l'affaiblissement du comportement mecanique du pergelisol du au rechauffement climatique

    NASA Astrophysics Data System (ADS)

    Buteau, Sylvie

    Le rechauffement climatique predit pour les prochaines decennies, aura des impacts majeurs sur le pergelisol qui sont tres peu documentes pour l'instant. La presente etude a pour but d'evaluer ces impacts sur les proprietes mecaniques du pergelisol et sa stabilite a long terme. Une nouvelle technique d'essai de penetration au cone a taux de deformation controle, a ete developpee pour caracteriser en place le pergelisol. Ces essais geotechniques et la mesure de differentes proprietes physiques ont ete effectues sur une butte de pergelisol au cours du printemps 2000. Le developpement et l'utilisation d'un modele geothermique 1D tenant compte de la thermodependance du comportement mecanique ont permis d'evaluer que les etendues de pergelisol chaud deviendraient instables a la suite d'un rechauffement de l'ordre de 5°C sur cent ans. En effet, la resistance mecanique du pergelisol diminuera alors rapidement jusqu'a 11,6 MPa, ce qui correspond a une perte relative de 98% de la resistance par rapport a un scenario sans rechauffement.

  7. Les carcinomes epidermoïdes du scrotum: à propos de 7 cas avec revue de la litterature

    PubMed Central

    Halfya, Ayoub; Elmortaji, Khalid; Redouane, Rabii; fethi, Meziane; Rafik, Amine; Mohamed, Ezzoubi; Abdessamad, Chlihi

    2015-01-01

    Quoique rare le carcinome épidermoïde du scrotum a un mauvais pronostic. Les Carcinomes du scrotum induite et - liées au travail sont moins fréquentes en raison d'une meilleure hygiène, vêtements de protection, et la sensibilisation de la cancérogénicité des huiles industrielles. L’épidémie à l'HPV a induit une augmentation de l'incidence. Le traitement de dépend toujours exérèse locale de la lésion primaire. La radiothérapie a peu de bénéfice thérapeutique dans le traitement d'un carcinome épidermoïde du scrotum. La bléomycine peut être utile comme traitement adjuvant pour les maladies ilio-inguinal généralisée avant la tentative exérèse, même si cela n'a pas encore été prouvé. Entre janvier 2011 au 1er janvier 2013, 7 patients atteints de carcinome épidermoïde ont été pris en charge, Trois patients ont présenté une localisation ganglionnaire. Les sept patients ont eu un traitement chirurgical par exérèse large avec reconstruction, Deux patients ont été adressé pour chimiothérapie.2 patients ont présenté une récidive, dont un est décédé. PMID:26113906

  8. Etude de facteurs de risque de la transmission du VIH de la mère à l'enfant dans la stratégie « option A » à Lubumbashi, République Démocratique du Congo

    PubMed Central

    Ngwej, Dieudonné Tshikwej; Mukuku, Olivier; Mudekereza, Rachel; Karaj, Eugénie; Odimba, Etienne Bwana Fwamba; Luboya, Oscar Numbi; Kakoma, Jean-Baptiste Sakatolo; Wembonyama, Stanis Okitotshio

    2015-01-01

    Introduction L'infection à VIH chez la femme enceinte a pour principal risque la contamination du nouveau-né. L'objectif est de déterminer le taux de transmission du VIH de la mère à l'enfant (TME) dans la ville de Lubumbashi et en évaluer les facteurs de risque. Méthodes Il s'agissait d'une étude prospective transversale à visée analytique de 157 accouchées séropositives au VIH et de leurs enfants dans 12 structures sanitaires de Lubumbashi (RDCongo) du 1er octobre 2012 au 31 décembre 2013. Les paramètres sociodémographiques, cliniques et les données relatives aux activités de PTME du VIH ont été étudiés. Les statistiques usuelles ont été utilisées pour analyser les résultats. Le seuil de significativité a été fixé à une valeur de p < 0,05. Résultats Le taux de transmission verticale du VIH était de 12,7% (20/157). Il n'y avait pas d'association significative entre les caractéristiques sociodémographiques maternelles telles que l’âge, la parité, le niveau d’étude, la profession et l’état-civil et la TME (p>0,05). La transmission verticale du VIH était significativement associée aux facteurs suivants: le stade clinique 3 de l'OMS (OR=5,18 (1,5-18,1)), la présence d'infection opportuniste (OR=8,7 (2,7-27,8)), le dépistage lors de l'accouchement (OR=6,3 (1,0-39,0)) ou au cours de l'allaitement (OR=7,1 (1,1-76,7)), au taux de CD4 maternel <350/mm3 (OR=2,9 (1,1-7,7)), l'absence de thérapie antirétrovirale chez la mère (OR=19,9 (4,8-81,9)), la naissance avant terme (OR=4,7 (1,4-16,0)), la rupture prématurée de membranes (OR=45,0 (7,4-454,6)), le faible poids de naissance (OR=5,6 (1,9-16,7)), la notion de réanimation néonatale (OR=12,4 (3,8-40,1)), la non administration de la névirapine à la naissance (OR=26,4 (7,6-92,3)) et l'alimentation mixte (OR=12,6 (1,3-115,9)). Le sexe du nourrisson et le mode d'accouchement n’étaient pas non plus associés à la transmission verticale du VIH (p>0,05). Conclusion Le taux

  9. Etude des phenomenes dynamiques ultrarapides et des caracteristiques impulsionnelles d'emission terahertz du supraconducteur YBCO

    NASA Astrophysics Data System (ADS)

    Savard, Stephane

    Les premieres etudes d'antennes a base de supraconducteurs a haute temperature critique emettant une impulsion electromagnetique dont le contenu en frequence se situe dans le domaine terahertz remontent a 1996. Une antenne supraconductrice est formee d'un micro-pont d'une couche mince supraconductrice sur lequel un courant continu est applique. Un faisceau laser dans le visible est focalise sur le micro-pont et place le supraconducteur dans un etat hors-equilibre ou des paires sont brisees. Grace a la relaxation des quasiparticules en surplus et eventuellement de la reformation des paires supraconductrices, nous pouvons etudier la nature de la supraconductivite. L'analyse de la cinetique temporelle du champ electromagnetique emis par une telle antenne terahertz supraconductrice s'est averee utile pour decrire qualitativement les caracteristiques de celle-ci en fonction des parametres d'operation tels que le courant applique, la temperature et la puissance d'excitation. La comprehension de l'etat hors-equilibre est la cle pour comprendre le fonctionnement des antennes terahertz supraconductrices a haute temperature critique. Dans le but de comprendre ultimement cet etat hors-equilibre, nous avions besoin d'une methode et d'un modele pour extraire de facon plus systematique les proprietes intrinseques du materiau qui compose l'antenne terahertz a partir des caracteristiques d'emission de celle-ci. Nous avons developpe une procedure pour calibrer le spectrometre dans le domaine temporel en utilisant des antennes terahertz de GaAs bombarde aux protons H+ comme emetteur et detecteur. Une fois le montage calibre, nous y avons insere une antenne emettrice dipolaire de YBa 2Cu3O7-delta . Un modele avec des fonctions exponentielles de montee et de descente du signal est utilise pour lisser le spectre du champ electromagnetique de l'antenne de YBa 2Cu3O7-delta, ce qui nous permet d'extraire les proprietes intrinseques de ce dernier. Pour confirmer la validite du modele

  10. Etudes des Reactions de Transfert LITHIUM-7/LITHIUM -6

    NASA Astrophysics Data System (ADS)

    Baddou, Djafer

    Les reactions de transfert de deux nucleons ^7Li/^6Li(^3He, rm p)^8Be/^9Be ont ete effectuees a partir d'um faisceau d'^3He initialement polarise et d'energie incidente egale a 4.58 MeV au centre de la cible. Le faisceau d'^3He est simplement ionise et il est accelere par l'accelerateur Van de Graaff de l'Universite Laval. Ce faisceau d' ^3He est de polarisation egale a 40% et il est obtenu a partir d'une source d'^3He a l'etat metastable. Nous avons decrit la reaction depuis la production et le transport du faisceau initial de l'^3 He jusqu'a la chambre de reaction. Par la suite, nous avons obtenu les distributions angulaires de la section efficace differentielle et du pouvoir d'analyse de ces reactions. Elles ont ete comparees a la theorie DWBA a l'approximation zero. La theorie a montre qu'il s'agit d'un transfert de deux particules independants (neutron, proton) pour le cas de la reaction ^7Li( ^3He,rm p)^9Be et d'un transfert de "cluster" deuteron pour le cas de la reaction ^6Li(^3He, rm p)^8Be. Notons que pour cette reaction l'instabilite du ^8Be ne nous permet pas d'avoir une diffusion elastique permettant la determination des parametres du modele optique entre ce noyau et la particule diffusee. Afin de contourner cette difficulte, nous supposons que le ^8 Be est un noyau compose de deux particules alpha et nous avons teste cette hypothese avec les reactions ^6Li(^3He, rm p)^8Be et ^7Li( ^3He,rm d)^8Be. Nous mentionnons a la fin que nous avons observe que l'etat fondamental de la reaction ^6Li( ^3He,rm p)^8Be et l'etat excite 2.43 MeV de la reaction ^7Li(^3He,rm p)^9Be sont des reactions directes alors que le premier etat excite (2.96 MeV) de la reaction ^6Li(^3He,rm p)^8Be et l'etat fondamental de la reaction ^7Li(^3He,rm p)^9Be peuvent etre domines par une reaction a noyau compose.

  11. Facteurs de risque cardiovasculaires au cours du lupus systémique

    PubMed Central

    Harzallah, Amel; Hajji, Mariem; Kaaroud, Hayet; Hamida, Fethi Ben; Abdallah, Taieb Ben

    2015-01-01

    Cette étude a pour objectif d’évaluer la fréquence des facteurs de risque cardiovasculaires au cours du lupus et de préciser leur prévalence. Etude rétrospective portant sur 250 patients ayant un lupus, diagnostiqué selon les critères de l'ACR, hospitalisés entre 1970 et 2013. Les données cliniques et para cliniques ont été recueillies à partir des observations médicales. Il s'agit de 228 femmes et 22 hommes d’âge moyen au diagnostic du lupus de 30, 32 ans (extrêmes: 16-69). La durée moyenne du suivi des patients était de 64 mois (extrêmes: 7 jours- 382mois). Quatre vingt dix patients (36%) étaient hypertendus, 74% avaient une hypercholestérolémie et 22% étaient diabétiques. Pour les autres facteurs de risque cardiovasculaire traditionnels, un âge > 50 ans a été retrouvé dans 40% des cas, le sexe masculin dans 8% des cas, l'obésité dans 76% des cas et le tabagisme dans 11% des cas. Les facteurs de risque surajoutés sont représentés par la présence des anticorps antiphospholipides (47% des cas), la néphropathie lupique (49% des cas), l'insuffisance rénale (42% des cas), la corticothérapie au long cours (74% des cas) et la chronicité de la maladie dans 35% des cas. Les complications cardiovasculaires retrouvées dans notre série étaient: les accidents vasculaires cérébraux (2%) et l'insuffisance coronarienne (5,6%). Devant l'importance du risque cardiovasculaire au cours du lupus, une surveillance rapprochée des facteurs de risque cardio-vasculaires semble primordiale chez les lupiques. PMID:27022427

  12. IL-7 receptor blockade following T cell depletion promotes long-term allograft survival

    PubMed Central

    Mai, Hoa-Le; Boeffard, Françoise; Longis, Julie; Danger, Richard; Martinet, Bernard; Haspot, Fabienne; Vanhove, Bernard; Brouard, Sophie; Soulillou, Jean-Paul

    2014-01-01

    T cell depletion is commonly used in organ transplantation for immunosuppression; however, a restoration of T cell homeostasis following depletion leads to increased memory T cells, which may promote transplant rejection. The cytokine IL-7 is important for controlling lymphopoiesis under both normal and lymphopenic conditions. Here, we investigated whether blocking IL-7 signaling with a mAb that targets IL-7 receptor α (IL-7Rα) alone or following T cell depletion confers an advantage for allograft survival in murine transplant models. We found that IL-7R blockade alone induced indefinite pancreatic islet allograft survival if anti–IL-7R treatment was started 3 weeks before graft. IL-7R blockade following anti-CD4– and anti-CD8–mediated T cell depletion markedly prolonged skin allograft survival. Furthermore, IL-7 inhibition in combination with T cell depletion synergized with either CTLA-4Ig administration or suboptimal doses of tacrolimus to induce long-term skin graft acceptance in this stringent transplant model. Together, these therapies inhibited T cell reconstitution, decreased memory T cell numbers, increased the relative frequency of Tregs, and abrogated both cellular and humoral alloimmune responses. Our data suggest that IL-7R blockade following T cell depletion has potential as a robust, immunosuppressive therapy in transplantation. PMID:24569454

  13. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia

    PubMed Central

    Vicente, Carmen; Schwab, Claire; Broux, Michaël; Geerdens, Ellen; Degryse, Sandrine; Demeyer, Sofie; Lahortiga, Idoya; Elliott, Alannah; Chilton, Lucy; La Starza, Roberta; Mecucci, Cristina; Vandenberghe, Peter; Goulden, Nicholas; Vora, Ajay; Moorman, Anthony V.; Soulier, Jean; Harrison, Christine J.; Clappier, Emmanuelle; Cools, Jan

    2015-01-01

    T-cell acute lymphoblastic leukemia is caused by the accumulation of multiple oncogenic lesions, including chromosomal rearrangements and mutations. To determine the frequency and co-occurrence of mutations in T-cell acute lymphoblastic leukemia, we performed targeted re-sequencing of 115 genes across 155 diagnostic samples (44 adult and 111 childhood cases). NOTCH1 and CDKN2A/B were mutated/deleted in more than half of the cases, while an additional 37 genes were mutated/deleted in 4% to 20% of cases. We found that IL7R-JAK pathway genes were mutated in 27.7% of cases, with JAK3 mutations being the most frequent event in this group. Copy number variations were also detected, including deletions of CREBBP or CTCF and duplication of MYB. FLT3 mutations were rare, but a novel extracellular mutation in FLT3 was detected and confirmed to be transforming. Furthermore, we identified complex patterns of pairwise associations, including a significant association between mutations in IL7R-JAK genes and epigenetic regulators (WT1, PRC2, PHF6). Our analyses showed that IL7R-JAK genetic lesions did not confer adverse prognosis in T-cell acute lymphoblastic leukemia cases enrolled in the UK ALL2003 trial. Overall, these results identify interconnections between the T-cell acute lymphoblastic leukemia genome and disease biology, and suggest a potential clinical application for JAK inhibitors in a significant proportion of patients with T-cell acute lymphoblastic leukemia. PMID:26206799

  14. Gain-of-function mutations in interleukin-7 receptor-α (IL7R) in childhood acute lymphoblastic leukemias

    PubMed Central

    Shochat, Chen; Tal, Noa; Bandapalli, Obul R.; Palmi, Chiara; Ganmore, Ithamar; te Kronnie, Geertruy; Cario, Gunnar; Cazzaniga, Giovanni; Kulozik, Andreas E.; Stanulla, Martin; Schrappe, Martin; Biondi, Andrea; Basso, Giuseppe; Bercovich, Dani; Muckenthaler, Martina U.

    2011-01-01

    Interleukin-7 receptor α (IL7R) is required for normal lymphoid development. Loss-of-function mutations in this gene cause autosomal recessive severe combined immune deficiency. Here, we describe somatic gain-of-function mutations in IL7R in pediatric B and T acute lymphoblastic leukemias. The mutations cause either a serine-to-cysteine substitution at amino acid 185 in the extracellular domain (4 patients) or in-frame insertions and deletions in the transmembrane domain (35 patients). In B cell precursor leukemias, the mutations were associated with the aberrant expression of cytokine receptor-like factor 2 (CRLF2), and the mutant IL-7R proteins formed a functional receptor with CRLF2 for thymic stromal lymphopoietin (TSLP). Biochemical and functional assays reveal that these IL7R mutations are activating mutations conferring cytokine-independent growth of progenitor lymphoid cells. A cysteine, included in all but three of the mutated IL-7R alleles, is essential for the constitutive activation of the receptor. This is the first demonstration of gain-of-function mutations of IL7R. Our current and recent observations of mutations in IL7R and CRLF2, respectively suggest that the addition of cysteine to the juxtamembranous domains is a general mechanism for mutational activation of type I cytokine receptors in leukemia. PMID:21536738

  15. Etude thermo-hydraulique de l'ecoulement du moderateur dans le reacteur CANDU-6

    NASA Astrophysics Data System (ADS)

    Mehdi Zadeh, Foad

    Etant donne la taille (6,0 m x 7,6 m) ainsi que le domaine multiplement connexe qui caracterisent la cuve des reacteurs CANDU-6 (380 canaux dans la cuve), la physique qui gouverne le comportement du fluide moderateur est encore mal connue de nos jours. L'echantillonnage de donnees dans un reacteur en fonction necessite d'apporter des changements a la configuration de la cuve du reacteur afin d'y inserer des sondes. De plus, la presence d'une zone intense de radiations empeche l'utilisation des capteurs courants d'echantillonnage. En consequence, l'ecoulement du moderateur doit necessairement etre etudie a l'aide d'un modele experimental ou d'un modele numerique. Pour ce qui est du modele experimental, la fabrication et la mise en fonction de telles installations coutent tres cher. De plus, les parametres de la mise a l'echelle du systeme pour fabriquer un modele experimental a l'echelle reduite sont en contradiction. En consequence, la modelisation numerique reste une alternative importante. Actuellement, l'industrie nucleaire utilise une approche numerique, dite de milieu poreux, qui approxime le domaine par un milieu continu ou le reseau des tubes est remplace par des resistances hydrauliques distribuees. Ce modele est capable de decrire les phenomenes macroscopiques de l'ecoulement, mais ne tient pas compte des effets locaux ayant un impact sur l'ecoulement global, tel que les distributions de temperatures et de vitesses a proximite des tubes ainsi que des instabilites hydrodynamiques. Dans le contexte de la surete nucleaire, on s'interesse aux effets locaux autour des tubes de calandre. En effet, des simulations faites par cette approche predisent que l'ecoulement peut prendre plusieurs configurations hydrodynamiques dont, pour certaines, l'ecoulement montre un comportement asymetrique au sein de la cuve. Ceci peut provoquer une ebullition du moderateur sur la paroi des canaux. Dans de telles conditions, le coefficient de reactivite peut varier de maniere

  16. Etude des facteurs de risque du retard de croissance intra-utérin à Lubumbashi

    PubMed Central

    Moyambe, Jules Ngwe Thaba; Bernard, Pierre; Khang'Mate, Faustin; Nkoy, Albert Mwembo Tambwe A; Mukalenge, Faustin Chenge; Makanda, Daudet; Twite, Eugene; Ndudula, Arthur Munkana; Lubamba, Cham; Kadingi, Arnauld Kabulu; Kayomb, Mutach; Kayamba, Prosper Kalenga Muenze

    2013-01-01

    Introduction Dans notre milieu, il n'existe aucune politique de prévention du Retard de Croissance Intra-Utérin (RCIU) clairement défini. L'objectif de ce travail était d'identifier les facteurs de risque de RCIU afin de proposer une stratégie de lutte contre cette pathologie en agissant surtout sur des facteurs pouvant faire l'objet d'une action préventive. Méthodes Une étude cas-témoins a été menée dans 11 centres hospitaliers de Lubumbashi en République Démocratique du Congo, de Janvier 2010 à Juin 2011, dans le but d'identifier les facteurs de risque du retard de croissance intra-utérin (RCIU). Au total 420 gestantes (cas et témoins) avec grossesse monofoetale d'au moins 24 semaines d'aménorrhée ont été inclues dans l'étude. Les cas correspondaient aux gestantes dont le poids du fœtus était resté inférieur au 10 eme percentile des courbes de référence d'Alexander, après 2 échographies successives réalisées à intervalle de 4 semaines. Les témoins correspondaient aux gestantes dont le poids du fœtus était supérieur ou égal au 10 eme percentile de mêmes courbes. A chaque cas a été apparié un témoin de même parité porteur d'une grossesse de même âge. Résultats L'analyse univariée a identifié comme facteurs de risque: la taille maternelle. Conclusion L'amélioration du niveau socio-économique des populations, la lutte contre le paludisme et les consultations prénatales mieux organisées couplées à une meilleure éducation sanitaire et nutritionnelle peuvent contribuer sensiblement à la réduction de la fréquence du RCIU à Lubumbashi. PMID:23504392

  17. Structure of T7 RNA polymerase complexed to the transcriptional inhibitor T7 lysozyme.

    PubMed Central

    Jeruzalmi, D; Steitz, T A

    1998-01-01

    The T7 RNA polymerase-T7 lysozyme complex regulates phage gene expression during infection of Escherichia coli. The 2.8 A crystal structure of the complex reveals that lysozyme binds at a site remote from the polymerase active site, suggesting an indirect mechanism of inhibition. Comparison of the T7 RNA polymerase structure with that of the homologous pol I family of DNA polymerases reveals identities in the catalytic site but also differences specific to RNA polymerase function. The structure of T7 RNA polymerase presented here differs significantly from a previously published structure. Sequence similarities between phage RNA polymerases and those from mitochondria and chloroplasts, when interpreted in the context of our revised model of T7 RNA polymerase, suggest a conserved fold. PMID:9670025

  18. 7TH Annual Anesthesia and Critical Care Symposium (7th) Held in Paris (France) on 22-24 April 1994,

    DTIC Science & Technology

    1994-09-30

    4006 6. AUTHOR(S) Christopher M. Grande, M.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS( ES ) 8. PERFORMING ORGANIZATION International Trauma...Anesthesia & Critical REPORT NUMBER Care Society (ITACCS) P.O. Box 4826 Baltimore, Maryland 21211 9. SPONSORING/ MONITORING AGENCY NAME(S) AND ADDRESS( ES ...nan accessibas la Iscompressian direare - sortagraphie p r usie pour usage parentbral, bolites de 1 I or-D SORT DU OCLICAMlT De-.i ap lasmar que courre

  19. Déclenchement du travail à terme par le misoprostol: expérience d'une maternité tunisienne

    PubMed Central

    Ouerdiane, Nadia; Tlili, Nihel; Othmani, Kaouther; Daaloul, Walid; Masmoudi, Abdelwaheb; Hamouda, Sonia Ben; Bouguerra, Badreddine

    2016-01-01

    Evaluer l'efficacité et l'innocuité de l'utilisation du misoprostol par voie vaginale pour le déclenchement du travail à terme. Etude prospective réalisée au service de gynécologie obstétrique B de l'hôpital Charles Nicolle de Tunis sur une durée de 4 mois. La population sélectionnée concernait les patientes à terme devant bénéficier d'une maturation cervicale. Le misoprostol à la dose de 50 µg par voie vaginale toutes les 12 h était utilisé. Les paramètres étudiés étaient les anomalies contractiles, les anomalies du RCF, le mode d'accouchement, le délai d'accouchement et l’état néonatal. 44 patientes ont bénéficié d'une maturation cervicale par misoprostol. Le terme moyen était de 40 SA. Le taux de nullipare était de 23/44 (52%). Le taux d'accouchement par voie basse était de 31/44 (70.4%). 84% des patientes ont reçu une seule dose de misoprostol. Les anomalies du RCF ont été notées dans 14/44 (32%). Le taux de liquides méconiaux était de 12/44 (27%). Un score d'Apgar à 5 mn inférieur à 7 était noté chez 7/44 (16%). Un cas de rupture utérine était survenue chez une primipare et ce après une seule prise de misoprostol. Nos résultats sont décevants en raison de la survenue d'une rupture utérine et d'une morbidité néonatale importante. D'autres études prospectives multicentriques restent utiles pour mieux s'assurer de l'efficacité mais surtout de l'innocuité du misoprostol à dose faible pour le déclenchement du travail à terme. PMID:27583092

  20. Propriétés optiques du silicium mésoporeux et ses applications potentielles

    NASA Astrophysics Data System (ADS)

    Lévy-Clément, C.; Bastide, S.

    2002-04-01

    Une couche de silicium poreux formée électrochimiquement à la surface de l'émetteur d'une jonction p-n+ peut jouer efficacement le rôle d'une couche antireflet pour les cellules solaires au silicium. En ajustant la densité de courant et le temps de formation, des simple et double-couches antireflet aux propriétés optiques optimisées ont pu être réalisées, conduisant à des réflectivités effectives respectives de 7.3 et 2.7 % sur l'ensemble du spectre solaire utile pour les cellules (400-1000 nm). De hauts rendements de conversion de l'énergie solaire, de l'ordre de 13-13.4 %, sont ainsi actuellement obtenus pour des cellules au silicium multicristallin avec une couche antireflet de silicium poreux.

  1. Constitutive Signaling from an Engineered IL7 Receptor Promotes Durable Tumor Elimination by Tumor-Redirected T Cells.

    PubMed

    Shum, Thomas; Omer, Bilal; Tashiro, Haruko; Kruse, Robert L; Wagner, Dimitrios L; Parikh, Kathan; Yi, Zhongzhen; Sauer, Tim; Liu, Daofeng; Parihar, Robin; Castillo, Paul; Liu, Hao; Brenner, Malcolm K; Metelitsa, Leonid S; Gottschalk, Stephen; Rooney, Cliona M

    2017-11-01

    Successful adoptive T-cell immunotherapy of solid tumors will require improved expansion and cytotoxicity of tumor-directed T cells within tumors. Providing recombinant or transgenic cytokines may produce the desired benefits but is associated with significant toxicities, constraining clinical use. To circumvent this limitation, we constructed a constitutively signaling cytokine receptor, C7R, which potently triggers the IL7 signaling axis but is unresponsive to extracellular cytokine. This strategy augments modified T-cell function following antigen exposure, but avoids stimulating bystander lymphocytes. Coexpressing the C7R with a tumor-directed chimeric antigen receptor (CAR) increased T-cell proliferation, survival, and antitumor activity during repeated exposure to tumor cells, without T-cell dysfunction or autonomous T-cell growth. Furthermore, C7R-coexpressing CAR T cells were active against metastatic neuroblastoma and orthotopic glioblastoma xenograft models even at cell doses that had been ineffective without C7R support. C7R may thus be able to enhance antigen-specific T-cell therapies against cancer. Significance: The constitutively signaling C7R system developed here delivers potent IL7 stimulation to CAR T cells, increasing their persistence and antitumor activity against multiple preclinical tumor models, supporting its clinical development. Cancer Discov; 7(11); 1238-47. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1201 . ©2017 American Association for Cancer Research.

  2. Gene 1.7 of bacteriophage T7 confers sensitivity of phage growth to dideoxythymidine.

    PubMed

    Tran, Ngoc Q; Rezende, Lisa F; Qimron, Udi; Richardson, Charles C; Tabor, Stanley

    2008-07-08

    Bacteriophage T7 DNA polymerase efficiently incorporates dideoxynucleotides into DNA, resulting in chain termination. Dideoxythymidine (ddT) present in the medium at levels not toxic to Escherichia coli inhibits phage T7. We isolated 95 T7 phage mutants that were resistant to ddT. All contained a mutation in T7 gene 1.7, a nonessential gene of unknown function. When gene 1.7 was expressed from a plasmid, T7 phage resistant to ddT still arose; analysis of 36 of these mutants revealed that all had a single mutation in gene 5, which encodes T7 DNA polymerase. This mutation changes tyrosine-526 to phenylalanine, which is known to increase dramatically the ability of T7 DNA polymerase to discriminate against dideoxynucleotides. DNA synthesis in cells infected with wild-type T7 phage was inhibited by ddT, suggesting that it resulted in chain termination of DNA synthesis in the presence of gene 1.7 protein. Overexpression of gene 1.7 from a plasmid rendered E. coli cells sensitive to ddT, indicating that no other T7 proteins are required to confer sensitivity to ddT.

  3. Reconstruction of 7T-Like Images From 3T MRI

    PubMed Central

    Bahrami, Khosro; Shi, Feng; Zong, Xiaopeng; Shin, Hae Won; An, Hongyu

    2016-01-01

    In the recent MRI scanning, ultra-high-field (7T) MR imaging provides higher resolution and better tissue contrast compared to routine 3T MRI, which may help in more accurate and early brain diseases diagnosis. However, currently, 7T MRI scanners are more expensive and less available at clinical and research centers. These motivate us to propose a method for the reconstruction of images close to the quality of 7T MRI, called 7T-like images, from 3T MRI, to improve the quality in terms of resolution and contrast. By doing so, the post-processing tasks, such as tissue segmentation, can be done more accurately and brain tissues details can be seen with higher resolution and contrast. To do this, we have acquired a unique dataset which includes paired 3T and 7T images scanned from same subjects, and then propose a hierarchical reconstruction based on group sparsity in a novel multi-level Canonical Correlation Analysis (CCA) space, to improve the quality of 3T MR image to be 7T-like MRI. First, overlapping patches are extracted from the input 3T MR image. Then, by extracting the most similar patches from all the aligned 3T and 7T images in the training set, the paired 3T and 7T dictionaries are constructed for each patch. It is worth noting that, for the training, we use pairs of 3T and 7T MR images from each training subject. Then, we propose multi-level CCA to map the paired 3T and 7T patch sets to a common space to increase their correlations. In such space, each input 3T MRI patch is sparsely represented by the 3T dictionary and then the obtained sparse coefficients are used together with the corresponding 7T dictionary to reconstruct the 7T-like patch. Also, to have the structural consistency between adjacent patches, the group sparsity is employed. This reconstruction is performed with changing patch sizes in a hierarchical framework. Experiments have been done using 13 subjects with both 3T and 7T MR images. The results show that our method outperforms previous

  4. L'etude de l'InP et du GaP suite a l'implantation ionique de Mn et a un recuit thermique

    NASA Astrophysics Data System (ADS)

    Bucsa, Ioan Gigel

    Cette these est dediee a l'etude des materiaux InMnP et GaMnP fabriques par implantation ionique et recuit thermique. Plus precisement nous avons investigue la possibilite de former par implantation ionique des materiaux homogenes (alliages) de InMnP et GaMnP contenant de 1 a 5 % atomiques de Mn qui seraient en etat ferromagnetique, pour des possibles applications dans la spintronique. Dans un premier chapitre introductif nous donnons les motivations de cette recherche et faisons une revue de la litterature sur ce sujet. Le deuxieme chapitre decrit les principes de l'implantation ionique, qui est la technique utilisee pour la fabrication des echantillons. Les effets de l'energie, fluence et direction du faisceau ionique sur le profil d'implantation et la formation des dommages seront mis en evidence. Aussi dans ce chapitre nous allons trouver des informations sur les substrats utilises pour l'implantation. Les techniques experimentales utilisees pour la caracterisation structurale, chimique et magnetique des echantillons, ainsi que leurs limitations sont presentees dans le troisieme chapitre. Quelques principes theoriques du magnetisme necessaires pour la comprehension des mesures magnetiques se retrouvent dans le chapitre 4. Le cinquieme chapitre est dedie a l'etude de la morphologie et des proprietes magnetiques des substrats utilises pour implantation et le sixieme chapitre, a l'etude des echantillons implantes au Mn sans avoir subi un recuit thermique. Notamment nous allons voir dans ce chapitre que l'implantation de Mn a plus que 1016 ions/cm 2 amorphise la partie implantee du materiau et le Mn implante se dispose en profondeur sur un profil gaussien. De point de vue magnetique les atomes implantes se trouvent dans un etat paramagnetique entre 5 et 300 K ayant le spin 5/2. Dans le chapitre 7 nous presentons les proprietes des echantillons recuits a basses temperatures. Nous allons voir que dans ces echantillons la couche implantee est polycristalline et les

  5. Hyperglycemia-Induced Changes in ZIP7 and ZnT7 Expression Cause Zn2+ Release From the Sarco(endo)plasmic Reticulum and Mediate ER Stress in the Heart.

    PubMed

    Tuncay, Erkan; Bitirim, Verda C; Durak, Aysegul; Carrat, Gaelle R J; Taylor, Kathryn M; Rutter, Guy A; Turan, Belma

    2017-05-01

    Changes in cellular free Zn 2+ concentration, including those in the sarco(endo)plasmic reticulum [S(E)R], are primarily coordinated by Zn 2+ transporters (ZnTs) whose identity and role in the heart are not well established. We hypothesized that ZIP7 and ZnT7 transport Zn 2+ in opposing directions across the S(E)R membrane in cardiomyocytes and that changes in their activity play an important role in the development of ER stress during hyperglycemia. The subcellular S(E)R localization of ZIP7 and ZnT7 was determined in cardiomyocytes and in isolated S(E)R preparations. Markedly increased mRNA and protein levels of ZIP7 were observed in ventricular cardiomyocytes from diabetic rats or high-glucose-treated H9c2 cells while ZnT7 expression was low. In addition, we observed increased ZIP7 phosphorylation in response to high glucose in vivo and in vitro. By using recombinant-targeted Förster resonance energy transfer sensors, we show that hyperglycemia induces a marked redistribution of cellular free Zn 2+ , increasing cytosolic free Zn 2+ and lowering free Zn 2+ in the S(E)R. These changes involve alterations in ZIP7 phosphorylation and were suppressed by small interfering RNA-mediated silencing of CK2α. Opposing changes in the expression of ZIP7 and ZnT7 were also observed in hyperglycemia. We conclude that subcellular free Zn 2+ redistribution in the hyperglycemic heart, resulting from altered ZIP7 and ZnT7 activity, contributes to cardiac dysfunction in diabetes. © 2017 by the American Diabetes Association.

  6. Cloning and expression of the gene for bacteriophage T7 RNA polymerase

    DOEpatents

    Studier, F.W.; Davanloo, P.; Rosenberg, A.H.; Moffatt, B.A.; Dunn, J.J.

    1997-12-02

    This application describes a means to clone a functional gene for bacteriophage T7 RNA polymerase. Active T7 RNA polymerase is produced from the cloned gene, and a plasmid has been constructed that can produce the active enzyme in large amounts. T7 RNA polymerase transcribes DNA very efficiently and is highly selective for a relatively long promoter sequence. This enzyme is useful for synthesizing large amounts of RNA in vivo or in vitro, and is capable of producing a single RNA selectively from a complex mixture of DNAs. The procedure used to obtain a clone of the R7 RNA polymerase gene can be applied to other T7-like phages to obtain clones that produce RNA polymerases having different promoter specificities, different bacterial hosts, or other desirable properties. T7 RNA polymerase is also used in a system for selective, high-level synthesis of RNAs and proteins in suitable host cells. 10 figs.

  7. Cloning and expression of the gene for bacteriophage T7 RNA polymerase

    DOEpatents

    Studier, F. William; Davanloo, Parichehre; Rosenberg, Alan H.; Moffatt, Barbara A.; Dunn, John J.

    1999-02-09

    This application describes a means to clone a functional gene for bacteriophage T7 RNA polymerase. Active T7 RNA polymerase is produced from the cloned gene, and a plasmid has been constructed that can produce the active enzyme in large amounts. T7 RNA polymerase transcribes DNA very efficiently and is highly selective for a relatively long promoter sequence. This enzyme is useful for synthesizing large amounts of RNA in vivo or in vitro, and is capable of producing a single RNA selectively from a complex mixture of DNAs. The procedure used to obtain a clone of the R7 RNA polymerase gene can be applied to other T7-like phages to obtain clones that produce RNA polymerases having different promoter specificities, different bacterial hosts, or other desirable properties. T7 RNA polymerase is also used in a system for selective, high-level synthesis of RNAs and proteins in suitable host cells.

  8. Cloning and expression of the gene for bacteriophage T7 RNA polymerase

    DOEpatents

    Studier, F. William; Davanloo, Parichehre; Rosenberg, Alan H.; Moffatt, Barbara A.; Dunn, John J.

    1997-12-02

    This application describes a means to clone a functional gene for bacteriophage T7 RNA polymerase. Active T7 RNA polymerase is produced from the cloned gene, and a plasmid has been constructed that can produce the active enzyme in large amounts. T7 RNA polymerase transcribes DNA very efficiently and is highly selective for a relatively long promoter sequence. This enzyme is useful for synthesizing large amounts of RNA in vivo or in vitro, and is capable of producing a single RNA selectively from a complex mixture of DNAs. The procedure used to obtain a clone of the R7 RNA polymerase gene can be applied to other T7-like phages to obtain clones that produce RNA polymerases having different promoter specificities, different bacterial hosts, or other desirable properties. T7 RNA polymerase is also used in a system for selective, high-level synthesis of RNAs and proteins in suitable host cells.

  9. Cloning and expression of the gene for bacteriophage T7 RNA polymerase

    DOEpatents

    Studier, F.W.; Davanloo, P.; Rosenberg, A.H.; Moffatt, B.A.; Dunn, J.J.

    1999-02-09

    This application describes a means to clone a functional gene for bacteriophage T7 RNA polymerase. Active T7 RNA polymerase is produced from the cloned gene, and a plasmid has been constructed that can produce the active enzyme in large amounts. T7 RNA polymerase transcribes DNA very efficiently and is highly selective for a relatively long promoter sequence. This enzyme is useful for synthesizing large amounts of RNA in vivo or in vitro, and is capable of producing a single RNA selectively from a complex mixture of DNAs. The procedure used to obtain a clone of the R7 RNA polymerase gene can be applied to other T7-like phages to obtain clones that produce RNA polymerases having different promoter specificities, different bacterial hosts, or other desirable properties. T7 RNA polymerase is also used in a system for selective, high-level synthesis of RNAs and proteins in suitable host cells. 10 figs.

  10. Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation

    PubMed Central

    Goldberg, Jenna D.; Yuan, Jianda; Koehne, Guenther; Lechner, Lauren; Papadopoulos, Esperanza B.; Young, James W.; Jakubowski, Ann A.; Zaidi, Bushra; Gallardo, Humilidad; Liu, Cailian; Rasalan, Teresa; Wolchok, Jedd D.; Croughs, Therese; Morre, Michel; Devlin, Sean M.; van den Brink, Marcel R. M.

    2012-01-01

    Delays in immune recovery after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and relapse. IL-7 has a central role in T-cell development and survival and enhances immune recovery in murine models of allo-HSCT. We performed a phase 1 trial of r-hIL-7 (CYT107) in recipients of T-cell depleted allo-HSCTs. Twelve patients were treated with escalating doses of r-hIL-7 administered weekly for 3 weeks. The study drug was well tolerated with only one patient developing acute skin GVHD. At baseline, patients were profoundly lymphopenic. CYT107 induced a doubling in CD4+ and CD8+ T cells. The main effect of IL-7 was an expansion of effector memory T cells, the predominant subset identified in our patients. There was no significant effect on CD4+CD25+FoxP3+ T cells, NK, or B cells. Importantly, we not only saw quantitative increases in T cells after a short course of IL-7 but also demonstrated an increase in functional T cells, including viral-specific T cells that recognize CMV. Enhanced TCR diversity was also observed after treatment. Our results indicate that r-hIL-7 can enhance immune recovery after a T cell–depleted allo-HSCT without causing significant GVHD or other serious toxicity (www.clinicaltrials.gov; NCT00684008). PMID:23012326

  11. Mathematical Model of Naive T Cell Division and Survival IL-7 Thresholds.

    PubMed

    Reynolds, Joseph; Coles, Mark; Lythe, Grant; Molina-París, Carmen

    2013-01-01

    We develop a mathematical model of the peripheral naive T cell population to study the change in human naive T cell numbers from birth to adulthood, incorporating thymic output and the availability of interleukin-7 (IL-7). The model is formulated as three ordinary differential equations: two describe T cell numbers, in a resting state and progressing through the cell cycle. The third is introduced to describe changes in IL-7 availability. Thymic output is a decreasing function of time, representative of the thymic atrophy observed in aging humans. Each T cell is assumed to possess two interleukin-7 receptor (IL-7R) signaling thresholds: a survival threshold and a second, higher, proliferation threshold. If the IL-7R signaling strength is below its survival threshold, a cell may undergo apoptosis. When the signaling strength is above the survival threshold, but below the proliferation threshold, the cell survives but does not divide. Signaling strength above the proliferation threshold enables entry into cell cycle. Assuming that individual cell thresholds are log-normally distributed, we derive population-average rates for apoptosis and entry into cell cycle. We have analyzed the adiabatic change in homeostasis as thymic output decreases. With a parameter set representative of a healthy individual, the model predicts a unique equilibrium number of T cells. In a parameter range representative of persistent viral or bacterial infection, where naive T cell cycle progression is impaired, a decrease in thymic output may result in the collapse of the naive T cell repertoire.

  12. Transverse water relaxation in whole blood and erythrocytes at 3T, 7T, 9.4T, 11.7T and 16.4T; determination of intracellular hemoglobin and extracellular albumin relaxivities.

    PubMed

    Grgac, Ksenija; Li, Wenbo; Huang, Alan; Qin, Qin; van Zijl, Peter C M

    2017-05-01

    Blood is a physiological substance with multiple water compartments, which contain water-binding proteins such as hemoglobin in erythrocytes and albumin in plasma. Knowing the water transverse (R 2 ) relaxation rates from these different blood compartments is a prerequisite for quantifying the blood oxygenation level-dependent (BOLD) effect. Here, we report the Carr-Purcell-Meiboom-Gill (CPMG) based transverse (R 2CPMG ) relaxation rates of water in bovine blood samples circulated in a perfusion system at physiological temperature in order to mimic blood perfusion in humans. R 2CPMG values of blood plasma, lysed packed erythrocytes, lysed plasma/erythrocyte mixtures, and whole blood at 3 T, 7 T, 9.4 T, 11.7 T and 16.4 T were measured as a function of hematocrit or hemoglobin concentration, oxygenation, and CPMG inter-echo spacing (τ cp ). R 2CPMG in lysed cells showed a small τ cp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than τ cp . This was contrary to the tangential dependence in whole blood, where a much slower exchange between cells and blood plasma applies. Whole blood data were fitted as a function of τ cp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R 2CPMG , and the intercept R 20blood at infinitely short τ cp was determined. The R 20blood values at different hematocrit and the R 2CPMG values of lysed erythrocyte/plasma mixtures at different hemoglobin concentration were used to determine the relaxivity of hemoglobin inside the erythrocyte (r 2Hb ) and albumin (r 2Alb ) in plasma. The r 2Hb values obtained from lysed erythrocytes and whole blood were comparable at full oxygenation. However, while r 2Hb determined from lysed cells showed a linear dependence on oxygenation, this dependence became quadratic in whole blood. This possibly suggests an additional relaxation effect inside intact cells, perhaps due to hemoglobin

  13. Survie au cancer du sein à Rabat (Maroc) 2005-2008

    PubMed Central

    Mechita, Nada Bennani; Tazi, Mohammed Adnane; Er-Raki, Abdelouahed; Mrabet, Mustapha; Saadi, Asma; Benjaafar, Noureddine; Razine, Rachid

    2016-01-01

    Introduction Le cancer du sein représente un problème de santé publique au Maroc. L’objectif de ce travail était d’estimer le taux de survie au cancer du sein chez les patientes habitant la ville de Rabat. Méthodes Etude pronostique réalisée chez les patientes diagnostiquées pour cancer du sein de 2005 à 2008, habitant la ville de Rabat et enregistrées au registre des cancers de Rabat. La date d’inclusion dans l’étude correspondait à la date de confirmation histologique du cancer. L’estimation de la survie a été réalisée par la méthode de Kaplan Meier, et la comparaison entre les différentes classes d’une variable a été réalisée par le test de log rank. L’étude des facteurs associés à la survie a été effectuée par le modèle de Cox. Résultats Durant la période d’étude 628 cas de cancer du sein ont été collectés. Le pourcentage de décès était de 19,9%. La survie globale à un an était de 97,1%, elle était de 89,2% à 3 ans et de 80,6 % à 5 ans. En analyse multivariée la survie au cancer du sein était statistiquement moins bonne chez les patientes âgées de plus de 70 ans (p<0,001), ayantune grande taille de tumeur (p<0,001), un stade avancé d’adénopathies (p=0,007), présentant des métastases (p<0,001) et non traitées par hormonothérapie (p=0,002). Conclusion Une grande taille de la tumeur et la présence de métastases sont des facteurs de mauvais pronostic du cancer du sein d’où la nécessité de renforcer les programmes de dépistage. PMID:28292106

  14. In-vitro Gd-DTPA Relaxometry Studies in Oxygenated Venous Human Blood and Aqueous Solution at 3 and 7T

    PubMed Central

    Kalavagunta, Chaitanya; Michaeli, Shalom; Metzger, Gregory J.

    2014-01-01

    In-vitro T1 and T2* relaxivities (r1 and r2*) of Gd-DTPA (GaD) in oxygenated human venous blood (OVB) and aqueous solution (AS) at 3T and 7T were calculated. GaD concentrations ([GaD]) in OVB and AS were prepared in the range 0–5 mM. All measurements were acquired at 37±2 °C. At both 3T and 7T, a linear relationship was observed between [GaD] and R1 in both AS and OVB. At 7T, r1 in AS decreased by 7.5% (p = 0.045) while there was a negligible change in OVB. With respect to R2*, a linear relationship with [GaD] was only observed in AS, while a more complex relationship was observed in OVB; quadratic below and linear above 2 mM at both field strengths. There was a significant increase of over four-fold in r2* with GaD in OVB at 7T (for [GaD] above 2mM, p ≪0.01) as compared to 3T. Furthermore, in comparison to r1, r2* in AS was less than two-fold higher at both field strengths while in OVB it was ~twenty-fold and ~ninety-fold higher at 3T and 7T, respectively. This observation emphasizes the importance of r2* knowledge at high magnetic fields, ≥3T. The comparison between r1 and r2* presented in this work is crucial in the design and optimization of high field MRI studies making use of paramagnetic contrast agents. This is especially true in multiple compartment systems such as blood where r2* dramatically increases while r1 remains relatively constant with increasing magnetic field strength. PMID:24523062

  15. Overexpression of Escherichia coli udk mimics the absence of T7 Gp2 function and thereby abrogates successful infection by T7 phage.

    PubMed

    Shadrin, Andrey; Sheppard, Carol; Savalia, Dhruti; Severinov, Konstantin; Wigneshweraraj, Sivaramesh

    2013-02-01

    Successful infection of Escherichia coli by bacteriophage T7 relies upon the transcription of the T7 genome by two different RNA polymerases (RNAps). The bacterial RNAp transcribes early T7 promoters, whereas middle and late T7 genes are transcribed by the T7 RNAp. Gp2, a T7-encoded transcription factor, is a 7 kDa product of an essential middle T7 gene 2, and is a potent inhibitor of the host RNAp. The essential biological role of Gp2 is to inhibit transcription of early T7 genes that fail to terminate efficiently in order to facilitate the coordinated usage of the T7 genome by both host and phage RNAps. Overexpression of the E. coli udk gene, which encodes a uridine/cytidine kinase, interferes with T7 infection. We demonstrate that overexpression of udk antagonizes Gp2 function in E. coli in the absence of T7 infection and thus independently of T7-encoded factors. It seems that overexpression of udk reduces Gp2 stability and functionality during T7 infection, which consequently results in inadequate inhibition of host RNAp and in the accumulation of early T7 transcripts. In other words, overexpression of udk mimics the absence of Gp2 during T7 infection. Our study suggests that the transcriptional regulation of the T7 genome is surprisingly complex and might potentially be affected at many levels by phage- and host-encoded factors.

  16. P2X7 receptor expression levels determine lethal effects of a purine based danger signal in T lymphocytes.

    PubMed

    Aswad, Fred; Dennert, Gunther

    2006-09-01

    Contact of T lymphocytes with nicotinamide adenine dinucleotide (NAD) or ATP causes cell death that requires expression of purinergic receptor P2X(7) (P2X(7)R). T cell subsets differ in their responses to NAD and ATP, which awaits a mechanistic explanation. Here, we show that sensitivity to ATP correlates with P2X(7)R expression levels in CD4 cells, CD8 cells and CD4(+)CD25(+) cells from both C57BL/6 and BALB/c mice. But P2X(7)R ligands do not only induce cell death but also shedding of CD62L. It is shown here that in CD62L(high) T cells, CD62L shedding correlates with low expression of P2X(7)Rs and lower cell death, whereas in CD62L(low) cells P2X(7)R expression and death are higher. The possibility is therefore investigated that P2X(7)Rs induce T cell activation. Experiments show that spontaneous T cell proliferation is somewhat higher in cells expressing P2X(7)Rs, but this effect we suggest is caused by P2X(7)R expression on accessory cells.

  17. Interventional loopless antenna at 7 T.

    PubMed

    Ertürk, Mehmet Arcan; El-Sharkawy, Abdel-Monem M; Bottomley, Paul A

    2012-09-01

    The loopless antenna magnetic resonance imaging detector is comprised of a tuned coaxial cable with an extended central conductor that can be fabricated at submillimeter diameters for interventional use in guidewires, catheters, or needles. Prior work up to 4.7 T suggests a near-quadratic gain in signal-to-noise ratio with field strength and safe operation at 3 T. Here, for the first time, the signal-to-noise ratio performance and radiofrequency safety of the loopless antenna are investigated both theoretically, using the electromagnetic method-of-moments, and experimentally in a standard 7 T human scanner. The results are compared with equivalent 3 T devices. An absolute signal-to-noise ratio gain of 5.7 ± 1.5-fold was realized at 7 T vs. 3 T: more than 20-fold higher than at 1.5 T. The effective field-of-view area also increased approximately 10-fold compared with 3 T. Testing in a saline gel phantom suggested that safe operation is possible with maximum local 1-g average specific absorption rates of <12 W kg(-1) and temperature increases of <1.9°C, normalized to a 4 W kg(-1) radiofrequency field exposure at 7 T. The antenna did not affect the power applied to the scanner's transmit coil. The signal-to-noise ratio gain enabled magnetic resonance imaging microscopy at 40-50 μm resolution in diseased human arterial specimens, offering the potential of high-resolution large-field-of-view or endoscopic magnetic resonance imaging for targeted intervention in focal disease. Copyright © 2011 Wiley Periodicals, Inc.

  18. Etude du pronostic maternel et périnatal au cours de l’accouchement chez l’adolescente à Lubumbashi, République Démocratique du Congo

    PubMed Central

    Luhete, Prosper Kakudji; Mukuku, Olivier; Tambwe, Albert Mwembo; Kayamba, Prosper Kalenga Muenze

    2017-01-01

    Introduction L’objectif de cette étude était de déterminer la fréquence et d’évaluer le pronostic maternel et périnatal lors de l’accouchement chez les adolescentes dans la ville de Lubumbashi. Méthodes C’était une étude cas-témoin des accouchées d’une grossesse monofoetale de Décembre 2013 à Mai 2014 dans 10 maternités de référence à Lubumbashi (RD Congo). Les adolescentes (< 20 ans) ont été comparées aux femmes âgées de 20-34 ans. Les paramètres sociodémographiques maternels, la morbi-mortalité maternelle et périnatale ont été analysées. Les statistiques usuelles et la régression logistique ont été utilisées pour analyser les résultats. Le seuil de signification a été fixé à une valeur de p<0,05. Résultats La fréquence d’accouchement chez les adolescentes était de 7,7%. Nous avons observé que la césarienne (ORa=1,9 (1,1-3,1)), l’épisiotomie (ORa=4,2 (2,9-5,9)), la délivrance pathologique (ORa= 2,7 (1,1-6,5)), l’éclampsie (ORa= 4,4 (1,3-14,5)) et le faible poids de naissance (ORa=2,0 (1,3-3,0)) ont été significativement plus élevés chez les adolescentes que chez les adultes. Conclusion L’accouchement chez les adolescentes, comparativement à celui de femmes âgées de 20-34 ans, reste associé à un mauvais pronostic. D’où l’organisation des séances de sensibilisation pour une meilleure fréquentation des services consultations prénatales, une optimisation du dépistage, de la surveillance et de la prévention des pathologies de la grossesse chez les adolescentes s’avère importante et urgente. Introduction This study aimed to determine the frequency and to assess maternal and perinatal prognosis for vaginal delivery in adolescent girls in the city of Lubumbashi. Methods We conducted a case-control study of vaginal deliveries in singleton pregnancy in 10 referral hospitals in Lubumbashi (DR Congo) from December 2013 to May 2014. Adolescent girls (< 20 years) were compared to older women

  19. A self-initiating eukaryotic transient gene expression system based on contransfection of bacteriophage T7 RNA polymerase and DNA vectors containing a T7 autogene.

    PubMed Central

    Chen, X; Li, Y; Xiong, K; Wagner, T E

    1994-01-01

    A novel cytoplasmic gene expression system has been developed. This system differs from other expression systems in that it relies on the co-delivery of plasmid DNA and T7 RNA polymerase (RNAP) during transfection. The plasmid contains a T7 RNAP gene driven by the T7 promoter (T7 autogene) and a functional/reporter gene driven by another T7 promoter (T7T7/T7-gene construct). Once this DNA-enzyme complex is introduced into eukaryotic cells, the transcription of the T7 RNAP and the functional/reporter genes is initiated by the co-delivered T7 RNAP. The T7 RNAP, which is responsible for the initiation and maintenance of expression of both T7 and functional/reporter genes, is replenished by translation of newly synthesized T7 mRNA. This T7 system was designed in such a manner that the expression of the functional/reporter genes can occur in the cytoplasm and does not require any nuclear involvement. When transfected by either a pT7T7/T7Luc or a pT7T7/T7hGH plasmids with the cointroduced T7 RNAP, mouse L cells were found to express high levels of luciferase immediately after transfection, apparently due to the cytoplasmic gene expression; the expression of human growth hormone (hGH) could be sustained for at least 6 days. Both T7 and hGH mRNA were expressed by the cells transfected with pT7T7/T7hGH. These results suggest that this cytoplasmic expression system may be used for certain targets of somatic gene therapy. Images PMID:8029020

  20. Facteurs de risque de la tuberculose multi-résistante dans la ville de Kinshasa en République Démocratique du Congo

    PubMed Central

    Misombo-Kalabela, André; Nguefack-Tsague, Georges; Kalla, Ginette Claude Mireille; Ze, Emmanuel Afane; Diangs, Kimpanga; Panda, Tshapenda; Kebela, Ilunga; Fueza, Serge Bisuta; Magazani, Nzanzu; Mbopi-Kéou, François-Xavier

    2016-01-01

    Introduction L'objectif de cette étude était de déterminer les facteurs de risque associés à la tuberculose multi résistance à Kinshasa en République Démocratique du Congo. Méthodes Il s'agissait d'une étude cas témoins. Les cas comprenaient tous les patients tuberculeux résistants à la rifampicine et à l'isoniazide notifiés à Kinshasa de janvier 2012 à juin 2013. Les témoins étaient les patients tuberculeux traités durant la même période que les cas et qui à la fin du traitement étaient déclarés guéris. Pour cette étude, nous avons obtenu une clairance éthique. Résultats L’échantillon était constitué de 213 participants dont 132 hommes (62%) et 81 femmes (38%). L’âge médian était de 31ans (16-73 ans). Les facteurs associés significatifs (p< 0,05) à la tuberculose multi résistante étaient le non-respect des heures de prise de médicaments (0R = 111) (80% chez les cas et 4% chez les témoins), l’échec au traitement (0R = 20) (76% chez les cas et 13% chez les témoins); la notion de tuberculose multi résistante dans la famille (0R = 6.4) (28% chez les cas et 6% chez les témoins); la méconnaissance de la tuberculose multi résistante (0R = 3.2) (31% chez les cas et 59% chez les témoins); un séjour en prison (0R = 7.6) (10% chez les cas et 1% chez les témoins) et l'interruption du traitement (0R = 6.1) ( 59% chez les cas et 19% chez les témoins). Conclusion L’émergence de la tuberculose multi résistante peut être évitée par la mise en place des stratégies de diagnostic et de traitement appropriées. PMID:27516818

  1. Zn2+-transporters ZIP7 and ZnT7 play important role in progression of cardiac dysfunction via affecting sarco(endo)plasmic reticulum-mitochondria coupling in hyperglycemic cardiomyocytes.

    PubMed

    Tuncay, Erkan; Bitirim, C Verda; Olgar, Yusuf; Durak, Aysegul; Rutter, Guy A; Turan, Belma

    2018-01-04

    Functional contribution of S(E)R-mitochondria coupling to normal cellular processes is crucial and any alteration in S(E)R-mitochondria axis may be responsible for the onset of diseases. Mitochondrial free Zn 2+ level in cardiomyocytes ([Zn 2+ ] Mit ) is lower comparison to either its cytosolic or S(E)R level under physiological condition. However, there is little information about distribution of Zn 2+ -transporters on mitochondria and role of Zn 2+ -dependent mitochondrial-function associated with [Zn 2+ ] Mit . Since we recently have shown how hyperglycemia (HG)-induced changes in ZIP7 and ZnT7 contribute to Zn 2+ -transport across S(E)R and contribute to S(E)R-stress in the heart, herein, we hypothesized that these transporters can also be localized to mitochondria and affect the S(E)R-mitochondria coupling, and thereby contribute to cellular Zn 2+ -muffling between S(E)R-mitochondria in HG-cells. Mitochondrial localizations of ZIP7 and ZnT7 were demonstrated using fluorescence technique while they were confirmed in isolated mitochondrial fractions using biochemical analysis. Markedly decreased ZIP7 and increased ZnT7 levels were measured in isolated mitochondrial fractions from either HG- or doxorubicin, DOX (as positive control)-treated cardiomyocytes. Significantly increases in [Zn 2+ ] Mit and ROS production levels and depolarized mitochondrial membrane potential were also measured in HG cells. The expression levels of some key proteins, responsible for proper S(E)R-mitochondria coupling such as Mfn-1, Fis-1, OPA1, BAP31, STIM1 and PML in either HG- or DOX-cells were supported our above hypothesis, strongly. Overall, this study provides an important description about the role of ZIP7 and ZnT7, localized to both mitochondria and S(E)R and contribute to cellular Zn 2+ -muffling between cellular-compartments in HG or hypertrophic cardiomyocytes via affecting S(E)R-mitochondria coupling. Any alteration in this axis and/or cellular [Zn 2+ ] may provide new

  2. 7 T renal MRI: challenges and promises.

    PubMed

    de Boer, Anneloes; Hoogduin, Johannes M; Blankestijn, Peter J; Li, Xiufeng; Luijten, Peter R; Metzger, Gregory J; Raaijmakers, Alexander J E; Umutlu, Lale; Visser, Fredy; Leiner, Tim

    2016-06-01

    The progression to 7 Tesla (7 T) magnetic resonance imaging (MRI) yields promises of substantial increase in signal-to-noise (SNR) ratio. This increase can be traded off to increase image spatial resolution or to decrease acquisition time. However, renal 7 T MRI remains challenging due to inhomogeneity of the radiofrequency field and due to specific absorption rate (SAR) constraints. A number of studies has been published in the field of renal 7 T imaging. While the focus initially was on anatomic imaging and renal MR angiography, later studies have explored renal functional imaging. Although anatomic imaging remains somewhat limited by inhomogeneous excitation and SAR constraints, functional imaging results are promising. The increased SNR at 7 T has been particularly advantageous for blood oxygen level-dependent and arterial spin labelling MRI, as well as sodium MR imaging, thanks to changes in field-strength-dependent magnetic properties. Here, we provide an overview of the currently available literature on renal 7 T MRI. In addition, we provide a brief overview of challenges and opportunities in renal 7 T MR imaging.

  3. Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP

    PubMed Central

    Mazzucchelli, Renata; Hixon, Julie A.; Spolski, Rosanne; Chen, Xin; Li, Wen Qing; Hall, Veronica L.; Willette-Brown, Jami; Hurwitz, Arthur A.; Leonard, Warren J.

    2008-01-01

    Interleukin-7 (IL-7), a cytokine produced by stromal cells, is required for thymic development and peripheral homeostasis of most major subsets of T cells. We examined whether regulatory T (Treg) cells also required the IL-7 pathway by analyzing IL-7Rα−/− mice. We observed a striking reduction in cells with the Treg surface phenotype (CD4, CD25, GITR (glucocorticoid-induced tumor necrosis factor [TNF]-like receptor), CD45RB, CD62L, CD103) or intracellular markers (cytotoxic T-lymphocyte–associated antigen-4, CTLA-4, and forkhead box transcription factor 3, Foxp3). Foxp3 transcripts were virtually absent in IL-7Rα−/− lymphoid tissues, and no Treg cell suppressive activity could be detected. There are 2 known ligands for IL-7Rα: IL-7 itself and thymic stromal lymphopoietin (TSLP). Surprisingly, mice deficient in IL-7 or the other chain of the TSLP receptor (TSLPR) developed relatively normal numbers of Treg cells. Combined deletion of IL-7 and TSLP receptor greatly reduced Treg cell development in the thymus but was not required for survival of mature peripheral Treg cells. We conclude that Treg cells, like other T cells, require signals from the IL-7 receptor, but unlike other T cells, do not require IL-7 itself because of at least partially overlapping actions of IL-7 and TSLP for development of Treg cells. PMID:18664628

  4. Etude descriptive et analytique du cancer de l’œsophage au Togo

    PubMed Central

    Oumboma, Bouglouga; Mawuli, Lawson-Ananissoh Laté; Aklesso, Bagny; Laconi, Kaaga; Datouda, Redah

    2014-01-01

    Introduction Décrire les aspects épidémiologiques, cliniques, endoscopiques et histologiques du cancer de l’œsophage (CO) au Togo. Méthodes Il s'agit d'une étude rétrospective descriptive et analytique menée sur 8 ans (Janvier 2005-Décembre 2012) dans le service d'hépato-gastroentérologie (HGE) du CHU Campus de Lomé. Etaient inclus les dossiers des patients hospitalisés pour CO confirmé histologiquement. Résultats Sur 8 ans, 24 patients remplissant nos critères d'inclusion ont été retenus soit 3cas de CO par an et 0,55% des hospitalisations. L’âge moyen des patients était de 57,08 ans (extrêmes: 32 et 82 ans). La dysphagie et l’épigastralgie étaient les motifs d'hospitalisation les plus rencontrés. L'alcool (n=15), le tabac (n=13) étaient les facteurs de risque les plus présents. A la fibroscopie, les lésions étaient ulcéro-bourgeonnantes et hémorragiques (n=12), ulcéro-bourgeonnantes (n=5); ces lésions siégeaient au niveau du 1/3 inférieur (n= 11), à l'union 1/3 supérieur 1/3moyen de l’œsophage (n= 13) et aucun au niveau du 1/3 supérieur. Seize lésions étaient des carcinomes épidermoïdes et 3 des adénocarcinomes. L’évolution dans le service a été fatale dans 2cas; 16 patients avaient été transférés en chirurgie pour des soins palliatifs et 5 patients (20,8%) étaient perdus de vue. Conclusion Le CO semble en augmentation au Togo. L'alcool et le tabac sont les facteurs de risque et le pronostic sévère dans notre série est lié au retard diagnostic. Son dépistage précoce passe par une consultation rapide devant toute dysphagie chez un sujet de 50 ans et plus. PMID:25883742

  5. Expression of MCM-3 and MCM-7 in Primary Cutaneous T-cell Lymphomas.

    PubMed

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Reich, Adam; Grzegrzolka, Jedrzej; Maj, Joanna; Dziegiel, Piotr

    2015-11-01

    Primary cutaneous T-cell lymphomas is a group of rare non-Hodgkin lymphomas, originally affecting the skin. Increased proliferation activity is a hallmark of diverse tumors and the proliferation rate, measured by the expression of various markers has a predictive value regarding the malignancy course. The aim of the present study was to evaluate the prognostic value and the potential correlation between the expression of proliferation markers Ki-67, MCM-3 and MCM-7, and clinicopathological data for different types of primary cutaneous T-cell lymphomas. Immunohistochemical reactions were performed on paraffin blocks obtained from 90 patients with mycosis fungoides (MF) and 21 patients with other CTCL (oCTCL), in comparison to 19 patients with benign inflammatory dermatosis (lichen planus, eczema), serving as control. Statistically significant differences in the expression of Ki-67, MCM-3 and MCM-7 were observed between oCTCL vs. the control group (29% vs. 5%; 17% vs. 5%; 13% vs. 1.5%, respectively, ANOVA with Scheffé post-hoc test: p<0.01). In both, MF and oCTCL Ki-67 expression highly correlated with the expression of MCM-3 (r=0.83; p<0.001 and r=0.91; p<0.001, respectively) and MCM-7 (r=0.84; p<0.001 and r=0.87; p<0.01, respectively; Pearson correlation test). Similarly, a strong positive correlation was observed between MCM-3 and MCM-7 (r=0.81, p<0.001 and r=0.85, p<0.001). Regarding the MF group, Ki-67 and MCM-3 expression was significantly higher in advanced compared to early stages (11% vs. 3% and 15.5% vs. 5.0%, respectively, Student's t-test: p<0.05). Advanced MF had also significantly higher labeling indexes for Ki-67, MCM-3 and MCM-7 compared to benign inflammatory dermatoses (Student's t-test: p<0.01, p<0.001 and p=0.02, respectively). Considering skin involvement in MF, T1b had a significantly higher expression of Ki-67, MCM-3 and MCM-7 than T1a (p<0.001 for all comparisons) with similar observations between T2b and T2a (p=0.02; p<0.01; p=0

  6. Aspects cliniques et thérapeutiques des anomalies de la jonction pyélo-urétérale au CHU du point G

    PubMed Central

    Tembely, Aly; Kassogué, Amadou; Berthé, Honoré; Ouattara, Zanafon

    2016-01-01

    Cette étude a été faite pour analyser les aspects cliniques et thérapeutiques des anomalies de la jonction pyélo-urétérale. Etude transversale et descriptive portant sur 35 cas d'anomalies de la jonction pyélo-urétérale (AJPU) colligés au service d'Urologie du CHU du Point G durant une période de 4 ans (Janvier 2010 au Décembre 2014). Les données ont été recueillies sur les fiches d'enquête, les dossiers médicaux et les registres du bloc. Les données sociodémographique, clinique et thérapeutique ont été saisies sur Microsoft Word 2007 et analysées sur Excel 2007 et SPSS 18.0. 35 cas d'AJPU ont été colligés en 4 ans. La moyenne d’âge était de 29,3 ans. La douleur lombaire était le motif de consultation le plus fréquent soit 40%. 20% des patients ont été en consultation pour la première fois 10 ans d’évolution symptomatique. Une destruction rénale avait été observée dans 28,6%. Le couple Echographie + UIV a permis d’établir le diagnostic chez 37,1%. La complication lithiasique était présente chez 17,1% des patients. 51,4% des patients ont reçu une pyéloplastie à ciel ouvert selon Anderson KUSS. L'anomalie de la jonction pyélo-urétérale dans notre étude a été caractérisée par un retard de consultation avec des complications redoutables. La chirurgie à ciel ouvert a été le gold standard avec des résultats satisfaisants. L'endopyéloplastie, la cure de la jonction coelioscopique sont des chirurgies mini invasives non disponible chez nous mais à encourager et à intégrer dans l'arsenal thérapeutique. PMID:27516821

  7. Analyse des facteurs histo-pronostiques du cancer du rectum non métastatique dans une série ouest Algérienne de 58 cas au CHU-Tlemcen

    PubMed Central

    Mesli, Smain Nabil; Regagba, Derbali; Tidjane, Anisse; Benkalfat, Mokhtar; Abi-Ayad, Chakib

    2016-01-01

    Introduction L'objectif de notre travail est d'analyser les facteurs histo-pronostiques des cancers du rectum non métastatique opérés au service de chirurgie «A» de Tlemcen à ouest Algérien durant une période de six ans. Méthodes Etude rétrospective de 58 patients qui avait un adénocarcinome rectal. Le critère de jugement était la survie. Les paramètres étudiés, le sexe, l’âge, stade tumoral, et les récidives tumorales. Résultats L’âge moyen était de 58 ans. Avec 52% d'hommes contre 48% femmes avec sex-ratio (1,08). Le siège tumoral était: moyen rectum avec 41,37%, 34,48% au bas rectum et dans 24,13% au haut rectum. La classification TNM avec 17,65% au stade I, 18,61% au stade II, 53, 44% au stade III et 7,84% au stade IV. La survie médiane globale était de 40 mois ±2,937 mois. La survie en fonction du stade tumoral, le stade III et IV avait un faible taux de survie (19%) a 3 ans contre le stade I, II avait un taux de survie de (75%) (P = 0,000) (IC 95%). Les patients avec récidives tumorales avaient un taux de survie faible à 3 ans par rapport à ceux n'ayant pas eu de récidive (30,85% Vs 64,30% P = 0,043). Conclusion Dans cette série, l’étude uni varié des différents facteurs pronostiques conditionnant la survie n'a permis de retenir que trois facteurs influençant la survie, à savoir la taille tumorale, le stade, et les récidives tumorales. En analyse multi variée en utilisant le modèle Cox un seul facteur été retenu la récidive tumorale. PMID:27583069

  8. Reconstruction de la surface de Fermi dans l'etat normal d'un supraconducteur a haute Tc: Une etude du transport electrique en champ magnetique intense

    NASA Astrophysics Data System (ADS)

    Le Boeuf, David

    Des mesures de resistance longitudinale et de resistance de Hall en champ magnetique intense transverse (perpendiculaire aux plans CuO2) ont ete effectuees au sein de monocristaux de YBa2Cu3Oy (YBCO) demacles, ordonnes et de grande purete, afin d'etudier l'etat fondamental des supraconducteurs a haute Tc dans le regime sous-dope. Cette etude a ete realisee en fonction du dopage et de l'orientation du courant d'excitation J par rapport a l'axe orthorhombique b de la structure cristalline. Les mesures en champ magnetique intense revelent par suppression de la supraconductivite des oscillations magnetiques des resistances longitudinale et de Hall dans YBa2Cu 3O6.51 et YBa2Cu4O8. La conformite du comportement de ces oscillations quantiques au formalisme de Lifshitz-Kosevich, apporte la preuve de l'existence d'une surface de Fermi fermee a caractere quasi-2D, abritant des quasiparticules coherentes respectant la statistique de Fermi-Dirac, dans la phase pseudogap d'YBCO. La faible frequence des oscillations quantiques, combinee avec l'etude de la partie monotone de la resistance de Hall en fonction de la temperature indique que la surface de Fermi d'YBCO sous-dope comprend une petite poche de Fermi occupee par des porteurs de charge negative. Cette particularite de la surface de Fermi dans le regime sous-dope incompatible avec les calculs de structure de bande est en fort contraste avec la structure electronique presente dans le regime surdope. Cette observation implique ainsi l'existence d'un point critique quantique dans le diagramme de phase d'YBCO, au voisinage duquel la surface de Fermi doit subir une reconstruction induite par l'etablissement d'une brisure de la symetrie de translation du reseau cristallin sous-jacent. Enfin, l'etude en fonction du dopage de la resistance de Hall et de la resistance longitudinale en champ magnetique intense suggere qu'un ordre du type onde de densite (DW) est responsable de la reconstruction de la surface de Fermi. L'analogie de

  9. Advances in the T7 phage display system (Review).

    PubMed

    Deng, Xiangying; Wang, Li; You, Xiaolong; Dai, Pei; Zeng, Yanhua

    2018-01-01

    The present review describes the advantages and updated applications of the T7 phage display system in bioscience and medical science. Current phage display systems are based on various bacteriophage vectors, including M13, T7, T4 and f1. Of these, the M13 phage display is the most frequently used, however, the present review highlights the advantages of the T7 system. As a phage display platform, M13 contains single‑stranded DNA, while the T7 phage consists of double‑stranded DNA, which exhibits increased stability and is less prone to mutation during replication. Additional characteristics of the T7 phage include the following: The T7 phage does not depend on a protein secretion pathway in the lytic cycle; expressed peptides and proteins are usually located on the C‑terminal region of capsid protein gp10B, which avoids problems associated with steric hindrance; and T7 phage particles exhibit high stability under various extreme conditions, including high temperature and low pH, which facilitates effective high‑throughput affinity elutriation. Recent applications of the T7 phage display system have been instrumental in uncovering mechanisms of molecular interaction, particularly in the fields of antigen discovery, vaccine development, protein interaction, and cancer diagnosis and treatment.

  10. Fentes labiopalatines dans la province du Katanga en République Démocratique du Congo: Aspects épidémiologiques, anatomocliniques et thérapeutiques

    PubMed Central

    Sangwa, Cedrick Milindi; Mukuku, Olivier; Tshisuz, Christian; Panda, Jules Mulefu; Kakinga, Mireille; Kitembo, Marius Feruzi; Mutomb, Jean-Felix; Odimba, Bwana Fwamba

    2014-01-01

    Les fentes labiopalatines sont les malformations les plus rencontrées de la sphère orofaciale. L'objectif est de décrire le profil épidémiologique, anatomoclinique et thérapeutique des fentes labiopalatines observées dans la province minière du Katanga au sud-est de la République Démocratique du Congo. Il s'agit d'une étude transversale réalisée dans quatre institutions hospitalières de la province du Katanga dans des districts sanitaires différents (Hôpital Jason Sendwe à Lubumbashi, Hôpital Gécamines Panda à Likasi, Hôpital Gécamines du personnel à Kolwezi, Hôpital General de référence de Kamina) et qui a porté sur 154 cas de fentes labiopalatines enregistrés au cours de la période allant du 1er mai 2010 au 30 septembre 2012. L'âge moyen de consultation était de 11,8 ans et une prédominance masculine (55,2%) était notée. Un pic était noté chez les deux premiers nés de la famille (55,8%). Nous avons enregistré 20,7% des cas de consanguinité dont 54,2% de premier degré. La fréquence des différents types de fentes labiopalatines diminue au fur à mesure que la fente s'étend de la lèvre supérieure au palais en passant par l'alvéole : 72% (labiales), 21,4% (labiopalatines) et 7,7% (palatines). Les variétés unilatérales sont plus fréquentes (76,7%) que les bilatérales (16,1%). Dans les formes unilatérales, le côté gauche est plus concerné (47,1%) par rapport au côté droit (38,6%). L'évaluation de la gravité selon Anastassov montre que 50,6% de nos patients étaient de degré moyen et 16,2% étaient à un degré sévère. Les malformations associées ont été retrouvées dans 5% des cas et elles sont à prédominance squelettique. C'est la technique de Millard qui a été la plus pratiquée (72/130). Les résultats étaient excellents dans 71,5% contre 1,5% de mauvais. Le séjour d'hospitalisation était de 3 jours et le taux de complications post opératoire était de 2,98%. PMID:25328615

  11. Assessment of MR-based R2* and quantitative susceptibility mapping for the quantification of liver iron concentration in a mouse model at 7T.

    PubMed

    Simchick, Gregory; Liu, Zhi; Nagy, Tamas; Xiong, May; Zhao, Qun

    2018-03-25

    To assess the feasibility of quantifying liver iron concentration (LIC) using R2* and quantitative susceptibility mapping (QSM) at a high field strength of 7 Tesla (T). Five different concentrations of Fe-dextran were injected into 12 mice to produce various degrees of liver iron overload. After mice were sacrificed, blood and liver samples were harvested. Ferritin enzyme-linked immunosorbent assay (ELISA) and inductively coupled plasma mass spectrometry were performed to quantify serum ferritin concentration and LIC. Multiecho gradient echo MRI was conducted to estimate R2* and the magnetic susceptibility of each liver sample through complex nonlinear least squares fitting and a morphology enabled dipole inversion method, respectively. Average estimates of serum ferritin concentration, LIC, R2*, and susceptibility all show good linear correlations with injected Fe-dextran concentration; however, the standard deviations in the estimates of R2* and susceptibility increase with injected Fe-dextran concentration. Both R2* and susceptibility measurements also show good linear correlations with LIC (R 2  = 0.78 and R 2  = 0.91, respectively), and a susceptibility-to-LIC conversion factor of 0.829 ppm/(mg/g wet) is derived. The feasibility of quantifying LIC using MR-based  R2* and QSM at a high field strength of 7T is demonstrated. Susceptibility quantification, which is an intrinsic property of tissues and benefits from being field-strength independent, is more robust than R2* quantification in this ex vivo study. A susceptibility-to-LIC conversion factor is presented that agrees relatively well with previously published QSM derived results obtained at 1.5T and 3T. © 2018 International Society for Magnetic Resonance in Medicine.

  12. Investigation of specific interactions between T7 promoter and T7 RNA polymerase by force spectroscopy using atomic force microscope.

    PubMed

    Zhang, Xiaojuan; Yao, Zhixuan; Duan, Yanting; Zhang, Xiaomei; Shi, Jinsong; Xu, Zhenghong

    2018-01-11

    The specific recognition and binding of promoter and RNA polymerase is the first step of transcription initiation in bacteria and largely determines transcription activity. Therefore, direct analysis of the interaction between promoter and RNA polymerase in vitro may be a new strategy for promoter characterization, to avoid interference due to the cell's biophysical condition and other regulatory elements. In the present study, the specific interaction between T7 promoter and T7 RNA polymerase was studied as a model system using force spectroscopy based on atomic force microscope (AFM). The specific interaction between T7 promoter and T7 RNA polymerase was verified by control experiments, and the rupture force in this system was measured as 307.2 ± 6.7 pN. The binding between T7 promoter mutants with various promoter activities and T7 RNA polymerase was analyzed. Interaction information including rupture force, rupture distance and binding percentage were obtained in vitro , and reporter gene expression regulated by these promoters was also measured according to a traditional promoter activity characterization method in vivo Using correlation analysis, it was found that the promoter strength characterized by reporter gene expression was closely correlated with rupture force and the binding percentage by force spectroscopy. These results indicated that the analysis of the interaction between promoter and RNA polymerase using AFM-based force spectroscopy was an effective and valid approach for the quantitative characterization of promoters. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  13. Bacteriophage T7 RNA polymerase-based expression in Pichia pastoris.

    PubMed

    Hobl, Birgit; Hock, Björn; Schneck, Sandra; Fischer, Reinhard; Mack, Matthias

    2013-11-01

    A novel Pichia pastoris expression vector (pEZT7) for the production of recombinant proteins employing prokaryotic bacteriophage T7 RNA polymerase (T7 RNAP) (EC 2.7.7.6) and the corresponding promoter pT7 was constructed. The gene for T7 RNAP was stably introduced into the P. pastoris chromosome 2 under control of the (endogenous) constitutive P. pastoris glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter (pGAP). The gene product T7 RNAP was engineered to contain a nuclear localization signal, which directed recombinant T7 RNAP to the P. pastoris nucleus. To promote translation of uncapped T7 RNAP derived transcripts, the internal ribosomal entry site from hepatitis C virus (HCV-IRES) was inserted directly upstream of the multiple cloning site of pEZT7. A P. pastoris autonomous replicating sequence (PARS1) was integrated into pEZT7 enabling propagation and recovery of plasmids from P. pastoris. Rapid amplification of 5' complementary DNA ends (5' RACE) experiments employing the test plasmid pEZT7-EGFP revealed that transcripts indeed initiated at pT7. HCV-IRES mediated translation of the latter mRNAs, however, was not observed. Surprisingly, HCV-IRES and the reverse complement of PARS1 (PARS1rc) were both found to display significant promoter activity as shown by 5' RACE. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Regulator of G Protein Signaling 7 (RGS7) Can Exist in a Homo-oligomeric Form That Is Regulated by Gαo and R7-binding Protein.

    PubMed

    Tayou, Junior; Wang, Qiang; Jang, Geeng-Fu; Pronin, Alexey N; Orlandi, Cesare; Martemyanov, Kirill A; Crabb, John W; Slepak, Vladlen Z

    2016-04-22

    RGS (regulator of G protein signaling) proteins of the R7 subfamily (RGS6, -7, -9, and -11) are highly expressed in neurons where they regulate many physiological processes. R7 RGS proteins contain several distinct domains and form obligatory dimers with the atypical Gβ subunit, Gβ5 They also interact with other proteins such as R7-binding protein, R9-anchoring protein, and the orphan receptors GPR158 and GPR179. These interactions facilitate plasma membrane targeting and stability of R7 proteins and modulate their activity. Here, we investigated RGS7 complexes using in situ chemical cross-linking. We found that in mouse brain and transfected cells cross-linking causes formation of distinct RGS7 complexes. One of the products had the apparent molecular mass of ∼150 kDa on SDS-PAGE and did not contain Gβ5 Mass spectrometry analysis showed no other proteins to be present within the 150-kDa complex in the amount close to stoichiometric with RGS7. This finding suggested that RGS7 could form a homo-oligomer. Indeed, co-immunoprecipitation of differentially tagged RGS7 constructs, with or without chemical cross-linking, demonstrated RGS7 self-association. RGS7-RGS7 interaction required the DEP domain but not the RGS and DHEX domains or the Gβ5 subunit. Using transfected cells and knock-out mice, we demonstrated that R7-binding protein had a strong inhibitory effect on homo-oligomerization of RGS7. In contrast, our data indicated that GPR158 could bind to the RGS7 homo-oligomer without causing its dissociation. Co-expression of constitutively active Gαo prevented the RGS7-RGS7 interaction. These results reveal the existence of RGS protein homo-oligomers and show regulation of their assembly by R7 RGS-binding partners. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Genetic requirements for sensitivity of bacteriophage t7 to dideoxythymidine.

    PubMed

    Tran, Ngoc Q; Tabor, Stanley; Richardson, Charles C

    2014-08-01

    We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373-9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. Genetic Requirements for Sensitivity of Bacteriophage T7 to Dideoxythymidine

    PubMed Central

    Tran, Ngoc Q.; Tabor, Stanley

    2014-01-01

    We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373–9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity. PMID:24858186

  17. IL-7 Receptor Mutations and Steroid Resistance in Pediatric T cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study

    PubMed Central

    Stubbs, Andrew P.; Vroegindeweij, Eric M.; Smits, Willem K.; van Marion, Ronald; Dinjens, Winand N. M.; Horstmann, Martin; Kuiper, Roland P.; Zaman, Guido J. R.; van der Spek, Peter J.; Pieters, Rob; Meijerink, Jules P. P.

    2016-01-01

    Background Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% of pediatric ALL cases and is considered a high-risk disease. T-ALL is often associated with resistance to treatment, including steroids, which are currently the cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival and cure. However, the cellular mechanisms underlying steroid resistance in T-ALL patients are poorly understood. In this study, we combined various genomic datasets in order to identify candidate genetic mechanisms underlying steroid resistance in children undergoing T-ALL treatment. Methods and Findings We performed whole genome sequencing on paired pre-treatment (diagnostic) and post-treatment (remission) samples from 13 patients, and targeted exome sequencing of pre-treatment samples from 69 additional T-ALL patients. We then integrated mutation data with copy number data for 151 mutated genes, and this integrated dataset was tested for associations of mutations with clinical outcomes and in vitro drug response. Our analysis revealed that mutations in JAK1 and KRAS, two genes encoding components of the interleukin 7 receptor (IL7R) signaling pathway, were associated with steroid resistance and poor outcome. We then sequenced JAK1, KRAS, and other genes in this pathway, including IL7R, JAK3, NF1, NRAS, and AKT, in these 69 T-ALL patients and a further 77 T-ALL patients. We identified mutations in 32% (47/146) of patients, the majority of whom had a specific T-ALL subtype (early thymic progenitor ALL or TLX). Based on the outcomes of these patients and their prednisolone responsiveness measured in vitro, we then confirmed that these mutations were associated with both steroid resistance and poor outcome. To explore how these mutations in IL7R signaling pathway genes cause steroid resistance and subsequent poor outcome, we

  18. Comparison of 7T and 3T MRI in patients with moyamoya disease.

    PubMed

    Oh, Byeong Ho; Moon, Hyeong Cheol; Baek, Hyeon Man; Lee, Youn Joo; Kim, Sang Woo; Jeon, Young Jai; Lee, Gun Seok; Kim, Hong Rae; Choi, Jai Ho; Min, Kyung Soo; Lee, Mou Seop; Kim, Young Gyu; Kim, Dong Ho; Kim, Won Seop; Park, Young Seok

    2017-04-01

    Magnetic resonance imaging and magnetic resonance angiography (MRI/MRA) are widely used for evaluating the moyamoya disease (MMD). This study compared the diagnostic accuracy of 7Tesla (T) and 3T MRI/MRA in MMD. In this case control study, 12 patients [median age: 34years; range (10-66years)] with MMD and 12 healthy controls [median age: 25years; range (22-59years)] underwent both 7T and 3T MRI/MRA. To evaluate the accuracy of MRI/MRA in MMD, five criteria were compared between imaging systems of 7T and 3T: Suzuki grading system, internal carotid artery (ICA) diameter, ivy sign, flow void of the basal ganglia on T2-weighted images, and high signal intensity areas of the basal ganglia on time-of-flight (TOF) source images. No difference was observed between 7T and 3T MRI/MRA in Suzuki stage, ICA diameter, and ivy sign score; while, 7T MRI/MRA showed a higher detection rate in the flow void on T2-weighted images and TOF source images (p<0.001). Receiver operating characteristic curves of both T2 and TOF criteria showed that 7T MRI/MRA had higher sensitivity and specificity than 3T MRI/MRA. Our findings indicate that 7T MRI/MRA is superior to 3T MRI/MRA for the diagnosis of MMD in point of detecting the flow void in basal ganglia by T2-weighted and TOF images. Copyright © 2016. Published by Elsevier Inc.

  19. T7-RNA Polymerase

    NASA Technical Reports Server (NTRS)

    1997-01-01

    T7-RNA Polymerase grown on STS-81. Structure-Function Relationships of RNA Polymerase: DNA-dependent RNA polymerase is the key enzyme responsible for the biosynthesis of RNA, a process known as transcription. Principal Investigator's include Dr. Dan Carter, Dr. B.C. Wang, and Dr. John Rose of New Century Pharmaceuticals.

  20. Detailing magnetic field strength dependence and segmental artifact distribution of myocardial effective transverse relaxation rate at 1.5, 3.0, and 7.0 T.

    PubMed

    Meloni, Antonella; Hezel, Fabian; Positano, Vincenzo; Keilberg, Petra; Pepe, Alessia; Lombardi, Massimo; Niendorf, Thoralf

    2014-06-01

    Realizing the challenges and opportunities of effective transverse relaxation rate (R2 *) mapping at high and ultrahigh fields, this work examines magnetic field strength (B0 ) dependence and segmental artifact distribution of myocardial R2 * at 1.5, 3.0, and 7.0 T. Healthy subjects were considered. Three short-axis views of the left ventricle were examined. R2 * was calculated for 16 standard myocardial segments. Global and mid-septum R2 * were determined. For each segment, an artifactual factor was estimated as the deviation of segmental from global R2 * value. The global artifactual factor was significantly enlarged at 7.0 T versus 1.5 T (P = 0.010) but not versus 3.0 T. At 7.0 T, the most severe susceptibility artifacts were detected in the inferior lateral wall. The mid-septum showed minor artifactual factors at 7.0 T, similar to those at 1.5 and 3.0 T. Mean R2 * increased linearly with the field strength, with larger changes for global heart R2 * values. At 7.0 T, segmental heart R2 * analysis is challenging due to macroscopic susceptibility artifacts induced by the heart-lung interface and the posterior vein. Myocardial R2 * depends linearly on the magnetic field strength. The increased R2 * sensitivity at 7.0 T might offer means for susceptibility-weighted and oxygenation level-dependent MR imaging of the myocardium. Copyright © 2013 Wiley Periodicals, Inc.

  1. Identification of direct target genes of miR-7, miR-9, miR-96, and miR-182 in the human breast cancer cell lines MCF-7 and MDA-MB-231.

    PubMed

    Moazzeni, Hamidreza; Najafi, Ali; Khani, Marzieh

    2017-08-01

    Some microRNAs have carcinogenic or tumor suppressive effects in breast cancer, which is the most common cancer in women worldwide. MiR-7 and miR-9 are tumor suppressor microRNAs, which induce apoptosis and inhibit proliferation in breast cancer cells. Moreover, miR-96 and miR-182 are onco-microRNAs that increase proliferation, migration, and tumorigenesis in breast cancer cells. This study aimed to identify the direct target genes of these four microRNAs in the human breast cancer cell lines MCF-7 and MDA-MB-231. Initially, bioinformatics tools were used to identify the target genes that have binding sites for miR-7, MiR-9, MiR-96, and miR-182 and are also associated with breast cancer. Subsequently, the findings of the bioinformatics analysis relating to the effects of these four microRNAs on the 3'-UTR activity of the potential target genes were confirmed using the dual luciferase assay in MCF-7 and MDA-MB-231 cells co-transfected with the vectors containing 3'-UTR segments of the target genes downstream of a luciferase coding gene and each of the microRNAs. Finally, the effects of microRNAs on the endogenous expression of potential target genes were assessed by the overexpression of each of the four microRNAs in MCF-7 and MDA-MB-231 cells. Respectively, three, three, three, and seven genes were found to have binding sites for miR-7, miR-9, miR-96, and miR-182 and were associated with breast cancer. The results of empirical studies including dual luciferase assays and real-time PCR confirmed that miR-7 regulates the expression of BRCA1 and LASP1; MiR-9 regulates the expression of AR; miR-96 regulates the expression of ABCA1; and miR-182 regulates the expression of NBN, TOX3, and LASP1. Taken together, our results suggest that the tumor suppressive effects of miR-7 may be mediated partly by regulating the expression of BRCA1 as a tumor suppressor gene in breast cancer. In addition, this microRNA and miR-182 may have effects on the nodal-positivity and tumor

  2. 7T: Physics, safety, and potential clinical applications.

    PubMed

    Kraff, Oliver; Quick, Harald H

    2017-12-01

    With more than 60 installed magnetic resonance imaging (MRI) systems worldwide operating at a magnetic field strength of 7T or higher, ultrahigh-field (UHF) MRI has been established as a platform for clinically oriented research in recent years. Profound technical and methodological developments have helped overcome the inherent physical challenges of UHF radiofrequency (RF) signal homogenization in the human body. The ongoing development of dedicated RF coil arrays was pivotal in realizing UHF body MRI, beyond mere brain imaging applications. Another precondition to clinical application of 7T MRI is the safety testing of implants and the establishment of safety concepts. Against this backdrop, 7T MRI and MR spectroscopy (MRS) recently have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. This article provides an overview of the immanent physical challenges of 7T UHF MRI and discusses recent technical solutions and safety concepts. Furthermore, recent clinically oriented studies are highlighted that span a broad application spectrum from 7T UHF brain to body MRI. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1573-1589. © 2017 International Society for Magnetic Resonance in Medicine.

  3. A T3 and T7 Recombinant Phage Acquires Efficient Adsorption and a Broader Host Range

    PubMed Central

    Lin, Tiao-Yin; Lo, Yi-Haw; Tseng, Pin-Wei; Chang, Shun-Fu; Lin, Yann-Tsyr; Chen, Ton-Seng

    2012-01-01

    It is usually thought that bacteriophage T7 is female specific, while phage T3 can propagate on male and female Escherichia coli. We found that the growth patterns of phages T7M and T3 do not match the above characteristics, instead showing strain dependent male exclusion. Furthermore, a T3/7 hybrid phage exhibits a broader host range relative to that of T3, T7, as well as T7M, and is able to overcome the male exclusion. The T7M sequence closely resembles that of T3. T3/7 is essentially T3 based, but a DNA fragment containing part of the tail fiber gene 17 is replaced by the T7 sequence. T3 displays inferior adsorption to strains tested herein compared to T7. The T3 and T7 recombinant phage carries altered tail fibers and acquires better adsorption efficiency than T3. How phages T3 and T7 recombine was previously unclear. This study is the first to show that recombination can occur accurately within only 8 base-pair homology, where four-way junction structures are identified. Genomic recombination models based on endonuclease I cleavages at equivalent and nonequivalent sites followed by strand annealing are proposed. Retention of pseudo-palindromes can increase recombination frequency for reviving under stress. PMID:22347414

  4. A T3 and T7 recombinant phage acquires efficient adsorption and a broader host range.

    PubMed

    Lin, Tiao-Yin; Lo, Yi-Haw; Tseng, Pin-Wei; Chang, Shun-Fu; Lin, Yann-Tsyr; Chen, Ton-Seng

    2012-01-01

    It is usually thought that bacteriophage T7 is female specific, while phage T3 can propagate on male and female Escherichia coli. We found that the growth patterns of phages T7M and T3 do not match the above characteristics, instead showing strain dependent male exclusion. Furthermore, a T3/7 hybrid phage exhibits a broader host range relative to that of T3, T7, as well as T7M, and is able to overcome the male exclusion. The T7M sequence closely resembles that of T3. T3/7 is essentially T3 based, but a DNA fragment containing part of the tail fiber gene 17 is replaced by the T7 sequence. T3 displays inferior adsorption to strains tested herein compared to T7. The T3 and T7 recombinant phage carries altered tail fibers and acquires better adsorption efficiency than T3. How phages T3 and T7 recombine was previously unclear. This study is the first to show that recombination can occur accurately within only 8 base-pair homology, where four-way junction structures are identified. Genomic recombination models based on endonuclease I cleavages at equivalent and nonequivalent sites followed by strand annealing are proposed. Retention of pseudo-palindromes can increase recombination frequency for reviving under stress.

  5. Etude aerodynamique d'un jet turbulent impactant une paroi concave

    NASA Astrophysics Data System (ADS)

    LeBlanc, Benoit

    Etant donne la demande croissante de temperatures elevees dans des chambres de combustion de systemes de propulsions en aerospatiale (turbomoteurs, moteur a reaction, etc.), l'interet dans le refroidissement par jets impactant s'est vu croitre. Le refroidissement des aubes de turbine permet une augmentation de temperature de combustion, ce qui se traduit en une augmentation de l'efficacite de combustion et donc une meilleure economie de carburant. Le transfert de chaleur dans les au bages est influence par les aspects aerodynamiques du refroidissement a jet, particulierement dans le cas d'ecoulements turbulents. Un manque de comprehension de l'aerodynamique a l'interieur de ces espaces confinees peut mener a des changements de transfert thermique qui sont inattendus, ce qui augmente le risque de fluage. Il est donc d'interet pour l'industrie aerospatiale et l'academie de poursuivre la recherche dans l'aerodynamique des jets turbulents impactant les parois courbes. Les jets impactant les surfaces courbes ont deja fait l'objet de nombreuses etudes. Par contre des conditions oscillatoires observees en laboratoire se sont averees difficiles a reproduire en numerique, puisque les structures d'ecoulements impactants des parois concaves sont fortement dependantes de la turbulence et des effets instationnaires. Une etude experimentale fut realisee a l'institut PPRIME a l'Universite de Poitiers afin d'observer le phenomene d'oscillation dans le jet. Une serie d'essais ont verifie les conditions d'ecoulement laminaires et turbulentes, toutefois le cout des essais experimentaux a seulement permis d'avoir un apercu du phenomene global. Une deuxieme serie d'essais fut realisee numeriquement a l'Universite de Moncton avec l'outil OpenFOAM pour des conditions d'ecoulement laminaire et bidimensionnel. Cette etude a donc comme but de poursuivre l'enquete de l'aerodynamique oscillatoire des jets impactant des parois courbes, mais pour un regime d'ecoulement transitoire, turbulent

  6. Key clinical benefits of neuroimaging at 7T.

    PubMed

    Trattnig, Siegfried; Springer, Elisabeth; Bogner, Wolfgang; Hangel, Gilbert; Strasser, Bernhard; Dymerska, Barbara; Cardoso, Pedro Lima; Robinson, Simon Daniel

    2018-03-01

    The growing interest in ultra-high field MRI, with more than 35.000 MR examinations already performed at 7T, is related to improved clinical results with regard to morphological as well as functional and metabolic capabilities. Since the signal-to-noise ratio increases with the field strength of the MR scanner, the most evident application at 7T is to gain higher spatial resolution in the brain compared to 3T. Of specific clinical interest for neuro applications is the cerebral cortex at 7T, for the detection of changes in cortical structure, like the visualization of cortical microinfarcts and cortical plaques in Multiple Sclerosis. In imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology may be visualized with excellent spatial resolution. Using Susceptibility Weighted Imaging, the plaque-vessel relationship and iron accumulations in Multiple Sclerosis can be visualized, which may provide a prognostic factor of disease. Vascular imaging is a highly promising field for 7T which is dealt with in a separate dedicated article in this special issue. The static and dynamic blood oxygenation level-dependent contrast also increases with the field strength, which significantly improves the accuracy of pre-surgical evaluation of vital brain areas before tumor removal. Improvement in acquisition and hardware technology have also resulted in an increasing number of MR spectroscopic imaging studies in patients at 7T. More recent parallel imaging and short-TR acquisition approaches have overcome the limitations of scan time and spatial resolution, thereby allowing imaging matrix sizes of up to 128×128. The benefits of these acquisition approaches for investigation of brain tumors and Multiple Sclerosis have been shown recently. Together, these possibilities demonstrate the feasibility and advantages of conducting routine diagnostic imaging and clinical research at 7T. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights

  7. Evaluation of 39 medical implants at 7.0 T

    PubMed Central

    Feng, David X; McCauley, Joseph P; Morgan–Curtis, Fea K; Salam, Redoan A; Pennell, David R; Loveless, Mary E

    2015-01-01

    Objective: With increased signal to noise ratios, 7.0-T MRI has the potential to contribute unique information regarding anatomy and pathophysiology of a disease. However, concerns for the safety of subjects with metallic medical implants have hindered advancement in this field. The purpose of the present research was to evaluate the MRI safety for 39 commonly used medical implants at 7.0 T. Methods: Selected metallic implants were tested for magnetic field interactions, radiofrequency-induced heating and artefacts using standardized testing techniques. Results: 5 of the 39 implants tested may be unsafe for subjects undergoing MRI at 7.0 T. Conclusion: Implants were deemed either “MR Conditional” or “MR Unsafe” for the 7.0-T MRI environment. Further research is needed to expand the existing database categorizing implants that are acceptable for patients referred for MRI examinations at 7.0 T. Advances in knowledge: Lack of MRI testing for common metallic medical implants limits the translational potential of 7.0-T MRI. For safety reasons, patients with metallic implants are not allowed to undergo a 7.0-T MRI scan, precluding part of the population that can benefit from the detailed resolution of ultra-high-field MRIs. This investigation provides necessary MRI testing of common medical implants at 7.0 T. PMID:26481696

  8. The robustness of T2 value as a trabecular structural index at multiple spatial resolutions of 7 Tesla MRI.

    PubMed

    Lee, D K; Song, Y K; Park, B W; Cho, H P; Yeom, J S; Cho, G; Cho, H

    2018-04-15

    To evaluate the robustness of MR transverse relaxation times of trabecular bone from spin-echo and gradient-echo acquisitions at multiple spatial resolutions of 7 T. The effects of MRI resolutions to T 2 and T2* of trabecular bone were numerically evaluated by Monte Carlo simulations. T 2 , T2*, and trabecular structural indices from multislice multi-echo and UTE acquisitions were measured in defatted human distal femoral condyles on a 7 T scanner. Reference structural indices were extracted from high-resolution microcomputed tomography images. For bovine knee trabecular samples with intact bone marrow, T 2 and T2* were measured by degrading spatial resolutions on a 7 T system. In the defatted trabecular experiment, both T 2 and T2* values showed strong ( |r| > 0.80) correlations with trabecular spacing and number, at a high spatial resolution of 125 µm 3 . The correlations for MR image-segmentation-derived structural indices were significantly degraded ( |r| < 0.50) at spatial resolutions of 250 and 500 µm 3 . The correlations for T2* rapidly dropped ( |r| < 0.50) at a spatial resolution of 500 µm 3 , whereas those for T 2 remained consistently high ( |r| > 0.85). In the bovine trabecular experiments with intact marrow, low-resolution (approximately 1 mm 3 , 2 minutes) T 2 values did not shorten ( |r| > 0.95 with respect to approximately 0.4 mm 3 , 11 minutes) and maintained consistent correlations ( |r| > 0.70) with respect to trabecular spacing (turbo spin echo, 22.5 minutes). T 2 measurements of trabeculae at 7T are robust with degrading spatial resolution and may be preferable in assessing trabecular spacing index with reduced scan time, when high-resolution 3D micro-MRI is difficult to obtain. © 2018 International Society for Magnetic Resonance in Medicine.

  9. Séroprévalence et facteurs associés à l’acceptation du Conseil et Dépistage Volontaire du VIH chez l’enfant à Lubumbashi, République Démocratique du Congo

    PubMed Central

    Ngwej, Dieudonné Tshikwej; Mukuku, Olivier; Malonga, Françoise Kaj; Luboya, Oscar Numbi; Kakoma, Jean-Baptiste Sakatolo; Wembonyama, Stanis Okitotsho

    2017-01-01

    Résumé Introduction Malgré le dépistage du VIH proposé lors de la naissance ou au cours des consultations préscolaires, la proportion des enfants qui croissent ou décèdent sous statut sérologique au VIH inconnu est importante en République Démocratique du Congo (RDC). L’objectif de cette étude était de déterminer la séroprévalence au cours d’un dépistage volontaire et d’identifier les facteurs associés à l’acceptation du conseil et dépistage du VIH (CDV) en dehors de la maladie ou de toute exposition au VIH dans une population pédiatrique à Lubumbashi, RDC. Méthodes Il s’agissait d’une étude prospective transversale à visée analytique menée du 1er août 2006 au 31 septembre 2007. Elle avait été réalisée dans 4 centres communautaires de CDV répartis dans 4 zones de santé de la ville de Lubumbashi en RDC (Lubumbashi, Ruashi, Kampemba et de Kenya). L’étude avait consisté à faire le dépistage volontaire du VIH chez les enfants de moins de 15 ans. Les caractéristiques sociodémographiques et les paramètres relatifs au conseil et dépistage volontaire ont été étudiés. Les analyses statistiques descriptives usuelles et une régression logistique ont été réalisées. Résultats Sur 463 enfants dépistés du VIH, 41 (8,9%; IC 95%: 6,5%-11,9%) ont été testés positifs. L’acceptation du conseil et dépistage volontaire du VIH en dehors de la maladie ou de l’exposition au VIH était significativement plus élevée lorsque l’enfant était âgé de plus de 2 ans (Odds ratio ajusté (ORa) = 3,6 [IC 95%: 1,1-12,2]), lorsque le statut sérologique du VIH des parents était négatif ou inconnu (ORa = 27,4 [IC 95%: 9,4-80,0]), lorsque l’un ou l’autre ou les deux parents biologiques étaient en vie (ORa = 24,9 [IC 95%: 2,4-250,8]) et lorsque la connaissance du lieu de dépistage était fait par des moyens autres que le professionnel de santé (ORa = 2,9 [IC 95%: 1,0-7,9]). Conclusion Notre étude montre une forte

  10. Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor beta receptor (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2).

    PubMed

    Ross, T S; Bernard, O A; Berger, R; Gilliland, D G

    1998-06-15

    We report the fusion of the Huntingtin interactin protein 1 (HIP1) gene to the platelet-derived growth factor betareceptor (PDGFbetaR) gene in a patient with chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone marrow cells with a PDGFbetaR gene probe demonstrated rearrangement of the PDGFbetaR gene. Anchored polymerase chain reaction using PDGFbetaR primers identified a chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGFbetaR gene on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid screening for proteins that interact with Huntingtin, the mutated protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFbetaR fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGFbetaR. The reciprocal PDGFbetaR/HIP1 transcript is not expressed. HIP1/PDGFbetaR is a 180-kD protein when expressed in the murine hematopoietic cell line, Ba/F3, and is constitutively tyrosine phosphorylated. Furthermore, HIP1/PDGFbetaR transforms the Ba/F3 cells to interleukin-3-independent growth. These data are consistent with an alternative mechanism for activation of PDGFbetaR tyrosine kinase activity by fusion with HIP1, leading to transformation of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis of hematopoietic malignancies.

  11. Portage vaginal du streptocoque du groupe B chez la femme enceinte au niveau de la région de Marrakech

    PubMed Central

    Bassir, Ahlam; Dhibou, Hanane; Farah, Majdi; Mohamed, Lharmis; Amal, Addebous; Nabila, Souraa; Abderahim, Aboulfalah; Asmouki, Hamid; Soummani, Abderraouf

    2016-01-01

    Introduction Le streptocoque du groupe B est le principal agent impliqué dans les infections materno-fœtales, les septicémies et les méningites du nouveau-né à terme. L'objectif est de déterminer le taux de portage maternel du streptocoque du groupe B (SGB) à terme. Méthodes Un prélèvement vaginal a été réalisé de manière prospective chez 275 parturientes lors de l'entrée en salle d'accouchement sur une période de 06 mois. Résultats Le taux de portage était de 20,2%. Le portage était variable en fonction de l’âge gestationnel, il constitue 57.5% entre 37 et 38 semaines d'aménorrhée. Aucun des facteurs de risque n'a était statistiquement prédictif du portage maternel du SGB. Conclusion Le dépistage doit être réalisé à partir de 37 semaines d'aménorrhée, et comme le portage est intermittent, un prélèvement négatif ne garantirait pas que le portage soit négatif à l'accouchement. PMID:27222693

  12. 7 CFR 29.3052 - Red color (R).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Red color (R). 29.3052 Section 29.3052 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Red color (R). A brownish red. [24 FR 8771, Oct. 29, 1959. Redesignated at 47 FR 51722, Nov. 17, 1982...

  13. 7 CFR 29.3052 - Red color (R).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Red color (R). 29.3052 Section 29.3052 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Red color (R). A brownish red. [24 FR 8771, Oct. 29, 1959. Redesignated at 47 FR 51722, Nov. 17, 1982...

  14. 7 CFR 29.3052 - Red color (R).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Red color (R). 29.3052 Section 29.3052 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Red color (R). A brownish red. [24 FR 8771, Oct. 29, 1959. Redesignated at 47 FR 51722, Nov. 17, 1982...

  15. 7 CFR 29.3052 - Red color (R).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Red color (R). 29.3052 Section 29.3052 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Red color (R). A brownish red. [24 FR 8771, Oct. 29, 1959. Redesignated at 47 FR 51722, Nov. 17, 1982...

  16. 7 CFR 29.3052 - Red color (R).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Red color (R). 29.3052 Section 29.3052 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Red color (R). A brownish red. [24 FR 8771, Oct. 29, 1959. Redesignated at 47 FR 51722, Nov. 17, 1982...

  17. Statistical power comparisons at 3T and 7T with a GO / NOGO task.

    PubMed

    Torrisi, Salvatore; Chen, Gang; Glen, Daniel; Bandettini, Peter A; Baker, Chris I; Reynolds, Richard; Yen-Ting Liu, Jeffrey; Leshin, Joseph; Balderston, Nicholas; Grillon, Christian; Ernst, Monique

    2018-07-15

    The field of cognitive neuroscience is weighing evidence about whether to move from standard field strength to ultra-high field (UHF). The present study contributes to the evidence by comparing a cognitive neuroscience paradigm at 3 Tesla (3T) and 7 Tesla (7T). The goal was to test and demonstrate the practical effects of field strength on a standard GO/NOGO task using accessible preprocessing and analysis tools. Two independent matched healthy samples (N = 31 each) were analyzed at 3T and 7T. Results show gains at 7T in statistical strength, the detection of smaller effects and group-level power. With an increased availability of UHF scanners, these gains may be exploited by cognitive neuroscientists and other neuroimaging researchers to develop more efficient or comprehensive experimental designs and, given the same sample size, achieve greater statistical power at 7T. Published by Elsevier Inc.

  18. Etude de la qualité bactériologique de l’eau utilisée dans l’industrie agroalimentaire dans le Nord du Maroc

    PubMed Central

    Haijoubi, El Houcine; Benyahya, Fatiha; Bendahou, Abdrezzak; Essadqui, Faima Zahra; Behhari, Mohammed El; El Mamoune, Ahmed Fouad; Ghailani, Naima Nourouti; Mechita, Mohcine Bennani; Barakat, Amina

    2017-01-01

    Introduction L'eau est utilisée d'une façon primordiale dans tout le processus de la fabrication des produits alimentaires. Les industries agroalimentaires du Nord du Maroc utilisent différentes sources d'eaux mais l'eau de réseau public et l'eau de puits sont les principales sources d'eau utilisée. Cette eau peut s'avérer la source principale des éventuelles contaminations et altérations des aliments. Notre but est d'évaluer la qualité bactériologique de l'eau utilisée par les industries agroalimentaires dans la région du Nord du Maroc, d'identifier les différents germes responsables de la pollution de ces eaux et de définir les principales causes de cette pollution. Méthodes Des échantillons d'eau prélevés aux robinets ou des puits ont été analysés pour la recherche des germes indicateurs de la pollution (coliformes totaux (CT), coliformes fécaux (CF), entérocoques intestinaux (E), microorganismes revivifiables (MOR), anaérobies sulfitoréducteurs) et les germes pathogènes (Salmonelles, Staphylocoques, Pseudomonas aeruginosa). Le dénombrement des bactéries a été fait par la technique de filtration et par incorporation en milieu solide en surfusion. Résultats Les résultats ont montré que les eaux du réseau public ont été de qualité bactériologique satisfaisante tandis que 40% des eaux des puits ont été non conformes aux normes à cause de la présence des indicateurs de pollution CT, CF, E et MOR. En revanche, les germes pathogènes, en particulier les Salmonelles, ont été absents dans les eaux de tous les puits analysés. Conclusion La pollution de ces puits a été généralement liée au non-respect des conditions de puisage hygiéniques. La qualité bactériologique des eaux de ces puits peut être améliorée par une protection adéquate. PMID:28450992

  19. Translocation by T7 RNA polymerase: a sensitively poised Brownian ratchet.

    PubMed

    Guo, Qing; Sousa, Rui

    2006-04-21

    Studies of halted T7 RNA polymerase (T7RNAP) elongation complexes (ECs) or of T7RNAP transcription against roadblocks due to DNA-bound proteins indicate that T7RNAP translocates via a passive Brownian ratchet mechanism. Crystal structures of T7RNAP ECs suggest that translocation involves an active power-stroke. However, neither solution studies of halted or slowed T7RNAP ECs, nor crystal structures of static complexes, are necessarily relevant to how T7RNAP translocates during rapid elongation. A recent single molecule study of actively elongating T7RNAPs provides support for the Brownian ratchet mechanism. Here, we obtain additional evidence for the existence of a Brownian ratchet during active T7RNAP elongation by showing that both rapidly elongating and halted complexes are equally sensitive to pyrophosphate. Using chemical nucleases tethered to the polymerase we achieve sub-ångström resolution in measuring the average position of halted T7RNAP ECs and find that the positional equilibrium of the EC is sensitively poised between pre-translocated and post-translocated states. This may be important in maximizing the sensitivity of the polymerase to sequences that cause pausing or termination. We also confirm that a crystallographically observed disorder to order transition in a loop formed by residues 589-612 also occurs in solution and is coupled to pyrophosphate or NTP release. This transition allows the loop to make interactions with the DNA that help stabilize the laterally mobile, ligand-free EC against dissociation.

  20. Dynamic Blue Light-Inducible T7 RNA Polymerases (Opto-T7RNAPs) for Precise Spatiotemporal Gene Expression Control.

    PubMed

    Baumschlager, Armin; Aoki, Stephanie K; Khammash, Mustafa

    2017-11-17

    Light has emerged as a control input for biological systems due to its precise spatiotemporal resolution. The limited toolset for light control in bacteria motivated us to develop a light-inducible transcription system that is independent from cellular regulation through the use of an orthogonal RNA polymerase. Here, we present our engineered blue light-responsive T7 RNA polymerases (Opto-T7RNAPs) that show properties such as low leakiness of gene expression in the dark state, high expression strength when induced with blue light, and an inducible range of more than 300-fold. Following optimization of the system to reduce expression variability, we created a variant that returns to the inactive dark state within minutes once the blue light is turned off. This allows for precise dynamic control of gene expression, which is a key aspect for most applications using optogenetic regulation. The regulators, which only require blue light from ordinary light-emitting diodes for induction, were developed and tested in the bacterium Escherichia coli, which is a crucial cell factory for biotechnology due to its fast and inexpensive cultivation and well understood physiology and genetics. Opto-T7RNAP, with minor alterations, should be extendable to other bacterial species as well as eukaryotes such as mammalian cells and yeast in which the T7 RNA polymerase and the light-inducible Vivid regulator have been shown to be functional. We anticipate that our approach will expand the applicability of using light as an inducer for gene expression independent from cellular regulation and allow for a more reliable dynamic control of synthetic and natural gene networks.

  1. Study of the Tributyl Phosphate--30 Percent Dodecane Solvent; ETUDE DU SOLVANT PHOSPHATE TRIBUTYLIQUE 30 PERCENT--DODECANE (in French)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leroy, P.

    1967-07-01

    This study, originating mainly from a literature survey, gives the principal chemical and physical features of the tributyl-phosphate (TBP) agent diluted at 30 volumes per cent in dodecane. The mixture is a very commonly used extractant in nuclear fuel processing. In this paper, the main following points are reported: -) the components (TBP and diluents) -) the TBP-diluents systems (non-loaded), -) the TBP-diluents-water systems, -) TBP-diluents-water-nitric acid systems, and -) industrial solvents. (author) [French] Cette etude, d'origine bibliographique, regroupe les caracteristiques physico-chimiques essentielles du phosphate tributylique (TBP) dilue a 30% en volume dans du dodecane. Ce melange constitue un agentmore » d'extraction tres utilise dans le traitement des combustibles nucleaires. Les principaux points traites sont les suivants: -) les constituants (TBP et diluants), -) les systemes TBP-diluants non charges, -) les systemes TBP-diluants-eau, -) les systemes TBP-diluants-eau-acide nitrique, et -) les solvants industriels. (auteur)« less

  2. Etude des aspects cliniques, échographiques et nutritionnels du syndrome des ovaires micropolykystiques (SOMPK) à Mbuji-Mayi, RD du Congo

    PubMed Central

    Kalenda, Louis Mbuyamba Ntobo; Mikenji, Justin Biayi; Nkoy, Albert Mwembo-Tambwe; Kayamba, Prosper Kalenga Muenze

    2014-01-01

    Introduction Le Syndrome des Ovaires Micropolykystiques (SOMPK) est polymorphe. L'objectif de cette étude était de déterminer la prévalence et rechercher les facteurs nutritionnels éventuellement associés. Méthodes Chez 300 patientes atteintes de SOMPK faisant l'objet de cette étude, les données anamnestiques, cliniques et échographiques, et les habitudes alimentaires ont été analysées. Les statistiques usuelles et les mesures d'association ont été utilisées pour analyser les résultats. Résultats La prévalence de SOMPK était de 23,6%. L’âge moyen des patientes avec SOMPK était 24 ± 7 ans et chez celles sans SOMPK 36 ± 7 ans (P < 0,05). Le risque de développer le SOMPK en présence d'un niveau de vie élevé était de 2,03 (RR = 2,03; IC à 95%: 1,73-2,38; P = 0,00). Le risque de développer le SOMPK en exerçant une activité légère est de 2,15 (RR = 2,15; IC à 95%: 1,87-2,87; P= 0,00). La proportion des patientes avec SOMPK ayant accumulé plus de 2400 kcal était de 59% vs 36% (P < 0,05) et le risque de développer le SOMPK lorsque l’énergie accumulée était supérieure à 2400 kcal était de 1,57 (RR = 1,57; IC à 95%: 1,33-1,85; P= 0,00). Conclusion Dans notre milieu la prévalence de SOMPK était de 23,6%. Les facteurs associés au SOMPK étaient l’âge, l’énergie accumulée de plus de 2400 Kcal, le niveau socio-économique élevé et l'activité physique légère. Des études analytiques plus poussées sont nécessaires, pour évaluer la force du risque que représentent ces différents facteurs étudiés. PMID:25870722

  3. 46 CFR 35.40-7 - Carbon dioxide alarm-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Carbon dioxide alarm-T/ALL. 35.40-7 Section 35.40-7... Requirements-TB/ALL. § 35.40-7 Carbon dioxide alarm—T/ALL. Adjacent to all carbon dioxide fire extinguishing... AT ONCE. CARBON DIOXIDE BEING RELEASED.” ...

  4. Hémophilie: état des lieux dans un service de pédiatrie dans la région de l'oriental du Maroc

    PubMed Central

    Benajiba, Noufissa; Boussaadni, Yousra EL; Aljabri, Mohammed; Bentata, Yassamine; Amrani, Rim; Rkain, Maria

    2014-01-01

    Pour les pays en voie de développement, l'hémophilie continue d’être une maladie de conséquence médicale et sociale désastreuse. Le but de ce travail est d'analyser le suivi d'une cohorte de patients hémophiles. Patients et méthodes: étude prospective étalée sur deux années et menée au centre référent d'hémophilie dans la région de l'orient du Maroc. Ont été inclus tous les patients présentant une hémophilie confirmée et âgé de moins de 18 ans. Résultats: sur 16 hémophiles, Quinze patients présentait une hémophilie A, l’âge moyen des patients était de 6,18 ans, la forme sévère, représentait 20,7%, la forme modérée: 33,3% et la forme mineure: 40%. Les circonstances de découverte étaient post circoncisionnelle chez 53,3% des patients, 20,7% post traumatique, 20% à l’âge de la marche; la durée d’évolution variait entre 2 mois et 10 ans. L'hémarthrose a été décrite au niveau des genoux, coudes et chevilles, avec une moyenne allant de 2 à 5 fois par an; l'arthropathie a été remarquée dans 33,3%. Le bilan immunologique a révélé des facteurs circulant inhibant chez deux patients. Le traitement était à base d'antalgiques, de plasma frais congelé. L'administration de facteurs VIII recombinés a été instaurée chez 40,6% des patients (plus de 90% des formes modérées et graves), grâce au programme national de prise en charge des hémophiles. Le décès était noté dans un seul cas lié à une hémorragie cérébrale. Conclusion: Nous insistons sur l'intérêt du programme national de prise en charge des hémophiles dernièrement instauré qui pourrait améliorer les conditions de vie de ces enfants. PMID:25404986

  5. Expression of fusion IL2-B7.1(IgV+C) and effects on T lymphocytes.

    PubMed

    Kong, Linghong; Li, Yaochen; Yang, Ye; Li, Kangsheng

    2007-12-01

    The search for an effective immunotherapeutic treatment for tumors is an important area of cancer research. To prepare a more effective form of the bifunctional fusion protein IL2-B7.1(IgV+C) and analyze its effect on the stimulation of T lymphocyte proliferation, we used DNAStar 5.03 software to predict the structural diversity and biochemical character of IL2-B7.1(IgV+C). We then prepared fusion protein IL2-B7.1(IgV+C) by establishing its prokaryotic expression system, and tested its effect on the stimulation of T lymphocytes in vitro. The results indicated that IL2-B7.1(IgV+C) correctly formed a secondary structure in which both IL2 and B7.1(IgV+C) maintained their original hydrophilicity and epitopes. Western blot analysis revealed that IL2-B7.1(IgV+C) was efficiently expressed. Our analysis of CTLL-2 and T-cell proliferation showed that recombinant human (rh) IL2-B7.1(IgV+C) exerted the combined stimulating effects of both rhIL2 and rh B7.1(IgV+C) on cell proliferation, and that these effects could be blocked by adding either anti-IL2 or anti-B7.1 monoclonal antibodies. A >2-fold increase in [3H]TdR incorporation compared with that of cells treated with recombinant protein IL2, or B7.1(IgV+C) alone, revealed that rhIL2-B7.1(IgV+C) had dose-dependent synergetic effects on T-cell activation in the presence of anti-CD3 monoclonal antibody. We concluded that the augmented potency of rhIL2-B7.1(IgV+C) resulted in a stronger stimulation of T-cell proliferation than either rhB7.1(IgV+C) or rhIL2 alone.

  6. Arabidopsis ARGONAUTE7 selects miR390 through multiple checkpoints during RISC assembly

    PubMed Central

    Endo, Yayoi; Iwakawa, Hiro-oki; Tomari, Yukihide

    2013-01-01

    Plant ARGONAUTE7 (AGO7) assembles RNA-induced silencing complex (RISC) specifically with miR390 and regulates the auxin-signalling pathway via production of TAS3 trans-acting siRNAs (tasiRNAs). However, how AGO7 discerns miR390 among other miRNAs remains unclear. Here, we show that the 5′ adenosine of miR390 and the central region of miR390/miR390* duplex are critical for the specific interaction with AGO7. Furthermore, despite the existence of mismatches in the seed and central regions of the duplex, cleavage of the miR390* strand is required for maturation of AGO7–RISC. These findings suggest that AGO7 uses multiple checkpoints to select miR390, thereby circumventing promiscuous tasiRNA production. PMID:23732541

  7. Arabidopsis ARGONAUTE7 selects miR390 through multiple checkpoints during RISC assembly.

    PubMed

    Endo, Yayoi; Iwakawa, Hiro-oki; Tomari, Yukihide

    2013-07-01

    Plant ARGONAUTE7 (AGO7) assembles RNA-induced silencing complex (RISC) specifically with miR390 and regulates the auxin-signalling pathway via production of TAS3 trans-acting siRNAs (tasiRNAs). However, how AGO7 discerns miR390 among other miRNAs remains unclear. Here, we show that the 5' adenosine of miR390 and the central region of miR390/miR390* duplex are critical for the specific interaction with AGO7. Furthermore, despite the existence of mismatches in the seed and central regions of the duplex, cleavage of the miR390* strand is required for maturation of AGO7-RISC. These findings suggest that AGO7 uses multiple checkpoints to select miR390, thereby circumventing promiscuous tasiRNA production.

  8. A validation of dynamic causal modelling for 7T fMRI.

    PubMed

    Tak, S; Noh, J; Cheong, C; Zeidman, P; Razi, A; Penny, W D; Friston, K J

    2018-07-15

    There is growing interest in ultra-high field magnetic resonance imaging (MRI) in cognitive and clinical neuroscience studies. However, the benefits offered by higher field strength have not been evaluated in terms of effective connectivity and dynamic causal modelling (DCM). In this study, we address the validity of DCM for 7T functional MRI data at two levels. First, we evaluate the predictive validity of DCM estimates based upon 3T and 7T in terms of reproducibility. Second, we assess improvements in the efficiency of DCM estimates at 7T, in terms of the entropy of the posterior distribution over model parameters (i.e., information gain). Using empirical data recorded during fist-closing movements with 3T and 7T fMRI, we found a high reproducibility of average connectivity and condition-specific changes in connectivity - as quantified by the intra-class correlation coefficient (ICC = 0.862 and 0.936, respectively). Furthermore, we found that the posterior entropy of 7T parameter estimates was substantially less than that of 3T parameter estimates; suggesting the 7T data are more informative - and furnish more efficient estimates. In the framework of DCM, we treated field-dependent parameters for the BOLD signal model as free parameters, to accommodate fMRI data at 3T and 7T. In addition, we made the resting blood volume fraction a free parameter, because different brain regions can differ in their vascularization. In this paper, we showed DCM enables one to infer changes in effective connectivity from 7T data reliably and efficiently. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Diagnostic et prévalence du syndrome métabolique chez les diabétiques suivis dans un contexte de ressources limitées: cas du Burkina-Faso

    PubMed Central

    Marceline, Yaméogo Téné; Issiaka, Sombié; Gilberte, Kyélem Carole; Nadège, Rouamba; Macaire, Ouédraogo Sampawindé; Arsène, Yaméogo Aimé; Djingri, Lankoandé; Apollinaire, Sawadogo; Joseph, Drabo Youssouf

    2014-01-01

    Introduction Les conséquences du syndrome métabolique impliquent son diagnostic effectif pour une prise en charge globale des comorbidités dépistées. Objectif: Déterminer la capacité à diagnostiquer le syndrome métabolique en routine, sa prévalence chez les diabétiques, leurs connaissances et pratiques vis-à-vis du risque cardio-métabolique. Méthodes Il s'est agi d'une étude transversale auprès de 388 diabétiques au CHU de Bobo-Dioulasso. Les critères de la fédération internationale du diabète (2009) ont été utilisés. Résultats l’âge moyen était de 53,5±13,5 ans, le sex ratio de 0,7. L'obésité abdominale était présente dans 61,9% des cas; L'HTA l’était dans 56,4% des cas. La prescription du bilan lipidique a été documentée dans 55,4% des cas pour le HDL et 56,2% pour les triglycérides pour un taux de réalisation de 49,3% et 62,9%. Le taux de dépistage des critères lipidiques était de 26,8%. Un taux de HDL bas a été noté dans 46 cas (43,4%) et une hypertriglycéridémie dans 24 cas (17,6%). In fine, la prévalence du syndrome métabolique était de 48,9% (n = 190). Seuls 27,4% savaient que d'autres facteurs de risque cardiovasculaire pouvaient être associés au diabète et seulement 6,7% pratiquaient une activité physique régulière. Conclusion Malgré la faible contribution du laboratoire, le syndrome métabolique est fréquent parmi nos diabétiques. Les patients sont peu sensibilisés sur le risque vasculaire et la pratique d'une activité physique régulière reste faible. Un programme d’éducation adaptée contribuerait à un meilleur dépistage et à une prise en charge optimale des cas. PMID:25932077

  10. Kinetics of the R + NO2 reactions (R = i-C3H7, n-C3H7, s-C4H9, and t-C4H9) in the temperature range 201-489 K.

    PubMed

    Rissanen, Matti P; Arppe, Suula L; Eskola, Arkke J; Tammi, Matti M; Timonen, Raimo S

    2010-04-15

    The bimolecular rate coefficients of four alkyl radical reactions with NO(2) have been measured in direct time-resolved experiments. Reactions were studied under pseudo-first-order conditions in a temperature-controlled tubular flow reactor coupled to a laser photolysis/photoionization mass spectrometer (LP-PIMS). The measured reaction rate coefficients are independent of helium bath gas pressure within the experimental ranges covered and exhibit negative temperature dependence. For i-C(3)H(7) + NO(2) and t-C(4)H(9) + NO(2) reactions, the dependence of ordinate (logarithm of reaction rate coefficients) on abscissa (1/T or log(T)) was nonlinear. The obtained results (in cm(3) s(-1)) can be expressed by the following equations: k(n-C(3)H(7) + NO(2)) = ((4.34 +/- 0.08) x 10(-11)) (T/300 K)(-0.14+/-0.08) (203-473 K, 1-7 Torr), k(i-C(3)H(7) + NO(2)) = ((3.66 +/- 2.54) x 10(-12)) exp(656 +/- 201 K/T)(T/300 K)(1.26+/-0.68) (220-489 K, 1-11 Torr), k(s-C(4)H(9) + NO(2)) = ((4.99 +/- 0.16) x 10(-11))(T/300 K)(-1.74+/-0.12) (241-485 K, 2 - 12 Torr) and k(t-C(4)H(9) + NO(2)) = ((8.64 +/- 4.61) x 10(-12)) exp(413 +/- 154 K/T)(T/300 K)(0.51+/-0.55) (201-480 K, 2-11 Torr), where the uncertainties shown refer only to the 1 standard deviations obtained from the fitting procedure. The estimated overall uncertainty in the determined bimolecular rate coefficients is about +/-20%.

  11. 46 CFR 35.40-7 - Carbon dioxide alarm-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Carbon dioxide alarm-T/ALL. 35.40-7 Section 35.40-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS OPERATIONS Posting and Marking Requirements-TB/ALL. § 35.40-7 Carbon dioxide alarm—T/ALL. Adjacent to all carbon dioxide fire extinguishing...

  12. Target-specific copper hybrid T7 phage particles.

    PubMed

    Dasa, Siva Sai Krishna; Jin, Qiaoling; Chen, Chin-Tu; Chen, Liaohai

    2012-12-18

    Target-specific nanoparticles have attracted significant attention recently, and have greatly impacted life and physical sciences as new agents for imaging, diagnosis, and therapy, as well as building blocks for the assembly of novel complex materials. While most of these particles are synthesized by chemical conjugation of an affinity reagent to polymer or inorganic nanoparticles, we are promoting the use of phage particles as a carrier to host organic or inorganic functional components, as well as to display the affinity reagent on the phage surface, taking advantage of the fact that some phages host well-established vectors for protein expression. An affinity reagent can be structured in a desired geometry on the surface of phage particles, and more importantly, the number of the affinity reagent molecules per phage particle can be precisely controlled. We previously have reported the use of the T7 phage capsid as a template for synthesizing target-specific metal nanoparticles. In this study herein, we reported the synthesis of nanoparticles using an intact T7 phage as a scaffold from which to extend 415 copies of a peptide that contains a hexahistidine (6His) motif for capture of copper ions and staging the conversion of copper ions to copper metal, and a cyclic Arginine-Glycine-Aspartic Acid (RGD4C) motif for targeting integrin and cancer cells. We demonstrated that the recombinant phage could load copper ions under low bulk copper concentrations without interfering with its target specificity. Further reduction of copper ions to copper metal rendered a very stable copper hybrid T7 phage, which prevents the detachment of copper from phage particles and maintains the phage structural integrity even under harsh conditions. Cancer cells (MCF-7) can selectively uptake copper hybrid T7 phage particles through ligand-mediated transmembrane transportation, whereas normal control cells (MCF-12F) uptake 1000-fold less. We further demonstrated that copper hybrid T7

  13. MicroRNA-24 promotes 3T3-L1 adipocyte differentiation by directly targeting the MAPK7 signaling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jin, Min, E-mail: min_jin@zju.edu.cn; Wu, Yutao; Wang, Jing

    Over the past years, MicroRNAs (miRNAs) act as a vital role in harmony with gene regulation and maintaining cellular homeostasis. It is well testified that miRNAshave been involved in numerous physiological and pathological processes, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes, and it is tightly modulated by a series of transcription factors such as peroxisome proliferator-activated receptor γ (PPAR-γ) and sterol regulatory-element binding proteins 1 (SREBP1). However, the molecular mechanisms underlying the connection between miRNAs and adipogenesis-related transcription factors remain obscure. In this study,more » we unveiled that miR- 24 was remarkably upregulated during 3T3-L1 adipogenesis. Overexpression of miR-24 significantly promoted 3T3-L1 adipogenesis, as evidenced by its ability to increase the expression of PPAR-γ and SREBP1, lipid droplet formation and triglyceride (TG) accumulation. Furthermore, we found that neither ectopic expression of miR-24nor miR-24 inhibitor affect cell proliferation and cell cycle progression. Finally, we demonstrated that miR-24 plays the modulational role by directly repressing MAPK7, a key number in the MAPK signaling pathway. These data indicate that miR-24 is a novel positive regulator of adipocyte differentiation by targeting MAPK7, which provides new insights into the molecular mechanism of miRNA-mediated cellular differentiation. -- Highlights: •We firstly found miR-24 was upregulated in 3T3-L1 pre-adipocytes differentiation. •miR-24 promoted 3T3-L1 pre-adipocytes differentiation while silencing the expression of miR-24 had an opposite function. •miR-24 regulated 3T3-L1 differentiation by directly targeting MAPK7 signaling pathway. •miR-24did not affect 3T3-L1 pre-adipocytes cellular proliferation.« less

  14. Functional Architecture of T7 RNA Polymerase Transcription Complexes

    PubMed Central

    Nayak, Dhananjaya; Guo, Qing; Sousa, Rui

    2007-01-01

    Summary T7 RNA polymerase is the best-characterized member of a widespread family of single-subunit RNA polymerases. Crystal structures of T7 RNA polymerase initiation and elongation complexes have provided a wealth of detailed information on RNA polymerase interactions with the promoter and transcription bubble, but the absence of DNA downstream of the melted region of the template in the initiation complex structure, and the absence of DNA upstream of the transcription bubble in the elongation complex structure means that our picture of the functional architecture of T7 RNA polymerase transcription complexes remains incomplete. Here we use the site-specifically tethered chemical nucleases and functional characterization of directed T7 RNAP mutants to both reveal the architecture of the duplex DNA that flanks the transcription bubble in the T7 RNAP initiation and elongation complexes, and to define the function of the interactions made by these duplex elements. We find that downstream duplex interactions made with a cluster of lysines (K711/K713/K714) are present during both elongation and initiation where they contribute to stabilizing a bend in the downstream DNA that is important for promoter opening. The upstream DNA in the elongation complex is also found to be sharply bent at the upstream edge of the transcription bubble, thereby allowing formation of upstream duplex:polymerase interactions that contribute to elongation complex stability. PMID:17580086

  15. Place du traitement chirurgical sous circulation extracorporelle à cœur battant dans les cancers du rein avec envahissement cave supra-diaphragmatique: à propos de sept cas

    PubMed Central

    Lahyani, Mounir; Karmouni, Tarik; Elkhader, Khalid; Koutani, Abdellatif; Andaloussi, Ahmed Ibn Attya

    2014-01-01

    Ce travail vise à analyser les résultats de la néphrectomie avec thrombectomie atrio-cave sous circulation extracorporelle (CEC) chez sept patients ayant un cancer du rein avec envahissement cave supra-diaphragmatique et de discuter les indications opératoires. Sept patients, six hommes et une femme dont l’âge varie entre 46ans et 65ans, ont été opérés d'un cancer du rein avec extension atrio-cave. L’écho-doppler a toujours permis la mise en évidence de l'extension veineuse mais la limite supérieure du thrombus était formellement identifiée par l'examen tomodensitométrique quatre fois, et par la résonance magnétique nucléaire dans tous les cas. Tous les patients ont été opérés sous CEC à cœur battant en normothermie. Un seul décès postopératoire est survenu. La durée du séjour en réanimation a été de 4,5 jours. Cinq patients ont eu à distance une dissémination métastatique. Cinq malades ont eu une médiane de survie de 11,5 mois (de 7 à16). Un malade a subi une métastasectomie pulmonaire 6 mois après la néphrectomie. L'exérèse des thrombi atrio-caves a été facilitée par la CEC avec une mortalité et une morbidité postopératoires acceptables mais les résultats à distance ont été décevants. Cette intervention ne peut être proposée qu'aux patients n'ayant aucune extension locorégionale et générale décelable, ce qui souligne l'importance des examens morphologiques préopératoires. PMID:25995777

  16. T2L2 on JASON-2: First Evaluation of the Flying Model

    DTIC Science & Technology

    2007-01-01

    Para, J.-M. Torre R&D Metrology CNRS/GEMINI Observatoire de la Côte d’Azur Caussol, France E-mail: philippe.guillemot@cnes.fr Abstract...Laser Link” experiment T2L2 [1], under development at OCA (Observatoire de la Côte d’Azur) and CNES (Centre National d’Etudes Spatiales), France, will be...Experimental Astronomy, 7, 191-207. [2] P. Fridelance and C. Veillet, 1995, “Operation and data analysis in the LASSO experiment,” Metrologia

  17. Cloning and expression of autogenes encoding RNA polymerases of T7-like bacteriophages

    DOEpatents

    Studier, F. William; Dubendorff, John W.

    1998-01-01

    This invention relates to the cloning and expression of autogenes encoding RNA polymerases of T7 and T7-like bacteriophages, in which the RNA polymerase gene is transcribed from a promoter which is recognized by the encoded RNA polymerase. Cloning of T7 autogenes was achieved by reducing the activity of the RNA polymerase sufficiently to permit host cell growth. T7 RNA polymerase activity was controlled by combining two independent methods: lac-repression of the recombinant lac operator-T7 promoter in the autogene and inhibition of the polymerase by T7 lysozyme. Expression systems for producing the RNA polymerases of T7 and other T7-like bacteriophages, and expression systems for producing selected gene products are described, as well as other related materials and methods.

  18. Cloning and expression of autogenes encoding RNA polymerases of T7-like bacteriophages

    DOEpatents

    Studier, F.W.; Dubendorff, J.W.

    1998-10-20

    This invention relates to the cloning and expression of autogenes encoding RNA polymerases of T7 and T7-like bacteriophages, in which the RNA polymerase gene is transcribed from a promoter which is recognized by the encoded RNA polymerase. Cloning of T7 autogenes was achieved by reducing the activity of the RNA polymerase sufficiently to permit host cell growth. T7 RNA polymerase activity was controlled by combining two independent methods: lac-repression of the recombinant lac operator-T7 promoter in the autogene and inhibition of the polymerase by T7 lysozyme. Expression systems for producing the RNA polymerases of T7 and other T7-like bacteriophages, and expression systems for producing selected gene products are described, as well as other related materials and methods. 12 figs.

  19. Cloning and expression of autogenes encoding RNA polymerases of T7-like bacteriophages

    DOEpatents

    Studier, F.W.; Dubendorff, J.W.

    1998-11-03

    This invention relates to the cloning and expression of autogenes encoding RNA polymerases of T7 and T7-like bacteriophages, in which the RNA polymerase gene is transcribed from a promoter which is recognized by the encoded RNA polymerase. Cloning of T7 autogenes was achieved by reducing the activity of the RNA polymerase sufficiently to permit host cell growth. T7 RNA polymerase activity was controlled by combining two independent methods: lac-repression of the recombinant lac operator-T7 promoter in the autogene and inhibition of the polymerase by T7 lysozyme. Expression systems for producing the RNA polymerases of T7 and other T7-like bacteriophages, and expression systems for producing selected gene products are described, as well as other related materials and methods. 12 figs.

  20. MEG-guided analysis of 7T-MRI in patients with epilepsy.

    PubMed

    Colon, A J; Osch, M J P van; Buijs, M; Grond, J V D; Hillebrand, A; Schijns, O; Wagner, G J; Ossenblok, P; Hofman, P; Buchem, M A V; Boon, P

    2018-05-26

    To study possible detection of structural abnormalities on 7T MRI that were not detected on 3T MRI and estimate the added value of MEG-guidance. For abnormalities found, analysis of convergence between clinical, MEG and 7T MRI localization of suspected epileptogenic foci. In adult patients with well-documented localization-related epilepsy in whom a previous 3T MRI did not demonstrate an epileptogenic lesion but MEG indicated a plausible epileptogenic focus, 7T MRI was performed. Based on semiologic data, visual analysis of the 7T images was performed as well as based on prior MEG results. Correlation with other data from the patient charts, for as far as these were available, was analysed. To establish the level of concordance between the three observers the generalized or Fleiss kappa was calculated. In 3/19 patients abnormalities that, based on semiology, could plausibly represent an epileptogenic lesion were detected using 7T MRI. In an additional 3/19 an abnormality was detected after MEG-guidance. However, in these later cases there was no concordance among the three observers with regard to the presence of a structural abnormality. In one of these three cases intracranial recording was performed, proving the possible abnormality on 7T MRI to be the epileptogenic focus. In 32% of patients 7T MRI showed abnormalities that could indicate an epileptogenic lesion whereas previous 3T MRI did not, especially when visual inspection was guided by the presence of focal interictal MEG abnormalities. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. Gold in the layered structures of R 3Au 7Sn 3: From relativity to versatility

    DOE PAGES

    Provino, Alessia; Steinberg, Simon Alexander; Smetana, Volodymyr; ...

    2016-07-11

    A new isotypic series of ternary rare earth element-gold-tetrel intermetallic compounds has been synthesized and their structures and properties have been characterized. R 3Au 7Sn 3 (R = Y, La-Nd, Sm, Gd-Tm, Lu) crystallize with the hexagonal Gd 3Au 7Sn 3 prototype (Pearson symbol hP26; P6 3/m, a = 8.110-8.372 Å, c = 9.351-9.609 Å, V cell = 532.7-583.3 Å3, Z = 2), an ordered variant of the Cu 10Sn 3-type. Their structure is built up by GdPt 2Sn-type layers, which feature edge-sharing Sn@Au 6 trigonal antiprisms connected by trigonal R3 groups. Additional insertion of gold atoms leads to themore » formation of new homoatomic Au clusters, Au@Au 6; alternatively, the structure can be considered as a superstructural polyhedral packing of the ZrBeSi-type. The magnetization, heat ca-pacity and electrical resistivity have been measured for R 3Au 7Sn 3 (R = Ce, Pr, Nd and Tb). All four compounds order antiferromagnetically with the highest T N of 13 K for Tb 3Au 7Sn 3. In Ce 3Au 7Sn 3, which has a T N of 2.9 K, the heat capacity and electrical resistivity data in zero and applied fields indicate the presence of Kondo interactions. The coefficient of the linear term in the electronic heat capacity, γ, derived from the heat capacity data below 0.5 K is 211 mJ/Ce mol K 2 suggesting strong electronic correlations due to the Kondo interaction. The electronic structure calculations based on the projector augmented wave method for particular representatives of the series suggest different tendencies of the localized R-4f AOs to hybridize with the valence states. LMTO-based bonding analysis on the non-magnetic La 3Au 7Sn 3 indicates that the integrated crystal orbital Hamilton popu-lations (COHPs) are dominated by the heteroatomic Au–Sn contacts; however, contributions from La–Au and La–Sn separations are significant, both together exceeding 40 % in the overall bonding. Furthermore, homoatomic Au–Au interactions are evident for the Au@Au 6 units but, despite of the

  2. Gold in the layered structures of R 3Au 7Sn 3: From relativity to versatility

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Provino, Alessia; Steinberg, Simon Alexander; Smetana, Volodymyr

    A new isotypic series of ternary rare earth element-gold-tetrel intermetallic compounds has been synthesized and their structures and properties have been characterized. R 3Au 7Sn 3 (R = Y, La-Nd, Sm, Gd-Tm, Lu) crystallize with the hexagonal Gd 3Au 7Sn 3 prototype (Pearson symbol hP26; P6 3/m, a = 8.110-8.372 Å, c = 9.351-9.609 Å, V cell = 532.7-583.3 Å3, Z = 2), an ordered variant of the Cu 10Sn 3-type. Their structure is built up by GdPt 2Sn-type layers, which feature edge-sharing Sn@Au 6 trigonal antiprisms connected by trigonal R3 groups. Additional insertion of gold atoms leads to themore » formation of new homoatomic Au clusters, Au@Au 6; alternatively, the structure can be considered as a superstructural polyhedral packing of the ZrBeSi-type. The magnetization, heat ca-pacity and electrical resistivity have been measured for R 3Au 7Sn 3 (R = Ce, Pr, Nd and Tb). All four compounds order antiferromagnetically with the highest T N of 13 K for Tb 3Au 7Sn 3. In Ce 3Au 7Sn 3, which has a T N of 2.9 K, the heat capacity and electrical resistivity data in zero and applied fields indicate the presence of Kondo interactions. The coefficient of the linear term in the electronic heat capacity, γ, derived from the heat capacity data below 0.5 K is 211 mJ/Ce mol K 2 suggesting strong electronic correlations due to the Kondo interaction. The electronic structure calculations based on the projector augmented wave method for particular representatives of the series suggest different tendencies of the localized R-4f AOs to hybridize with the valence states. LMTO-based bonding analysis on the non-magnetic La 3Au 7Sn 3 indicates that the integrated crystal orbital Hamilton popu-lations (COHPs) are dominated by the heteroatomic Au–Sn contacts; however, contributions from La–Au and La–Sn separations are significant, both together exceeding 40 % in the overall bonding. Furthermore, homoatomic Au–Au interactions are evident for the Au@Au 6 units but, despite of the

  3. α7nAchR/NMDAR coupling affects NMDAR function and object recognition.

    PubMed

    Li, Shupeng; Nai, Qiang; Lipina, Tatiana V; Roder, John C; Liu, Fang

    2013-12-20

    The α7 nicotinic acetylcholine receptor (nAchR) and NMDA glutamate receptor (NMDAR) are both ligand-gated ion channels permeable to Ca2+ and Na+. Previous studies have demonstrated functional modulation of NMDARs by nAchRs, although the molecular mechanism remains largely unknown. We have previously reported that α7nAchR forms a protein complex with the NMDAR through a protein-protein interaction. We also developed an interfering peptide that is able to disrupt the α7nAchR-NMDAR complex and blocks cue-induced reinstatement of nicotine-seeking in rat models of relapse. In the present study, we investigated whether the α7nAchR-NMDAR interaction is responsible for the functional modulation of NMDAR by α7nAchR using both electrophysiological and behavioral tests. We have found that activation of α7nAchR upregulates NMDAR-mediated whole cell currents and LTP of mEPSC in cultured hippocampal neurons, which can be abolished by the interfering peptide that disrupts the α7nAchR-NMDAR interaction. Moreover, administration of the interfering peptide in mice impairs novel object recognition but not Morris water maze performance. Our results suggest that α7nAchR/NMDAR coupling may selectively affect some aspects of learning and memory.

  4. Magnetic resonance spectroscopy of the canine brain at 3.0 T and 7.0 T.

    PubMed

    Martin-Vaquero, Paula; da Costa, Ronaldo C; Echandi, Rita L; Sammet, Christina L; Knopp, Michael V; Sammet, Steffen

    2012-08-01

    The purpose of this study was to evaluate the feasibility of proton magnetic resonance spectroscopy (1H MRS) to study the concentration of metabolites in the brain of dogs at 3.0 and 7.0 T. Four healthy male beagles were scanned using 3.0 T and 7.0 T human magnetic resonance imaging (MRI) units. The results obtained showed that all dogs had excellent quality spectra for a small (1 cm3) and large (8 cm3) voxel at 3.0 T, whereas only 2 dogs had high quality spectra at 7.0 T due to insufficient water suppression. 1H MRS at 3.0 T appears to be a reliable method to study metabolite concentrations in the canine brain. The development of more advanced water suppression techniques is necessary to improve the results at 7.0 T. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Engineering T7 bacteriophage as a potential DNA vaccine targeting delivery vector.

    PubMed

    Xu, Hai; Bao, Xi; Wang, Yiwei; Xu, Yue; Deng, Bihua; Lu, Yu; Hou, Jibo

    2018-03-20

    DNA delivery with bacteriophage by surface-displayed mammalian cell penetrating peptides has been reported. Although, various phages have been used to facilitate DNA transfer by surface displaying the protein transduction domain of human immunodeficiency virus type 1 Tat protein (Tat peptide), no similar study has been conducted using T7 phage. In this study, we engineeredT7 phage as a DNA targeting delivery vector to facilitate cellular internalization. We constructed recombinant T7 phages that displayed Tat peptide on their surface and carried eukaryotic expression box (EEB) as a part of their genomes (T7-EEB-Tat). We demonstrated that T7 phage harboring foreign gene insertion had packaged into infective progeny phage particles. Moreover, when mammalian cells that were briefly exposed to T7-EEB-Tat, expressed a significant higher level of the marker gene with the control cells infected with the wide type phage without displaying Tat peptides. These data suggested that the potential of T7 phage as an effective delivery vector for DNA vaccine transfer.

  6. Structural reorganization of the interleukin-7 signaling complex

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McElroy, Craig A.; Holland, Paul J.; Zhao, Peng

    2012-06-29

    We report here an unliganded receptor structure in the common gamma-chain ({gamma}{sub c}) family of receptors and cytokines. The crystal structure of the unliganded form of the interleukin-7 alpha receptor (IL-7R{alpha}) extracellular domain (ECD) at 2.15 {angstrom} resolution reveals a homodimer forming an 'X' geometry looking down onto the cell surface with the C termini of the two chains separated by 110 {angstrom} and the dimer interface comprising residues critical for IL-7 binding. Further biophysical studies indicate a weak association of the IL-7R{alpha} ECDs but a stronger association between the {gamma}{sub c}/IL-7R{alpha} ECDs, similar to previous studies of the full-lengthmore » receptors on CD4{sup +} T cells. Based on these and previous results, we propose a molecular mechanism detailing the progression from the inactive IL-7R{alpha} homodimer and IL-7R{alpha}-{gamma}{sub c} heterodimer to the active IL-7-IL-7R{alpha}-{gamma}{sub c} ternary complex whereby the two receptors undergo at least a 90{sup o} rotation away from the cell surface, moving the C termini of IL-7R{alpha} and {gamma}{sub c} from a distance of 110 {angstrom} to less than 30 {angstrom} at the cell surface. This molecular mechanism can be used to explain recently discovered IL-7- and {gamma}{sub c}-independent gain-of-function mutations in IL-7R{alpha} from B- and T-cell acute lymphoblastic leukemia patients. The mechanism may also be applicable to other {gamma}{sub c} receptors that form inactive homodimers and heterodimers independent of their cytokines.« less

  7. Myristic Acid-Modified DA7R Peptide for Whole-Process Glioma-Targeted Drug Delivery.

    PubMed

    Ying, Man; Wang, Songli; Zhang, Mingfei; Wang, Ruifeng; Zhu, Hangchang; Ruan, Huitong; Ran, Danni; Chai, Zhilan; Wang, Xiaoyi; Lu, Weiyue

    2018-06-13

    The clinical treatment of aggressive glioma has been a great challenge, mainly because of the complexity of the glioma microenvironment and the existence of the blood-brain tumor barrier (BBTB)/blood-brain barrier (BBB), which severely hampers the effective accumulation of most therapeutic agents in the glioma region. Additionally, vasculogenic mimicry (VM), angiogenesis, and glioma stem cells (GSC) in malignant glioma also lead to the failure of clinical therapy. To address the aforementioned issues, a whole-process glioma-targeted drug delivery strategy was proposed. The D A7R peptide has effective BBTB-penetrating and notable glioma-, angiogenesis-, and VM-targeting abilities. Herein, we designed a myristic acid modified D A7R ligand (MC- D A7R), which combines tumor-homing D A7R with BBB-penetrable MC. MC- D A7R was then immobilized to PEGylated liposomes (MC- D A7R-LS) to form a whole-process glioma-targeting system. MC- D A7R-LS exhibited exceptional internalization in glioma, tumor neovascular, and brain capillary endothelial cells. Enhanced BBTB- and BBB-traversing efficiencies were also observed on MC- D A7R-LS. Ex vivo imaging on brain tumors also demonstrated the feasibility of MC- D A7R-LS in intracranial glioma-homing, whereas the immunofluorescence studies demonstrated its GSC and angiogenesis homing. Furthermore, doxorubicin-loaded MC- D A7R-LS accomplished a remarkable therapeutic outcome, as a result of a synergistic improvement on the glioma microenvironment. Our study highlights the potential of the MC-modified D A7R peptide as a great candidate for the whole-process glioma-targeted drug delivery.

  8. Feasibility of imaging superficial palmar arch using micro-ultrasound, 7T and 3T magnetic resonance imaging.

    PubMed

    Pruzan, Alison N; Kaufman, Audrey E; Calcagno, Claudia; Zhou, Yu; Fayad, Zahi A; Mani, Venkatesh

    2017-02-28

    To demonstrate feasibility of vessel wall imaging of the superficial palmar arch using high frequency micro-ultrasound, 7T and 3T magnetic resonance imaging (MRI). Four subjects (ages 22-50 years) were scanned on a micro-ultrasound system with a 45-MHz transducer (Vevo 2100, VisualSonics). Subjects' hands were then imaged on a 3T clinical MR scanner (Siemens Biograph MMR) using an 8-channel special purpose phased array carotid coil. Lastly, subjects' hands were imaged on a 7T clinical MR scanner (Siemens Magnetom 7T Whole Body Scanner) using a custom built 8-channel transmit receive carotid coil. All three imaging modalities were subjectively analyzed for image quality and visualization of the vessel wall. Results of this very preliminary study indicated that vessel wall imaging of the superficial palmar arch was feasible with a whole body 7T and 3T MRI in comparison with micro-ultrasound. Subjective analysis of image quality (1-5 scale, 1: poorest, 5: best) from B mode, ultrasound, 3T SPACE MRI and 7T SPACE MRI indicated that the image quality obtained at 7T was superior to both 3T MRI and micro-ultrasound. The 3D SPACE sequence at both 7T and 3T MRI with isotropic voxels allowed for multi-planar reformatting of images and allowed for less operator dependent results as compared to high frequency micro-ultrasound imaging. Although quantitative analysis revealed that there was no significant difference between the three methods, the 7T Tesla trended to have better visibility of the vessel and its wall. Imaging of smaller arteries at the 7T is feasible for evaluating atherosclerosis burden and may be of clinical relevance in multiple diseases.

  9. CoRoT-7b: SUPER-EARTH OR SUPER-Io?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barnes, Rory; Kaib, Nathan A.; Raymond, Sean N.

    2010-02-01

    CoRoT-7b, a planet about 70% larger than the Earth orbiting a Sun-like star, is the first-discovered rocky exoplanet, and hence has been dubbed a 'super-Earth'. Some initial studies suggested that since the planet is so close to its host star, it receives enough insolation to partially melt its surface. However, these past studies failed to take into consideration the role that tides may play in this system. Even if the planet's eccentricity has always been zero, we show that tidal decay of the semimajor axis could have been large enough that the planet formed on a wider orbit which receivedmore » less insolation. Moreover, CoRoT-7b could be tidally heated at a rate that dominates its geophysics and drives extreme volcanism. In this case, CoRoT-7b is a 'super-Io' that, like Jupiter's volcanic moon, is dominated by volcanism and rapid resurfacing. Such heating could occur with an eccentricity of just 10{sup -5}. This small value could be driven by CoRoT-7c if its own eccentricity is larger than {approx}10{sup -4}. CoRoT-7b may be the first of a class of planetary super-Ios likely to be revealed by the CoRoT and Kepler spacecraft.« less

  10. Gadolinium-based magnetic resonance contrast agents at 7 Tesla: in vitro T1 relaxivities in human blood plasma.

    PubMed

    Noebauer-Huhmann, Iris M; Szomolanyi, Pavol; Juras, Vladimír; Kraff, Oliver; Ladd, Mark E; Trattnig, Siegfried

    2010-09-01

    PURPOSE/INTRODUCTION: The aim of this study was to determine the T1 relaxivities (r1) of 8 gadolinium (Gd)-based MR contrast agents in human blood plasma at 7 Tesla, compared with 3 Tesla. Eight commercially available Gd-based MR contrast agents were diluted in human blood plasma to concentrations of 0, 0.25, 0.5, 1, and 2 mmol/L. In vitro measurements were performed at 37 degrees C, on a 7 Tesla and on a 3 Tesla whole-body magnetic resonance imaging scanner. For the determination of T1 relaxation times, Inversion Recovery Sequences with inversion times from 0 to 3500 ms were used. The relaxivities were calculated. The r1 relaxivities of all agents, diluted in human blood plasma at body temperature, were lower at 7 Tesla than at 3 Tesla. The values at 3 Tesla were comparable to those published earlier. Notably, in some agents, a minor negative correlation of r1 with a concentration of up to 2 mmol/L could be observed. This was most pronounced in the agents with the highest protein-binding capacity. At 7 Tesla, the in vitro r1 relaxivities of Gd-based contrast agents in human blood plasma are lower than those at 3 Tesla. This work may serve as a basis for the application of Gd-based MR contrast agents at 7 Tesla. Further studies are required to optimize the contrast agent dose in vivo.

  11. Cloning and expression of the gene for bacteriophage T7 RNA polymerase

    DOEpatents

    Studier, F. William; Davanloo, Parichehre; Rosenberg, Alan H.; Moffatt, Barbara A.; Dunn, John J.

    1990-01-01

    This application describes a means to clone a functional gene for bacteriophage T7 RNA polymerase. Active T7 RNA polymerase is produced from the cloned gene, and a plasmid has been constructed that can produce the active enzyme in large amounts. T7 RNA polymerase transcribes DNA very efficiently and is highly selective for a relatively long promoter sequence. This enzyme is useful for synthesizing large amounts of RNA in vivo or in vitro, and is capable of producing a single RNA selectively from a complex mixture of DNAs. The procedure used to obtain a clone of the T7 RNA polymerase gene can be applied to other T7-like phages to obtain clones that produce RNA polymerases having different promoter specificities, different bacterial hosts, or other desirable properties. T7 RNA polymerase is also used in a system for selective, high-level synthesis of RNAs and proteins in suitable host cells.

  12. RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling

    PubMed Central

    Ostrovskaya, Olga; Xie, Keqiang; Masuho, Ikuo; Fajardo-Serrano, Ana; Lujan, Rafael; Wickman, Kevin; Martemyanov, Kirill A

    2014-01-01

    In the hippocampus, the inhibitory neurotransmitter GABA shapes the activity of the output pyramidal neurons and plays important role in cognition. Most of its inhibitory effects are mediated by signaling from GABAB receptor to the G protein-gated Inwardly-rectifying K+ (GIRK) channels. Here, we show that RGS7, in cooperation with its binding partner R7BP, regulates GABABR-GIRK signaling in hippocampal pyramidal neurons. Deletion of RGS7 in mice dramatically sensitizes GIRK responses to GABAB receptor stimulation and markedly slows channel deactivation kinetics. Enhanced activity of this signaling pathway leads to decreased neuronal excitability and selective disruption of inhibitory forms of synaptic plasticity. As a result, mice lacking RGS7 exhibit deficits in learning and memory. We further report that RGS7 is selectively modulated by its membrane anchoring subunit R7BP, which sets the dynamic range of GIRK responses. Together, these results demonstrate a novel role of RGS7 in hippocampal synaptic plasticity and memory formation. DOI: http://dx.doi.org/10.7554/eLife.02053.001 PMID:24755289

  13. Diagnostic moléculaire du complexe Mycobacterium tuberculosis résistant à l'isoniazide et à la rifampicine au Burkina Faso

    PubMed Central

    Désire, Ilboudo; Cyrille, Bisseye; Florencia, Djigma; Souba, Diande; Albert, Yonli; Valerie, Bazie Jean Telesphore; Rebecca, Compaore; Charlemagne, Gnoula; Tamboura, Djibril; Rémy, Moret; Virginio, Pietra; Simplice, Karou Damintoti; Martial, Ouedraogo; Jacques, Simpore

    2015-01-01

    Introduction Cette étude a eu pour objectifs de diagnostiquer la tuberculose pulmonaire par l'examen microscopique et par la PCR des crachats et de déterminer les bases moléculaires de la résistance à la rifampicine et à l'isoniazide. Méthodes Le diagnostic du Complexe Mycobacterium Tuberculosis (CMTB) a été effectué par microscopie après coloration au Ziehl Nielsen et par PCR en temps réel en utilisant le kit d'identification du complexe MTB (Sacace Biotechnologie, Italie). Les résistances à la Rifampicine et à l'Isoniazide ont été étudiées par la technique de la PCR en utilisant le kit MTB résistance 8 (Sacace, Biotechnologie). Résultats Sur les 59 patients diagnostiqués pour la tuberculose pulmonaire, 59,3% étaient positifs en microscopie optique et 44,1% étaient positifs par PCR en Temps réel. Les résistances à la rifampicine (rpoB) et à l'isoniazide (katG et inhA) ont été observées chez 9 patients. La résistance à la rifampicine était due aux mutations (Asp516Val, Ser531Trp, Leu533Pro) et celle à l'isoniazide par les substitutions Ser315Thr du gène katG et C209T du gène inhA. Les multi résistances à la rifampicine et à l'isoniazide ont été observées dans 55,5% des échantillons et concernaient les associations: ropBAsp513Val + inhAC209T et rpoBLeu533Pro + katGSer315Thr. Conclusion La PCR en temps réel qui permet l'identification des allèles mutants rpoB, katG et inhA de M. tuberculosis est un outil de diagnostic épidémiologique de grande importance car elle permet de déterminer le niveau de résistance à la rifampicine et à l'isoniazide. PMID:26491516

  14. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

    PubMed

    Feng, Yifan; Wang, Jing; Yuan, Yuanzhi; Zhang, Xi; Shen, Minqian; Yuan, Fei

    2018-03-01

    Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes. Blockade of CXCR7 activation via CXCR7 knockdown or neutralizing Ab administration inhibited SDF-1-induced cell survival and the tubular formation of human retinal microvascular endothelial cells (HRMECs) in vitro and reduced CNV leakage and lesion size in vivo. By using microRNA array screening and bioinformatic analyses, we identified miR-539-5p as a regulator of CXCR7. Transfection of HRMECs and choroid-retinal endothelial (RF/6A) cells with the miR-539-5p mimic inhibited their survival and tube formation, whereas CXCR7 overexpression rescued the suppressive effect of miR-539-5p. The antiangiogenic activities of the miR-539-5p mimic were additionally demonstrated in vivo by intravitreal injection. ERK1/2 and AKT signaling downstream of CXCR7 is involved in the miR-539-5p regulation of endothelial cell behaviors. These findings suggest that the manipulation of miR-539-5p/CXCR7 levels may have important therapeutic implications in CNV-associated diseases.-Feng, Y., Wang, J., Yuan, Y., Zhang, X., Shen, M., Yuan, F. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

  15. Sevoflurane represses the self-renewal ability by regulating miR-7a,7b/Klf4 signalling pathway in mouse embryonic stem cells.

    PubMed

    Wang, Qimin; Li, Guifeng; Li, Baolin; Chen, Qiu; Lv, Dongdong; Liu, Jiaying; Ma, Jieyu; Sun, Nai; Yang, Longqiu; Fei, Xuejie; Song, Qiong

    2016-10-01

    Sevoflurane is a frequently-used clinical inhalational anaesthetic and can cause toxicity to embryos during foetal development. Embryonic stem cells (ESCs) are derived from the inner cell mass of blastospheres and can be used as a useful model of early development. Here, we found that sevoflurane significantly influenced self-renewal ability of mESCs on stemness maintenance and cell proliferation. The cell cycle was arrested via G1 phase delay. We further found that sevoflurane upregulated expression of miR-7a,7b to repress self-renewal. Next we performed rescue experiments and found that after adding miR-7a,7b inhibitor into mESCs treated with sevoflurane, its influence on self-renewal could be blocked. Further we identified stemness factor Klf4 as the direct target of miR-7a,7b. Overexpression of Klf4 restored self-renewal ability repressed by miR-7a,7b or sevoflurane. In this work, we determined that sevoflurane repressed self-renewal ability by regulating the miR-7a,7b/Klf4 signalling pathway in mESCs. Our study demonstrated molecular mechanism underlying the side effects of sevoflurane during early development, laying the foundation for studies on safe usage of inhalational anaesthetic during non-obstetric surgery. © 2016 John Wiley & Sons Ltd.

  16. T7 phage factor required for managing RpoS in Escherichia coli.

    PubMed

    Tabib-Salazar, Aline; Liu, Bing; Barker, Declan; Burchell, Lynn; Qimron, Udi; Matthews, Steve J; Wigneshweraraj, Sivaramesh

    2018-06-05

    T7 development in Escherichia coli requires the inhibition of the housekeeping form of the bacterial RNA polymerase (RNAP), Eσ 70 , by two T7 proteins: Gp2 and Gp5.7. Although the biological role of Gp2 is well understood, that of Gp5.7 remains to be fully deciphered. Here, we present results from functional and structural analyses to reveal that Gp5.7 primarily serves to inhibit Eσ S , the predominant form of the RNAP in the stationary phase of growth, which accumulates in exponentially growing E. coli as a consequence of the buildup of guanosine pentaphosphate [(p)ppGpp] during T7 development. We further demonstrate a requirement of Gp5.7 for T7 development in E. coli cells in the stationary phase of growth. Our finding represents a paradigm for how some lytic phages have evolved distinct mechanisms to inhibit the bacterial transcription machinery to facilitate phage development in bacteria in the exponential and stationary phases of growth.

  17. Cultural Resources Survey, Harry S. Truman Dam and Reservoir Project, Missouri. Volume 7. Archeological Test Excavations: 1975

    DTIC Science & Technology

    1983-02-01

    Cultural Resources Survey, Harry S. Truman Dam 3 1 ,1rd Reservoir Projert, Missouri, Volumes I - X 6 PERFORMING ORG. REPORT NUMBER N/A 7. AUrHOR(*)Curtis H...A05TNACr ( towfs.e du e 81 f nevee" Old fdfliffV bw block niatber) The ten volumes report the results of a cultural resources survey in the Harry S...and Surf icial Geology of the Harry S. Truman Reservoir Area, West Central Missouri, by R. A. Ward and T. L. Thompson, pp. 1-21 part II: Report on

  18. Comparison of 3T and 7T susceptibility-weighted angiography of the substantia nigra in diagnosing Parkinson disease.

    PubMed

    Cosottini, M; Frosini, D; Pesaresi, I; Donatelli, G; Cecchi, P; Costagli, M; Biagi, L; Ceravolo, R; Bonuccelli, U; Tosetti, M

    2015-03-01

    Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study. © 2015 by American Journal of Neuroradiology.

  19. 46 CFR 39.20-7 - Tankship liquid overfill protection-T/ALL.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Tankship liquid overfill protection-T/ALL. 39.20-7 Section 39.20-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS Design and Equipment § 39.20-7 Tankship liquid overfill protection—T/ALL. (a) Each cargo tank of a...

  20. 46 CFR 39.20-7 - Tankship liquid overfill protection-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Tankship liquid overfill protection-T/ALL. 39.20-7 Section 39.20-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS Design and Equipment § 39.20-7 Tankship liquid overfill protection—T/ALL. (a) Each cargo tank of a...

  1. 46 CFR 39.20-7 - Tankship liquid overfill protection-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Tankship liquid overfill protection-T/ALL. 39.20-7 Section 39.20-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS Design and Equipment § 39.20-7 Tankship liquid overfill protection—T/ALL. (a) Each cargo tank of a...

  2. miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7.

    PubMed

    Hao, Haibin; Xia, Guangfeng; Wang, Chao; Zhong, Fuping; Liu, Laipeng; Zhang, Dong

    2017-06-01

    Autophagy-related gene 7 (ATG7) and miR-106a play an important role in cancer cell autophagy and apoptosis, but the outcome of ATG7 and miR-106a in colorectal cancer (CRC) still remains not clear. In this study, we found that ATG7 and miR-106a expression were mutually related with cell death and prognosis in CRC patients. In addition, we also showed that ATG7 and miR-106a expression were changeable in colorectal cancer cell lines when compared with normal cell lines, but ATG7 and miR-106a mRNA level was negatively correlated. Furthermore, ATG7 protein and mRNA levels decreased after over-expression of miR-106a, whereas the suppression of ATG7 had the opposite effect. We confirmed that miR-106a down-regulated ATG7 mRNA level by binding the specific sequence of ATG7 mRNA 3'UTR region. Moreover, the over-expression of ATG7 induced CRC cells death both in vitro and in vivo. Taken together, our study data demonstrated that ATG7 aggravated the cell death of CRC, which was inhibited by miR-106a.

  3. Cloning and expression of autogenes encoding RNA poly,erases of T7-like bacteriophages

    DOEpatents

    Studier, F. William; Dubendorff, John W.

    1998-01-01

    This invention relates to the cloning and expression of autogenes encoding RNA polymerases of T7 and T7-like bacteriophages, in which the RNA polymerase gene is transcribed from a promoter which is recognized by the encoded RNA polymerase. Cloning of T7 autogenes was achieved by reducing the activity of the RNA polymerase sufficiently to permit host cell growth. T7 RNA polymerase activity was controlled by combining two independent methods: lac-repression of the recombinant lac operator-T7 promoter in the autogene and inhibition of the polymerase by T7 lysozyme. Expression systems for producing the RNA polymerases of T7 and other T7-like bacteriophages, and expression systems for producing selected gene products are described, as well as other related materials and methods.

  4. Cloning and expression of the gene for bacteriophage T7 RNA polymerase

    DOEpatents

    Studier, F.W.; Davanloo, P.; Rosenberg, A.H.

    1984-03-30

    This application describes a means to clone a functional gene for bacteriophage T7 RNA polymerase. Active T7 RNA polymerase is produced from the cloned gene, and a plasmid has been constructed that can produce the active enzyme in large amounts. T7 RNA polymerase transcribes DNA very efficiently and is highly selective for a relatively long promoter sequence. This enzyme is useful for synthesizing large amounts of RNA in vivo or in vitro, and is capable of producing a single RNA selectively from a complex mixture of DNAs. The procedure used to obtain a clone of the T7 RNA polymerase gene can be applied to other T7-like phages to obtain clones that produce RNA polymerases having different promoter specificities, different bacterial hosts, or other desirable properties.

  5. N7-Methylguanine at position 46 (m7G46) in tRNA from Thermus thermophilus is required for cell viability at high temperatures through a tRNA modification network.

    PubMed

    Tomikawa, Chie; Yokogawa, Takashi; Kanai, Tamotsu; Hori, Hiroyuki

    2010-01-01

    N(7)-methylguanine at position 46 (m(7)G46) in tRNA is produced by tRNA (m(7)G46) methyltransferase (TrmB). To clarify the role of this modification, we made a trmB gene disruptant (DeltatrmB) of Thermus thermophilus, an extreme thermophilic eubacterium. The absence of TrmB activity in cell extract from the DeltatrmB strain and the lack of the m(7)G46 modification in tRNA(Phe) were confirmed by enzyme assay, nucleoside analysis and RNA sequencing. When the DeltatrmB strain was cultured at high temperatures, several modified nucleotides in tRNA were hypo-modified in addition to the lack of the m(7)G46 modification. Assays with tRNA modification enzymes revealed hypo-modifications of Gm18 and m(1)G37, suggesting that the m(7)G46 positively affects their formations. Although the lack of the m(7)G46 modification and the hypo-modifications do not affect the Phe charging activity of tRNA(Phe), they cause a decrease in melting temperature of class I tRNA and degradation of tRNA(Phe) and tRNA(Ile). (35)S-Met incorporation into proteins revealed that protein synthesis in DeltatrmB cells is depressed above 70 degrees C. At 80 degrees C, the DeltatrmB strain exhibits a severe growth defect. Thus, the m(7)G46 modification is required for cell viability at high temperatures via a tRNA modification network, in which the m(7)G46 modification supports introduction of other modifications.

  6. Trinucleotide cassettes increase diversity of T7 phage-displayed peptide library.

    PubMed

    Krumpe, Lauren R H; Schumacher, Kathryn M; McMahon, James B; Makowski, Lee; Mori, Toshiyuki

    2007-10-05

    Amino acid sequence diversity is introduced into a phage-displayed peptide library by randomizing library oligonucleotide DNA. We recently evaluated the diversity of peptide libraries displayed on T7 lytic phage and M13 filamentous phage and showed that T7 phage can display a more diverse amino acid sequence repertoire due to differing processes of viral morphogenesis. In this study, we evaluated and compared the diversity of a 12-mer T7 phage-displayed peptide library randomized using codon-corrected trinucleotide cassettes with a T7 and an M13 12-mer phage-displayed peptide library constructed using the degenerate codon randomization method. We herein demonstrate that the combination of trinucleotide cassette amino acid codon randomization and T7 phage display construction methods resulted in a significant enhancement to the functional diversity of a 12-mer peptide library. This novel library exhibited superior amino acid uniformity and order-of-magnitude increases in amino acid sequence diversity as compared to degenerate codon randomized peptide libraries. Comparative analyses of the biophysical characteristics of the 12-mer peptide libraries revealed the trinucleotide cassette-randomized library to be a unique resource. The combination of T7 phage display and trinucleotide cassette randomization resulted in a novel resource for the potential isolation of binding peptides for new and previously studied molecular targets.

  7. Revisiting the Acanthamoeba species that form star-shaped cysts (genotypes T7, T8, T9, and T17): characterization of seven new Brazilian environmental isolates and phylogenetic inferences.

    PubMed

    Magliano, Ana C M; Teixeira, Marta M G; Alfieri, Silvia C

    2012-01-01

    Free-living amoebae of the genus Acanthamoeba are the agents of both opportunistic and non-opportunistic infections and are frequently isolated from the environment. Of the 17 genotypes (T1-T17) identified thus far, 4 (T7, T8, T9, and T17) accommodate the rarely investigated species of morphological group I, those that form large, star-shaped cysts. We report the isolation and characterization of 7 new Brazilian environmental Acanthamoeba isolates, all assigned to group I. Phylogenetic analyses based on partial (~1200 bp) SSU rRNA gene sequences placed the new isolates in the robustly supported clade composed of the species of morphological group I. One of the Brazilian isolates is closely related to A. comandoni (genotype T9), while the other 6, together with 2 isolates recently assigned to genotype T17, form a homogeneous, well-supported group (2·0% sequence divergence) that likely represents a new Acanthamoeba species. Thermotolerance, osmotolerance, and cytophatic effects, features often associated with pathogenic potential, were also examined. The results indicated that all 7 Brazilian isolates grow at temperatures up to 40°C, and resist under hyperosmotic conditions. Additionally, media conditioned by each of the new Acanthamoeba isolates induced the disruption of SIRC and HeLa cell monolayers.

  8. Etude theorique des fluctuations structurales dans les composes organiques a dimensionnalite reduite

    NASA Astrophysics Data System (ADS)

    Dumoulin, Benoit

    Les systemes a dimensionnalite reduite constituent maintenant une branche entiere de la physique de la matiere condensee. Cette derniere s'est developpee rapidement au cours des dernieres annees, avec la decouverte des materiaux organiques qui presentent, justement, des proprietes physiques fortement anisotropes. Cette these presente une etude en trois parties de plusieurs composes organiques qui, bien que tres differents du point de vue de leurs compositions chimiques et de leurs proprietes physiques a haute temperature, subissent tous une instabilite structurale a tres basse temperature. De plus, dans chacun des cas, l'instabilite structurale est precedee d'un important regime fluctuatif a partir duquel les proprietes physiques changent de maniere significative. Notre etude suit un ordre chronologique inverse puisque nous nous attardons en premier lieu au cas de composes recemment decouverts: les composes de la famille des (BCPTTF)2X (X = PF6 , AsF6). Ces derniers sont des isolants magnetiques a la temperature ambiante et subissent une instabilite structurale de type spin-Peierls a une temperature appelee TSP. En particulier, nous nous interessons a l'etude des proprietes physiques de ces systemes dans le regime fluctuatif, qui precede cette instabilite. Notre etude theorique nous permet de comprendre en detail comment ces systemes s'approchent de l'instabilite struturale. Dans la seconde partie de cette these, nous etudions le regime fluctuatif (pre-transitionnel) observe experimentalement dans le compose de (TMTTF)2PF6. Ce compose organique, dont la structure s'apparente aux sels de Bechgaard, subit une instabilite de type spin-Peierls a une temperature T SP = 19K. Bien que ce compose possede la particularite d'etre un bon conducteur a la temperature ambiante, il subit une transition de type Mott-Hubbard a une temperature Trho ≈ 220K et devient alors un isolant magnetique, analogue aux composes de la famille des (BCPTTF)2X. Le regime fluctuatif precedant l

  9. miR-Let7A Modulates Autophagy Induction in LPS-Activated Microglia

    PubMed Central

    Song, Juhyun; Oh, Yumi

    2015-01-01

    Microglia regulate the secretion of various immunomediators in central nervous system diseases. Microglial autophagy is the crucial process for cell's survival and cytokine productions. Recent studies have reported that several microRNAs are involved in the autophagy system. miR-Let7A is such a microRNA that plays a role in various inflammation responses, and is magnified as a key modulator particularly in the autophagy system. In present study, we investigated whether miR-Let7A is involved in autophagy in activating microglia. Overexpression of miR-Let7A in LPS-stimulated BV2 microglial cells promoted the induction of the autophagy related factors such as LC3II, Beclin1, and ATG3. Our results suggest a potential role of miR-Let7A in the autophagy process of microglia during CNS inflammation. PMID:26113790

  10. 7T MRI in focal epilepsy with unrevealing conventional field strength imaging.

    PubMed

    De Ciantis, Alessio; Barba, Carmen; Tassi, Laura; Cosottini, Mirco; Tosetti, Michela; Costagli, Mauro; Bramerio, Manuela; Bartolini, Emanuele; Biagi, Laura; Cossu, Massimo; Pelliccia, Veronica; Symms, Mark R; Guerrini, Renzo

    2016-03-01

    To assess the diagnostic yield of 7T magnetic resonance imaging (MRI) in detecting and characterizing structural lesions in patients with intractable focal epilepsy and unrevealing conventional (1.5 or 3T) MRI. We conducted an observational clinical imaging study on 21 patients (17 adults and 4 children) with intractable focal epilepsy, exhibiting clinical and electroencephalographic features consistent with a single seizure-onset zone (SOZ) and unrevealing conventional MRI. Patients were enrolled at two tertiary epilepsy surgery centers and imaged at 7T, including whole brain (three-dimensional [3D] T1 -weighted [T1W] fast-spoiled gradient echo (FSPGR), 3D susceptibility-weighted angiography [SWAN], 3D fluid-attenuated inversion recovery [FLAIR]) and targeted imaging (2D T2*-weighted dual-echo gradient-recalled echo [GRE] and 2D gray-white matter tissue border enhancement [TBE] fast spin echo inversion recovery [FSE-IR]). MRI studies at 1.5 or 3T deemed unrevealing at the referral center were reviewed by three experts in epilepsy imaging. Reviewers were provided information regarding the suspected localization of the SOZ. The same team subsequently reviewed 7T images. Agreement in imaging interpretation was reached through consensus-based discussions based on visual identification of structural abnormalities and their likely correlation with clinical and electrographic data. 7T MRI revealed structural lesions in 6 (29%) of 21 patients. The diagnostic gain in detection was obtained using GRE and FLAIR images. Four of the six patients with abnormal 7T underwent epilepsy surgery. Histopathology revealed focal cortical dysplasia (FCD) in all. In the remaining 15 patients (71%), 7T MRI remained unrevealing; 4 of the patients underwent epilepsy surgery and histopathologic evaluation revealed gliosis. 7T MRI improves detection of epileptogenic FCD that is not visible at conventional field strengths. A dedicated protocol including whole brain FLAIR and GRE images at 7T

  11. Antisense miR-7 impairs insulin expression in developing pancreas and in cultured pancreatic buds.

    PubMed

    Nieto, Margarita; Hevia, Pedro; Garcia, Enrique; Klein, Dagmar; Alvarez-Cubela, Silvia; Bravo-Egana, Valia; Rosero, Samuel; Damaris Molano, R; Vargas, Nancy; Ricordi, Camillo; Pileggi, Antonello; Diez, Juan; Domínguez-Bendala, Juan; Pastori, Ricardo L

    2012-01-01

    MicroRNAs regulate gene expression by inhibiting translation or inducing target mRNA degradation. MicroRNAs regulate organ differentiation and embryonic development, including pancreatic specification and islet function. We showed previously that miR-7 is highly expressed in human pancreatic fetal and adult endocrine cells. Here we determined the expression profile of miR-7 in the mouse-developing pancreas by RT-PCR and in situ hybridization. MiR-7 expression was low between embryonic days e10.5 and e11.5, then began to increase at e13.5 through e14.5, and eventually decreased by e18. In situ hybridization and immunostaining analysis showed that miR-7 colocalizes with endocrine marker Isl1, suggesting that miR-7 is expressed preferentially in endocrine cells. Whole-mount in situ hybridization shows miR-7 highly expressed in the embryonic neural tube. To investigate the role of miR-7 in development of the mouse endocrine pancreas, antisense miR-7 morpholinos (MO) were delivered to the embryo at an early developmental stage (e10.5 days) via intrauterine fetal heart injection. Inhibition of miR-7 during early embryonic life results in an overall downregulation of insulin production, decreased β-cell numbers, and glucose intolerance in the postnatal period. This phenomenon is specific for miR-7 and possibly due to a systemic effect on pancreatic development. On the other hand, the in vitro inhibition of miR-7 in explanted pancreatic buds leads to β-cell death and generation of β-cells expressing less insulin than those in MO control. Therefore, in addition to the potential indirect effects on pancreatic differentiation derived from its systemic downregulation, the knockdown of miR-7 appears to have a β-cell-specific effect as well. These findings suggest that modulation of miR-7 expression could be utilized in the development of stem cell therapies to cure diabetes.

  12. Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function

    PubMed Central

    1994-01-01

    Antigen-specific T cell activation requires the engagement of the T cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. The most extensively characterized pathway of costimulation has been that involving the interaction of CD28 and CTLA4 on the T cell with B7 (now termed B7-1) on antigen presenting cells. Recently, B7-2 a second costimulatory ligand for CTLA4, was described, demonstrating the potential complexity of costimulatory interactions. This report examines and compares the expression and function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2 can be expressed by multiple cell types, including B cells, T cells, macrophages, and dendritic cells, all of which are therefore candidate populations for delivering costimulatory signals mediated by these molecules; (b) stimulating B cells with either LPS or anti-IgD-dextran induced expression of both B7- 1 and B7-2, and peak expression of both costimulatory molecules occurred after 18-42 h of culture. Expression of B7-2 on these B cell populations was significantly higher than expression of B7-1 at all times assayed after stimulation; (c) blocking of B7-2 costimulatory activity inhibited TCR-dependent T cell proliferation and cytokine production, without affecting early consequences of TCR signaling such as induction of CD69 or interleukin 2 receptor alpha (IL-2R alpha); and (d) expression of B7-1 and of B7-2 can be regulated by a variety of stimuli. Moreover, expression of B7-1 and B7-2 can be independently regulated by the same stimulus, providing an additional complexity in the mechanisms available for regulating costimulation and hence immune response. PMID:7519245

  13. Le surpoids, l’obésité et le contrôle glycémique chez les diabétiques du centre de référence provincial de diabète (CRD), Kénitra, Maroc

    PubMed Central

    Lotfi, Zeghari; Aboussaleh, Youssef; Sbaibi, Rachid; Achouri, Imane; Benguedour, Rachid

    2017-01-01

    Introduction Le diabète est définit comme un trouble de l'assimilation, de l'utilisation et du stockage des sucres apportés par l'alimentation, sa prise en charge est assurée par le suivi du surpoids et l'obésité et le contrôle glycémique régulier. L'objectif de ce travail était l'étude du surpoids, l'obésité et le contrôle glycémique chez 2227 diabétiques de différent type (type 1, 2 et gestationnel), consultants le centre de référence provincial de diabète (CRD), Kénitra-Maroc. Méthodes L'étude s'est déroulée sur une période d'une année du mois janvier au mois décembre 2015, L'évaluation du surpoids et l'obésité a été effectuée par le calcul de l'Indice de Masse Corporelle (IMC=Poids/Taille2 (Kg/m2)), elles sont définit respectivement par IMC > 25 Kg/m2, et IMC > 30 Kg/m2, le poids et la taille ont été mesurés selon les recommandations de l'organisation mondiale de santé (OMS), Le contrôle glycémique a été effectué par l'analyse sanguine de l'Hémoglobine glycosylée et de la Glycémie à jeun. Les normes sont 7% pour l'Hémoglobine glycosylée et 0,70g/l à 1,10g/l pour la Glycémie à jeun. Résultats L'intervalle d'âges des patients est compris entre 8 mois et 80 ans, avec une dominance des diabétiques provenant du milieu urbain (74%) par rapport à ceux provenant du milieu rural (26%). Le surpoids touche l'ensemble de cette population. L'IMC moyen des femmes tends vers l'obésité (IMC≈30): (29,21 Kg/m2 ± 3,1) pour le diabète gestationnel et (29,15 Kg/m2 ± 3,2) pour le diabète de type 2. Les valeurs du contrôle glycémique sont supérieures aux normes: avec 8,5% ± 2,6 > 7% pour l'hémoglobine glycosylée et 1,5 g/l ± 1,3 > 1,10g/l pour la Glycémie à jeun. La différence entre les valeurs de l'hémoglobine glycosylée entre les hommes (8,5 7% ± 2,6) et les femmes (8,1% ± 2,3) n'est pas significative (P > 0,05), même chose pour la Glycémie capillaire à jeun: pour les hommes (1,44 g/l ± 1,1) et les

  14. Genomewide screens for Escherichia coli genes affecting growth of T7 bacteriophage

    PubMed Central

    Qimron, Udi; Marintcheva, Boriana; Tabor, Stanley; Richardson, Charles C.

    2006-01-01

    Use of bacteriophages as a therapy for bacterial infection has been attempted over the last century. Such an endeavor requires the elucidation of basic aspects of the host–virus interactions and the resistance mechanisms of the host. Two recently developed bacterial collections now enable a genomewide search of the genetic interactions between Escherichia coli and bacteriophages. We have screened >85% of the E. coli genes for their ability to inhibit growth of T7 phage and >90% of the host genes for their ability to be used by the virus. In addition to identifying all of the known interactions, several other interactions have been identified. E. coli CMP kinase is essential for T7 growth, whereas overexpression of the E. coli uridine/cytidine kinase inhibits T7 growth. Mutations in any one of nine genes that encode enzymes for the synthesis of the E. coli lipopolysaccharide receptor for T7 adsorption leads to T7 resistance. Selection of T7 phage that can recognize these altered receptors has enabled the construction of phage to which the host is 100-fold less resistant. PMID:17135349

  15. Actes du colloque sur le bilinguisme, Universite de Neuchatel, 14/15 Septembre, 1981 (Proceedings of the Colloquium on Bilingualism, University of Neuchatel, September 14-15, 1981).

    ERIC Educational Resources Information Center

    TRANEL, 1982

    1982-01-01

    This issue contains proceedings of a colloquium on linguistics at the University of Neuchatel: (1) "Propositions epistemologiques pour une etude du bilinguisme (Epistemological Propositions for a Study of Bilingualism)," by B. Py; (2) "Comment on di ca? Prolegomenes a une etude de la composante semantique du langage des migrants (How Do You Say…

  16. Evaluation du niveau de connaissance des patients sur la gestion du traitement par les antis vitamines K dans le service de cardiologie de Ouagadougou

    PubMed Central

    Samadoulougou, André; Temoua Naibe, Dangwé; Mandi, Germain; Yameogo, Relwendé Aristide; Kabore, Elisé; Millogo, Georges; Yameogo, Nobila Valentin; Kologo, Jonas Koudougou; Thiam/Tall, Anna; Toguyeni, Boubacar Jean Yves; Zabsonre, Patrice

    2014-01-01

    Introduction Les antivitamines K (AVK), traitement anticoagulant oral le plus largement prescrit, posent un réel problème de santé publique du fait de leur risque iatrogène. L'objectif de cette étude était de préciser le niveau de connaissance des patients sur la gestion de leur traitement par les AVK. Méthodes Il s'est agi d'une enquête transversale descriptive réalisée au CHU-Yalgado Ouédraogo, sur une période de 03 mois : du 1er mars au 31 mai 2012. Un questionnaire a été administré aux patients bénéficiant d'un traitement AVK depuis au moins un mois. Résultats Soixante-dix patients ont été inclus dans l'étude dont 30 hommes. L'âge moyen était de 49 ans ± 16 ans. Les cardiopathies et la maladie thromboembolique veineuse justifiant l'institution du traitement AVK étaient retrouvées respectivement dans 58,6% et 41,4% des cas. Le nom de l'AVK et la raison exacte du traitement étaient connus respectivement dans 91,4% et 67,1% des cas. Plus de la moitié des patients (68,6%) savaient que les AVK rendaient le sang plus fluide. Quarante-six patients (65,7%) citaient l'INR comme examen biologique de surveillance du traitement et seulement 28 patients (40%) connaissaient les valeurs cibles. La majorité des patients ne connaissait pas les risques encourus en cas de surdosage (72,8%) et de sous-dosage (71,4%). Une automédication par anti-inflammatoire non stéroïdien était signalée par 18 patients (25,7%). Les choux (74,3%) et la laitue (62,9%), aliments à consommer avec modération, étaient les plus cités. Conclusion Les connaissances des patients sur la gestion des AVK étaient fragmentaires et insuffisantes pour assurer la sécurité et l'efficacité du traitement. La création d'un programme d'éducation thérapeutique sur les AVK s'avère alors nécessaire. PMID:25870741

  17. Molecular and Cytological Comparisons of Chromosomes 7el₁, 7el₂, 7E(e), and 7E ⁱ Derived from Thinopyrum.

    PubMed

    Guo, Jun; He, Fang; Cai, Jin-Jin; Wang, Hong-Wei; Li, An-Fei; Wang, Hong-Gang; Kong, Ling-Rang

    2015-01-01

    Thinopyrum chromosomes 7el1, 7el2, 7E(e), and 7E(i), homoeologous to group 7 chromosomes of common wheat (Triticum aestivum), were determined to have many useful agronomical traits for wheat improvement. To analyze the genetic relationships among the 4 Thinopyrum 7E chromosomes, the conserved orthologous set markers, genomic in situ hybridization (GISH), and meiotic chromosome pairing were used in this study. The unweighted pair-group method with arithmetical averages (UPGMA) analysis indicated that 7el1, derived from T. ponticum, and 7E(i), derived from T. intermedium, were the most closely related. 7el2, derived from T. ponticum, was relatively distant from the 7el1-7E(i) complex. While 7E(e), derived from T. elongatum, was more distantly related to 7el1, 7el2, and 7E(i). This is the first report showing that 7el1 and 7E(i) may be similar, which could be explained by the similar chromosome signal distribution revealed by GISH as well as UPGMA analysis revealed by both molecular markers and the highest frequency of meiotic pairing. The newly developed genome-specific molecular markers may be useful for marker-assisted selection of Lr19, Bdv3, and Fhblop. © 2015 S. Karger AG, Basel.

  18. Discordance gradient-surface dans le rétrécissement mitral: le gradient moyen transmitral est-il un critère de sévérité ou un indice de tolérance du rétrécissement mitral serré?

    PubMed Central

    Najih, Hayat; Arous, Salim; Laarje, Aziza; Baghdadi, Dalila; Benouna, Mohamed Ghali; Azzouzi, Leila; Habbal, Rachida

    2016-01-01

    Le rétrécissement mitral (RM) rhumatismal demeure une valvulopathie fréquente dans les pays en voie de développement. Cependant, les pays industrialisés ont vu l'émergence ces dernières années de nouvelles étiologies de RM; notamment l'origine médicamenteuse et/ou toxique responsable de valvulopathies restrictives aussi bien sténosantes que régurgitantes. Pour cette raison, l'évaluation échocardiographique du RM et surtout, la définition de critères objectifs pour conclure au caractère serré du RM reste toujours d'actualité. Les objectifs du travail sont: évaluer l'existence ou non d'une corrélation directe entre le gradient moyen transmitral (GMT) et la sévérité du RM chez les patients porteurs d'un RM serré ou très serré (critère primaire) et analyser les différents paramètres qui conditionnent le gradient moyen transmitral (GMT) (Critère secondaire). Il s'agit d'une étude transversale monocentrique incluant tous les patients admis au service de Cardiologie du CHU Ibn Rochd de Casablanca pour un RM serré ou très serré, sur une période d'une année (Janvier 2014 à Décembre 2014). Nous avons analysés séparément deux groupes de patients : ceux avec un gradient moyen transmitral<10 mmHg (groupe 1) et ceux avec un gradient>10mmHg (groupe2). 50 patients porteurs d'un RM serré ou très serré ont été inclus. L'âge moyen de nos patients est de 41,7 ans avec prédominance féminine (sex ratio: 0,25). 64% de nos patients avaient un RM serré et 36% avaient un RM très serré. 52% (26 patients) avaient un GMT <10mmHg et 48% (24 patients) avaient un gradient moyen >10mmHg, ce qui suggère l'absence de corrélation directe entre la sévérité du RM et le GMT (coefficient de Pearson R: -0,137). Pour la dyspnée, 80% des patients du groupe 1 étaient dyspnéiques stade II de la NYHA et 70% des patients du groupe 2 étaient dyspnéiques stade III (41%) ou IV (29%) de la NYHA, ce qui signifie l'existence d'une corr

  19. The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function.

    PubMed

    Araud, Tanguy; Graw, Sharon; Berger, Ralph; Lee, Michael; Neveu, Estele; Bertrand, Daniel; Leonard, Sherry

    2011-10-15

    The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [(125)I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function

    PubMed Central

    Araud, Tanguy; Graw, Sharon; Berger, Ralph; Lee, Michael; Neveu, Estelle; Bertrand, Daniel; Leonard, Sherry

    2011-01-01

    The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca++, that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [125I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. PMID:21718690

  1. Etude hyperfrequence et ultrasonore des supraconducteurs organiques kappa-(ET)(2)X (X = copper(thiocyanogen), copper[N(CN)(2)]bromine)

    NASA Astrophysics Data System (ADS)

    Frikach, Kamal

    2001-09-01

    Dans ce travail je presente une etude de l'impedance de surface, ainsi que de l'attenuation et la variation de la vitesse ultrasonores dans les etats normal et supraconducteur sur les composes organiques k-(ET)2X (X = Cu(SCN) 2, Cu[N(CN)2]Br). A partir des mesures d'impedance de surface, les deux composantes sigma 1 et sigma2 de la conductivite complexe sont extraites en utilisant le modele de Drude. Ces mesures montrent que la symetrie du parametre d'ordre dans ces composes est differente de celle du cas BCS. Afin de comprendre le profil de sigma1 (T) nous avons etudie les fluctuations supraconductrices a partir de la paraconductivite sigma'( T). Cette etude est rendue possible grace a la structure quasi-2D des composes k-(ET)2X dans lesquelles les fluctuations supraconductrices sont fortes. Ces dernieres sont observees sur deux decades de temperatures dans le Cu(SCN)2. L'application du modele de Aslamazov-Larkin 2D et 3D montre la possibilite du passage du regime 2D a haute temperature au regime 3D au voisinage de Tc. En se basant sur ce resultat, nous avons calcule la paraconductivite en utilisant une approche a l'ordre d'une boucle a partir du modele de Lawrence-Doniach. En tenant compte de la correction par la self energie dans la limite dynamique (17 GHz), l'ajustement de la paraconductivite calculee est en bon accord avec les donnees experimentales. Le couplage interplan obtenu est compatible avec le caractere quasi-2D des composes organiques. Le temps de relaxation des quasi-particules dans l'etat supraconducteur est ensuite extrait pour la premiere fois dans ces composes dont le comportement en fonction de la temperature est compatible avec la presence des noeuds dans le gap. Dans l'etat normal, la variation de la vitesse ultrasonore presente un comportement anormal caracterise par un fort ramollissement a T = 38 K et 50 K dans k-(ET) 2Cu(SCN)2 et k-(ET)2Cu[N(CN) 2]Br respectivement dont l'amplitude est independante du champ magnetique jusqu'a H = Hc 2

  2. Ising versus XY anisotropy in frustrated R(2)Ti(2)O(7) compounds as "Seen" by Polarized Neutrons.

    PubMed

    Cao, H; Gukasov, A; Mirebeau, I; Bonville, P; Decorse, C; Dhalenne, G

    2009-07-31

    We studied the field induced magnetic order in R(2)Ti(2)O(7) pyrochlore compounds with either uniaxial (R=Ho, Tb) or planar (R=Er, Yb) anisotropy, by polarized neutron diffraction. The determination of the local susceptibility tensor {chi(parallel to),chi(perpendicular)} provides a universal description of the field induced structures in the paramagnetic phase (2-270 K), whatever the field value (1-7 T) and direction. Comparison of the thermal variations of chi(parallel to) and chi(perpendicular) with calculations using the rare earth crystal field shows that exchange and dipolar interactions must be taken into account. We determine the molecular field tensor in each case and show that it can be strongly anisotropic.

  3. Interdependent IL-7 and IFN-γ signalling in T-cell controls tumour eradication by combined α-CTLA-4+α-PD-1 therapy

    PubMed Central

    Shi, Lewis Zhichang; Fu, Tihui; Guan, Baoxiang; Chen, Jianfeng; Blando, Jorge M.; Allison, James P.; Xiong, Liangwen; Subudhi, Sumit K.; Gao, Jianjun; Sharma, Padmanee

    2016-01-01

    Combination therapy with α-CTLA-4 and α-PD-1 has shown significant clinical responses in different types of cancer. However, the underlying mechanisms remain elusive. Here, combining detailed analysis of human tumour samples with preclinical tumour models, we report that concomitant blockade of CTLA-4 and PD-1 improves anti-tumour immune responses and synergistically eradicates tumour. Mechanistically, combination therapy relies on the interdependence between IL-7 and IFN-γ signalling in T cells, as lack of either pathway abrogates the immune-boosting and therapeutic effects of combination therapy. Combination treatment increases IL-7Rα expression on tumour-infiltrating T cells in an IFN-γ/IFN-γR signalling-dependent manner, which may serve as a potential biomarker for clinical trials with immune checkpoint blockade. Our data suggest that combining immune checkpoint blockade with IL-7 signalling could be an effective modality to improve immunotherapeutic efficacy. Taken together, we conclude that combination therapy potently reverses immunosuppression and eradicates tumours via an intricate interplay between IFN-γ/IFN-γR and IL-7/IL-7R pathways. PMID:27498556

  4. Musculoskeletal MRI at 3.0 T and 7.0 T: a comparison of relaxation times and image contrast.

    PubMed

    Jordan, Caroline D; Saranathan, Manojkumar; Bangerter, Neal K; Hargreaves, Brian A; Gold, Garry E

    2013-05-01

    The purpose of this study was to measure and compare the relaxation times of musculoskeletal tissues at 3.0 T and 7.0 T, and to use these measurements to select appropriate parameters for musculoskeletal protocols at 7.0 T. We measured the T₁ and T₂ relaxation times of cartilage, muscle, synovial fluid, bone marrow and subcutaneous fat at both 3.0 T and 7.0 T in the knees of five healthy volunteers. The T₁ relaxation times were measured using a spin-echo inversion recovery sequence with six inversion times. The T₂ relaxation times were measured using a spin-echo sequence with seven echo times. The accuracy of both the T₁ and T₂ measurement techniques was verified in phantoms at both magnetic field strengths. We used the measured relaxation times to help design 7.0 T musculoskeletal protocols that preserve the favorable contrast characteristics of our 3.0 T protocols, while achieving significantly higher resolution at higher SNR efficiency. The T₁ relaxation times in all tissues at 7.0 T were consistently higher than those measured at 3.0 T, while the T₂ relaxation times at 7.0 T were consistently lower than those measured at 3.0 T. The measured relaxation times were used to help develop high resolution 7.0 T protocols that had similar fluid-to-cartilage contrast to that of the standard clinical 3.0 T protocols for the following sequences: proton-density-weighted fast spin-echo (FSE), T₂-weighted FSE, and 3D-FSE-Cube. The T₁ and T₂ changes were within the expected ranges. Parameters for musculoskeletal protocols at 7.0 T can be optimized based on these values, yielding improved resolution in musculoskeletal imaging with similar contrast to that of standard 3.0 T clinical protocols. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Papillomavirus E7 Oncoproteins Share Functions with Polyomavirus Small T Antigens

    PubMed Central

    White, Elizabeth A.; Kramer, Rebecca E.; Hwang, Justin H.; Pores Fernando, Arun T.; Naetar, Nana; Hahn, William C.; Roberts, Thomas M.; Schaffhausen, Brian S.; Livingston, David M.

    2014-01-01

    ABSTRACT Many of the small DNA tumor viruses encode transforming proteins that function by targeting critical cellular pathways involved in cell proliferation and survival. In this study, we have examined whether some of the functions of the polyomavirus small T antigens (ST) are shared by the E6 and E7 oncoproteins of two oncogenic papillomaviruses. Using three different assays, we have found that E7 can provide some simian virus 40 (SV40) or murine polyomavirus (PyV) ST functions. Both human papillomavirus 16 (HPV16) and bovine papillomavirus (BPV1) E7 proteins are capable of partially substituting for SV40 ST in a transformation assay that also includes SV40 large T antigen, the catalytic subunit of cellular telomerase, and oncogenic Ras. Like SV40 ST, HPV16 E7 has the ability to override a quiescence block induced by mitogen deprivation. Like PyV ST, it also has the ability to inhibit myoblast differentiation. At least two of these activities are dependent upon the interaction of HPV16 E7 with retinoblastoma protein family members. For small T antigens, interaction with PP2A is needed for each of these functions. Even though there is no strong evidence that E6 or E7 share the ability of small T to interact with PP2A, E7 provides these functions related to cellular transformation. IMPORTANCE DNA tumor viruses have provided major insights into how cancers develop. Some viruses, like the human papillomaviruses, can cause cancer directly. Both the papillomaviruses and the polyomaviruses have served as tools for understanding pathways that are often perturbed in cancer. Here, we have compared the functions of transforming proteins from several DNA tumor viruses, including two papillomaviruses and two polyomaviruses. We tested the papillomavirus E6 and E7 oncoproteins in three functional assays and found that E7 can provide some or all of the functions of the SV40 small T antigen, another well-characterized oncoprotein, in two of these assays. In a third assay

  6. EPA Region 7 Aquatic Focus Areas (ECO_RES.R7_AQUATIC_FOCUS_AREAS)

    EPA Pesticide Factsheets

    This shapefile consists of 347 individual Aquatic Ecological System (AES) polygons that are the Aquatic Conservation Focus Areas for EPA Region 7. The focus areas are those areas within each aquatic ecological system types that, if preserved, would maintain the biological and ecological diversity extant within that ecological system type. The layer consists of those polygons from the R7_AES.shp shapefile that had the highest ranks. The AES polygons in the Missouri portion of the file were appended and are those that contain the 158 aquatic conservation opportunity areas identified in Missouri as part of another project (Missouri Department of Conservation Aquatic Biodiversity Assessment 2005). Note that the identifiers in the Missouri portion of this file will not match the ID's in any Missouri specific files.

  7. Genome sequence of the Lotus spp. microsymbiont Mesorhizobium loti strain R7A.

    PubMed

    Kelly, Simon; Sullivan, John; Ronson, Clive; Tian, Rui; Bräu, Lambert; Munk, Christine; Goodwin, Lynne; Han, Cliff; Woyke, Tanja; Reddy, Tatiparthi; Huntemann, Marcel; Pati, Amrita; Mavromatis, Konstantinos; Markowitz, Victor; Ivanova, Natalia; Kyrpides, Nikos; Reeve, Wayne

    2014-01-01

    Mesorhizobium loti strain R7A was isolated in 1993 in Lammermoor, Otago, New Zealand from a Lotus corniculatus root nodule and is a reisolate of the inoculant strain ICMP3153 (NZP2238) used at the site. R7A is an aerobic, Gram-negative, non-spore-forming rod. The symbiotic genes in the strain are carried on a 502-kb integrative and conjugative element known as the symbiosis island or ICEMlSym(R7A). M. loti is the microsymbiont of the model legume Lotus japonicus and strain R7A has been used extensively in studies of the plant-microbe interaction. This report reveals that the genome of M. loti strain R7A does not harbor any plasmids and contains a single scaffold of size 6,529,530 bp which encodes 6,323 protein-coding genes and 75 RNA-only encoding genes. This rhizobial genome is one of 100 sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project.

  8. UV irradiation experiments under simulated martian surface conditions: Bio-effects on glycine, phage T7 and isolated T7 DNA

    NASA Astrophysics Data System (ADS)

    Bérces, Attila; ten Kate, I. L.; Fekete, A.; Hegedus, M.; Garry, J. R. C.; Lammer, Helmut; Ehrenfreund, Pascale; Peeters, Zan; Kovacs, G.; Ronto, G.

    Mars is considered as a main target for astrobiologically relevant exploration programmes. In order to explain the non-detection of organic material to a detection level of several parts per billion (ppb) by the Viking landers, several hypotheses have been suggested, including degradation processes occurring on the martian surface and in the martian soil and subsurface. UV exposure experiments have been performed in which thin layers of glycine ( 300 nm), and aqueous suspensions of phage T7 and isolated T7 DNA were irradiated with a Deuterium lamp and for comparison with a Xenon arc lamp, modified to simulate the solar irradiation on the surface of Mars (MarsUV). The glycine sample was subjected to 24 hours of irradiation with MarsUV. The results of this glycine experiment show a destruction rate comparable to the results of previous experiments in which thin layers of glycine were irradiated with a deuterium lamp (ten Kate et al., 2005, 2006). After exposure of different doses of simulated Martian UV radiation a decrease of the biological activity of phages and characteristic changes in the UV absorption spectrum have been detected, indicating the UV damage of isolated and intraphage T7 DNA. The results of our experiments show that intraphage DNA is 4 times more sensitive to simulated martian UV and deuterium lamp radiation than isolated T7 DNA. This result indicates the significant role that phage proteins play in the UV damage. The effect of simulated martian radiation is smaller than the biological defects observed after the exposure with a deuterium lamp for both cases, in intraphage and isolated DNA, despite of the 100 times larger intensity of the MarsUV lamp. The detected spectral differences are about ten times smaller; the biological activity is about 3 - 4 times smaller, indicating that the shorter wavelength UV radiation from the deuterium lamp is more effective in inducing DNA damage, irrespective of being intraphage or isolated.

  9. Le Programme d’enseignement décentralisé et la rétention des médecins omnipraticiens dans la région du Bas-Saint-Laurent au Québec

    PubMed Central

    Bustinza, Ray; Gagnon, Suzanne; Burigusa, Guillaume

    2009-01-01

    Résumé OBJECTIF Le but de cette étude était d’évaluer l’impact sur la rétention des médecins omnipraticiens du programme d’enseignement décentralisé, des mesures incitatives financières et de l’origine du médecin. DEVIS Nos données sont tirées de la banque du suivi des effectifs médicaux de la Régie régionale de la santé et des services sociaux du Bas-Saint-Laurent. Les questionnaires complétés par les médecins dans le cadre de cette étude ont été envoyés par la poste. MILIEU Bas-Saint-Laurent, Qué. PARTICIPANTS Des médecins omnipraticiens pratiquant depuis 1985 à août 2003 dans la région. MÉTHODOLOGIE Pour les analyses statistiques, nous avons fait appel à l’analyse multivariée, en utilisant le modèle des taux proportionnels de Cox de l’analyse de survie. RÉSULTATS La probabilité ajustée de demeurer en région, selon l’exposition aux stages de résidence en région, présente une tendance positive avec un rapport de 2,12 (P = 0,15). La probabilité de rester dans la région grimpe jusqu’à 4,5 fois plus (P < 0,01) pour un médecin originaire du Bas-Saint-Laurent. Le lien avec les mesures incitatives financières montre que la probabilité ajustée de demeurer dans le Bas-Saint-Laurent n’est pas significativement différente selon qu’ils aient ou non reçu les primes d’installation ou la bourse de la Régie de l’assurance-maladie du Québec. CONCLUSION Les facteurs les plus prometteurs pour retenir les médecins omnipraticiens en région touchent le recrutement en médecine de candidats des régions rurales et la formation décentralisée. PMID:19752242

  10. Elucidating the pH-Dependent Structural Transition of T7 Bacteriophage Endolysin.

    PubMed

    Sharma, Meenakshi; Kumar, Dinesh; Poluri, Krishna Mohan

    2016-08-23

    Bacteriophages are the most abundant and diverse biological entities on earth. Bacteriophage endolysins are unique peptidoglycan hydrolases and have huge potential as effective enzybiotics in various infectious models. T7 bacteriophage endolysin (T7L), also known as N-acetylmuramoyl-l-alanine amidase or T7 lysozyme, is a 17 kDa protein that lyses a range of Gram-negative bacteria by hydrolyzing the amide bond between N-acetylmuramoyl residues and the l-alanine of the peptidoglycan layer. Although the activity profiles of several of the T7 family members have been known for many years, the molecular basis for their pH-dependent differential activity is not clear. In this study, we explored the pH-induced structural, stability, and activity characteristics of T7L by applying a variety of biophysical techniques and protein nuclear magnetic resonance (NMR) spectroscopy. Our studies established a reversible structural transition of T7L below pH 6 and the formation of a partially denatured conformation at pH 3. This low-pH conformation is thermally stable and exposed its hydrophobic pockets. Further, NMR relaxation measurements and structural analysis unraveled that T7L is highly dynamic in its native state and a network of His residues are responsible for the observed pH-dependent conformational dynamics and transitions. As bacteriophage chimeric and engineered endolysins are being developed as novel therapeutics against multiple drug resistance pathogens, we believe that our results are of great help in designing these entities as broadband antimicrobial and/or antibacterial agents.

  11. Utilisation d'images aeroportees a tres haute resolution spatiale pour l'estimation de la vigueur des peuplements forestiers du nord-ouest du Nouveau-Brunswick

    NASA Astrophysics Data System (ADS)

    Louis, Ognel Pierre

    Le but de cette etude est de developper un outil permettant d'estimer le niveau de risque de perte de vigueur des peuplements forestiers de la region de Gounamitz au nord-ouest du Nouveau-Brunswick via des donnees d'inventaires forestiers et des donnees de teledetection. Pour ce faire, un marteloscope de 100m x 100m et 20 parcelles d'echantillonnages ont ete delimites. A l'interieur de ces derniers, le niveau de risque de perte de vigueur des arbres ayant un DHP superieur ou egal a 9 cm a ete determine. Afin de caracteriser le risque de perte de vigueur des arbres, leurs positions spatiales ont ete repertoriees a partir d'un GPS en tenant compte des defauts au niveau des tiges. Pour mener a bien ce travail, les indices de vegetation et de textures et les bandes spectrales de l'image aeroportee ont ete extraits et consideres comme variables independantes. Le niveau de risque de perte de vigueur obtenu par espece d'arbre a travers les inventaires forestiers a ete considere comme variable dependante. En vue d'obtenir la superficie des peuplements forestiers de la region d'etude, une classification dirigee des images a partir de l'algorithme maximum de vraisemblance a ete effectuee. Le niveau de risque de perte de vigueur par type d'arbre a ensuite ete estime a l'aide des reseaux de neurones en utilisant un reseau dit perceptron multicouches. Il s'agit d'un modele de reseau de neurones compose de : 11 neurones sur la couche d'entree, correspondant aux variables independantes, 35 neurones sur la couche cachee et 4 neurones sur la couche de sortie. La prediction a partir des reseaux de neurones produit une matrice de confusion qui permet d'obtenir des mesures quantitatives d'estimation, notamment un pourcentage de classification globale de 91,7% pour la prediction du risque de perte de vigueur du peuplement de resineux et de 89,7% pour celui du peuplement de feuillus. L'evaluation de la performance des reseaux de neurones fournit une valeur de MSE globale de 0,04, et une

  12. Investigation of the B1 field distribution and RF power deposition in a birdcage coil as functions of the number of coil legs at 4.7 T, 7.0 T, and 11.7 T

    NASA Astrophysics Data System (ADS)

    Seo, Jeung-Hoon; Han, Sang-Doc; Kim, Kyoung-Nam

    2015-06-01

    The proper design of birdcage (BC) coils plays a very important role in the acquisition of highresolution magnetic resonance imaging (MRI) of small animals such as rodents. In this context, we investigate multiple-leg (8-, 16-, 32-, 64-, and 128-leg) BC coils operating at ultra-high fields (UHF) of 7.0 T and 11.7 T and a high-field (HF) of 4.7 T for rodent magnetic resonance imaging (MRI). Primarily, Our study comparatively examines the parameters of the radiofrequency (RF) transmission (|B1 +|)-field, the magnetic flux (|B1|)-field, and RF power deposition (RF-PD) as functions of the number of BC-coil legs via finite-difference time-domain (FDTD) calculations under realistic loading conditions with a biological phantom. In particular, the specific ratio |E/B1 +| is defined for predicting RF-PD values in different coil structures. Our results indicate that the optimal number of legs of the BC coil can be chosen for different resonance frequencies of 200 MHz, 300 MHz, and 500 MHz and that this choice can be lead to superior |B1 +|-field intensity and |B1|-field homogeneity and decreased RF-PD. We believe that our approach to determining the optimal number of legs for a BC coil can contribute to rodent MR imaging.

  13. The highly efficient T7 RNA polymerase: A wonder macromolecule in biological realm.

    PubMed

    Borkotoky, Subhomoi; Murali, Ayaluru

    2018-05-27

    The study of bacteriophage has always been of keen interest for biologists to understand the fundamentals of biology. Bacteriophage T7 was first isolated in 1945 and its first comprehensive genetic map of was published in 1969. Since then, it gained immense attention of researchers and became a prime model system for experimental biologists. The major gene product of T7 phage, T7 RNA polymerase (T7RNAP), continues to attract researchers since a long time due to its high and specific processivity with a single subunit structure and its capability of transcribing a complete gene without additional proteins. Since the first review article in 1993 there has been around nine reviews on this polymerase till year 2009, most of which focussed on particular aspects of T7RNAP such as structure and function. However, this review encapsulates a broad view on T7RNAP, one of the simplest macromolecule catalyzing RNA synthesis including recent updates on its applications, structure, activators and inhibitors. Thus this brief review bridges the huge gap on the recent updates on this polymerase and will help the biologists in their endeavours that include the use of T7RNAP. Copyright © 2017. Published by Elsevier B.V.

  14. T7 replisome directly overcomes DNA damage

    NASA Astrophysics Data System (ADS)

    Sun, Bo; Pandey, Manjula; Inman, James T.; Yang, Yi; Kashlev, Mikhail; Patel, Smita S.; Wang, Michelle D.

    2015-12-01

    Cells and viruses possess several known `restart' pathways to overcome lesions during DNA replication. However, these `bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single-molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase-DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly.

  15. Cholesterol 7alpha-hydroxylase (CYP7A1) activity is modified after chronic ingestion of depleted uranium in the rat.

    PubMed

    Racine, R; Grandcolas, L; Grison, S; Stefani, J; Delissen, O; Gourmelon, P; Veyssière, G; Souidi, M

    2010-05-01

    Depleted uranium (DU) is a radioactive heavy metal derived from the nuclear energy production. Its wide use in civilian and military items increases the risk of its environmental dissemination, and thus the risk of internal contamination of populations living in such contaminated territories. Previous studies have shown that vitamin D and cerebral cholesterol metabolisms were affected following chronic ingestion of DU. Even more than the brain, the liver is a crucial organ in cholesterol homeostasis since it regulates cholesterol distribution and elimination at body level. The aim of this work was to assess the impact of a low-level chronic ingestion of DU on hepatic cholesterol metabolism. Rats were contaminated with DU in their drinking water at a concentration of 40mg/l for 9 months. The major effect induced by DU was a decrease of CYP7A1 specific activity (-60%) correlated with a matching decrease of its product 7alpha-hydroxycholesterol in the plasma. Hepatic gene expression of transporters ABC A1, ABC G5, ABC G8 and of nuclear receptor RXR was increased, whereas that of catabolism enzyme CYP7B1 was decreased. Thus, after a chronic ingestion of DU, rats experience a modulation of cholesterol catabolism but overcome it, since their cholesterolemia is preserved and no pathology is declared.

  16. Expression of zinc transporter ZnT7 in mouse superior cervical ganglion

    USDA-ARS?s Scientific Manuscript database

    The superior cervical ganglion (SCG) neurons contain a considerable amount of zinc ions, but little is known about zinc homeostasis in the SCG. It is known that zinc transporter 7 (ZnT7, Slc30a7), a member of the Slc30 ZnT family, is involved in mobilizing zinc ions from the cytoplasm into the Golgi...

  17. Séroprévalence des marqueurs viraux sur les dons du sang au Centre de Transfusion Sanguine, Hôpital Militaire d’Instruction Mohammed V de Rabat

    PubMed Central

    Uwingabiye, Jean; Zahid, Hafidi; Unyendje, Loubet; Hadef, Rachid

    2016-01-01

    Le but de ce travail était de déterminer la prévalence du virus de l’immunodéficience humaine (VIH), du virus de l’hépatite B (VHB) et C (VHC) sur les dons du sang collectés au Centre de transfusion sanguine(CTS) de l’hôpital militaire d’instruction Mohammed V entre 2010 et 2012. Etude rétrospective menée auprès des donneurs de sang militaires âgés de 18 à 50 ans avec prédominance masculine (95%). L’entretien médical pré-don constitue la première barrière de sélection des sujets à risque. Le dépistage biologique était réalisé par technique immuno-enzymatique en milieu liquide utilisant des anticorps et/ou des antigènes. L’ELISA (enzyme linked immuno-sorbent assay) combiné de quatrième génération pour VHC et VIH a été utilisé. La confirmation a été faite en réalisant la même technique en double au CTS et au laboratoire de virologie. Dans notre série de 25661 échantillons testés, la prévalence du VHB était 3,97‰ (n=102), celle de VHC était 2,45 ‰ (n=63), celle de VIH était 0,15 ‰ (n=4). Un seul cas de coïnfection (0,039 ‰) par le VHB et VHC a été noté, aucune association entre VIH-VHB, VIH-VHC ou VHB, VHC et VIH n’a été enregistrée. Les taux faibles de séroprévalence des marqueurs viraux de notre étude montrent l’amélioration des mesures préventives en ce qui concerne la sélection des donneurs et des tests de dépistage. Cette prévalence constatée incite à maintenir l’utilisation du réactif combiné qui est la seule alternative à la biologie moléculaire pour les pays en voie de développement. PMID:28292147

  18. Intermittent IL-7 Signaling Essential for T cell Homeostasis | Center for Cancer Research

    Cancer.gov

    In order for the immune system to mount an appropriate response to foreign antigens throughout a person’s life, the body must maintain a sufficient population of circulating mature, naïve T cells, a process known as T cell homeostasis. Previous studies revealed that this process depends upon signaling from the cytokine interleukin-7 (IL-7) as well as from the T cell antigen receptor (TCR). Intriguingly, signals from each pathway affect the other and lead to their alternating activation: IL-7 binding to its receptor leads to increasing expression of the TCR co-receptor CD8; sufficient CD8 expression allows TCRs to signal when bound to self-ligands, blocking IL-7 signaling; suppressed IL-7 signals lead to down-regulation of CD8 and ligand disengagement, which allows T cells to again respond to IL-7. Alfred Singer, M.D., and his colleagues in CCR’s Experimental Immunology Branch set out to understand how this intricate pathway promotes T cell survival.

  19. Transport and thermoelectric properties of Sr{sub 3}(Ti{sub 0.95}R{sub 0.05}){sub 2}O{sub 7} (R = Ta, Nb, W) oxides

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sun, R. R.; Qin, X. Y.; Li, L. L.

    2012-12-15

    The Sr{sub 3}(Ti{sub 0.95}R{sub 0.05}){sub 2}O{sub 7} (R = Ta, Nb, W) polycrystalline compounds were fabricated, and their transport and thermoelectric properties were investigated. The results indicate that at T > 300 K electrical resistivity {rho} for all the doped compounds increases monotonically with temperature, and basically can be described by a relation {rho}{proportional_to}T{sup M} at T > {approx}650 K, with M = 1.39, 1.66, and 1.77 for R = Ta, Nb, and W, respectively, implying that at the high temperatures the acoustic phonon scattering dominates the scattering process. Although the resistivity {rho} of Sr{sub 3}(Ti{sub 0.95}Ta{sub 0.05}){sub 2}O{sub 7}more » exhibits a metallic-like behavior at the temperature as low as 5 K, a transition from metallic state (d{rho}/dT > 0) to semiconductor-like state (d{rho}/dT < 0) was observed at a critical low temperature {approx}41 K and {approx}79 K for R = Nb and W, respectively. At T < {approx}22 K, {approx}57 K, and {approx}80 K, a relation of {sigma}{proportional_to}T{sup 1/2} (here conductivity {sigma} = 1/{rho}) holds for the doped compounds with R = Nb, Ta, and W, respectively, suggesting that at the low temperatures the main transport mechanism is electron-electron interaction due to the presence of disorder induced by the dopants. The thermoelectric figure of merit (ZT) for Ta-doped compound increases more steeply with increasing temperature among the three compounds and reaches 0.066 at 1000 K.« less

  20. T7 RNA Polymerase Functions In Vitro without Clustering

    PubMed Central

    Finan, Kieran; Torella, Joseph P.; Kapanidis, Achillefs N.; Cook, Peter R.

    2012-01-01

    Many nucleic acid polymerases function in clusters known as factories. We investigate whether the RNA polymerase (RNAP) of phage T7 also clusters when active. Using ‘pulldowns’ and fluorescence correlation spectroscopy we find that elongation complexes do not interact in vitro with a Kd<1 µM. Chromosome conformation capture also reveals that genes located 100 kb apart on the E. coli chromosome do not associate more frequently when transcribed by T7 RNAP. We conclude that if clustering does occur in vivo, it must be driven by weak interactions, or mediated by a phage-encoded protein. PMID:22768341

  1. Photocatalytic properties of amine functionalized Bi2Sn2O7/rGO nanocomposites

    NASA Astrophysics Data System (ADS)

    Gnanamoorthy, G.; Muthamizh, S.; Sureshbabu, K.; Munusamy, S.; Padmanaban, A.; Kaaviya, A.; Nagarajan, R.; Stephen, A.; Narayanan, V.

    2018-07-01

    The binary metal oxide nanomaterials are having applications in various fields like sensors, optics, electrocatalyst and photocatalyst so on. Bi2Sn2O7 with pyrochlore structure is having low band gap energy; hence it is utilized in battery storage and gas sensor applications. In the present work, we have made an attempt to synthesis amine-functionalized Bi2Sn2O7/rGO nanocomposites by a thermal decomposition method and in-situ method; the synthesized nanocomposites were confirmed by XRD, FT-IR and Raman analysis. The AF-Bi2Sn2O7/rGO nanocomposites morphology was confirmed by FE-SEM along with EDX spectroscopy, we obtained different flowers and nest-like morphology. The pure and composite material band gap energy is decreases from 2.6 eV to 1.6 eV. All three nanomaterials Bi2Sn2O7, AF-Bi2Sn2O7, AF-Bi2Sn2O7/rGO nanocomposites (AF-amine functionalized) were utilized for the photocatalytic degradation of methylene blue dye under visible light irradiation. AF-Bi2Sn2O7/rGO nanocomposite showed an excellent photocatalytic activity than pure Bi2Sn2O7 and AF- Bi2Sn2O7.

  2. Etude séro-épidémiologique de la leishmaniose canine au centre du Maroc

    PubMed Central

    Fellah, Hajiba; Doughmi, Oursula; Maniar, Saâd; Lalami, Abdelhakim El Ouali

    2014-01-01

    Dans le monde, la leishmaniose viscérale humaine est connue pour avoir comme principale source d'infection les Canidés domestiques et sauvages. Au centre du Maroc, les données épidémiologiques, cliniques et parasitologiques sur la leishmaniose canine, sont quasiment inexistantes. Ce travail traite une étude prospective au cours de laquelle 61 sérums canins ont été analysés par un test rapide et par l'immunofluorescence indirecte. La sensibilité du test rapide par rapport à celle de l'immunofluorescence indirecte (IFI) est de 33,33%. La fréquence de la maladie chez les chiens s’élève à 9,83% (Test Rapide) et 24,59% (IFI). 73,33% des cas canins positifs à la sérologie sont asymptomatiques. Ce sont les jeunes chiens de moins de 5 ans qui sont les plus fréquemment atteints avec une sensibilité de la race Berger Allmand à l'infection. Cette étude a permis de mettre en évidence la présence de chiens leishmaniens (15 chiens séropositifs parmi 61) et de prouver l'existence du réservoir canin. Une stratégie de prévention active doit être mise en place. PMID:25852791

  3. C-terminal Phenylalanine of Bacteriophage T7 Single-stranded DNA-binding Protein Is Essential for Strand Displacement Synthesis by T7 DNA Polymerase at a Nick in DNA*

    PubMed Central

    Ghosh, Sharmistha; Marintcheva, Boriana; Takahashi, Masateru; Richardson, Charles C.

    2009-01-01

    Single-stranded DNA-binding protein (gp2.5), encoded by gene 2.5 of bacteriophage T7, plays an essential role in DNA replication. Not only does it remove impediments of secondary structure in the DNA, it also modulates the activities of the other replication proteins. The acidic C-terminal tail of gp2.5, bearing a C-terminal phenylalanine, physically and functionally interacts with the helicase and DNA polymerase. Deletion of the phenylalanine or substitution with a nonaromatic amino acid gives rise to a dominant lethal phenotype, and the altered gp2.5 has reduced affinity for T7 DNA polymerase. Suppressors of the dominant lethal phenotype have led to the identification of mutations in gene 5 that encodes the T7 DNA polymerase. The altered residues in the polymerase are solvent-exposed and lie in regions that are adjacent to the bound DNA. gp2.5 lacking the C-terminal phenylalanine has a lower affinity for gp5-thioredoxin relative to the wild-type gp2.5, and this affinity is partially restored by the suppressor mutations in DNA polymerase. gp2.5 enables T7 DNA polymerase to catalyze strand displacement DNA synthesis at a nick in DNA. The resulting 5′-single-stranded DNA tail provides a loading site for T7 DNA helicase. gp2.5 lacking the C-terminal phenylalanine does not support this event with wild-type DNA polymerase but does to a limited extent with T7 DNA polymerase harboring the suppressor mutations. PMID:19726688

  4. C-terminal phenylalanine of bacteriophage T7 single-stranded DNA-binding protein is essential for strand displacement synthesis by T7 DNA polymerase at a nick in DNA.

    PubMed

    Ghosh, Sharmistha; Marintcheva, Boriana; Takahashi, Masateru; Richardson, Charles C

    2009-10-30

    Single-stranded DNA-binding protein (gp2.5), encoded by gene 2.5 of bacteriophage T7, plays an essential role in DNA replication. Not only does it remove impediments of secondary structure in the DNA, it also modulates the activities of the other replication proteins. The acidic C-terminal tail of gp2.5, bearing a C-terminal phenylalanine, physically and functionally interacts with the helicase and DNA polymerase. Deletion of the phenylalanine or substitution with a nonaromatic amino acid gives rise to a dominant lethal phenotype, and the altered gp2.5 has reduced affinity for T7 DNA polymerase. Suppressors of the dominant lethal phenotype have led to the identification of mutations in gene 5 that encodes the T7 DNA polymerase. The altered residues in the polymerase are solvent-exposed and lie in regions that are adjacent to the bound DNA. gp2.5 lacking the C-terminal phenylalanine has a lower affinity for gp5-thioredoxin relative to the wild-type gp2.5, and this affinity is partially restored by the suppressor mutations in DNA polymerase. gp2.5 enables T7 DNA polymerase to catalyze strand displacement DNA synthesis at a nick in DNA. The resulting 5'-single-stranded DNA tail provides a loading site for T7 DNA helicase. gp2.5 lacking the C-terminal phenylalanine does not support this event with wild-type DNA polymerase but does to a limited extent with T7 DNA polymerase harboring the suppressor mutations.

  5. 7T MRI subthalamic nucleus atlas for use with 3T MRI.

    PubMed

    Milchenko, Mikhail; Norris, Scott A; Poston, Kathleen; Campbell, Meghan C; Ushe, Mwiza; Perlmutter, Joel S; Snyder, Abraham Z

    2018-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in most patients with Parkinson disease (PD), yet may produce untoward effects. Investigation of DBS effects requires accurate localization of the STN, which can be difficult to identify on magnetic resonance images collected with clinically available 3T scanners. The goal of this study is to develop a high-quality STN atlas that can be applied to standard 3T images. We created a high-definition STN atlas derived from seven older participants imaged at 7T. This atlas was nonlinearly registered to a standard template representing 56 patients with PD imaged at 3T. This process required development of methodology for nonlinear multimodal image registration. We demonstrate mm-scale STN localization accuracy by comparison of our 3T atlas with a publicly available 7T atlas. We also demonstrate less agreement with an earlier histological atlas. STN localization error in the 56 patients imaged at 3T was less than 1 mm on average. Our methodology enables accurate STN localization in individuals imaged at 3T. The STN atlas and underlying 3T average template in MNI space are freely available to the research community. The image registration methodology developed in the course of this work may be generally applicable to other datasets.

  6. CHEMOKINE RECEPTOR 7 (CCR7)-EXPRESSION AND IFNγ PRODUCTION DEFINE VACCINE-SPECIFIC CANINE T CELL SUBSETS

    PubMed Central

    Hartley, Ashley N.; Tarleton, Rick L.

    2015-01-01

    Canines suffer from and serve as strong translational animals models for many immunological disorders and infectious diseases. Routine vaccination has been a mainstay of protecting dogs through the stimulation of robust antibody responses and expansion of memory T cell populations. Commercially available reagents and described techniques are limited for identifying and characterizing canine T cell subsets and evaluating T cell-specific effector function. To define reagents for delineating naïve versus activated T cells and identify antigen-specific T cells, we tested anti-human and anti-bovine T-cell specific cell surface marker reagents for cross-reactivity with canine peripheral blood mononuclear cells (PBMCs. Both CD4+ and CD8+ T cells from healthy canine donors showed reactivity to CCL19-Ig, a CCR7 ligand, and coexpression with CD62L. An in vitro stimulation with concanavalin A validated downregulation of CCR7 and CD62L expression on stimulated healthy control PBMCs, consistent with an activated T cell phenotype. Anti-IFNγ antibodies identified antigen-specific IFNγ-producing CD4+ and CD8+ T cells upon in vitro vaccine antigen PBMC stimulation. PBMC isolation within 24 hours of sample collection allowed for efficient cell recovery and accurate T cell effector function characterization. These data provide a reagent and techniques platform via flow cytometry for identifying canine T cell subsets and characterizing circulating antigen-specific canine T cells for potential use in diagnostic and field settings. PMID:25758065

  7. Re-entrant relaxor behavior of Ba{sub 5}RTi{sub 3}Nb{sub 7}O{sub 30} (R = La, Nd, Sm) tungsten bronze ceramics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Kun; Li Zhu, Xiao; Qiang Liu, Xiao

    2013-03-18

    Ba{sub 5}RTi{sub 3}Nb{sub 7}O{sub 30} (R = La, Nd, Sm) tungsten bronze ceramics were prepared, and the dielectric and ferroelectric properties were investigated over a broad temperature range. The relaxor nature was determined for all compositions in their permittivity curves, and a second anomaly of the dielectric loss (tan {delta}) was observed around 250 K in Ba{sub 5}NdTi{sub 3}Nb{sub 7}O{sub 30} and around 275 K in Ba{sub 5}SmTi{sub 3}Nb{sub 7}O{sub 30}. Both the maximum and remanent polarization tended to decrease and vanish at low temperatures in the ferroelectric phase for all compositions, which was referred to as the low temperaturemore » re-entrant relaxor behavior. The remanent polarization increased with decreasing temperature first and then reached the maximum value at the re-entrant temperature (T{sub r}). For Ba{sub 5}RTi{sub 3}Nb{sub 7}O{sub 30} (R = La, Nd, Sm), T{sub r} decreased with the radius of R{sup 3+} cations and the applied field amplitude.« less

  8. Etude longitudinale de la névralgie cervico-brachiale dans le service de neurologie du CHU Gabriel Touré, Bamako (Mali)

    PubMed Central

    Maiga, Youssoufa; Fara, Amina Ahmed; Sogoba, Youssouf; Diango, Djibo; Diakite, Sara; Diallo, Mohamed; Ak, Hadiza; Diallo, Gangaly; Traore, Hamar Alassane

    2013-01-01

    Introduction La Névralgie Cervico-Brachiale (NCB) est une pathologie relativement fréquente dans la pratique courante. Elle est pourvoyeuse d'importants coûts médicaux et socio-économiques. Peu de données existent sur la NCB en Afrique. Méthodes Il s'agit d'une étude longitudinale, descriptive et prospective qui s'est déroulée du 1er novembre 2009 au 30 Août 2010 au CHU Gabriel Touré de Bamako, Mali. Elle a pour objectif d’étudier les caractéristiques épidémiologiques et cliniques de la NCB. Le diagnostic à été strictement clinique, et la DN4 a permis de déterminer les caractéristiques de cette névralgie. L'intensité de la douleur a été évaluée par l’échelle verbale simple (EVS). L’échelle concis de la douleur et l’échelle HAD ont permis d’étudier l'impact de la douleur sur la qualité de vie des patients. Résultats La fréquence de la NCB est de 10,9%. Les ménagères sont les plus touchées, 21(40,4%). L’âge moyen des patients est de 48 ±7 ans. La tranche d’âge de 50-59 ans représente la classe modale. La douleur est à prédominance nocturne chez 75,0% des patients. Les décharges électriques sont la caractéristique principale soit 48,1% des patients et 57,7% malades présentent une douleur intense. Sur le plan topographique, la racine C7, est la plus atteinte soit 50,0%. Sur la qualité de la vie, 44,2% des malades présentent des troubles du sommeil. Sur le plan thérapeutique l’évolution a été favorable chez 78,8% des patients sous AINS, Tramadol et Amitriptilline. Conclusion otre travail à l'instar des études antérieures sur la NCB montre que cette pathologie reste une entité clinique relativement courante. Le pronostic généralement favorable est fonction d'un diagnostic précoce et d'une prise en charge adaptée. PMID:24648859

  9. Identification and utilization of cleistogamy gene cl7(t) in rice (Oryza sativa L.).

    PubMed

    Ni, Da-Hu; Li, Juan; Duan, Yong-Bo; Yang, Ya-Chun; Wei, Peng-Cheng; Xu, Rong-Fang; Li, Chun-Rong; Liang, Dan-Dan; Li, Hao; Song, Feng-Shun; Ni, Jin-Long; Li, Li; Yang, Jian-Bo

    2014-05-01

    Gene transformation is an important method for improvement of plants into elite varieties. However, the possibility of gene flow between genetically modified (GM) crops and similar species is a serious public issue that may potentially endanger ecological stability. Cleistogamy is expected to be an ideal genetic tool for preventing transgene propagation from GM crops. A rice mutant, cl7(t), was created by ethyl methanesulfonate mutagenesis. The mutant exhibited cleistogamy, and had closed spikelets, reduced plant height, and altered morphology of the leaves, panicle, and seeds. Anatomical investigations revealed that the cl7(t) mutant contained more vascular bundles and thicker stems than the wild type, which increased the mechanical strength of its internodes, and anti-lodging ability. Further studies demonstrated that the force required to open the lemma and palea was higher in the cl7(t) mutant, and there was weak swelling ability in the lodicules, which leads to cleistogamy. Allelic analyses and complementation tests indicated that cl7(t) was a novel allele of dep2, a mutant that was previously reported to have similar panicle morphology. Sequence analysis showed that cl7(t) had a single nucleotide substitution (C to A) in the third exon that leads to a Ser substitution with a stop codon, giving a truncated DEP2 protein. Quantitative RT-PCR and in situ hybridization tests demonstrated that there was lower CL7(t) expression level in the spikelets and weaker CL7(t) signals in the lodicules of the cl7(t) mutant compared with wild type, which implies that CL7(t) might participate in the development of lodicules. To improve the agronomic traits of cl7(t) to fit the needs of field production, the cl7(t) mutant was crossed with an intermediate-type rice variety named Guanghui102, which bears some important agronomic traits, including increased grain numbers and high rate of seed setting. Through multi-generational pedigree selection, cleistogamy lines with improved

  10. Haute prévalence du Burnout dans les unités Tunisiennes prenant en charge des patients en fin de vie

    PubMed Central

    Amamou, Badii; Bannour, Ahmed Souhaiel; Ben Hadj Yahia, Meriem; Ben Nasr, Selma; Ben Hadj Ali, Bechir

    2014-01-01

    Introduction Chez le personnel soignant, le burnout touche un infirmier sur trois. Ce taux est plus élevé dans les unités prenant en charge des patients en fin de vie. L'objectif de notre travail était d'évaluer la fréquence du burnout chez les infirmiers qui travaillent en soins de fin de vie. Méthodes Il s'agit d'une étude descriptive transversale réalisée entre le 1er Avril et le 31 Mai 2010. 60 infirmiers de six services de Sousse et de Monastir (Tunisie) ont été recrutés. L'évaluation du burnout a été réalisée par deux échelles: MBI (Maslach Burnout Inventory) et BMS (Burnout Measure Short version). Résultats La prévalence du burnout était de 70%; il était élevé chez 81.7%. 80% avaient un niveau élevé d'épuisement émotionnel, 70% avaient un niveau élevé de dépersonnalisation et 17% avaient un niveau bas de sentiment d'accomplissement personnel. Le burnout était plus élevé chez les hommes (70,8% vs 69,4%; p=0,013); ceux qui voulaient améliorer les conditions du travail (70.2% vs. 66.7%; p= 0.017); du salaire (70.2% vs. 66.7%; p= 0.017) et chez les infirmiers suivi en psychiatrie (71.4% vs. 69.8%; p= 0.008). Conclusion Dans notre étude le niveau de burnout était élevé chez les infirmiers prenant en charge des patients en fin de vie. Il était associé au sexe masculin et à l'insatisfaction des conditions de travail et du salaire. D'autres études longitudinales sont nécessaires pour suivre l'évolution de ce syndrome et mettre des stratégies de prévention adéquates. PMID:25584122

  11. Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients.

    PubMed

    Meng, Xiaodan; Joosse, Simon A; Müller, Volkmar; Trillsch, Fabian; Milde-Langosch, Karin; Mahner, Sven; Geffken, Maria; Pantel, Klaus; Schwarzenbach, Heidi

    2015-11-03

    Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC. Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines. Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I-II and III-IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III-IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III-IV (P=0.02). Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.

  12. Etude du champ magnetique dans les nuages moleculaires

    NASA Astrophysics Data System (ADS)

    Houde, Martin

    2001-12-01

    Ce travail est une étude du champ magnétique duns l'environnement circumstellaire des étoiles jeunes. Il a pour origine la certitude qu'avait l'auteur qu'il se devait d'être possible de détecter la présence d'un champ magnétique, et de possiblement le caractériser, par le biais d'observations de profils spectraux d'espèces moléculaires ioniques. Il en découle donc qu'un des buts principaux était de prouver que cela est effectivement possible. La thèse comporte alors des éléments théoriques et expérimentaux qui sont à la fois complémentaires et intimement liés. L'aspect théorique est basé sur l'interaction mutuelle que des particules neutres et chargées peuvent avoir l'une sur l'autre daps un plasma faiblement ionisé comme ceux existants daps les nuages moléculaires sites de formation stellaire. Il appert que la présence d'un champ magnétique a un effet direct sur le comportement des ions (via la force de Lorentz) et indirect sur les molécules neutres (via les nombreuses collisions entre les deux types de particules). Une telle interaction est, comme il est maintenant bien connu, présente dans les premières étapes de la formation dune étoile. Il s'agit bien sûr de la diffusion ambipolaire. Nous montrerons qu'il existe cependant un autre type de diffusion, jusqu'ici inconnue, qui se manifeste plus tard au tours de l'évolution des nuages moléculaires. Celle-ci peut avoir un effet dramatique sur l'apparence des profils spectraux (de rotation moléculaire) des espèces ioniques lorsque comparés à ceux qu'exhibent des espèces neutres coexistantes. Mais pour ce faire, il doit y avoir existence de mouvements organisés (des flots ou jets) de matière ou encore la présence de turbulence dans les régions considérées. Une distribution de vélocité du type maxwellienne ne révèlera pas la présence du champ magnétique. Les observations, qui ont pour but de confirmer la théorie, se situent dans le domaine des longueurs d

  13. Microstrip Butler matrix design and realization for 7 T MRI.

    PubMed

    Yazdanbakhsh, Pedram; Solbach, Klaus

    2011-07-01

    This article presents the design and realization of 8 × 8 and 16 × 16 Butler matrices for 7 T MRI systems. With the focus on low insertion loss and high amplitude/phase accuracy, the microstrip line integration technology (microwave-integrated circuit) was chosen for the realization. Laminate material of high permittivity (ε(r) = 11) and large thickness (h = 3.2 mm) is shown to allow the best trade-off of circuit board size versus insertion loss, saving circuit area by extensive folding of branch-line coupler topology and meandering phase shifter and connecting strip lines and reducing mutual coupling of neighboring strip lines by shield structures between strip lines. With this approach, 8 × 8 Butler matrices were produced in single boards of 310 mm × 530 mm, whereas the 16 × 16 Butler matrices combined two submatrices of 8 × 8 with two smaller boards. Insertion loss was found at 0.73 and 1.1 dB for an 8 × 8 matrix and 16 × 16 matrix, respectively. Measured amplitude and phase errors are shown to represent highly pure mode excitation with unwanted modes suppressed by 40 and 35 dB, respectively. Both types of matrices were implemented with a 7 T MRI system and 8- and 16-element coil arrays for RF mode shimming experiments and operated successfully with 8 kW of RF power. Copyright © 2011 Wiley-Liss, Inc.

  14. Single-shot spiral imaging at 7T.

    PubMed

    Engel, Maria; Kasper, Lars; Barmet, Christoph; Schmid, Thomas; Vionnet, Laetitia; Wilm, Bertram; Pruessmann, Klaas P

    2018-03-25

    The purpose of this work is to explore the feasibility and performance of single-shot spiral MRI at 7T, using an expanded signal model for reconstruction. Gradient-echo brain imaging is performed on a 7T system using high-resolution single-shot spiral readouts and half-shot spirals that perform dual-image acquisition after a single excitation. Image reconstruction is based on an expanded signal model including the encoding effects of coil sensitivity, static off-resonance, and magnetic field dynamics. The latter are recorded concurrently with image acquisition, using NMR field probes. The resulting image resolution is assessed by point spread function analysis. Single-shot spiral imaging is achieved at a nominal resolution of 0.8 mm, using spiral-out readouts of 53-ms duration. High depiction fidelity is achieved without conspicuous blurring or distortion. Effective resolutions are assessed as 0.8, 0.94, and 0.98 mm in CSF, gray matter and white matter, respectively. High image quality is also achieved with half-shot acquisition yielding image pairs at 1.5-mm resolution. Use of an expanded signal model enables single-shot spiral imaging at 7T with unprecedented image quality. Single-shot and half-shot spiral readouts deploy the sensitivity benefit of high field for rapid high-resolution imaging, particularly for functional MRI and arterial spin labeling. © 2018 International Society for Magnetic Resonance in Medicine.

  15. Tamoxifen Inhibition of Kv7.2/Kv7.3 Channels

    PubMed Central

    Ferrer, Tania; Aréchiga-Figueroa, Ivan Arael; Shapiro, Mark S.; Tristani-Firouzi, Martin; Sanchez-Chapula, José A.

    2013-01-01

    KCNQ genes encode five Kv7 K+ channel subunits (Kv7.1–Kv7.5). Four of these (Kv7.2–Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the principal molecular components of the slow voltage-gated M-channel, which regulates neuronal excitability. In this study, we demonstrate that tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibits Kv7.2/Kv7.3 currents heterologously expressed in human embryonic kidney HEK-293 cells. Current inhibition by tamoxifen was voltage independent but concentration-dependent. The IC50 for current inhibition was 1.68 ± 0.44 µM. The voltage-dependent activation of the channel was not modified. Tamoxifen inhibited Kv7.2 homomeric channels with a higher potency (IC50 = 0.74 ± 0.16 µM). The mutation Kv7.2 R463E increases phosphatidylinositol- 4,5-bisphosphate (PIP2) - channel interaction and diminished dramatically the inhibitory effect of tamoxifen compared with that for wild type Kv7.2. Conversely, the mutation Kv7.2 R463Q, which decreases PIP2 -channel interaction, increased tamoxifen potency. Similar results were obtained on the heteromeric Kv7.2 R463Q/Kv7.3 and Kv7.2 R463E/Kv7.3 channels, compared to Kv7.2/Kv7.3 WT. Overexpression of type 2A PI(4)P5-kinase (PIP5K 2A) significantly reduced tamoxifen inhibition of Kv7.2/Kv7.3 and Kv7.2 R463Q channels. Our results suggest that tamoxifen inhibited Kv7.2/Kv7.3 channels by interfering with PIP2-channel interaction because of its documented interaction with PIP2 and the similar effect of tamoxifen on various PIP2 sensitive channels. PMID:24086693

  16. Tamoxifen inhibition of kv7.2/kv7.3 channels.

    PubMed

    Ferrer, Tania; Aréchiga-Figueroa, Ivan Arael; Shapiro, Mark S; Tristani-Firouzi, Martin; Sanchez-Chapula, José A

    2013-01-01

    KCNQ genes encode five Kv7 K(+) channel subunits (Kv7.1-Kv7.5). Four of these (Kv7.2-Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the principal molecular components of the slow voltage-gated M-channel, which regulates neuronal excitability. In this study, we demonstrate that tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibits Kv7.2/Kv7.3 currents heterologously expressed in human embryonic kidney HEK-293 cells. Current inhibition by tamoxifen was voltage independent but concentration-dependent. The IC50 for current inhibition was 1.68 ± 0.44 µM. The voltage-dependent activation of the channel was not modified. Tamoxifen inhibited Kv7.2 homomeric channels with a higher potency (IC50 = 0.74 ± 0.16 µM). The mutation Kv7.2 R463E increases phosphatidylinositol- 4,5-bisphosphate (PIP2) - channel interaction and diminished dramatically the inhibitory effect of tamoxifen compared with that for wild type Kv7.2. Conversely, the mutation Kv7.2 R463Q, which decreases PIP2 -channel interaction, increased tamoxifen potency. Similar results were obtained on the heteromeric Kv7.2 R463Q/Kv7.3 and Kv7.2 R463E/Kv7.3 channels, compared to Kv7.2/Kv7.3 WT. Overexpression of type 2A PI(4)P5-kinase (PIP5K 2A) significantly reduced tamoxifen inhibition of Kv7.2/Kv7.3 and Kv7.2 R463Q channels. Our results suggest that tamoxifen inhibited Kv7.2/Kv7.3 channels by interfering with PIP2-channel interaction because of its documented interaction with PIP2 and the similar effect of tamoxifen on various PIP2 sensitive channels.

  17. Spiral MR fingerprinting at 7T with simultaneous B1 estimation.

    PubMed

    Buonincontri, Guido; Schulte, Rolf F; Cosottini, Mirco; Tosetti, Michela

    2017-09-01

    Magnetic resonance fingerprinting is an efficient, new approach for quantitative imaging with MR. We aimed to extend this technique to cases with B1+ inhomogeneities within the imaging volume. Previous approaches have used abrupt changes in flip angles to estimate the B1+ field simultaneously with T1 and T2, using a Cartesian approach in a small-animal scanner at 4.7T. Here, we evaluated whether a similar approach would be suitable for imaging human brains using spiral readouts with a 7T scanner. We found that our modified scheme could significantly reduce the adverse effects of B1+ inhomogeneities even in extreme cases, reducing both the bias and the variance in T2 estimations by an order of magnitude when compared to literature methods. Acquisitions used less than 1.5W/kg SAR and could be performed in 12s per slice. In conclusion, our approach can be used to perform quantitative imaging of the brain at 7T in a short time, simultaneously estimating the B1+ profile. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. First Application of 7T Magnetic Resonance Imaging in Endoscopic Endonasal Surgery of Skull Base Tumors

    PubMed Central

    Barrett, Thomas F; Dyvorne, Hadrien A; Padormo, Francesco; Pawha, Puneet S; Delman, Bradley N; Shrivastava, Raj K; Balchandani, Priti

    2018-01-01

    Background Successful endoscopic endonasal surgery for the resection of skull base tumors is reliant on preoperative imaging to delineate pathology from the surrounding anatomy. The increased signal-to-noise ratio afforded by 7T MRI can be used to increase spatial and contrast resolution, which may lend itself to improved imaging of skull base. In this study, we apply a 7T imaging protocol to patients with skull base tumors and compare the images to clinical standard of care. Methods Images were acquired at 7T on 11 patients with skull base lesions. Two neuroradiologists evaluated clinical 1.5T, 3T, and 7T scans for detection of intracavernous cranial nerves and ICA branches. Detection rates were compared. Images were utilized for surgical planning and uploaded to a neuronavigation platform and used to guide surgery. Results Image analysis yielded improved detection rates of cranial nerves and ICA branches at 7T. 7T images were successfully incorporated into preoperative planning and intraoperative neuronavigation. Conclusion Our study represents the first application of 7T MRI to the full neurosurgical workflow for endoscopic endonasal surgery. We detected higher rates of cranial nerves and ICA branches at 7T MRI compared to 3T and 1.5 T, and found that integration of 7T into surgical planning and guidance was feasible. These results suggest a potential for 7T MRI to reduce surgical complications. Future studies comparing standardized 7T, 3T, and 1.5 T MRI protocols in a larger number of patients are warranted to determine the relative benefit of 7T MRI for endonasal endoscopic surgical efficacy. PMID:28359922

  19. Quantitation of enantiomers of r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]-pyrene in human urine: evidence supporting metabolic activation of benzo[a]pyrene via the bay region diol epoxide.

    PubMed

    Hecht, Stephen S; Hochalter, Jon Bradley

    2014-09-01

    Benzo[a]pyrene (BaP), a potent polycyclic aromatic hydrocarbon carcinogen, is widely distributed in the human environment. All humans are exposed to BaP through the diet and contact with the general environment; cigarette smokers have higher exposure. An important pathway of BaP metabolism proceeds through formation of diol epoxides including the 'bay region diol epoxide' 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [BaP-(7R,8S)-diol-(9S,10R)-epoxide] and the 'reverse diol epoxide' 9S,10R-dihydroxy-7R,8S-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene [BaP-(9S,10R)-diol-(7R,8S)-epoxide]. The bay region diol epoxide is considered a major ultimate carcinogen of BaP based on studies in cell culture and laboratory animals, but the available data in humans are less convincing. The bay region diol epoxide and the reverse diol epoxide react with H2O to produce enantiomeric BaP-tetraols that are excreted in the urine. We used chiral stationary-phase high-performance liquid chromatography and gas chromatography-negative ion chemical ionisation-tandem mass spectrometry to quantify these enantiomeric BaP-tetraols in the urine of 25 smokers and 25 non-smokers. The results demonstrated that the BaP-tetraol enantiomer representing the carcinogenic bay region diol epoxide pathway accounted for 68±6% (range 56-81%) of total BaP-tetraol in smokers and 64±6% (range 46-78%) in non-smokers. Levels of the major BaP-tetraol enantiomer decreased by 75% in smokers who quit smoking. These data provide convincing evidence in support of the bay region diol epoxide mechanism of BaP carcinogenesis in humans. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Etude du comportement et de la modélisation viscoplastique du zircaloy 4recristallisé sous chargements monotones et cycliques uni et multiaxes

    NASA Astrophysics Data System (ADS)

    Delobelle, P.; Robinet, P.

    1994-08-01

    The results of experiment performed on a recrystallized zircaloy 4 alloy in the intermediate temperature domain 20 leqslant T leqslant 400 ^{circ}C are presented. To characterize the anisotropy, especially at 350 ^{circ}C, the tests were made under both monotonic and cyclic uni- and bidirectional loadings, i.e. tension-compression, tension-torsion and tension-internal pressure tests. The different anisotropy coefficients and especially R^p = \\varepsilon^p_{θθ} /\\varepsilon^ p _ {{^-_-}{^-_-} } seem to be temperature independent. An important feature of the behavior of this alloy in the neighbourhood of 300 ^{circ}C is attributed to the dislocations-point defects interactions (dynamic strain aging), phenomena often observed in the solid solutions. For the 2D cyclic non proportional loadings it is shown that a weak supplementary hardening appears, which is a function of the degree of the phase lag. We propose to particularize and to apply a unified viscoplastic model with internal variables to the considered alloy, as the model as already been developed and identified elsewhere for other isotropic materials. From a general point of view the introduction of the anisotropy in the model is made by four tensors of rank 4 ; [ M] is assigned to the flow directions, [ N] to the linear parts of the kinematical hardening variables and [ Q] , [ R] respectively to the dynamic and static recoveries of these tensorial variables. This phenomenological formulation leads to a correct representation of the set of the experimental results presented at 350 ^{circ}C, which provides an a posteriori confirmation of the formalism used. On étudie, entre 20 et 400 ^{circ}C, à l'aide d'essais sous chargements multiaxiaux monotones et cycliques (traction, torsion et pression interne) les propriétés viscoplastiques anisotropes de tube de zircaloy 4 recristallisé. A la température de 350 ^{circ}C, l'anisotropie a été quantifiée de façon détaillée. Les quelques résultats obtenus

  1. Functional Human α7 Nicotinic Acetylcholine Receptor (nAChR) Generated from Escherichia coli.

    PubMed

    Tillman, Tommy S; Alvarez, Frances J D; Reinert, Nathan J; Liu, Chuang; Wang, Dawei; Xu, Yan; Xiao, Kunhong; Zhang, Peijun; Tang, Pei

    2016-08-26

    Human Cys-loop receptors are important therapeutic targets. High-resolution structures are essential for rational drug design, but only a few are available due to difficulties in obtaining sufficient quantities of protein suitable for structural studies. Although expression of proteins in E. coli offers advantages of high yield, low cost, and fast turnover, this approach has not been thoroughly explored for full-length human Cys-loop receptors because of the conventional wisdom that E. coli lacks the specific chaperones and post-translational modifications potentially required for expression of human Cys-loop receptors. Here we report the successful production of full-length wild type human α7nAChR from E. coli Chemically induced chaperones promote high expression levels of well-folded proteins. The choice of detergents, lipids, and ligands during purification determines the final protein quality. The purified α7nAChR not only forms pentamers as imaged by negative-stain electron microscopy, but also retains pharmacological characteristics of native α7nAChR, including binding to bungarotoxin and positive allosteric modulators specific to α7nAChR. Moreover, the purified α7nAChR injected into Xenopus oocytes can be activated by acetylcholine, choline, and nicotine, inhibited by the channel blockers QX-222 and phencyclidine, and potentiated by the α7nAChR specific modulators PNU-120596 and TQS. The successful generation of functional human α7nAChR from E. coli opens a new avenue for producing mammalian Cys-loop receptors to facilitate structure-based rational drug design. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes.

    PubMed Central

    Tabor, S; Richardson, C C

    1985-01-01

    The RNA polymerase gene of bacteriophage T7 has been cloned into the plasmid pBR322 under the inducible control of the lambda PL promoter. After induction, T7 RNA polymerase constitutes 20% of the soluble protein of Escherichia coli, a 200-fold increase over levels found in T7-infected cells. The overproduced enzyme has been purified to homogeneity. During extraction the enzyme is sensitive to a specific proteolysis, a reaction that can be prevented by a modification of lysis conditions. The specificity of T7 RNA polymerase for its own promoters, combined with the ability to inhibit selectively the host RNA polymerase with rifampicin, permits the exclusive expression of genes under the control of a T7 RNA polymerase promoter. We describe such a coupled system and its use to express high levels of phage T7 gene 5 protein, a subunit of T7 DNA polymerase. Images PMID:3156376

  3. Antibody modified gold nanoparticles for fast and selective, colorimetric T7 bacteriophage detection.

    PubMed

    Lesniewski, Adam; Los, Marcin; Jonsson-Niedziółka, Martin; Krajewska, Anna; Szot, Katarzyna; Los, Joanna M; Niedziolka-Jonsson, Joanna

    2014-04-16

    Herein, we report a colorimetric immunosensor for T7 bacteriophage based on gold nanoparticles modified with covalently bonded anti-T7 antibodies. The new immunosensor allows for a fast, simple, and selective detection of T7 virus. T7 virions form immunological complexes with the antibody modified gold nanoparticles which causes them to aggregate. The aggregation can be observed with the naked eye as a color change from red to purple, as well as with a UV-vis spectrophotometer. The aggregate formation was confirmed with SEM imaging. Sensor selectivity against the M13 bacteriophage was demonstrated. The limit of detection (LOD) is 1.08 × 10(10) PFU/mL (18 pM) T7. The new method was compared with a traditional plaque test. In contrast to biological tests the colorimetric method allows for detection of all T7 phages, not only those biologically active. This includes phage ghosts and fragments of virions. T7 virus has been chosen as a model organism for adenoviruses. The described method has several advantages over the traditional ones. It is much faster than a standard plaque test. It is more robust since no bacteria-virus interactions are utilized in the detection process. Since antibodies are available for a large variety of pathogenic viruses, the described concept is very flexible and can be adapted to detect many different viruses, not only bacteriophages. Contrary to the classical immunoassays, it is a one-step detection method, and no additional amplification, e.g., enzymatic, is needed to read the result.

  4. Amplified 7q21-22 gene MCM7 and its intronic miR-25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features.

    PubMed

    Tamilzhalagan, Sembulingam; Rathinam, Dhanasekaran; Ganesan, Kumaresan

    2017-06-01

    Frequent amplification of 7q21-22 genomic region is known in gastric cancer. Multiple genes including SHFM1, MCM7, and COL1A2 were reported to be the potential cancer candidate genes of this 20 Mb amplicon. This amplicon has two polycistrionic miRNA clusters and in the present study, miR-106b-25 cluster located in intron-13 of MCM7 was identified to express in gastric tumors. Among the 7q21-22 candidate genes, SHFM1 and MCM7 are expressed in intestinal type gastric tumors, whereas COL1A2 is expressed in diffuse type gastric tumors. Across gastric tumors, miR-25 was identified to co-express with MCM7 and SHFM1. On the other hand, negative correlation was observed between miR-25 and COL1A2 expression. miR-25 originating from MCM7 was found capable of selectively targeting the adjacent gene COL1A2. Silencing of miR-25 was found capable of elevating the expression of COL1A2 and inhibiting E-cadherin expression, revealing the diffuse type gastric cancer suppressive role conferred by miR-25. miR-25 was also found to suppress p53, and activate c-Src revealing its intestinal type gastric cancer associated oncogenic functions. Genome-wide expression profiling upon miR-25 silencing reveals that miR-25 is capable of suppressing 40 genes which are co-expressed with COL1A2, involved in epithelial to mesenchymal transition and angiogenesis which are the typical diffuse type gastric cancer features. The results clearly demonstrate 7q21-22 amplification, MCM7, and its intronic miR-25 are the major molecular switches involved in the complex oncogenic circuits of gastric cancer. © 2017 Wiley Periodicals, Inc.

  5. Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study.

    PubMed

    Guzmán-Fulgencio, María; Berenguer, Juan; Jiménez-Sousa, María A; Pineda-Tenor, Daniel; Aldámiz-Echevarria, Teresa; García-Broncano, Pilar; Carrero, Ana; García-Álvarez, Mónica; Tejerina, Francisco; Diez, Cristina; Vazquez-Morón, Sonia; Resino, Salvador

    2015-06-30

    Interleukin-7 (IL-7) is a critical factor for T cell development and for maintaining and restoring homeostasis of mature T cells. Polymorphisms at α-chain of the IL-7 receptor (IL7R or CD127) gene are related to evolution of HIV-infection, but there are no data concerning the evolution of hepatitis C virus (HCV) infection. The aim of this study was to analyze the association between IL7R polymorphisms and severe liver disease in HCV/HIV coinfected patients. We performed a cross-sectional study in 220 naïve patients who underwent a liver biopsy. IL7R polymorphisms (rs6897932, rs987106 and rs3194051) were genotyped using the GoldenGate(®) assay. The outcome variables were: (a) liver biopsy: advanced fibrosis (F ≥ 3), severe activity grade (A3); (b) non-invasive indexes: advanced fibrosis (APRI ≥1.5 and FIB-4 ≥3.25). Logistic regression analysis was used to investigate the association between IL7R polymorphisms and outcome variables. This test gives the differences between groups and the odds ratio (OR) for liver disease. Patients with rs6897932 CC genotype had higher likelihood of having A3 than patients with rs6897932 CT/TT (adjusted odds ratio (aOR) = 4.16; p = 0.026). Patients with rs987106 TT genotype had higher odds of having F ≥ 3 (aOR = 3.09; p = 0.009) than rs987106 AA/AT carriers. Finally, patients with rs3194051 AA genotype had higher odds of having severe liver fibrosis (F ≥ 3; APRI ≥1.5, and FIB4 ≥3.25) than patients with rs3194051 AG/GG genotype [aOR = 2.73 (p = 0.010); aOR = 2.52 (p = 0.029); and aOR = 4.01 (p = 0.027); respectively]. The CTA haplotype (comprised of rs6897932, rs987106, and rs3194051) carriers had higher odds of having F ≥ 3 (aOR = 1.85; p = 0.012), APRI ≥1.5 (aOR = 1.94; p = 0.023), and FIB4 ≥3.25 (aOR = 2.47; p = 0.024). Conversely, the CAG haplotype carriers had lower odds of having F ≥ 3 (aOR = 0.48; p = 0.011), APRI ≥1.5 (aOR = 0.48; p = 0.029), and FIB4 ≥3.25 (aOR = 0.29; p = 0.010). The presence of IL

  6. Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy

    PubMed Central

    Smith, Jenessa B; Lanitis, Evripidis; Dangaj, Denarda; Buza, Elizabeth; Poussin, Mathilde; Stashwick, Caitlin; Scholler, Nathalie; Powell, Daniel J

    2016-01-01

    B7-H4 protein is frequently overexpressed in ovarian cancer. Here, we engineered T cells with novel B7-H4-specific chimeric antigen receptors (CARs) that recognized both human and murine B7-H4 to test the hypothesis that B7-H4 CAR T cell therapy can be applied safely in preclinical models. B7-H4 CAR T cells specifically secreted IFN-γ and lysed B7-H4(+) targets. In vivo, B7-H4 CAR T cells displayed antitumor reactivity against B7-H4(+) human ovarian tumor xenografts. Unexpectedly, B7-H4 CAR T cell treatment reproducibly showed delayed, lethal toxicity 6–8 weeks after therapy. Comprehensive assessment of murine B7-H4 protein distribution uncovered expression in ductal and mucosal epithelial cells in normal tissues. Postmortem analysis revealed the presence of widespread histologic lesions that correlated with B7-H4(+) expression, and were inconsistent with graft versus host disease. Lastly, expression patterns of B7-H4 protein in normal human tissue were comparable to distribution in mice, advancing our understanding of B7-H4. We conclude that B7-H4 CAR therapy mediates control of cancer outgrowth. However, long-term engraftment of B7-H4 CAR T cells mediates lethal, off-tumor toxicity that is likely due to wide expression of B7-H4 in healthy mouse organs. This model system provides a unique opportunity for preclinical evaluation of safety approaches that limit CAR-mediated toxicity after tumor destruction in vivo. PMID:27439899

  7. Effects of tocotrienols on cell viability and apoptosis in normal murine liver cells (BNL CL.2) and liver cancer cells (BNL 1ME A.7R.1), in vitro.

    PubMed

    Har, Chan Hooi; Keong, Chan Kok

    2005-01-01

    The effects of tocotrienols on murine liver cell viability and their apoptotic events were studied over a dose range of 0-32 microg mL(-1). Normal murine liver cells (BNL CL.2) and murine liver cancer cells (BNL 1ME A.7R.1) were treated with tocotrienols (T(3)), alpha tocopherol (alpha-T) and the chemo drug, Doxorubicin (Doxo, as a positive control). Cell viability assay showed that T(3) significantly (P < or = 0.05) lowered the percentage of BNL 1ME A.7R.1 cell viability in a dose-responsive manner (8-16 microg mL(-1)), whereas T did not show any significant (P>0.05) inhibition in cell viability with increasing treatment doses of 0-16 microg mL(-1). The IC(50) for tocotrienols were 9.8, 8.9, 8.1, 9.7, 8.1 and 9.3 microg mL(-1) at 12, 24, 36, 48, 60 and 72 hours respectively. Early apoptosis was detected 6 hours following T(3) treatment of BNL 1ME A.7R.1 liver cancer cells, using Annexin V-FITC fluorescence microscopy assay for apoptosis, but none were observed for the non-treated liver cancer cells at the average IC(50) of 8.98 microg mL(-1) tocotrienols for liver cancer cells. Several apoptotic bodies were detected in BNL 1ME A.7R.1 liver cancer cells at 6 hours post-treatment with tocotrienols (8.98 microg mL(-1)) using Acridine Orange/Propidium Iodide fluorescence assay. However, only a couple of apoptotic bodies were seen in the non-treated liver cancer cells and the BNL CL.2 normal liver cells. Some mitotic bodies were also observed in the T(3)-treated BNL 1ME A.7R.1 liver cancer cells but were not seen in the untreated BNL 1ME A.7R.1 cells and the BNL CL.2 liver cells. Following T(3)-treatment (8.98 microg mL(-1)) of the BNL 1ME A.7R.1 liver cancer cells, 24.62%, 25.53% and 44.90% of the cells showed elevated active caspase 3 activity at 9, 12 and 24 hours treatment period, respectively. DNA laddering studies indicated DNA fragmentation occurred in the T(3)-treated liver cancer cells, BNL 1ME A.7R.1 but not in non-treated liver cancer cells and the T(3

  8. Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

    PubMed Central

    Wells, Alexandria C; Daniels, Keith A; Angelou, Constance C; Fagerberg, Eric; Burnside, Amy S; Markstein, Michele; Alfandari, Dominique; Welsh, Raymond M; Pobezinskaya, Elena L; Pobezinsky, Leonid A

    2017-01-01

    The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses. DOI: http://dx.doi.org/10.7554/eLife.26398.001 PMID:28737488

  9. Les fractures luxations du cotyle: prise en charge et pronostic à long terme; étude rétrospective portant sur 40 cas

    PubMed Central

    Chagou, Aniss; Hmouri, Ismail; Rhanim, Abdelkarim; Lahlou, Abdou; Berrada, Mohammed Saleh; Yaacoubi, Moradh

    2014-01-01

    Les fractures luxations du cotyle sont le plus souvent dues à des traumatismes de haute énergie. Elles constituent une urgence thérapeutique, l'association de la luxation à une fracture du cotyle fait apparaître la question du choix thérapeutique entre traitement orthopédique et traitement médical. L'objectif de l’étude est de mettre le point sur l'aspect thérapeutique dans ces lésions mais aussi leurs pronostics à long terme. Nous rapportons une étude rétrospective portant sur 40 cas colligés au service d'orthopédie du centre hospitalier universitaire de Rabat. Nous avons évalué les résultats de notre prise en charge mais aussi le pronostic à court et à long terme. Dans notre série, vingt cinq patients ont bénéficié d'un traitement orthopédique alors que les quinze restants ont été opérés, la voie d'abord la plus utilisée est la voie postérieure. Les résultats fonctionnels ont été évalués, après un recul de 3 à 8 ans, selon la cotation de Merle d'Aubigné. Nous avons obtenu 90% de résultats satisfaisants. La comparaison de nos résultats à ceux de la littérature montre que le résultat des traitements orthopédiques et chirurgicaux dépend essentiellement du type de fracture. Le pronostic à long terme reste imprévisible. La survenue des complications tardives telle que la nécrose céphalique et de l'arthrose reste toujours imprévisible, ce qui impose un suivi régulier et prolongé des patients. PMID:25722763

  10. 7. Historic American Buildings Survey Nathaniel R. Ewan, Photographer May ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Historic American Buildings Survey Nathaniel R. Ewan, Photographer May 24, 1938 INTERIOR - FIREPLACE DETAIL - LIVING ROOM #2 - Boudinot Mansion, 1073 East Jersey Avenue, Elizabeth, Union County, NJ

  11. Measurement of T1 of human arterial and venous blood at 7T.

    PubMed

    Rane, Swati D; Gore, John C

    2013-04-01

    Techniques for measuring cerebral perfusion require accurate longitudinal relaxation (T1) of blood, an MRI parameter that is field dependent. T1 of arterial and venous human blood was measured at 7T using three different sources - pathology laboratory, blood bank and in vivo. The T1 of venous blood was measured from sealed samples from a pathology lab and in vivo. Samples from a blood bank were oxygenated and mixed to obtain different physiological concentrations of hematocrit and oxygenation. T1 relaxation times were estimated using a three-point fit to a simple inversion recovery equation. At 37°C, the T1 of blood at arterial pO2 was 2.29±0.1s and 2.07±0.12 at venous pO2. The in vivo T1 of venous blood, in three subjects, was slightly longer at 2.45±0.11s. T1 of arterial and venous blood at 7T was measured and found to be significantly different. The T1 values were longer in vivo than in vitro. While the exact cause for the discrepancy is unknown, the additives in the blood samples, degradation during experiment, oxygenation differences, and the non-stagnant nature of blood in vivo could be potential contributors to the lower values of T1 in the venous samples. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Expression of alkyl hydroperoxide reductase is regulated negatively by OxyR1 and positively by RpoE2 sigma factor in Azospirillum brasilense Sp7.

    PubMed

    Singh, Sudhir; Dwivedi, Susheel Kumar; Singh, Vijay Shankar; Tripathi, Anil Kumar

    2016-10-01

    OxyR proteins are LysR-type transcriptional regulators, which play an important role in responding to oxidative stress in bacteria. Azospirillum brasilense Sp7 harbours two copies of OxyR. The inactivation of the oxyR1, the gene organized divergently to ahpC in A. brasilense Sp7, led to an increased tolerance to alkyl hydroperoxides, which was corroborated by an increase in alkyl hydroperoxide reductase (AhpC) activity, enhanced expression of ahpC :lacZ fusion and increased synthesis of AhpC protein in the oxyR1::km mutant. The upstream region of ahpC promoter harboured a putative OxyR binding site, T-N11-A. Mutation of T, A or both in the T-N11-Amotif caused derepression of ahpC in A. brasilense suggesting that T-N11-A might be the binding site for a negative regulator. Retardation of the electrophoretic mobility of the T-N11-A motif harbouring oxyR1-ahpC intergenic DNA by recombinant OxyR1, under reducing as well as oxidizing conditions, indicated that OxyR1 acts as a negative regulator of ahpC in A. brasilense. Sequence of the promoter of ahpC, predicted on the basis of transcriptional start site, and an enhanced expression of ahpC:lacZ fusion in chrR2::km mutant background suggested that ahpC promoter was RpoE2 dependent. Thus, this study shows that in A. brasilense Sp7, ahpC expression is regulated negatively by OxyR1 but is regulated positively by RpoE2, an oxidative-stress-responsive sigma factor. It also shows that OxyR1 regulates the expression RpoE1, which is known to play an important role during photooxidative stress in A. brasilense.

  13. Interleukin-7 negatively regulates the development of mature T cells in fetal thymus organ cultures.

    PubMed

    DeLuca, Dominick; Clark, Dawn R

    2002-05-01

    We added antibody specific for interleukin-7 (IL-7) to chimeric fetal thymus organ cultures (FTOC) to investigate the involvement of this cytokine at distinct stages of T cell development. We report that the neutralization of IL-7 early in fetal T cell development results in a decrease in the production of mature CD4 or CD8 ('single positive', SP) or CD4/8 negative ('double negative', DN) T cell phenotypes, as defined by their expression of CD3. This loss of T cell development was not complete, but it did include the development of gammadelta T cells. However, if IL-7 was neutralized at later stages of FTOC, the production of CD4/8 positive ('double positive', DP) T cells was increased, and if the addition of the antibody was delayed further, the production of mature SP T cells was increased. This last result could be extended to both alphabeta and gammadelta T cells. These data suggested that IL-7 played a negative regulatory role in the development of progressively mature T cells. Tissue sections of FTOC showed that IL-7 was expressed in the subcapsular region of the tissue where immature T cells reside. However, IL-7 was not detected in the medullary region where mature T cells are located. These data suggest that IL-7 not only supports the development of immature fetal T cells, but it may inhibit the development of mature T cells. The production of mature fetal T cells may, therefore, be delayed until their precursors enter the medullary microenvironment, where IL-7 production is low. In this way, T cells may be prevented from maturing until negative selection or anergy events eliminate or inactivate autoreactive clones.

  14. Library of synthetic transcriptional AND gates built with split T7 RNA polymerase mutants

    PubMed Central

    Shis, David L.; Bennett, Matthew R.

    2013-01-01

    The construction of synthetic gene circuits relies on our ability to engineer regulatory architectures that are orthogonal to the host’s native regulatory pathways. However, as synthetic gene circuits become larger and more complicated, we are limited by the small number of parts, especially transcription factors, that work well in the context of the circuit. The current repertoire of transcription factors consists of a limited selection of activators and repressors, making the implementation of transcriptional logic a complicated and component-intensive process. To address this, we modified bacteriophage T7 RNA polymerase (T7 RNAP) to create a library of transcriptional AND gates for use in Escherichia coli by first splitting the protein and then mutating the DNA recognition domain of the C-terminal fragment to alter its promoter specificity. We first demonstrate that split T7 RNAP is active in vivo and compare it with full-length enzyme. We then create a library of mutant split T7 RNAPs that have a range of activities when used in combination with a complimentary set of altered T7-specific promoters. Finally, we assay the two-input function of both wild-type and mutant split T7 RNAPs and find that regulated expression of the N- and C-terminal fragments of the split T7 RNAPs creates AND logic in each case. This work demonstrates that mutant split T7 RNAP can be used as a transcriptional AND gate and introduces a unique library of components for use in synthetic gene circuits. PMID:23479654

  15. Library of synthetic transcriptional AND gates built with split T7 RNA polymerase mutants.

    PubMed

    Shis, David L; Bennett, Matthew R

    2013-03-26

    The construction of synthetic gene circuits relies on our ability to engineer regulatory architectures that are orthogonal to the host's native regulatory pathways. However, as synthetic gene circuits become larger and more complicated, we are limited by the small number of parts, especially transcription factors, that work well in the context of the circuit. The current repertoire of transcription factors consists of a limited selection of activators and repressors, making the implementation of transcriptional logic a complicated and component-intensive process. To address this, we modified bacteriophage T7 RNA polymerase (T7 RNAP) to create a library of transcriptional AND gates for use in Escherichia coli by first splitting the protein and then mutating the DNA recognition domain of the C-terminal fragment to alter its promoter specificity. We first demonstrate that split T7 RNAP is active in vivo and compare it with full-length enzyme. We then create a library of mutant split T7 RNAPs that have a range of activities when used in combination with a complimentary set of altered T7-specific promoters. Finally, we assay the two-input function of both wild-type and mutant split T7 RNAPs and find that regulated expression of the N- and C-terminal fragments of the split T7 RNAPs creates AND logic in each case. This work demonstrates that mutant split T7 RNAP can be used as a transcriptional AND gate and introduces a unique library of components for use in synthetic gene circuits.

  16. First Application of 7-T Magnetic Resonance Imaging in Endoscopic Endonasal Surgery of Skull Base Tumors.

    PubMed

    Barrett, Thomas F; Dyvorne, Hadrien A; Padormo, Francesco; Pawha, Puneet S; Delman, Bradley N; Shrivastava, Raj K; Balchandani, Priti

    2017-07-01

    Successful endoscopic endonasal surgery for the resection of skull base tumors is reliant on preoperative imaging to delineate pathology from the surrounding anatomy. The increased signal-to-noise ratio afforded by 7-T MRI can be used to increase spatial and contrast resolution, which may lend itself to improved imaging of the skull base. In this study, we apply a 7-T imaging protocol to patients with skull base tumors and compare the images with clinical standard of care. Images were acquired at 7 T on 11 patients with skull base lesions. Two neuroradiologists evaluated clinical 1.5-, 3-, and 7-T scans for detection of intracavernous cranial nerves and internal carotid artery (ICA) branches. Detection rates were compared. Images were used for surgical planning and uploaded to a neuronavigation platform and used to guide surgery. Image analysis yielded improved detection rates of cranial nerves and ICA branches at 7 T. The 7-T images were successfully incorporated into preoperative planning and intraoperative neuronavigation. Our study represents the first application of 7-T MRI to the full neurosurgical workflow for endoscopic endonasal surgery. We detected higher rates of cranial nerves and ICA branches at 7-T MRI compared with 3- and 1.5-T MRI, and found that integration of 7 T into surgical planning and guidance was feasible. These results suggest a potential for 7-T MRI to reduce surgical complications. Future studies comparing standardized 7-, 3-, and 1.5-T MRI protocols in a larger number of patients are warranted to determine the relative benefit of 7-T MRI for endonasal endoscopic surgical efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. IL-7 signaling imparts polyfunctionality and stemness potential to CD4+ T cells

    PubMed Central

    Ding, Zhi-Chun; Liu, Chufeng; Cao, Yang; Habtetsion, Tsadik; Kuczma, Michal; Pi, Wenhu; Kong, Heng; Cacan, Ercan; Greer, Susanna F.; Cui, Yan; Blazar, Bruce R.; Munn, David H.; Zhou, Gang

    2016-01-01

    ABSTRACT The functional status of CD4+ T cells is a critical determinant of antitumor immunity. Polyfunctional CD4+ T cells possess the ability to concomitantly produce multiple Th1-type cytokines, exhibiting a functional attribute desirable for cancer immunotherapy. However, the mechanisms by which these cells are induced are neither defined nor it is clear if these cells can be used therapeutically to treat cancer. Here, we report that CD4+ T cells exposed to exogenous IL-7 during antigenic stimulation can acquire a polyfunctional phenotype, characterized by their ability to simultaneously express IFNγ, IL-2, TNFα and granzyme B. This IL-7-driven polyfunctional phenotype was associated with increased histone acetylation in the promoters of the effector genes, indicative of increased chromatin accessibility. Moreover, forced expression of a constitutively active (CA) form of STAT5 recapitulated IL-7 in inducing CD4+ T-cell polyfunctionality. Conversely, the expression of a dominant negative (DN) form of STAT5 abolished the ability of IL-7 to induce polyfunctional CD4+ T cells. These in-vitro-generated polyfunctional CD4+ T cells can traffic to tumor and expand intratumorally in response to immunization. Importantly, adoptive transfer of polyfunctional CD4+ T cells following lymphodepletive chemotherapy was able to eradicate large established tumors. This beneficial outcome was associated with the occurrence of antigen epitope spreading, activation of the endogenous CD8+ T cells and persistence of donor CD4+ T cells exhibiting memory stem cell attributes. These findings indicate that IL-7 signaling can impart polyfunctionality and stemness potential to CD4+ T cells, revealing a previously unknown property of IL-7 that can be exploited in adoptive T-cell immunotherapy. PMID:27471650

  18. alpha(4)beta(7) independent pathway for CD8(+) T cell-mediated intestinal immunity to rotavirus.

    PubMed

    Kuklin, N A; Rott, L; Darling, J; Campbell, J J; Franco, M; Feng, N; Müller, W; Wagner, N; Altman, J; Butcher, E C; Greenberg, H B

    2000-12-01

    Rotavirus (RV), which replicates exclusively in cells of the small intestine, is the most important cause of severe diarrhea in young children worldwide. Using a mouse model, we show that expression of the intestinal homing integrin alpha(4)ss(7) is not essential for CD8(+) T cells to migrate to the intestine or provide immunity to RV. Mice deficient in ss7 expression (ss7(-/-)) and unable to express alpha(4)ss(7) integrin were found to clear RV as quickly as wild-type (wt) animals. Depletion of CD8(+) T cells in ss7(-/-) animals prolonged viral shedding, and transfer of immune ss7(-/-) CD8(+) T cells into chronically infected Rag-2-deficient mice resolved RV infection as efficiently as wt CD8(+) T cells. Paradoxically, alpha(4)ss(7)(hi) memory CD8(+) T cells purified from wt mice that had been orally immunized cleared RV more efficiently than alpha(4)ss(7)(low) CD8(+) T cells. We explained this apparent contradiction by demonstrating that expression of alpha(4)ss(7) on effector CD8(+) T cells depends upon the site of initial antigen exposure: oral immunization generates RV-specific CD8(+) T cells primarily of an alpha(4)ss(7)(hi) phenotype, but subcutaneous immunization yields both alpha(4)ss(7)(hi) and alpha(4)ss(7)(low) immune CD8(+) T cells with anti-RV effector capabilities. Thus, alpha(4)ss(7) facilitates normal intestinal immune trafficking to the gut, but it is not required for effective CD8(+) T cell immunity.

  19. Facteurs de risque de mortalité chez les nouveaux-nés transférés au service de néonatologie de l'Hôpital Jason Sendwe de Lubumbashi, République Démocratique du Congo

    PubMed Central

    Katamea, Tina; Mukuku, Olivier; Kamona, Lewis; Mukelenge, Kethye; Mbula, Otikeke; Baledi, Lambert; Ntambwe, Emile; Mutombo, Augustin Mulangu; Wembonyama, Stanis Okitotsho; Luboya, Oscar Numbi

    2014-01-01

    Introduction La mortalité néonatale reste préoccupante dans notre milieu et plusieurs facteurs dont ceux liés à l'organisation du transfert de nouveau-nés au niveau des structures de prise en charge y contribuent. Les objectifs de notre étude sont de déterminer la fréquence du transfert néonatal extrahospitalier à l'unité de néonatologie et identifier les facteurs de risque de mortalité dans notre milieu. Méthodes Il s'agit d'une étude prospective et analytique menée sur une période de douze mois allant du 1er Janvier 2012 au 31 décembre 2012 ayant ciblé tous les nouveau-nés transférés des maternités extérieurs, traités et suivis dans le service de néonatologie de l'hôpital Sendwe. Les caractéristiques maternelles (âge, parité, état-civil, profession, niveau d’étude, antécédents médicaux et toxicologiques) et perpartales (âge gestationnel, état de la poche des eaux, voie d'accouchement) et néonataux (âge lors du transfert, sexe, poids de naissance, moyen de transfert, motif de transfert et évolution (guérison ou décès)) ont été étudiés. La saisie et l'analyse des données ont été faites sur le logiciel Epi Info 2011 (version 7.0.8.3) et le seuil de signification de 5%. Résultats La fréquence du transfert néonatal extrahospitalier est de 12,9%. La mortalité était significativement liée à la profession (vendeuse ou travailleuse) de la mère (OR = 7,43 (1,38-39,97)), au niveau d’étude élevé (OR = 4,22 (1,18-15,10)), à l’âge gestationnel <37 SA (OR=3,21 (1,46-7,06)), à l’accouchement par voie basse de manière dystocique (OR=6,50 (1,54-27,38)), au sexe masculin du nouveau-né (OR=2,43 (1,08-5,46)), au poids de naissance <1500 grammes (OR=15,3 (5,73-40,78)) et à la prématurité comme motif de transfert (OR=5,56 (1,47-20,98)). Conclusion Le bilan de la mortalité néonatale est lourd dans les pays en développement où les nouveau-nés continuent de mourir pour des causes souvent évitables. La r

  20. Classification of the venous architecture of the pineal gland by 7T MRI.

    PubMed

    Cho, Zang-Hee; Choi, Sang-Han; Chi, Je-Gun; Kim, Young-Bo

    2011-10-01

    Magnetic resonance imaging (MRI) at 7.0 Tesla (7T) can show many details of anatomical structures with unprecedented resolution and contrast. In this report, we describe for the first time the unexpected wide variation in pineal gland structure, as visualized by MR images obtained with 7T in a group of healthy young volunteers. A total of 34 volunteers (22 men and 12 women) were enrolled in the study. Their 7T MR images revealed such wide variations in pineal gland shape that it led us to attempt to classify the patterns seen in these pineal glands. Indeed, they were successfully correlated with a previous human cadaver study of venous structures by Tamaki et al., who classified the venous structures of the pineal gland into three categories. This is the first human in vivo pineal vein imaging study using 7T MRI. Pineal venous imaging may permit the early diagnosis of a pineal tumor. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  1. An 8-channel transceiver 7-channel receive RF coil setup for high SNR ultrahigh-field MRI of the shoulder at 7T.

    PubMed

    Rietsch, Stefan H G; Pfaffenrot, Viktor; Bitz, Andreas K; Orzada, Stephan; Brunheim, Sascha; Lazik-Palm, Andrea; Theysohn, Jens M; Ladd, Mark E; Quick, Harald H; Kraff, Oliver

    2017-12-01

    In this work, we present an 8-channel transceiver (Tx/Rx) 7-channel receive (Rx) radiofrequency (RF) coil setup for 7 T ultrahigh-field MR imaging of the shoulder. A C-shaped 8-channel Tx/Rx coil was combined with an anatomically close-fitting 7-channel Rx-only coil. The safety and performance parameters of this coil setup were evaluated on the bench and in phantom experiments. The 7 T MR imaging performance of the shoulder RF coil setup was evaluated in in vivo measurements using a 3D DESS, a 2D PD-weighted TSE sequence, and safety supervision based on virtual observation points. Distinct SNR gain and acceleration capabilities provided by the additional 7-channel Rx-only coil were demonstrated in phantom and in vivo measurements. The power efficiency indicated good performance of each channel and a maximum B 1 + of 19 μT if the hardware RF power limits of the MR system were exploited. MR imaging of the shoulder was demonstrated with clinically excellent image quality and submillimeter spatial resolution. The presented 8-channel transceiver 7-channel receive RF coil setup was successfully applied for in vivo 7 T MRI of the shoulder providing a clear SNR gain vs the transceiver array without the additional receive array. Homogeneous images across the shoulder region were obtained using 8-channel subject-specific phase-only RF shimming. © 2017 American Association of Physicists in Medicine.

  2. Prévalence du portage asymptomatique du plasmodium chez les donneurs bénévoles de sang à Kisangani, République Démocratique du Congo

    PubMed Central

    Bassandja, Jacques Ossinga; Agasa, Salomon Batina; Likwela, Joris Losimba

    2014-01-01

    Introduction Le paludisme transfusionnel est une réalité en Afrique Sub-saharienne, en raison des transfusions sanguines répétées, peu ou non contrôlées et où les donneurs sont en majorité potentiellement porteurs d'hématozoaires. L'objectif de cette étude était de déterminer la prévalence du portage asymptomatique du plasmodium chez les donneurs bénévoles de sang à Kisangani. Méthodes Une étude transversale a été menée au Centre Provincial de Transfusion Sanguine à Kisangani du 1er Décembre 2012 au 31 Mars 2013 et a concerné 480 donneurs bénévoles de sang. Résultats La prévalence du portage asymptomatique du plasmodium chez les donneurs bénévoles de sang était de 28,3%. Plasmodium falciparum était l'espèce la plus répandue (96,3%). Près de la moitié des donneurs avait une parasitémie supérieure à 2000 parasites/µl. Les facteurs qui étaient significativement associés à la parasitémie étaient le jeune âge, le 1er don, et la non utilisation de la moustiquaire imprégnée d'insecticide à longue durée (MILD). Conclusion Les résultats de cette étude montrent que la prévalence du portage asymptomatique du plasmodium chez les donneurs bénévoles de sang était élevée, constituant ainsi un risque important de transmission du parasite aux receveurs souvent en mauvais état général. Cependant, l'utilisation de la MILD et la fidélisation des donneurs bénévoles semblent constituer des moyens utiles de réduction du risque de portage asymptomatique du Plasmodium. Une sensibilisation et éventuellement des distributions ciblées de MILD aux donneurs, en particuliers les plus jeunes, pourraient réduire considérablement le portage du Plasmodium parmi les donneurs de sang et ainsi réduire le risque de paludisme transfusionnel. PMID:25328616

  3. Immunization with M2e-Displaying T7 Bacteriophage Nanoparticles Protects against Influenza A Virus Challenge

    PubMed Central

    Hashemi, Hamidreza; Pouyanfard, Somayeh; Bandehpour, Mojgan; Noroozbabaei, Zahra; Kazemi, Bahram; Saelens, Xavier; Mokhtari-Azad, Talat

    2012-01-01

    Considering the emergence of highly pathogenic influenza viruses and threat of worldwide pandemics, there is an urgent need to develop broadly-protective influenza vaccines. In this study, we demonstrate the potential of T7 bacteriophage-based nanoparticles with genetically fused ectodomain of influenza A virus M2 protein (T7-M2e) as a candidate universal flu vaccine. Immunization of mice with non-adjuvanted T7-M2e elicited M2e-specific serum antibody responses that were similar in magnitude to those elicited by M2e peptide administered in Freund’s adjuvant. Comparable IgG responses directed against T7 phage capsomers were induced following vaccination with wild type T7 or T7-M2e. T7-M2e immunization induced balanced amounts of IgG1 and IgG2a antibodies and these antibodies specifically recognized native M2 on the surface of influenza A virus-infected mammalian cells. The frequency of IFN-γ-secreting T cells induced by T7-M2e nanoparticles was comparable to those elicited by M2e peptide emulsified in Freund’s adjuvant. Emulsification of T7-M2e nanoparticles in Freund’s adjuvant, however, induced a significantly stronger T cell response. Furthermore, T7-M2e-immunized mice were protected against lethal challenge with an H1N1 or an H3N2 virus, implying the induction of hetero-subtypic immunity in our mouse model. T7-M2e-immunized mice displayed considerable weight loss and had significantly reduced viral load in their lungs compared to controls. We conclude that display of M2e on the surface of T7 phage nanoparticles offers an efficient and economical opportunity to induce cross-protective M2e-based immunity against influenza A. PMID:23029232

  4. Let-7b promotes alpaca hair growth via transcriptional repression of TGFβR I.

    PubMed

    Yan, Shen; Yu, Zhang; Ning, Liu; Hai-Dong, Wang; Jian-Shan, Xie; Shu-Yuan, Gao; Jia-Qi, Cheng; Xiu-Ju, Yu; Ting, Wang; Chang-Sheng, Dong; Xiao-Yan, He

    2016-02-10

    The young male alpaca ear and the back skins were used to investigate the effect of transforming growth factor receptor-β I (TGFβR I) on alpaca hair follicles and hair growth. The expression level and location of TGFβR I in alpaca ear and dorsal skin were detected through real-time quantitative PCR (RT-PCR) and paraffin section immunohistochemical technique (ICC-P). The results shown TGFβR I was lower expression in back skin compared to ear skin and the mean density of the positive reaction in ear skin was significantly higher than back skin. The targeted relationship with let-7b was detected using the dual-luciferase reporter vector of TGFβR I, which showed a significant target relationship between let-7b and TGFβR I. After transfection with let-7b eukaryotic expression vector, the relative mRNA expression of TGFβR I in alpaca skin fibroblasts did not differ, while the relative protein level was significantly decreased. In summary, a higher TGFβR I expression level in the ear skin suggests that TGFβR I may inhibit coat hair elongation. Further studies showed TGFβR I protein was downregulated by let-7b through transcriptional repression. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 46 CFR 35.40-7 - Carbon dioxide and clean agent alarms-T/ALL.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Carbon dioxide and clean agent alarms-T/ALL. 35.40-7 Section 35.40-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS OPERATIONS Posting and Marking Requirements-TB/ALL § 35.40-7 Carbon dioxide and clean agent alarms—T/ALL. Each carbon dioxide or clean agent fire extinguishing alarm...

  6. Loss of syd-1 from R7 Neurons Disrupts Two Distinct Phases of Presynaptic Development

    PubMed Central

    Holbrook, Scott; Finley, Jennifer K.; Lyons, Eric L.

    2012-01-01

    Genetic analyses in both worm and fly have identified the RhoGAP-like protein Syd-1 as a key positive regulator of presynaptic assembly. In worm, loss of syd-1 can be fully rescued by overexpressing wild-type Liprin-α, suggesting that the primary function of Syd-1 in this process is to recruit Liprin-α. We show that loss of syd-1 from Drosophila R7 photoreceptors causes two morphological defects that occur at distinct developmental time points. First, syd-1 mutant R7 axons often fail to form terminal boutons in their normal M6 target layer. Later, those mutant axons that do contact M6 often project thin extensions beyond it. We find that the earlier defect coincides with a failure to localize synaptic vesicles, suggesting that it reflects a failure in presynaptic assembly. We then analyze the relationship between syd-1 and Liprin-α in R7s. We find that loss of Liprin-α causes a stronger early R7 defect and provide a possible explanation for this disparity: we show that Liprin-α promotes Kinesin-3/Unc-104/Imac-mediated axon transport independently of Syd-1 and that Kinesin-3/Unc-104/Imac is required for normal R7 bouton formation. Unlike loss of syd-1, loss of Liprin-α does not cause late R7 extensions. We show that overexpressing Liprin-α partly rescues the early but not the late syd-1 mutant R7 defect. We therefore conclude that the two defects are caused by distinct molecular mechanisms. We find that Trio overexpression rescues both syd-1 defects and that trio and syd-1 have similar loss- and gain-of-function phenotypes, suggesting that the primary function of Syd-1 in R7s may be to promote Trio activity. PMID:23238725

  7. Lack of chemopreventive effects of P2X7R inhibitors against pancreatic cancer

    PubMed Central

    Mohammed, Altaf; Janakiram, Naveena B.; Madka, Venkateshwar; Pathuri, Gopal; Li, Qian; Ritchie, Rebekah; Biddick, Laura; Kutche, Hannah; Zhang, Yuting; Singh, Anil; Gali, Hariprasad; Lightfoot, Stan; Steele, Vernon E.; Suen, Chen S.; Rao, Chinthalapally V.

    2017-01-01

    Pancreatic cancer (PC) is an almost uniformly lethal disease with inflammation playing an important role in its progression. Sustained stimulation of purinergic receptor P2X7 drives induction of NLRP inflammasome activation. To understand the role of P2X7 receptor and inflammasome, we performed transcriptomic analysis of p48Cre/+-LSL-KrasG12D/+ mice pancreatic tumors by next generation sequencing. Results showed that P2X7R's key inflammasome components, IL-1β and caspase-1 are highly expressed (p < 0.05) in pancreatic tumors. Hence, to target P2X7R, we tested effects of two P2X7R antagonists, A438079 and AZ10606120, on pancreatic intraepithelial neoplasms (PanINs) and their progression to PC in p48Cre/+-LSL-KrasG12D/+ mice. Following dose optimization studies, for chemoprevention efficacy, six-week-old p48Cre/+-LSL-KrasG12D/+ mice (24–36/group) were fed modified AIN-76A diets containing 0, 50 or 100 ppm A438079 and AZ10606120 for 38 weeks. Pancreata were collected, weighed, and evaluated for PanINs and PDAC. Control diet-fed male mice showed 50% PDAC incidence. Dietary A438079 and AZ10606120 showed 60% PDAC incidence. A marginal increase of PanIN 3 (carcinoma in-situ) was observed in drug-treated mice. Importantly, the carcinoma spread in untreated mice was 24% compared to 43–53% in treatment groups. Reduced survival rates were observed in mice exposed to P2X7R inhibitors. Both drugs showed a decrease in caspase-3, caspase-1, p21 and Cdc25c. Dietary A438079 showed modest inhibition of P2X7R, NLRP3, and IL-33, whereas AZ10606120 had no effects. In summary, targeting the P2X7R pathway by A438079 and AZ10606120 failed to show chemopreventive effects against PC and slightly enhanced PanIN progression to PDAC. Hence, caution is needed while treating high-risk individuals with P2X7R inhibitors. PMID:29228654

  8. Evaluation of non-selective refocusing pulses for 7 T MRI

    PubMed Central

    Moore, Jay; Jankiewicz, Marcin; Anderson, Adam W.; Gore, John C.

    2011-01-01

    There is a continuing need for improved RF pulses that achieve proper refocusing in the context of ultra-high field (≥ 7 T) human MRI. Simple block or sinc pulses are highly susceptible to RF field inhomogeneities, and adiabatic pulses are generally considered too SAR intensive for practical use at 7 T. The performance of the array of pulses falling between these extremes, however, has not been systematically evaluated. The aim of this work was to compare the performances of 21 non-selective refocusing pulses spanning a range of durations and SAR levels. The evaluation was based upon simulations and both phantom and in vivo human brain experiments conducted at 7 T. Tested refocusing designs included block, composite block, BIR-4, hyperbolic secant, and numerically optimized composite waveforms. These pulses were divided into three SAR classes and two duration categories, and, based on signal gain in a 3-D spin echo sequence, practical recommendations on usage are made within each category. All evaluated pulses were found to produce greater volume-averaged signals relative to a 180° block pulse. Although signal gains often come with the price of increased SAR or duration, some pulses were found to result in significant signal enhancement while also adhering to practical constraints. This work demonstrates the signal gains and losses realizable with single-channel refocusing pulse designs and should assist in the selection of suitable refocusing pulses for practical 3-D spin-echo imaging at 7 T. It further establishes a reference against which future pulses and multi-channel designs can be compared. PMID:22177384

  9. The structural changes of T7 RNA polymerase from transcription initiation to elongation

    PubMed Central

    Steitz, Thomas A

    2010-01-01

    Summary The structures of T7 RNA polymerase (T7 RNAP) captured in the initiation and elongation phases of transcription, as well as an intermediate stage provide insights into how this RNA polymerase protein can initiate RNA synthesis and synthesize 7 to 10 nucleotides of RNA while remaining bound to the DNA promoter site. Recently, the structures of T7 RNAP bound to it promoter DNA along with either a 7 nucleotide or 8 nucleotide transcript show an elongated product site resulting from a 40° or 45° rotation of the promoter and domain that binds it. The different functional properties of the initiation and elongation phases of transcription are illuminated from structures of the initiation and elongation complexes. Structural insights into the translocation of the product transcript of RNAP, its separation of the downstream duplex DNA and its removal of the transcript from the heteroduplex are provided by the structures of several states of nucleotide incorporation. A conformational change in the “fingers” domain that results from the binding or dissociation of incoming NTP or PPi appears to be associated with the state of translocation of T7 RNAP. PMID:19811903

  10. MicroRNA let-7, T cells, and patient survival in colorectal cancer

    PubMed Central

    Dou, Ruoxu; Nishihara, Reiko; Cao, Yin; Hamada, Tsuyoshi; Mima, Kosuke; Masuda, Atsuhiro; Masugi, Yohei; Shi, Yan; Gu, Mancang; Li, Wanwan; da Silva, Annacarolina; Nosho, Katsuhiko; Zhang, Xuehong; Meyerhardt, Jeffrey A.; Giovannucci, Edward L.; Chan, Andrew T.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji

    2016-01-01

    Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis. Logistic regression analysis and Cox proportional hazards regression were used to assess associations of let-7a (and let-7b) expression (quartile predictor variables) with T-cell densities (binary outcome variables) and mortality, respectively, controlling for tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Compared with cases in the lowest quartile of let-7a expression, those in the highest quartile were associated with lower densities of CD3+ [multivariate odds ratio (OR), 0.40; 95% confidence interval (CI), 0.23 to 0.67; Ptrend = 0.003] and CD45RO+ cells (multivariate OR, 0.31; 95% CI, 0.17 to 0.58; Ptrend = 0.0004), and higher colorectal cancer-specific mortality (multivariate hazard ratio, 1.82; 95% CI, 1.42 to 3.13; Ptrend = 0.001). In contrast, let-7b expression was not significantly associated with T-cell density or colorectal cancer prognosis. Our data support the role of let-7a in suppressing antitumor immunity in colorectal cancer, and suggest let-7a as a potential target of immunotherapy. PMID:27737877

  11. Symmetry and light stuffing of H o 2 T i 2 O 7 ,   E r 2 T i 2 O 7 , and Y b 2 T i 2 O 7 characterized by synchrotron x-ray diffraction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baroudi, Kristen; Gaulin, Bruce D.; Lapidus, Saul H.

    2015-07-01

    The Ho2Ti2O7, Er2Ti2O7 and Yb2Ti2O7 pyrochlores were studied by synchrotron X-ray diffraction to determine whether the (002) peak, forbidden in the pyrochlore space group Fd-3m but observed in single crystal neutron scattering measurements, is present due to a deviation of their pyrochlore structure from Fd-3m symmetry. Synchrotron diffraction measurements on precisely synthesized stoichiometric and non-stoichiometric powders and a crushed floating zone crystal of Ho2Ti2O7 revealed that the (002) reflection is absent in all cases to a sensitivity of approximately one part in 30,000 of the strongest X-ray diffraction peak. This indicates to high sensitivity that the structural space group ofmore » these rare earth titanate pyrochlores is Fd-3m, and that thus the (002) peak observed in the neutron scattering experiments has a non-structural origin. The cell parameters and internal strain for lightly stuffed Ho2+xTi2-xO7 are also presented.« less

  12. Etude par resistivite electrique du comportement d'un alliage amorphe Fe 40Ni 38Mo 4B 18 deforme par traction

    NASA Astrophysics Data System (ADS)

    Hoang, Long Phan; Sacovy, Paulette; Delaplace, Jean

    1983-02-01

    Des rubans d'alliages amorphes Metglas du type Fe 40Ni 38Mo 4B 18 à l'état brut de trempe ont été déformés par traction à la température ambiante et l'on a suivi les variations de la résistance électrique des échantillons au cours de la déformation. Il ressort de ces essais que la déformation plastique qui est de l'ordre de 0.5% avant rupture ne se produit pas de faĉon homogène dans l'échantillon. Les mesures électriques effectuées au cours de la déformation mettent en évidence dans le domaine élastique un effet d'élastorésistance, relativement important ( K ≠ 1); elles montrent que dans le domaine plastique la déformation permanente des échantillons s'accompagne d'une diminution de la résistivité électrique du matériau. Deux hypothèses sont discutées pour expliquer cet effet inattendu, l'un qui fait appel à l'existence de volumes libres, l'autre qui suppose une cristallisation localisée du matériau sous l'effet de la contrainte.

  13. Eight new T4.5-T7.5 dwarfs discovered in the UKIDSS Large Area Survey Data Release 1

    NASA Astrophysics Data System (ADS)

    Lodieu, N.; Pinfield, D. J.; Leggett, S. K.; Jameson, R. F.; Mortlock, D. J.; Warren, S. J.; Burningham, B.; Lucas, P. W.; Chiu, K.; Liu, M. C.; Venemans, B. P.; McMahon, R. G.; Allard, F.; Baraffe, I.; Barrado y Navascués, D.; Carraro, G.; Casewell, S. L.; Chabrier, G.; Chappelle, R. J.; Clarke, F.; Day-Jones, A. C.; Deacon, N. R.; Dobbie, P. D.; Folkes, S. L.; Hambly, N. C.; Hewett, P. C.; Hodgkin, S. T.; Jones, H. R. A.; Kendall, T. R.; Magazzù, A.; Martín, E. L.; McCaughrean, M. J.; Nakajima, T.; Pavlenko, Y.; Tamura, M.; Tinney, C. G.; Zapatero Osorio, M. R.

    2007-08-01

    We present eight new T4.5-T7.5 dwarfs identified in the UKIRT (United Kingdom Infrared Telescope) Infrared Deep Sky Survey (UKIDSS) Large Area Survey (LAS) Data Release 1 (DR1). In addition we have recovered the T4.5 dwarf SDSSJ020742.91+000056.2 and the T8.5 dwarf ULASJ003402.77-005206.7. Photometric candidates were picked up in two-colour diagrams over 190deg2 (DR1) and selected in at least two filters. All candidates exhibit near-infrared spectra with strong methane and water absorption bands characteristic of T dwarfs and the derived spectral types follow the unified scheme of Burgasser et al.. We have found six new T4.5-T5.5 dwarfs, one T7 dwarf, one T7.5 dwarf and recovered a T4.5 dwarf and a T8.5 dwarf. We provide distance estimates which lie in the 15-85pc range; the T7.5 and T8.5 dwarfs are probably within 25pc of the Sun. We conclude with a discussion of the number of T dwarfs expected after completion of the LAS, comparing these initial results to theoretical simulations. Based on observations made with the United Kingdom Infrared Telescope, operated by the Joint Astronomy Centre on behalf of the UK Particle Physics and Astronomy Research Council. E-mail: nlodieu@iac.es ‡ Alfred P. Sloan Research Fellow.

  14. 26 CFR 1.382-7T - Built-in gains and losses (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Built-in gains and losses (temporary). 1.382-7T... TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.382-7T Built-in gains and losses... recognized built-in gain. The term prepaid income means any amount received prior to the change date that is...

  15. Neuroprotective Activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in Rodent Models of Brain Ischemia

    PubMed Central

    Xu, Zhenfeng; Mu, Chaofeng; Alvarez, Paloma; Ford, Byron D.; El Sayed, Khalid; Eterovic, Vesna A.; Ferchmin, Pedro A.; Hao, Jiukuan

    2015-01-01

    (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volume (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volume (120±65 mm3) than those in the rats of DMSO group (291±95 mm3). The results from in vitro experiments indicate that 4R decreased neuro2a cells (neuroblastoma cells) apoptosis induced by oxygen glucose deprivation (OGD), and improved the population spikes (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to bEND5 cells (murine brain-derived endothelial cells) and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R. PMID:25677097

  16. Response of bacteriophage T7 biological dosimeter to dehydration and extraterrestrial solar UV radiation

    NASA Astrophysics Data System (ADS)

    Hegedüs, M.; Fekete, A.; Módos, K.; Kovács, G.; Rontó, Gy.; Lammer, H.; Panitz, C.

    2007-02-01

    The experiment "Phage and uracil response" (PUR) will be accommodated in the EXPOSE facility of the ISS. Bacteriophage T7/isolated T7 DNA will be exposed to different subsets of extreme environmental parameters in space, in order to study the Responses of Organisms to the Space Environment (ROSE). Launch into orbit is preceded by EXPOSE Experiment Verification Tests (EVT) to optimize the methods and the evaluation. Bacteriophage T7/isolated T7 DNA thin layers were exposed to vacuum ( 10-6Pa), to monochromatic (254 nm) and polychromatic (200-400 nm) UV radiation in air as well as in simulated space vacuum. Using neutral density (ND) filters dose-effect curves were performed in order to define the maximum doses tolerated. The effect of temperature fluctuation in vacuum was also studied. The structural/chemical effects on bacteriophage T7/isolated T7 DNA were analyzed by spectroscopic and microscopical methods. Characteristic changes in the absorption spectrum and in the electrophoretic pattern of phage/DNA have been detected indicating the damage of isolated and intraphage DNA. DNA damage was also determined by quantitative PCR (QPCR) using 555 and 3826 bp fragments of T7 DNA. We obtained substantial evidence that DNA lesions (e.g. strand breaks, DNA-protein cross-links, cyclobutane pirimidine dimers (CPDs) etc.) accumulate throughout exposure. Preliminary results suggest a synergistic action of space vacuum and UV radiation with DNA being the critical target.

  17. Monoamine uptake inhibitors block alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation.

    PubMed

    Long, Cheng; Chen, Mei-Fang; Sarwinski, Susan J; Chen, Po-Yi; Si, Minliang; Hoffer, Barry J; Evans, M Steven; Lee, Tony J F

    2006-07-01

    We have proposed that activation of cerebral perivascular sympathetic alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) by nicotinic agonists releases norepinephrine, which then acts on parasympathetic nitrergic nerves, resulting in release of nitric oxide and vasodilation. Using patch-clamp electrophysiology, immunohistochemistry, and in vitro tissue bath myography, we tested this axo-axonal interaction hypothesis further by examining whether blocking norepinephrine reuptake enhanced alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation. The results indicated that choline- and nicotine-induced alpha7-nAChR-mediated nitrergic neurogenic relaxation in endothelium-denuded isolated porcine basilar artery rings was enhanced by desipramine and imipramine at lower concentrations (0.03-0.1 microM) but inhibited at higher concentrations (0.3-10 microM). In cultured superior cervical ganglion (SCG) neurons of the pig and rat, choline (0.1-30 mM)-evoked inward currents were reversibly blocked by 1-30 microM mecamylamine, 1-30 microM methyllycaconitine, 10-300 nM alpha-bungarotoxin, and 0.1-10 microM desipramine and imipramine, providing electrophysiological evidence for the presence of similar functional alpha7-nAChRs in cerebral perivascular sympathetic neurons of pigs and rats. In alpha7-nAChR-expressing Xenopus oocytes, choline-elicited inward currents were attenuated by alpha-bungarotoxin, imipramine, and desipramine. These monoamine uptake inhibitors appeared to directly block the alpha7-nAChR, resulting in diminished nicotinic agonist-induced cerebral nitrergic vasodilation. The enhanced nitrergic vasodilation by lower concentrations of monoamine uptake inhibitors is likely due to a greater effect on monoamine uptake than on alpha7-nAChR blockade. These results further support the hypothesis of axo-axonal interaction in nitrergic regulation of cerebral vascular tone.

  18. Two R7 RGS proteins shape retinal bipolar cell signaling

    PubMed Central

    Mojumder, Deb Kumar; Qian, Yan; Wensel, Theodore G.

    2009-01-01

    RGS7, RGS11, and their binding partner Gβ5 are localized to the dendritic tips of retinal ON bipolar cells (ON-BPC), where mGluR6 responds to glutamate released from photoreceptor terminals by activation of the RGS7/RGS11 substrate, Gαo. To determine their functions in retinal signaling, we investigated cell-specific expression patterns of RGS7 and RGS11 by immunostaining, and measured light responses by electroretinography (ERG) in mice with targeted disruptions of the genes encoding them. RGS7 staining is present in dendritic tips of all rod ON-BPC, but missing in those for subsets of cone ON-BPC, whereas the converse was true for RGS11 staining. Genetic disruption of either RGS7 or RGS11 produced delays in the ON-BPC-derived electroretinogram b-wave, but no changes in the photoreceptor-derived a-wave. Homozygous RGS7 mutant mice had delays in rod-driven b-waves, whereas, RGS11 mutant mice had delays in rod-driven, and especially in cone-driven b-waves. The b-wave delays were further enhanced in mice homozygous for both RGS7 and RGS11 gene disruptions. Thus, RGS7 and RGS11 act in parallel to regulate the kinetics of ON bipolar cell responses, with differential impacts on the rod and cone pathways. PMID:19535587

  19. Hexagonally packed DNA within bacteriophage T7 stabilized by curvature stress.

    PubMed Central

    Odijk, T

    1998-01-01

    A continuum computation is proposed for the bending stress stabilizing DNA that is hexagonally packed within bacteriophage T7. Because the inner radius of the DNA spool is rather small, the stress of the curved DNA genome is strong enough to balance its electrostatic self-repulsion so as to form a stable hexagonal phase. The theory is in accord with the microscopically determined structure of bacteriophage T7 filled with DNA within the experimental margin of error. PMID:9726924

  20. In vivo replication of T4 and T7 bacteriophages in germ-free mice colonized with Escherichia coli.

    PubMed

    Weiss, Marietta; Denou, Emmanuel; Bruttin, Anne; Serra-Moreno, Ruth; Dillmann, Marie-Lise; Brüssow, Harald

    2009-10-10

    The gut transit of T4 phages was studied in axenic mice mono-colonized with the non-pathogenic Escherichia coli strain K-12. Thirty minutes, 1 and 2 h after phage feeding, T4 phage had reached the jejunum, ileum and cecum, respectively. Phage was found in the lumen and was also associated with the mucosa. One day later no phage was detected in the feces. Compared to germ-free control animals, oral T4 phage led to a 300-fold higher fecal phage titer in mice mono-colonized with E. coli strain WG-5. The in vivo T4 phage replication was transient and reached peak fecal titers about 8 h after oral phage application followed by a rapid titer decrease over two days. Similar data were obtained in mice colonized with E. coli strain Nissle. In contrast, orally applied T7 phage experienced a massive and sustained in vivo replication in mice mono-colonized with E. coli strain WG-5 irrespective whether phage or E. coli host was applied first. T7 phage replication occurred mainly in the large intestine. High titers of T7 phage and high E. coli cell counts coexisted in the feces. The observation of only 20% T7 phage-resistant fecal E. coli colonies suggests a refuge model where phage-sensitive E. coli cells are physically or physiologically protected from phage infection in the gut. The difference between T7 and T4 with respect to gut replication might partly reflect their distinct in vitro capacity to replicate on slowly growing cells.

  1. T7 lytic phage-displayed peptide libraries: construction and diversity characterization.

    PubMed

    Krumpe, Lauren R H; Mori, Toshiyuki

    2014-01-01

    In this chapter, we describe the construction of T7 bacteriophage (phage)-displayed peptide libraries and the diversity analyses of random amino acid sequences obtained from the libraries. We used commercially available reagents, Novagen's T7Select system, to construct the libraries. Using a combination of biotinylated extension primer and streptavidin-coupled magnetic beads, we were able to prepare library DNA without applying gel purification, resulting in extremely high ligation efficiencies. Further, we describe the use of bioinformatics tools to characterize library diversity. Amino acid frequency and positional amino acid diversity and hydropathy are estimated using the REceptor LIgand Contacts website http://relic.bio.anl.gov. Peptide net charge analysis and peptide hydropathy analysis are conducted using the Genetics Computer Group Wisconsin Package computational tools. A comprehensive collection of the estimated number of recombinants and titers of T7 phage-displayed peptide libraries constructed in our lab is included.

  2. La plastie en rail dans le traitement des brides rétractiles du creux poplite

    PubMed Central

    Achbouk, A.; Khales, A.; Bourra, K.; Tourabi, K.; Ababou, K.; Ihrai, H.

    2011-01-01

    Summary Les Auteurs décrivent le cas d’un patient âgé de 45 ans atteint de brûlures thermiques par flammes suite à la déflagration d’une bonbonne de gaz. Les lésions initiales intéressaient les quatre membres (en particulier, le genou) et le tronc. La prise en charge initiale a consisté en une excision-greffe précoce des membres. L’évolution a été marquée par la survenue de cicatrices hypertrophiques au niveau des zones non greffées et à la bordure de la greffe ainsi que la survenue de brides rétractiles. Devant l’handicap fonctionnel engendré par la bride à cause de la limitation importante de l’extension, le patient a été admis pour cure chirurgicale. Grâce à la technique en rail décrite, le patient a pu récupérer une fonction normale du genou. Les suites ont été simples avec une durée d’hospitalisation d’un mois. Le résultat esthétique est relativement satisfaisant. La technique en rail est un moyen parmi l’arsenal thérapeutique qui permet de traiter la bride du creux poplité. Sa simplicité, sa facilité technique et son résultat satisfaisant ainsi que ses suites simples permettent de la rendre une technique très prisée dans le traitement de ce type de bride. PMID:21991240

  3. Etude comparative des complications liées à l'utilisation du cathéter veineux périphérique avec et sans système clos à bouchon hépariné

    PubMed Central

    Liu, Ying Chun; Seydou, Togo; Sadio, Yéna; Liang, Tu Zheng; Ge, jin

    2015-01-01

    Introduction L'utilisation correcte du système clos à bouchon hépariné sur les cathéters périphériques pendant les perfusions est une pratique courante dans les pays développés et aussi dans plusieurs pays en développement selon un consensus international établi. Nous comparons les résultats de la formation de thrombus et de l'infection liées au cathéter veineux périphérique chez les patients ayant bénéficié de perfusion avec système clos à bouchon hépariné (groupe expérimentale) et ceux qui ont été perfusé sans bouchon hépariné (groupe témoin). Méthodes Nous avons colligé 100 patients hospitalisés pendant la période de Juillet 2014 à Décembre 2014 dans le service d'hospitalisation de chirurgie thoracique de l'hôpital du Mali qui ont été repartis en 2 groupes de 50 patients chacun pour une analyse comparative. L'observation du thrombus dans la lumière du cathéter est effectuée puis enregistré et tous les cathéters ont été repris pour réalisation de culture bactérienne au laboratoire dans les 2 groupes. Résultats Dans le groupe témoin, il existe un thrombus dans la lumière du cathéter dans 36 cas (72%) et l'examen de culture bactérienne était positif dans 90%. Tandis que dans le groupe expérimental on retrouve 3 cas (6%) de thrombose du cathéter et on note une absence de germe dans l'examen bactériologique. Conclusion L'utilisation correcte du système clos à bouchon hépariné lors des perfusions peut réduire et prévenir de façon significative les complications liées au cathéter notamment l'occlusion par thrombus, leur migration et la survenue de l'infection. PMID:26600900

  4. PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging.

    PubMed

    den Hartog, A G; Bovens, S M; Koning, W; Hendrikse, J; Pasterkamp, G; Moll, F L; de Borst, G J

    2011-02-01

    In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk.

  5. PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging

    PubMed Central

    den Hartog, A.G; Bovens, S.M; Koning, W; Hendrikse, J; Pasterkamp, G; Moll, F.L; de Borst, G.J

    2011-01-01

    Introduction: In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. Study objective: The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. Design: We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. Discussion: We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk. PMID:22294972

  6. Production du baryon Sigma+ dans les collisions e+e- au LEP

    NASA Astrophysics Data System (ADS)

    Joly, Andre

    Les mécanismes de production des baryons dans les interactions e+e- font l'objet de nombreuses études. De plus, les modes de production des baryons étranges semblent faire appel A des processus spécifiques, qui sont encore mal compris. Notre étude de la production des baryons Σ+ dans les interactions e+e- nous permet de formuler certaines remarques sur l'état des connaîssances acquises sur le sujet. Une methode de reconstruction originale et des critères de sélection spécifiques ont été développés afin d'identifier des baryons Σ+ de haute Energie ( ES+ > 5 GeV), partir de leur canal de désintégration en un proton et un π0 (S+-->p+p0 ). Trois mesures principales sont réalisées à partir de notre échantillon de baryons reconstruits. Le nombre mesuré de baryons Σ+ produits par événement e +e- à 91 GeV est de: =0.102+/-0.006(stat.) +/-0.008(syst.) +/-0.003(extrap.) où les erreurs sont dues à la statistique, aux systématiques et à la procédure d'extrapolation. Ce résultat est en accord avec ceux obtenus précédemment, mais avec des erreurs réduites. La section efficace différentielle en fonction de l'energie est mesurée et comparée aux prédictions des principaux générateurs Monte-Carlo (JETSET7.4(MOPS), JETSET7.4 et HERWIG5.9). A haute énergie, HERWIG ne semble pas reproduire les mesures, aussi bien que les deux versions de JETSET. Enfin, la position du maximum de la section efficace différentielle de production des baryons Σ+ en fonction de l'impulsion est mesurée. On trouve: overlinexoverlineS+=2.32+/- 0.47 Une étude spécifique du générateur JETSET7.4(MOPS) est réalisee, afin de mieux comprendre les mécanismes de production de l'étrangeté et du spin dans la production des baryons. Aucun générateur ne semble capable de décrire de manière simultanée la production du spin et de l'étrangeté.

  7. Etude du strabisme chez des enfants de 0 à 15 ans suivis a Lubumbashi, République Démocratique du Congo: analyse des aspects épidémiologiques et cliniques

    PubMed Central

    Bienvenu, Yogolelo Asani; Angel, Musau Nkola; Sebastien, Mbuyi Musanzayi; Philippe, Cilundika Mulenga; Léon, Kabamba Ngombe; Eugene, Twite Kabange; Chami, Cham Lubamba; Prosper, Kalenga Muenze Kayamba; Claude, Speeg-Schatz; Gaby, Chenge Borasisi

    2015-01-01

    Introduction Le strabisme est défini comme un syndrome à double composante: motrice et sensorielle. Le but de ce travail est de décrire les aspects épidémiologiques et cliniques du strabisme chez l'enfant congolais de 0 à 15 ans dans la ville de Lubumbashi. Méthodes Il s'agit d'une étude descriptive longitudinale sur les aspects épidémiologiques et cliniques du strabisme chez l'enfant congolais de 0 à 15 ans dans la ville de Lubumbashi entre Décembre 2012 à Décembre 2013. Nous avons recueilli l’âge des patients, leur sexe, leur provenance, le type de strabisme, la réfraction, le fond d'oeil, les antécédents (hérédité) ainsi que le type de la déviation strabique observé sur 70 patients. Résultats Nous avons observé 70 cas de strabisme manifeste dont 31 cas (44,28%) étaient dans la tranche d’âge comprise entre 0 et 5 ans. L’âge moyen de nos patients était de 6,7 ans avec une prédominance du sexe féminin, soit 51,42%. Le strabisme était convergent dans 65,71%, divergent dans 30%, et vertical dans 4,28%. Les ésotropies représentaient 65 cas (92,85%), quatre cas (5,71%) avaient un antécédent familial de strabisme au premier degré de parenté, 21 cas (30%) au second degré de parenté, 45 cas (64,28%) n'avaient pas cet antécédent. L'oeil gauche était le plus dominé dans 30% des cas. Les facteurs favorisant le strabisme étaient inconnus dans 54 cas (77,14%). Le strabisme était secondaire à l'hypermétropie chez 32 patients (42,71%). Conclusion La fréquence du strabisme dans la ville de Lubumbashi chez les enfants âgés de 0 à 15 ans est de 0,50%. Comme dans la plupart des études sur le strabisme de l'enfant, c'est l’ésotropie qui est la déviation la plus commune. PMID:26834919

  8. Distribution épidémiologique de l'infection à VIH chez les femmes enceintes dans les dix régions du Cameroun et implications stratégiques pour les programmes de prévention

    PubMed Central

    Billong, Serge-Clotaire; Fokam, Joseph; Billong, Edson-Joan; Nguefack-Tsague, Georges; Essi, Marie-Josée; Fodjo, Raoul; Sosso, Samuel-Martin; Gomba, Armelle; Mosoko-Jembia, Joseph; Loni-Ekali, Gabriel; Colizzi, Vittorio; Bissek, Anne-Cécile Zoung-Kani; Monebenimp, Francisca; Nfetam, Jean-Bosco Elat

    2015-01-01

    Introduction Le Cameroun se situe dans un contexte d’épidémie généralisée du VIH. La sous-population des femmes enceintes, facilement accessible au sein de la population générale, représente une cible probante pour mener la surveillance du VIH et estimer l’évolution épidémiologique. L'objectif de notre étude était d’évaluer la distribution épidémiologique du VIH chez les femmes enceintes. Méthodes Étude transversale menée en 2012 chez 6521 femmes enceintes (49,3% âgées de 15-24 ans) en première consultation prénatale (CPN1) dans 60 sites des 10 régions Camerounaises. L'algorithme en série a été utilisé pour le sérodiagnostic du VIH. Résultats La prévalence du VIH était de 7,8% (508/6521), avec une différence non significative (p = 0,297) entre milieu rural (7,4%) et milieu urbain (8,1%). En zone rurale, cette prévalence variait de 0,7% à l'Extrême-Nord à 11,8% au Sud. Cependant, en zone urbaine elle variait de 4% à l'Ouest à 11,1% au Sud-Ouest. Suivant l’âge, la prévalence était plus élevée (11,3%) chez les femmes de 35-39 ans. Suivant le niveau de scolarisation, la prévalence du VIH était plus faible (4,4%) chez celles non-scolarisées, et plus élevée (9,3%) chez celles ayant un niveau primaire. Selon la profession, l'infection était plus élevée chez les coiffeuses (15,5%), secrétaires (14,8%), commerçantes (12,9%) et institutrices/enseignantes (10,8%). Conclusion La prévalence du VIH reste élevée chez les femmes enceintes au Cameroun, sans distinction entre milieux rural et urbain. Les stratégies de prévention devraient s'orienter préférentiellement chez les femmes enceintes âgées, celles du niveau d'instruction primaire, et celles du secteur des petites et moyennes entreprises. PMID:26090037

  9. miR-7-1 POTENTIATED ESTROGEN RECEPTOR AGONISTS FOR FUNCTIONAL NEUROPROTECTION IN VSC4.1 MOTONEURONS

    PubMed Central

    CHAKRABARTI, M.; BANIK, N. L.; RAY, S. K.

    2013-01-01

    Protection of motoneurons is an important goal in the treatment of spinal cord injury (SCI). We tested whether neuroprotective microRNAs (miRs) like miR-206, miR-17, miR-21, miR-7-1, and miR-106a could enhance efficacy of estrogen receptor (ER) agonists such as 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT, ERα agonist), Way200070 (WAY, ERβ agonist), and estrogen (EST, ERα and ERβ agonist) in preventing apoptosis in the calcium ionophore (CI) insulted VSC4.1 motoneurons. We determined that 200 nM CI induced 70% cell death. Treatment with 50 nM PPT, 100 nM WAY, and 150 nM EST induced overexpression of ERα, ERβ, and both receptors, respectively, at mRNA and protein levels. Treatment with ER agonists significantly upregulated miR-206, miR-17, and miR-7-1 in the CI insulted VSC4.1 motoneurons. Transfection with miR-206, miR-17, or miR-7-1 mimic potentiated WAY or EST to inhibit apoptosis in the CI insulted VSC4.1 motoneurons. Overexpression of miR-7-1 maximally increased efficacy of WAY and EST for down regulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2. A search using miRDB indicated that miR-7-1 could inhibit expression of L-type Ca2+ channel protein alpha 1C (CPα1C). miR-7-1 overexpression and WAY or EST treatment down regulated CPα1C but upregulated p-Akt to trigger cell survival signaling. The same therapeutic strategy increased expression of the Ca2+/calmodulin-dependent protein kinase II beta (CaMKIIβ) and the phosphorylated cAMP response element binding protein (p-CREB) so as to promote Bcl-2 transcription. Whole cell membrane potential and mitochondrial membrane potential studies indicated that miR-7-1 highly potentiated EST to preserve functionality in the CI insulted VSC4.1 motoneurons. In conclusion, our data indicated that miR-7-1 most significantly potentiated efficacy of EST for functional neuroprotection and this therapeutic strategy could be used in the future to attenuate apoptosis of motoneurons in SCI. PMID

  10. Cirque du Monde en tant qu’intervention en santé

    PubMed Central

    Fournier, Cynthia; Drouin, Mélodie-Anne; Marcoux, Jérémie; Garel, Patricia; Bochud, Emmanuel; Théberge, Julie; Aubertin, Patrice; Favreau, Gil; Fleet, Richard

    2014-01-01

    Résumé Objectif Présenter le programme Cirque du Monde du Cirque du Soleil et son potentiel en tant qu’intervention en soins de santé de première ligne pour les médecins de famille. Sources des données Une revue de la littérature menée dans les bases de données PubMed, Cochrane Library, PsycINFO, La Presse, Eureka, Google Scholar et Érudit à l’aide des mots-clés circus, social circus, Cirque du Monde et Cirque du Soleil. Une initiative à Montréal nommée Espace Transition qui s’inspire directement de Cirque du Monde. Communication personnelle avec le conseiller principal en formation en cirque social du Cirque du Soleil. Sélection d’études Les 50 premiers articles ou sites Internet répertoriés pour chaque mot-clé dans chacune des bases de données ciblées ont été révisés sur la base des titres et des résumés, s’il s’agissait d’un article, ou sur la base du titre et du contenu de la page, s’il s’agissait d’une page Internet. Ensuite, les articles et les sites Internet qui étudiaient un aspect du cirque social ou qui présentaient une intervention impliquant le cirque étaient retenus pour une révision. Aucune contrainte d’année de publication n’a été appliquée étant donné qu’on cherchait une littérature générale sur le cirque social. Synthèse Aucun article n’a été trouvé sur le cirque social en tant qu’intervention en santé. Nous avons trouvé une étude sur l’utilisation du cirque en tant qu’intervention en milieu scolaire. Cette étude a démontré une augmentation de l’estime personnelle des enfants grâce à l’intervention. Nous avons trouvé une étude sur l’utilisation du cirque en tant qu’intervention sur une réserve amérindienne. Cette étude présente des résultats qualitatifs non spécifiques au programme du cirque social. Les autres articles répertoriés n’étaient que des descriptions du cirque social. Un site web concernant l’utilisation du cirque social pour

  11. Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia.

    PubMed

    Martins, Antonio H; Hu, Jing; Xu, Zhenfeng; Mu, Chaofeng; Alvarez, Paloma; Ford, Byron D; El Sayed, Khalid; Eterovic, Vesna A; Ferchmin, Pedro A; Hao, Jiukuan

    2015-04-16

    (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volumes (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volumes (120±65 mm3) than those in the rats of the DMSO group (291±95 mm3). The results from in vitro experiments indicate that 4R decreased neuro2a cell (neuroblastoma cells) apoptosis induced by oxygen-glucose deprivation (OGD), and improved the population spikes' (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to murine brain-derived endothelial (bEND5) cells and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Rupture simultanée du ligament croisé antérieur et du ligament patellaire: à propos d'un cas

    PubMed Central

    Achkoun, Abdessalam; Houjairi, Khalid; Quahtan, Omar; Hassoun, Jalal; Arssi, Mohamed; Rahmi, Mohamed; Garch, Abdelhak

    2016-01-01

    La rupture simultanée du tendon rotulien et du ligament croisé antérieur est une lésion relativement rare. Son diagnostic peut facilement manquer lors de l'examen initial. Les options de traitement incluent la réparation immédiate du tendon rotulien avec soit la reconstruction simultanée ou différée de ligament croisé antérieur. Nous rapportons le cas d'une rupture combinée du tendon rotulien et du ligament croisé antérieur chez un jeune footballeur de 22 ans. Une approche de traitement en deux temps a été effectuée avec un excellent résultat fonctionnel. PMID:27366288

  13. Identifying the cellular targets of natural products using T7 phage display.

    PubMed

    Piggott, Andrew M; Karuso, Peter

    2016-05-04

    Covering: up to the end of 2015While Nature continues to deliver a myriad of potent and structurally diverse biologically active small molecules, the cellular targets and modes of action of these natural products are rarely identified, significantly hindering their development as new chemotherapeutic agents. This article provides an introductory tutorial on the use of T7 phage display as a tool to rapidly identify the cellular targets of natural products and is aimed specifically at natural products chemists who may have only limited experience in molecular biology. A brief overview of T7 phage display is provided, including its strengths, weaknesses, and the type of problems that can and cannot be tackled with this technology. Affinity probe construction is reviewed, including linker design and natural product derivatisation strategies. A detailed description of the T7 phage biopanning procedure is provided, with valuable tips for optimising each step in the process, as well as advice for identifying and avoiding the most commonly encountered challenges and pitfalls along the way. Finally, a brief discussion is provided on techniques for validating the cellular targets identified using T7 phage display.

  14. La reconstruction du sourcil par greffon composite du cuir chevelu: une astuce pour faciliter la technique

    PubMed Central

    El Omari, Mounia; El Mazouz, Samir; Gharib, Noureddine; EL Abbassi, Abdallah

    2015-01-01

    Les sourcils jouent un rôle important dans l’équilibre esthétique du visage. Leur reconstruction ou ophriopoïése, après séquelle de brûlure fait partie intégrante du programme de réhabilitation de la face brûlée. Plusieurs techniques ont été décrites. Nous insistons ici sur l'intérêt d'une technique simple, à la portée de tous les chirurgiens, et dont la méthode et les résultats peuvent être améliorés par un dessin bien planifié des zones donneuse et receveuse: la greffe composite prélevée au niveau du cuir chevelu dessinée à l'aide d'un calque du sourcil controlatéral. PMID:26401195

  15. 17 CFR 240.15b7-3T - Operational capability in a Year 2000 environment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Operational capability in a Year 2000 environment. 240.15b7-3T Section 240.15b7-3T Commodity and Securities Exchanges SECURITIES... § 240.15b7-3T Operational capability in a Year 2000 environment. (a) This section applies to every...

  16. 17 CFR 240.15b7-3T - Operational capability in a Year 2000 environment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Operational capability in a Year 2000 environment. 240.15b7-3T Section 240.15b7-3T Commodity and Securities Exchanges SECURITIES... § 240.15b7-3T Operational capability in a Year 2000 environment. (a) This section applies to every...

  17. 17 CFR 240.15b7-3T - Operational capability in a Year 2000 environment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Operational capability in a Year 2000 environment. 240.15b7-3T Section 240.15b7-3T Commodity and Securities Exchanges SECURITIES... § 240.15b7-3T Operational capability in a Year 2000 environment. (a) This section applies to every...

  18. 17 CFR 240.15b7-3T - Operational capability in a Year 2000 environment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Operational capability in a Year 2000 environment. 240.15b7-3T Section 240.15b7-3T Commodity and Securities Exchanges SECURITIES... § 240.15b7-3T Operational capability in a Year 2000 environment. (a) This section applies to every...

  19. 17 CFR 240.15b7-3T - Operational capability in a Year 2000 environment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Operational capability in a Year 2000 environment. 240.15b7-3T Section 240.15b7-3T Commodity and Securities Exchanges SECURITIES... § 240.15b7-3T Operational capability in a Year 2000 environment. (a) This section applies to every...

  20. Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Managlia, Elizabeth Z.; Landay, Alan; Al-Harthi, Lena

    2006-07-05

    Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NF{kappa}B. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated inductionmore » of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFN{gamma}, all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 as an in vivo immune modulator.« less

  1. IL-7–dependent STAT1 activation limits homeostatic CD4+ T cell expansion

    PubMed Central

    Le Saout, Cecile; Luckey, Megan A.; Villarino, Alejandro V.; Smith, Mindy; Hasley, Rebecca B.; Myers, Timothy G.; Imamichi, Hiromi; Park, Jung-Hyun; O’Shea, John J.; Lane, H. Clifford

    2017-01-01

    IL-7 regulates homeostatic mechanisms that maintain the overall size of the T cell pool throughout life. We show that, under steady-state conditions, IL-7 signaling is principally mediated by activation of signal transducers and activators of transcription 5 (STAT5). In contrast, under lymphopenic conditions, there is a modulation of STAT1 expression resulting in an IL-7–dependent STAT1 and STAT5 activation. Consequently, the IL-7–induced transcriptome is altered with enrichment of IFN-stimulated genes (ISGs). Moreover, STAT1 overexpression was associated with reduced survival in CD4+ T cells undergoing lymphopenia-induced proliferation (LIP). We propose a model in which T cells undergoing LIP upregulate STAT1 protein, “switching on” an alternate IL-7–dependent program. This mechanism could be a physiological process to regulate the expansion and size of the CD4+ T cell pool. During HIV infection, the virus could exploit this pathway, leading to the homeostatic dysregulation of the T cell pools observed in these patients. PMID:29202461

  2. Intermittent IL-7 Signaling Essential for T cell Homeostasis | Center for Cancer Research

    Cancer.gov

    In order for the immune system to mount an appropriate response to foreign antigens throughout a person’s life, the body must maintain a sufficient population of circulating mature, naïve T cells, a process known as T cell homeostasis. Previous studies revealed that this process depends upon signaling from the cytokine interleukin-7 (IL-7) as well as from the T cell antigen

  3. Electrically tunable transport and high-frequency dynamics in antiferromagnetic S r3I r2O7

    NASA Astrophysics Data System (ADS)

    Seinige, Heidi; Williamson, Morgan; Shen, Shida; Wang, Cheng; Cao, Gang; Zhou, Jianshi; Goodenough, John B.; Tsoi, Maxim

    2016-12-01

    We report dc and high-frequency transport properties of antiferromagnetic S r3I r2O7 . Temperature-dependent resistivity measurements show that the activation energy of this material can be tuned by an applied dc electrical bias. The latter allows for continuous variations in the sample resistivity of as much as 50% followed by a reversible resistive switching at higher biases. Such a switching is of high interest for antiferromagnetic applications in high-speed memory devices. Interestingly, we found the switching behavior to be strongly affected by a high-frequency (microwave) current applied to the sample. The microwaves at 3-7 GHz suppress the dc switching and produce resonancelike features that we tentatively associated with the dissipationless magnonics recently predicted to occur in antiferromagnetic insulators subject to ac electric fields. We have characterized the effects of microwave irradiation on electronic transport in S r3I r2O7 as a function of microwave frequency and power, strength and direction of external magnetic field, strength and polarity of applied dc bias, and temperature. Our observations support the potential of antiferromagnetic materials for high-speed/high-frequency spintronic applications.

  4. La matério-vigilance dans un Centre Hospitalo-Universitaire du Centre-Est tunisien: enquête auprès des médecins

    PubMed Central

    Mahjoub, Mohamed; Jedidi, Maher; Masmoudi, Tasnim; Bouafia, Nabiha; Njah, Mansour

    2016-01-01

    Introduction Pour la meilleure gestion des risques en milieu hospitalier et l’amélioration de la qualité et la sécurité de nos soins, le CHU de Sousse (Tunisie), a mis en place, suite aux recommandations de l’ANCSEP (Agence Nationale de Contrôle Sanitaire et Environnementale des Produits) un système de matério-vigilance (MV). En Tunisie l’absence d’un cadre réglementaire organisant la MV est l’obstacle majeur à l’implication des soignants à ce système. L’objectif de cette étude est de déterminer les connaissances, attitudes et pratiques des médecins du CHU quant à la mise en place du système de MV. Méthodes Etude descriptive de type CAP (connaissances, attitudes et pratiques) transversale auprès de tous les médecins titulaires exerçant au CHU de Sousse (Tunisie) qui sont utilisateurs des dispositifs médicaux (DMs) lors de leur pratique d’activité de soin. Un questionnaire auto-administré, préétabli et pré-testé a été établi. Saisie et l’analysée des données par logiciel SPSS20.0. Résultats Le taux de réponse de 51,9 % (183/95), un manque des connaissances relatif à la MV a été rapporté. Plus de la moitié des répondants ne connaissent pas le correspondant local de son établissement et l’existence d’un formulaire standardisé de signalement. Concernant les attitudes, 89,5 % notifient l’intérêt de mise en place du système de MV et 37,5 % reconnaissent que le signalement doit émaner du soignant constatant l’incident. Pour les pratiques, la majorité confirment l’absence d’une gestion organisée de la maintenance des DMs dans leurs services. 90,5 % expriment leurs souhaits de recevoir une information mais peu d’entre eux expriment leurs désirs de suivre une formation (57,9 %). Conclusion Un manque d’information et de formation dans un domaine pourtant sensible et devant être lourdement réglementé est soulevé. La promulgation de textes réglementaires est nécessaire afin de promouvoir le

  5. Up-Regulation of MiR-300 Promotes Proliferation and Invasion of Osteosarcoma by Targeting BRD7

    PubMed Central

    Xue, Zhen; Zhao, Jindong; Niu, Liyuan; An, Gang; Guo, Yashan; Ni, Linying

    2015-01-01

    Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression and function of miR-300 in osteosarcoma is still unknown. In our study, we found that the expression of miR-300 was up-regulated in osteosarcoma tissues and cells compared with paired adjacent non-tumor bone tissues and osteoblastic cells using RT-qPCR. The enforced expression of miR-300 could promote cell proliferation, invasion and epithelial-mesenchymal transition (EMT). Moreover, we identified that bromodomain-containing protein 7 (BRD7), a new tumor suppressor gene, was a direct target of miR-300. Ectopic expression of BRD7 could significantly inhibit miR-300-promoted proliferation, invasion and EMT. Therefore, our results identify an important role for miR-300 in osteosarcoma through regulating BRD7 expression. PMID:26010572

  6. Up-Regulation of MiR-300 Promotes Proliferation and Invasion of Osteosarcoma by Targeting BRD7.

    PubMed

    Xue, Zhen; Zhao, Jindong; Niu, Liyuan; An, Gang; Guo, Yashan; Ni, Linying

    2015-01-01

    Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression and function of miR-300 in osteosarcoma is still unknown. In our study, we found that the expression of miR-300 was up-regulated in osteosarcoma tissues and cells compared with paired adjacent non-tumor bone tissues and osteoblastic cells using RT-qPCR. The enforced expression of miR-300 could promote cell proliferation, invasion and epithelial-mesenchymal transition (EMT). Moreover, we identified that bromodomain-containing protein 7 (BRD7), a new tumor suppressor gene, was a direct target of miR-300. Ectopic expression of BRD7 could significantly inhibit miR-300-promoted proliferation, invasion and EMT. Therefore, our results identify an important role for miR-300 in osteosarcoma through regulating BRD7 expression.

  7. 7. Anthony Bley, Photographer September, 1976 L TO R: TWO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Anthony Bley, Photographer September, 1976 L TO R: TWO CHICKEN HOUSES, PIG BARN, MILKSHED, BARN - Dundore Farm, State Route 183 & Church Road vicinity, Penn Township (moved to Brownsville vicinity, Lower Heidelberg Township, Berks County), Mount Pleasant, Berks County, PA

  8. IL-7 and CD4 T Follicular Helper Cells in HIV-1 Infection

    PubMed Central

    Chiodi, Francesca; Bekele, Yonas; Lantto Graham, Rebecka; Nasi, Aikaterini

    2017-01-01

    IL-7 was previously shown to upregulate the expression of molecules important for interaction of CD4+ T cells with B cells. It is poorly studied whether IL-7 has a role in the biology of T follicular helper (Tfh) cells and whether IL-7 dysregulates the expression of B-cell costimulatory molecules on Tfh cells. We review the literature and provide arguments in favor of IL-7 being involved in the biology of human Tfh cells. The CD127 IL-7 receptor is expressed on circulating Tfh and non-Tfh cells, and we show that IL-7, but not IL-6 or IL-21, upregulates the expression of CD70 and PD-1 on these cells. We conclude that IL-7, a cytokine whose level is elevated during HIV-1 infection, may have a role in increased expression of B cell costimulatory molecules on Tfh cells and lead to abnormal B cell differentiation. PMID:28473831

  9. IL-7 and CD4 T Follicular Helper Cells in HIV-1 Infection.

    PubMed

    Chiodi, Francesca; Bekele, Yonas; Lantto Graham, Rebecka; Nasi, Aikaterini

    2017-01-01

    IL-7 was previously shown to upregulate the expression of molecules important for interaction of CD4+ T cells with B cells. It is poorly studied whether IL-7 has a role in the biology of T follicular helper (Tfh) cells and whether IL-7 dysregulates the expression of B-cell costimulatory molecules on Tfh cells. We review the literature and provide arguments in favor of IL-7 being involved in the biology of human Tfh cells. The CD127 IL-7 receptor is expressed on circulating Tfh and non-Tfh cells, and we show that IL-7, but not IL-6 or IL-21, upregulates the expression of CD70 and PD-1 on these cells. We conclude that IL-7, a cytokine whose level is elevated during HIV-1 infection, may have a role in increased expression of B cell costimulatory molecules on Tfh cells and lead to abnormal B cell differentiation.

  10. P2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation

    PubMed Central

    PENG, KUANG; LIU, LUSHAN; WEI, DANGHENG; LV, YUNCHENG; WANG, GANG; XIONG, WENHAO; WANG, XIAOQING; ALTAF, AFRASYAB; WANG, LILI; HE, DAN; WANG, HONGYAN; QU, PENG

    2015-01-01

    Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic lesions. However, the mechanisms through which P2X7R participates in the inflammatory response in atherosclerosis remain largely unknown. The aim of the present study was to investigate the role of P2X7R in atherosclerosis and the mechanisms of action of the NLRP3 inflammasome following stimulation with oxidized low-density lipoprotein (oxLDL). We observed the expression and distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from an autopsy specimen and in that of the aortic sinuses of apoE−/− mice by immunohistochemistry and immunofluorescence staining. The specificity of short interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT-qPCR and western blot analysis were used to analyze mRNA and protein expression, respectively. Co-immunoprecipitation was used to examine the interaction between protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed at high levels in the atherosclerotic plaque in the coronary arteries. Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1β expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic lesions in the aortic sinuses of apoE−/− mice, P2X7R expression was found at high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis in the apoE−/− mice. In conclusion, our results demonstrate that P2X7R plays a significant role in the development of atherosclerosis and regulates NLRP3 inflammasome activation by promoting PKR phosphorylation. PMID:25761252

  11. mGluR7 genetics and alcohol: intersection yields clues for addiction.

    PubMed

    Gyetvai, Beatrix; Simonyi, Agnes; Oros, Melinda; Saito, Mariko; Smiley, John; Vadász, Csaba

    2011-06-01

    Development of addiction to alcohol or other substances can be attributed in part to exposure-dependent modifications at synaptic efficacy leading to an organism which functions at an altered homeostatic setpoint. Genetic factors may also influence setpoints and the stability of the homeostatic system of an organism. Quantitative genetic analysis of voluntary alcohol drinking, and mapping of the involved genes in the quasi-congenic Recombinant QTL Introgression strain system, identified Eac2 as a Quantitative Trait Locus (QTL) on mouse chromosome 6 which explained 18% of the variance with an effect size of 2.09 g/kg/day alcohol consumption, and Grm7 as a quantitative trait gene underlying Eac2 [Vadasz et al. in Neurochem Res 32:1099-1112, 100, Genomics 90:690-702, 102]. In earlier studies, the product of Grm7 mGluR7, a G protein-coupled receptor, has been implicated in stress systems [Mitsukawa et al. in Proc Natl Acad Sci USA 102:18712-18717, 63], anxiety-like behaviors [Cryan et al. in Eur J Neurosci 17:2409-2417, 14], memory [Holscher et al. in Learn Mem 12:450-455, 26], and psychiatric disorders (e.g., [Mick et al. in Am J Med Genet B Neuropsychiatr Genet 147B:1412-1418, 61; Ohtsuki et al. in Schizophr Res 101:9-16, 72; Pergadia et al. in Paper presented at the 38th Annual Meeting of the Behavior Genetics Association, Louisville, Kentucky, USA, 76]. Here, in experiments with mice, we show that (1) Grm7 knockout mice express increased alcohol consumption, (2) sub-congenic, and congenic mice carrying a Grm7 variant characterized by higher Grm7 mRNA drink less alcohol, and show a tendency for higher circadian dark phase motor activity in a wheel running paradigm, respectively, and (3) there are significant genetic differences in Grm7 mRNA abundance in the mouse brain between congenic and background mice identifying brain areas whose function is implicated in addiction related processes. We hypothesize that metabotropic glutamate receptors may function as

  12. Traitement préventif intermittent à la sulfadoxine – pyriméthamine du paludisme chez les femmes enceintes: efficacité et observance dans deux hôpitaux urbains du Burkina Faso

    PubMed Central

    Bamba, Sanata; Séré, Adama; Nikiéma, Rodrigues; Halidou, Tinto; Thiéba, Blandine; Dao, Blami; Guiguemdé, Robert Tinga

    2013-01-01

    Introduction La présente étude prospective se propose dévaluer l'efficacité thérapeutique du traitement préventif intermittent à la sulfadoxine - pyriméthamine et son observance chez la femme enceinte dans deux hôpitaux urbains au Burkina Faso. Méthodes Chaque femme répondant aux critères d'inclusion a été soumise à un questionnaire pour la collecte des données socio - démographiques et des renseignements sur la grossesse. A l'accouchement, une apposition placentaire a été réalisée systématiquement. La lecture a été faite au microscope à lobjectif 100 à immersion. Résultats Au total, 542 femmes ont été incluses avec un âge moyen de 26,0 ± 6,45 ans (extrêmes 13- 43 ans). Le taux de couverture du TPI à la sulfadoxine- pyriméthamine a été de 80%. Le taux d'infestation placentaire a été de 4,7%. Il a diminué avec le nombre de dose de traitement préventif intermittent. Il a augmenté cependant de juillet à octobre. De 42,9% en octobre, il a diminué significativement à 9,5% en novembre (p < 0,05). Le taux global de bonne d'observance a été de 55%. Il a augmenté avec l’âge (p < 0,05). Conclusion Le taux de couverture de la sulfadoxine - pyriméthamine a été de 80%. Ce résultat est en conformité avec les objectifs du plan stratégique 2006-2010 de lutte contre le paludisme au Burkina Faso, qui préconisait un taux de couverture en sulfadoxine - pyriméthamine de 80% pour 2010. L'augmentation de la fréquence d'infestation de juillet à octobre, serait liée à la recrudescence de la transmission palustre pendant la saison des pluies (mai-octobre). PMID:23717719

  13. MiR-7-1 potentiated estrogen receptor agonists for functional neuroprotection in VSC4.1 motoneurons.

    PubMed

    Chakrabarti, M; Banik, N L; Ray, S K

    2014-01-03

    Protection of motoneurons is an important goal in the treatment of spinal cord injury (SCI). We tested whether neuroprotective microRNAs (miRs) like miR-206, miR-17, miR-21, miR-7-1, and miR-106a could enhance efficacy of estrogen receptor (ER) agonists such as 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT, ERα agonist), Way200070 (WAY, ERβ agonist), and estrogen (EST, ERα and ERβ agonist) in preventing apoptosis in the calcium ionophore (CI)-insulted ventral spinal cord 4.1 (VSC4.1) motoneurons. We determined that 200 nM CI induced 70% cell death. Treatment with 50 nM PPT, 100 nM WAY, and 150 nM EST induced overexpression of ERα, ERβ, and both receptors, respectively, at mRNA and protein levels. Treatment with ER agonists significantly upregulated miR-206, miR-17, and miR-7-1 in the CI-insulted VSC4.1 motoneurons. Transfection with miR-206, miR-17, or miR-7-1 mimic potentiated WAY or EST to inhibit apoptosis in the CI-insulted VSC4.1 motoneurons. Overexpression of miR-7-1 maximally increased efficacy of WAY and EST for down regulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2. A search using microRNA database (miRDB) indicated that miR-7-1 could inhibit the expression of L-type Ca(2+) channel protein alpha 1C (CPα1C). miR-7-1 overexpression and WAY or EST treatment down regulated CPα1C but upregulated p-Akt to trigger cell survival signaling. The same therapeutic strategy increased expression of the Ca(2+)/calmodulin-dependent protein kinase II beta (CaMKIIβ) and the phosphorylated cAMP response element binding protein (p-CREB) so as to promote Bcl-2 transcription. Whole cell membrane potential and mitochondrial membrane potential studies indicated that miR-7-1 highly potentiated EST to preserve functionality in the CI-insulted VSC4.1 motoneurons. In conclusion, our data indicated that miR-7-1 most significantly potentiated efficacy of EST for functional neuroprotection and this therapeutic strategy could be used in the future

  14. Characterization of the R162W Kir7.1 mutation associated with snowflake vitreoretinopathy

    PubMed Central

    Zhang, Wei; Zhang, Xiaoming; Wang, Hui; Sharma, Anil K.; Edwards, Albert O.

    2013-01-01

    KCNJ13 encodes Kir7.1, an inwardly rectifying K+ channel that is expressed in multiple ion-transporting epithelia. A mutation in KCNJ13 resulting in an arginine-to-tryptophan change at residue 162 (R162W) of Kir7.1 was associated with snowflake vitreoretinal degeneration, an inherited autosomal-dominant disease characterized by vitreous degeneration and mild retinal degeneration. We used the Xenopus laevis oocyte expression system to assess the functional properties of the R162W (mutant) Kir7.1 channel and determine how wild-type (WT) Kir7.1 is affected by the presence of the mutant subunit. Recordings obtained via the two-electrode voltage-clamp technique revealed that injection of oocytes with mutant Kir7.1 cRNA resulted in currents and cation selectivity that were indistinguishable from those in water-injected oocytes, suggesting that the mutant protein does not form functional channels in the plasma membrane. Coinjection of oocytes with equal amounts of mutant and WT Kir7.1 cRNAs resulted in inward K+ and Rb+ currents with amplitudes that were ∼17% of those in oocytes injected with WT Kir7.1 cRNA alone, demonstrating a dominant-negative effect of the mutant subunit. Similar to oocytes injected with WT Kir7.1 cRNA alone, coinjected oocytes exhibited inwardly rectifying Rb+ currents that were more than seven times larger than K+ currents, indicating that mutant subunits did not alter Kir7.1 channel selectivity. Immunostaining of Xenopus oocytes or Madin-Darby canine kidney cells expressing mutant or WT Kir7.1 demonstrated distribution of both proteins primarily in the plasma membrane. Our data suggest that the R162W mutation suppresses Kir7.1 channel activity, possibly by negatively impacting gating by membrane phosphadidylinositol 4,5-bisphosphate. PMID:23255580

  15. Long-Term Heart Transplant Survival by Targeting the Ionotropic Purinergic Receptor P2X7

    PubMed Central

    Vergani, Andrea; Tezza, Sara; D’Addio, Francesca; Fotino, Carmen; Liu, Kaifeng; Niewczas, Monika; Bassi, Roberto; Molano, R. Damaris; Kleffel, Sonja; Petrelli, Alessandra; Soleti, Antonio; Ammirati, Enrico; Frigerio, Maria; Visner, Gary; Grassi, Fabio; Ferrero, Maria E.; Corradi, Domenico; Abdi, Reza; Ricordi, Camillo; Sayegh, Mohamed H.; Pileggi, Antonello; Fiorina, Paolo

    2013-01-01

    Background Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes as well as with the development of complications including infections and malignancies. The development of a novel, short-term and effective immunomodulatory protocol will thus be an important achievement. The purine adenosine 5′-triphosphate (ATP), released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation. Methods and Results We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP (oATP) promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T cell activation, Th1/Th17 differentiation and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate Th1/Th17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well. Conclusions P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival. PMID:23250993

  16. Mise au point du rheometre a cisaillement annulaire pour l'etude de rheologie d'un mastic bitumineux avec verre incorpore =

    NASA Astrophysics Data System (ADS)

    El Mansouri, Souleimane

    Dans le domaine viscoelastique lineaire (VEL, domaine des petites deformations), le comportement thermomecanique du bitume et du mastic bitumineux (melange uniforme de bitume et de fillers) a ete caracterise au Laboratoire des Chaussees et Materiaux Bitumineux (LCMB) de l'Ecole de technologie superieure (ETS) avec l'appui de nos partenaires externes : la Societe des Alcools du Quebec (SAQ) et Eco Entreprises Quebec (EEQ). Les proprietes rheologiques des bitumes et des mastics ont ete mesurees grâce a un nouvel outil d'investigation appele, Rheometre a Cisaillement Annulaire (RCA), sous differentes conditions de chargement. Cet appareil permet non seulement de solliciter des eprouvettes de tailles importantes par rapport a celles utilisees lors des essais classiques, mais aussi d'effectuer des essais en conditions quasi-homogenes, ce qui permet de donner acces a la loi de comportement des materiaux. Les essais sont realises sur une large gamme de temperatures et de frequences (de -15 °C a 45°C et de 0,03Hz a 10 Hz). Cette etude a ete menee principalement pour comparer le comportement d'un bitume avec celui d'un mastic bitumineux dans le domaine des petites deformations. neanmoins, dans une seconde perspective, on s'interesse a l'influence des fillers de verre de post-consommation sur le comportement d'un mastic a faibles niveaux de deformations en comparant l'evolution des modules complexes de cisaillements (G*) d'un mastic avec fillers de verre et un mastic avec fillers conventionnels (calcaire). Enfin, le modele analogique 2S2P1D est utilise pour simuler le comportement viscoelastique lineaire des bitumes et des mastics bitumineux testes lors de la campagne experimentale.

  17. Cooperative interplay of let-7 mimic and HuR with MYC RNA

    PubMed Central

    Gunzburg, Menachem J; Sivakumaran, Andrew; Pendini, Nicole R; Yoon, Je-Hyun; Gorospe, Myriam; Wilce, Matthew Cj; Wilce, Jacqueline A

    2015-01-01

    Both RNA-binding proteins (RBP) and miRNA play important roles in the regulation of mRNA expression, often acting together to regulate a target mRNA. In some cases the RBP and miRNA have been reported to act competitively, but in other instances they function cooperatively. Here, we investigated HuR function as an enhancer of let-7-mediated translational repression of c-Myc despite the separation of their binding sites. Using an in vitro system, we determined that a let-7 mimic, consisting of single-stranded (ss)DNA complementary to the let-7 binding site, enhanced the affinity of HuR for a 122-nt MYC RNA encompassing both binding sites. This finding supports the biophysical principle of cooperative binding by an RBP and miRNA purely through interactions at distal mRNA binding sites. PMID:26177105

  18. Cooperative interplay of let-7 mimic and HuR with MYC RNA.

    PubMed

    Gunzburg, Menachem J; Sivakumaran, Andrew; Pendini, Nicole R; Yoon, Je-Hyun; Gorospe, Myriam; Wilce, Matthew C J; Wilce, Jacqueline A

    2015-01-01

    Both RNA-binding proteins (RBP) and miRNA play important roles in the regulation of mRNA expression, often acting together to regulate a target mRNA. In some cases the RBP and miRNA have been reported to act competitively, but in other instances they function cooperatively. Here, we investigated HuR function as an enhancer of let-7-mediated translational repression of c-Myc despite the separation of their binding sites. Using an in vitro system, we determined that a let-7 mimic, consisting of single-stranded (ss)DNA complementary to the let-7 binding site, enhanced the affinity of HuR for a 122-nt MYC RNA encompassing both binding sites. This finding supports the biophysical principle of cooperative binding by an RBP and miRNA purely through interactions at distal mRNA binding sites.

  19. HBA1c: clinical and biological agreement for standardization of assay methods. Report by the experts of ALFEDIAM (Association de Langue Française pour lEtude du Diabète et des Maladies Métabolique) and SFBC (Société Française de Biologie Clinique).

    PubMed

    Gillery, P; Bordas-Fonfrède, M; Chapelle, J P; Drouin, P; Hue, G; Lévy-Marchal, C; Périer, C; Sélam, J L; Slama, G; Thivolet, C; Vialettes, B

    1999-09-01

    Glycohaemoglobin, and particularly haemoglobin A1c(HbA1c), assays have been used for many years to retrospectively evaluate the glycaemic control of diabetic patients. Cut-off values have been established for deciding treatment modifications. The techniques used in the laboratories however exhibit varying quality, and all of them are not yet standardized. The consequence is an under-utilization of this test, especially in non-hospital practice. In this context, working groups of Société Française de Biologie Clinique (SFBC), Association de Langue Française pour l'Etude du Diabète et des Maladies Métaboliques (ALFEDIAM) and Société Française d'Endocrinologie (SFE) have met together, in order to analyze the national status, and to propose practical recommendations for implementing a standardization process on the basis of international experiences. It is recommended to exclusively express results as HbA1c percentage, using methods standardized and certified by comparison to reference methods such as those using Diabetes Control and Complications Trial (DCCT) values. Simultaneously, contacts have been established with manufacturers, and the realisation of periodic quality control surveys was encouraged.

  20. Role of CTA1R7K-COL-DD as a novel therapeutic mucosal tolerance-inducing vector for treatment of collagen-induced arthritis.

    PubMed

    Hasselberg, Annemarie; Schön, Karin; Tarkowski, Andrej; Lycke, Nils

    2009-06-01

    To determine whether a cholera toxin-derived, novel immunomodulating fusion protein, CTA1R7K-COL-DD, carrying the class II major histocompatibility complex H-2q-restricted type II collagen peptide aa 259-274, can induce therapeutic tolerance and prevent collagen-induced arthritis (CIA) when administered intranasally in DBA/1 mice, and to assess whether ADP-ribosylation at the mucosal membranes exerts a regulatory function such that the outcome of tolerance or immune enhancement can be controlled. DBA/1 mice with CIA were treated intranasally with CTA1R7K-COL-DD. The therapeutic effect was monitored for 46 days after the onset of disease. Clinical scoring of disease, histologic examination of inflammation, and bone erosion were assessed, and cytokine levels were determined in the serum or supernatants from splenocytes stimulated with recall antigen. The protective effect of CTA1R7K-COL-DD resulted in roughly 60% of the mice having no clinical signs or histologic evidence of disease after treatment, and those with CIA had significantly milder disease with less bone erosion. The protective status was associated with lower serum titers of IgG1, IgG2a, IgG2b, and IgG3 anticollagen and a substantial decrease in the production of interleukin-6 (IL-6), IL-17, and interferon-gamma, while levels of IL-10 were markedly up-regulated both in the serum and at the T cell level. The enzymatically inactive mutant fusion protein CTA1R7K-COL-DD provided substantial therapeutic protection against CIA following intranasal administration. The mechanism behind the effect appears to be mediated by peptide-specific regulatory T cells induced by mucosal exposure to the peptide containing CTA1R7K-COL-DD vector. In addition, ADP-ribosylation at the mucosal membranes acts as a key regulator controlling mucosal tolerance or immunity.

  1. Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13.

    PubMed

    Scherer, Stephanie L; Cain, Matthew D; Kanai, Stanley M; Kaltenbronn, Kevin M; Blumer, Kendall J

    2017-06-16

    The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ 5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G i/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G i/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα 13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα 13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα 13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα 13 ·R7-RGS complexes. Because Gα 13 /R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ 5 with or without R7BP. We found that neurite retraction evoked by Gα 12/13 -dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα 12/13 but not Gα i/o These findings provide the first evidence that R7-RGS heterotrimers interact with Gα 13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by

  2. Brain extraction in partial volumes T2*@7T by using a quasi-anatomic segmentation with bias field correction.

    PubMed

    Valente, João; Vieira, Pedro M; Couto, Carlos; Lima, Carlos S

    2018-02-01

    Poor brain extraction in Magnetic Resonance Imaging (MRI) has negative consequences in several types of brain post-extraction such as tissue segmentation and related statistical measures or pattern recognition algorithms. Current state of the art algorithms for brain extraction work on weighted T1 and T2, being not adequate for non-whole brain images such as the case of T2*FLASH@7T partial volumes. This paper proposes two new methods that work directly in T2*FLASH@7T partial volumes. The first is an improvement of the semi-automatic threshold-with-morphology approach adapted to incomplete volumes. The second method uses an improved version of a current implementation of the fuzzy c-means algorithm with bias correction for brain segmentation. Under high inhomogeneity conditions the performance of the first method degrades, requiring user intervention which is unacceptable. The second method performed well for all volumes, being entirely automatic. State of the art algorithms for brain extraction are mainly semi-automatic, requiring a correct initialization by the user and knowledge of the software. These methods can't deal with partial volumes and/or need information from atlas which is not available in T2*FLASH@7T. Also, combined volumes suffer from manipulations such as re-sampling which deteriorates significantly voxel intensity structures making segmentation tasks difficult. The proposed method can overcome all these difficulties, reaching good results for brain extraction using only T2*FLASH@7T volumes. The development of this work will lead to an improvement of automatic brain lesions segmentation in T2*FLASH@7T volumes, becoming more important when lesions such as cortical Multiple-Sclerosis need to be detected. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation.

    PubMed

    Hosoi, Yoshio; Uno, Yasuhiro; Murayama, Norie; Fujino, Hideki; Shukuya, Mitsunori; Iwasaki, Kazuhide; Shimizu, Makiko; Utoh, Masahiro; Yamazaki, Hiroshi

    2012-12-15

    Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V(max) and low K(m) values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V(max) and V(max)/K(m) values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Miniature lowpass filters in low loss 9k7 LTCC

    DOE PAGES

    Dai, Steve; Hsieh, Lung -Hwa

    2015-07-01

    DuPont 9k7 low temperature cofired ceramic (LTCC) is a low loss, or high quality factor Q, tape system targeting at radio frequency (RF) applications. This paper reports the effect of a critical process parameter, heating rate, on the densification and dielectric properties of the 9k7 LTCC. The role of competing densification and crystallization during the sintering of 9k7 is discussed. The high Q of DuPont 9K7 can be used to improve RF system performance, for example a better receiver noise figure, by designing embedded passive RF components such as inductors, capacitors and filters. As a result, miniaturized multilayer low passmore » filters (LPF) with a wide stopband were fabricated to showcase the technology.« less

  5. Miniature lowpass filters in low loss 9k7 LTCC

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dai, Steve; Hsieh, Lung -Hwa

    DuPont 9k7 low temperature cofired ceramic (LTCC) is a low loss, or high quality factor Q, tape system targeting at radio frequency (RF) applications. This paper reports the effect of a critical process parameter, heating rate, on the densification and dielectric properties of the 9k7 LTCC. The role of competing densification and crystallization during the sintering of 9k7 is discussed. The high Q of DuPont 9K7 can be used to improve RF system performance, for example a better receiver noise figure, by designing embedded passive RF components such as inductors, capacitors and filters. As a result, miniaturized multilayer low passmore » filters (LPF) with a wide stopband were fabricated to showcase the technology.« less

  6. IL-7Rαlow memory CD8+ T cells are significantly elevated in patients with systemic lupus erythematosus.

    PubMed

    Kim, Jung-Sik; Cho, Bon-A; Sim, Ji Hyun; Shah, Kamini; Woo, Connie M; Lee, Eun Bong; Lee, Dong-Sup; Kang, Jae Seung; Lee, Wang Jae; Park, Chung-Gyu; Craft, Joe; Kang, Insoo; Kim, Hang-Rae

    2012-09-01

    Human effector memory (EM) CD8(+) T cells include IL-7Rα(high) and IL-7Rα(low) cells with distinct cellular characteristics, including the expression of cytotoxic molecules. Both NK cells and the NK cell-associated molecule 2B4 that is expressed on CD8(+) T cells promote cytotoxicity. Here we analysed the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells and its contribution to cytotoxicity. We also analysed the frequency of IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells in patients with SLE or lupus and in healthy individuals given the potential role of cytotoxic CD8(+) T cells in the pathogenesis of lupus. We used flow cytometry to measure the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells as well as the frequency of these cell populations in the peripheral blood of healthy individuals and patients with SLE. Also, 2B4-mediated cytotoxicity was quantitated in IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells using target cells with CD48 antigen. We found that IL-7Rα(high) EM CD8(+) T cells had higher levels of 2B4 expression compared with IL-7Rα(low) EM CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7Rα(low) EM CD8(+) T cells against target cells. We also noticed that patients with SLE had an increased frequency of IL-7Rα(low) EM CD8(+) T cells that correlated with disease manifestation. Our findings show that SLE patients have increased IL-7Rα(low) EM CD8(+) T cells, possibly contributing to tissue damage through 2B4-mediated cytotoxicity.

  7. The B7 family of immunoregulatory receptors: A comparative and evolutionary perspective

    USGS Publications Warehouse

    Hansen, J.D.; Pasquier, L.D.; Lefranc, M.-P.; Lopez, V.; Benmansour, A.; Boudinot, P.

    2009-01-01

    In mammals, T cell activation requires specific recognition of the peptide-MHC complex by the TcR and co-stimulatory signals. Important co-stimulatory receptors expressed by T cells are the molecules of the CD28 family, that regulate T cell activation, proliferation and tolerance. These receptors recognize B7s and B7-homologous (B7H) molecules that are typically expressed by the antigen presenting cells. In teleost fish, typical T cell responses have been described and the TcR, MHC and CD28/CTLA4 genes have been characterized. In contrast, the members of the B7 gene family have only been described in mammals and birds and have yet to be addressed in lower vertebrates. To learn more about the evolution of components guiding T cell activation in vertebrates, we performed a systematic genomic survey for the B7 co-stimulatory and co-inhibitory IgSF receptors in lower vertebrates with an emphasis on teleost fish. Our search identified fish sequences that are orthologous to B7, B7-H1/B7-DC, B7-H3 and B7-H4 as defined by sequence identity, phylogeny and combinations of short or long-range syntenic relationships. However, we were unable to identify clear orthologs for B7-H2 (CD275, ICOS ligand) in bony fish, which correlates with our prior inability to find ICOS in fish. Interestingly, our results indicate that teleost fish possess a single B7.1/B7.2 (CD80/86) molecule that likely interacts with CD28/CTLA4 as the ligand-binding regions seem to be conserved in both partners. Overall, our analyses implies that gene duplication (and loss) have shaped a molecular repertoire of B7-like molecules that was recruited for the refinement of T cell activation during the evolution of the vertebrates.

  8. Exploring structure and function of sensory cortex with 7T MRI.

    PubMed

    Schluppeck, Denis; Sanchez-Panchuelo, Rosa-Maria; Francis, Susan T

    2018-01-01

    In this paper, we present an overview of 7T magnetic resonance imaging (MRI) studies of the detailed function and anatomy of sensory areas of the human brain. We discuss the motivation for the studies, with particular emphasis on increasing the spatial resolution of functional MRI (fMRI) using reduced field-of-view (FOV) data acquisitions. MRI at ultra-high-field (UHF) - defined here as 7T and above - has several advantages over lower field strengths. The intrinsic signal-to-noise ratio (SNR) of images is higher at UHF, and coupled with the increased blood-oxygen-level-dependent (BOLD) signal change, this results in increased BOLD contrast-to-noise ratio (CNR), which can be exploited to improve spatial resolution or detect weaker signals. Additionally, the BOLD signal from the intra-vascular (IV) compartment is relatively diminished compared to lower field strengths. Together, these properties make 7T functional MRI an attractive proposition for high spatial specificity measures. But with the advantages come some challenges. For example, increased vulnerability to susceptibility-induced geometric distortions and signal loss in EPI acquisitions tend to be much larger. Some of these technical issues can be addressed with currently available tools and will be discussed. We highlight the key methodological considerations for high resolution functional and structural imaging at 7 T. We then present recent data using the high spatial resolution available at UHF in studies of the visual and somatosensory cortex to highlight promising developments in this area. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Characterization of FaDu-R, a radioresistant head and neck cancer cell line, and cancer stem cells.

    PubMed

    Cho, Kwang-Jae; Park, Eun-Ji; Kim, Min-Sik; Joo, Young-Hoon

    2018-06-01

    The aim of this study was to evaluate the impact of CSC on insensitivity to radiotherapy in HNSCC. A radioresistant cell line, FaDu-R, was established using fractionated ionizing radiation. Cells with high and low CD44/ALDH activity were isolated. FaDu-R cells demonstrated significantly increased cell viability after radiation exposure compared with parental cells. CD44 high /ALDH high FaDu-R cells demonstrated significantly faster wound closure (p<0.05) and more efficient invasion (p<0.05) compared to the CD44 high /ALDH high FaDu cells or the CD44 low /ALDH low FaDu-R cells. There was a significant difference in tumor volume between the CD44 high /ALDH high FaDu-R cells and the CD44 high /ALDH high FaDu cells (p<0.05) as well as the CD44 low /ALDH low FaDu-R cells (p<0.05). Cancer stem cells (CSC) were associated with invasion and tumorigenesis in a radioresistant head and neck squamous cell carcinoma (HNSCC) cell line. This concept might help to improve the understanding of these mechanisms and to develop drugs that can overcome radioresistance during radiotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. TRAV7-2*02 Expressing CD8+ T Cells Are Responsible for Palladium Allergy

    PubMed Central

    Takeda, Yuri; Suto, Yoshiko; Ito, Koyu; Hashimoto, Wataru; Nishiya, Tadashi; Ueda, Kyosuke; Narushima, Takayuki; Takahashi, Tetsu; Ogasawara, Kouetsu

    2017-01-01

    While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8+ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8+ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8+ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy. PMID:28561797

  11. Multi-turn multi-gap transmission line resonators - Concept, design and first implementation at 4.7T and 7T.

    PubMed

    Frass-Kriegl, Roberta; Laistler, Elmar; Hosseinnezhadian, Sajad; Schmid, Albrecht Ingo; Moser, Ewald; Poirier-Quinot, Marie; Darrasse, Luc; Ginefri, Jean-Christophe

    2016-12-01

    A novel design scheme for monolithic transmission line resonators (TLRs) is presented - the multi-turn multi-gap TLR (MTMG-TLR) design. The MTMG-TLR design enables the construction of TLRs with multiple turns and multiple gaps. This presents an additional degree of freedom in tuning self-resonant TLRs, as their resonance frequency is fully determined by the coil geometry (e.g. diameter, number of turns, conductor width, etc.). The novel design is evaluated at 4.7T and 7T by simulations and experiments, where it is demonstrated that MTMG-TLRs can be used for MRI, and that the B 1 distribution of MTMG-TLRs strongly depends on the number and distribution of turns. A comparison to conventional loop coils revealed that the B 1 performance of MTMG-TLRs is comparable to a loop coil with the same mean diameter; however, lower 10g SAR values were found for MTMG-TLRs. The MTMG-TLR design is expected to bring most benefits at high static field, where it allows for independent size and frequency selection, which cannot be achieved with standard TLR design. However, it also enables more accurate geometric optimization at low static field. Thereby, the MTMG-TLR design preserves the intrinsic advantages of TLRs, i.e. mechanical flexibility, high SAR efficiency, mass production, and coil miniaturization. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Apigenin sensitizes hepatocellular carcinoma cells to doxorubic through regulating miR-520b/ATG7 axis.

    PubMed

    Gao, Ai-Mei; Zhang, Xiao-Yu; Hu, Juan-Ni; Ke, Zun-Ping

    2018-01-25

    Chemo-resistance is a serious obstacle for successful treatment of cancer. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in various malignant cancers. This study aimed to investigate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM. We observed that apigenin significantly enhanced doxorubicin sensitivity, induced miR-520b expression and inhibited ATG7-dependent autophagy in BEL-7402/ADM cells. In addition, we also showed that miR-520b mimics increased doxorubicin sensitivity and inhibited ATG7-dependent autophagy. Meanwhile, we indicated that ATG7 was a potential target of miR-520b. Furthermore, APG inhibited the growth of hepatocellar carcinoma xenografts in nude mice by up-regulating miR-520b and inhibiting ATG7. Our finding provides evidence that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-520b/ATG7 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. 46 CFR 35.40-7 - Carbon dioxide and clean agent alarms-T/ALL.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Carbon dioxide and clean agent alarms-T/ALL. 35.40-7... Marking Requirements-TB/ALL § 35.40-7 Carbon dioxide and clean agent alarms—T/ALL. Each carbon dioxide or...: “WHEN ALARM SOUNDS VACATE AT ONCE. [CARBON DIOXIDE/CLEAN AGENT—as appropriate] BEING RELEASED.” [USCG...

  14. 46 CFR 35.40-7 - Carbon dioxide and clean agent alarms-T/ALL.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 1 2014-10-01 2014-10-01 false Carbon dioxide and clean agent alarms-T/ALL. 35.40-7... Marking Requirements-TB/ALL § 35.40-7 Carbon dioxide and clean agent alarms—T/ALL. Each carbon dioxide or...: “WHEN ALARM SOUNDS VACATE AT ONCE. [CARBON DIOXIDE/CLEAN AGENT—as appropriate] BEING RELEASED.” [USCG...

  15. B7-H4 as a Target for Breast Cancer Immunotherapy

    DTIC Science & Technology

    2012-06-01

    lymphoma and leukemia cell lines. CEM, Karpas 299, and TLBR -1, cell lines derived from acute T-cell lymphoblastic leukemia, large cell anaplastic...Accomplishments  Generation of human B7-H4-Fc fusion protein (antigen).  Discovery of a B7-H4 receptor on CEM, Karpas 299, and TLBR -1 cell lines...CEM Karpas 299 TLBR -1 Jurkat B7-H4R Figure 3. B7-H4 binding to human T-cell lymphoma cell lines. Red

  16. Immunogenicity of T7 bacteriophage nanoparticles displaying G-H loop of foot-and-mouth disease virus (FMDV).

    PubMed

    Xu, Hai; Bao, Xi; Lu, Yu; Liu, Yamei; Deng, Bihua; Wang, Yiwei; Xu, Yue; Hou, Jibo

    2017-06-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals that causes severe economic losses worldwide. The G-H loop of the FMDV VP1 structural protein is the major neutralizing antigenic site. However, a fully protective G-H loop peptide vaccine requires the addition of promiscuous Th sites from a source outside VP1. Thus, we demonstrated the potential of T7 bacteriophage based nanoparticles displaying a genetically fused G-H loop peptide (T7-GH) as a FMDV vaccine candidate. Recombinant T7-GH phage was constructed by inserting the G-H loop coding region into the T7 Select 415-1b vector. Purified T7-GH phage nanoparticles were analyzed by SDS-PAGE, Western blot and Dot-ELISA. Pigs seronegative for FMDV exposure were immunized with T7-GH nanoparticles along with the adjuvant Montanide ISA206, and two commercially available FMDV vaccines (InactVac and PepVac). Humoral and cellular immune responses, as well as protection against virulent homologous virus challenge were assessed following single dose immunization. Pigs immunized T7-GH developed comparable anti-VP1 antibody titers to PepVac, although lower LPBE titers than was induced by InactVac. Antigen specific lymphocyte proliferation was detected in T7-GH group similar to that of PepVac group, however, weaker than InactVac group. Pigs immunized with T7-GH developed a neutralizing antibody response stronger than PepVac, but weaker than InactVac. Furthermore, 80% (4/5) of T7-GH immunized pigs were protected from challenge with virulent homologous virus. These findings demonstrate that the T7-GH phage nanoparticles were effective in eliciting antigen specific immune responses in pigs, highlighting the value of such an approach in the research and development of FMDV vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. States of phage T3/T7 capsids: buoyant density centrifugation and cryo-EM.

    PubMed

    Serwer, Philip; Wright, Elena T; Demeler, Borries; Jiang, Wen

    2018-04-01

    Mature double-stranded DNA bacteriophages have capsids with symmetrical shells that typically resist disruption, as they must to survive in the wild. However, flexibility and associated dynamism assist function. We describe biochemistry-oriented procedures used to find previously obscure flexibility for capsids of the related phages, T3 and T7. The primary procedures are hydration-based buoyant density ultracentrifugation and purified particle-based cryo-electron microscopy (cryo-EM). We review the buoyant density centrifugation in detail. The mature, stable T3/T7 capsid is a shell flexibility-derived conversion product of an initially assembled procapsid (capsid I). During DNA packaging, capsid I expands and loses a scaffolding protein to form capsid II. The following are observations made with capsid II. (1) The in vivo DNA packaging of wild type T3 generates capsid II that has a slight (1.4%), cryo-EM-detected hyper-expansion relative to the mature phage capsid. (2) DNA packaging in some altered conditions generates more extensive hyper-expansion of capsid II, initially detected by hydration-based preparative buoyant density centrifugation in Nycodenz density gradients. (3) Capsid contraction sometimes occurs, e.g., during quantized leakage of DNA from mature T3 capsids without a tail.

  18. Low-field spin dynamics of Cr7Ni and Cr7Ni-Cu -Cr 7Ni molecular rings as detected by μ SR

    NASA Astrophysics Data System (ADS)

    Sanna, S.; Arosio, P.; Bordonali, L.; Adelnia, F.; Mariani, M.; Garlatti, E.; Baines, C.; Amato, A.; Sabareesh, K. P. V.; Timco, G.; Winpenny, R. E. P.; Blundell, S. J.; Lascialfari, A.

    2017-11-01

    Muon spin rotation measurements were used to investigate the spin dynamics of heterometallic Cr7Ni and Cr7Ni -Cu-Cr7Ni molecular clusters. In Cr7Ni the magnetic ions are arranged in a quasiplanar ring and interact via an antiferromagnetic exchange coupling constant J , while Cr7Ni -Cu-Cr7Ni is composed of two Cr7Ni linked by a bridging moiety containing one Cu ion, that induces an inter-ring ferromagnetic interaction J'≪J . The longitudinal muon relaxation rate λ collected at low magnetic fields μ0H <0.15 Tesla, shows that the two systems present differences in spin dynamics vs temperature. While both samples exhibit a main peak in the muon relaxation rate vs temperature, at T ˜10 K for Cr7Ni and T ˜8 K for Cr7Ni -Cu-Cr7Ni , the two compounds have distinct additional features: Cr7Ni shows a shoulder in λ (T ) for T <8 K, while Cr7Ni -Cu-Cr7Ni shows a flattening of λ (T ) for T <2 K down to temperatures as low as T =20 mK. The main peak of both systems is explained by a Bloembergen-Purcell-Pound (BPP)-like heuristic fitting model that takes into account of a distribution of electronic spin characteristic times for T >5 K, while the shoulder presented by Cr7Ni can be reproduced by a BPP function that incorporates a single electronic characteristic time theoretically predicted to dominate for T <5 K. The flattening of λ (T ) in Cr7Ni -Cu-Cr7Ni occurring at very low temperature can be tentatively attributed to field-dependent quantum effects and/or to an inelastic term in the spectral density of the electronic spin fluctuations.

  19. MiR-let-7a inhibits cell proliferation, migration, and invasion by down-regulating PKM2 in cervical cancer

    PubMed Central

    Guo, Man; Zhao, Xinying; Yuan, Xiaolei; Jiang, Jing; Li, Peiling

    2017-01-01

    In recent decades, miRNA has been reported as a crucial modulator in some biology progressions. This work aims to assess the expression and role of miR-let-7a and pyruvate kinase muscle isozyme M2 (PKM2) in CC tissues and cell lines. Here, we identified that miR-let-7a expression was decreased in CC tissues, and SiHa and HeLa cells (all P < 0.001), however, PKM2 expression was increased in these samples. Statistically, miR-let-7a was inversely associated with PKM2 mRNA or protein (p = 0.013, p = 0.015, respectively). In-vitro assays revealed that ectopic miR-let-7a expression repressed SiHa and HeLa cell proliferation, migration and invasion, and enhanced SiHa and HeLa cell apoptosis. Furthermore, luciferase reporter assays revealed the 3′-UTR of PKM2 was identified a target of miR-let-7a, by which miR-let-7a affected the expression of PKM2 in SiHa and HeLa cells. Besides, PKM2 plasmids partially abrogated the inhibitory effects of miR-let-7a, while si-PKM2 enhanced the inhibitory effects of miR-let-7a. In vivo, miR-let-7a mimics indeed repressed tumor growth in mice xenograft model. In conclusion, our results demonstrated that miR-let-7a inhibits cell proliferation, migration and invasion by down-regulation of PKM2 in cervical cancer. miR-let-7a/PKM2 pathway may be a useful therapeutic target for CC patients. PMID:28415668

  20. 26 CFR 1.414(r)-7 - Determination of the employees of an employer's qualified separate lines of business.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... qualified separate lines of business. 1.414(r)-7 Section 1.414(r)-7 Internal Revenue INTERNAL REVENUE..., Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(r)-7 Determination of the employees of an employer's... residual shared employee as defined in § 1.414(r)-11(b)(2) and (4)) is assigned to a single qualified...

  1. 26 CFR 1.414(r)-7 - Determination of the employees of an employer's qualified separate lines of business.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... qualified separate lines of business. 1.414(r)-7 Section 1.414(r)-7 Internal Revenue INTERNAL REVENUE..., Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(r)-7 Determination of the employees of an employer's... residual shared employee as defined in § 1.414(r)-11(b)(2) and (4)) is assigned to a single qualified...

  2. 26 CFR 1.414(r)-7 - Determination of the employees of an employer's qualified separate lines of business.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... qualified separate lines of business. 1.414(r)-7 Section 1.414(r)-7 Internal Revenue INTERNAL REVENUE..., Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(r)-7 Determination of the employees of an employer's... residual shared employee as defined in § 1.414(r)-11(b)(2) and (4)) is assigned to a single qualified...

  3. 26 CFR 1.414(r)-7 - Determination of the employees of an employer's qualified separate lines of business.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... qualified separate lines of business. 1.414(r)-7 Section 1.414(r)-7 Internal Revenue INTERNAL REVENUE..., Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(r)-7 Determination of the employees of an employer's... residual shared employee as defined in § 1.414(r)-11(b)(2) and (4)) is assigned to a single qualified...

  4. 26 CFR 1.414(r)-7 - Determination of the employees of an employer's qualified separate lines of business.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... qualified separate lines of business. 1.414(r)-7 Section 1.414(r)-7 Internal Revenue INTERNAL REVENUE...-Sharing, Stock Bonus Plans, Etc. § 1.414(r)-7 Determination of the employees of an employer's qualified... residual shared employee as defined in § 1.414(r)-11(b)(2) and (4)) is assigned to a single qualified...

  5. B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma

    PubMed Central

    Hua, Dong; Sun, Jing; Mao, Yong; Chen, Lu-Jun; Wu, Yu-Yu; Zhang, Xue-Guang

    2012-01-01

    AIM: To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment. METHODS: One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study. Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells. Data was analyzed with statistical software. RESULTS: Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found congregated in CRC tumor nest and stroma. Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P < 0.0001) and tumor stroma (P = 0.0200) of 102 cases of CRC tissues. Among the total T cells, a variable amount of regulatory T cells with a clear Foxp3+ (forkhead box P3) staining could be detected in CRC tissues and patients’ blood. Interestingly, in the 33 samples (15 cases of B7-H1high CRC tissues and 18 cases of B7-H1low CRC tissues) of freshly isolated mononuclear cells from CRC tissues, the percentages of CD4+Foxp3+ and CD8+Foxp3+ regulatory T cells were found remarkably higher in B7-H1high CRC tissues than in B7-H1low CRC tissues (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in proliferation of regulatory T cell. No significant difference was found in CRC peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell, which is expressed by activated T cell. Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells

  6. B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma.

    PubMed

    Hua, Dong; Sun, Jing; Mao, Yong; Chen, Lu-Jun; Wu, Yu-Yu; Zhang, Xue-Guang

    2012-03-07

    To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment. One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study. Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells. Data was analyzed with statistical software. Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found congregated in CRC tumor nest and stroma. Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P < 0.0001) and tumor stroma (P = 0.0200) of 102 cases of CRC tissues. Among the total T cells, a variable amount of regulatory T cells with a clear Foxp3⁺ (forkhead box P3) staining could be detected in CRC tissues and patients' blood. Interestingly, in the 33 samples (15 cases of B7-H1(high) CRC tissues and 18 cases of B7-H1(low) CRC tissues) of freshly isolated mononuclear cells from CRC tissues, the percentages of CD4⁺Foxp3⁺ and CD8⁺Foxp3⁺ regulatory T cells were found remarkably higher in B7-H1(high) CRC tissues than in B7-H1(low) CRC tissues (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in proliferation of regulatory T cell. No significant difference was found in CRC peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell, which is expressed by activated T cell. Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells (CD4

  7. The role of IL-1beta in reduced IL-7 production by stromal and epithelial cells: a model for impaired T-cell numbers in the gut during HIV-1 infection.

    PubMed

    Thang, P H; Ruffin, N; Brodin, D; Rethi, B; Cam, P D; Hien, N T; Lopalco, L; Vivar, N; Chiodi, F

    2010-08-01

    Interleukin (IL)-7 is a key cytokine in T-cell homeostasis. Stromal cells, intestinal epithelial cells and keratinocytes are known to produce this cytokine. The mechanisms and cellular factors regulating IL-7 production are still unclear. We assessed whether IL-1beta and interferon (IFN)-gamma, cytokines produced during inflammatory conditions, may impact on IL-7 production. We used human intestinal epithelial cells (DLD-1 cell line) and bone marrow stromal cells (HS27 cell line), known to produce IL-7; IL-7 production was evaluated at the mRNA and protein levels. To assess whether treatment of HS27 cells with IL-1beta and/or IFN-gamma leads to changes in the gene expression of cytokines, Toll-like receptors (TLRs) and chemokines, we analysed gene expression profiles using the whole-genome microarray Human Gene 1.0 ST. We found that IFN-gamma enhanced the expression of IL-7 mRNA (P < 0.001) in both cell lines. IL-1beta treatment led to a significant down-regulation (P < 0.001) of IL-7 mRNA expression in both cell lines. The IL-7 concentration in supernatants collected from treated DLD-1 and HS27 cell cultures reflected the trend of IL-7 mRNA levels. The gene profiles revealed dramatic changes in expression of cytokines and their receptors (IL-7/IL-7R alpha; IL-1alpha,IL-1beta/IL-1R1; IFN-gamma/IFN-gammaR1), of IFN regulatory factors (IRF-1 and 2), of TLRs and of important chemo-attractants for T cells. The microarray results were verified by additional methods. Our results are discussed in the setting of inflammation and T-cell survival in the gut compartment during HIV-1 infection where stromal and epithelial cells may produce factors that contribute to impaired IL-7 homeostasis and homing of T cells.

  8. Unclassified Publications of Lincoln Laboratory. Volume 7

    DTIC Science & Technology

    1979-12-15

    4984 IA-4774, JA-4846, .)A-4849, JA-41)38; ADAPTIVE ARRAY MS-4856 TN-1978- 1 , TN-1979-8 ALTAIR ADAPTIVE CONTROL TN-1978-6, TN-1979-41; .IA-4952 MS-5090...8217 ~CI. ,\\ SS IFIEIJ Pl i UI.ICATIO~ S OF 1 . 1 ’ c : o 1 . \\ 1 . .\\ n o n ,, T o n Y VOLUME 7 15 DECEMBER 1979 Requests for informat ion should be...L I ’:-J C 0 L \\ L .-\\ B 0 R :\\ T 0 R Y L 1 :::\\ I \\ G T 0 \\. \\ 1 .-\\ ~ S :\\ C H l S E T T S The work liste~ in this bibliography was performed at

  9. Myh7b/miR-499 gene expression is transcriptionally regulated by MRFs and Eos

    PubMed Central

    Yeung, Fan; Chung, Eunhee; Guess, Martin G.; Bell, Matthew L.; Leinwand, Leslie A.

    2012-01-01

    The sarcomeric myosin gene, Myh7b, encodes an intronic microRNA, miR-499, which regulates cardiac and skeletal muscle biology, yet little is known about its transcriptional regulation. To identify the transcription factors involved in regulating Myh7b/miR-499 gene expression, we have mapped the transcriptional start sites and identified an upstream 6.2 kb region of the mouse Myh7b gene whose activity mimics the expression pattern of the endogenous Myh7b gene both in vitro and in vivo. Through promoter deletion analysis, we have mapped a distal E-box element and a proximal Ikaros site that are essential for Myh7b promoter activity in muscle cells. We show that the myogenic regulatory factors, MyoD, Myf5 and Myogenin, bind to the E-box, while a lymphoid transcription factor, Ikaros 4 (Eos), binds to the Ikaros motif. Further, we show that through physical interaction, MyoD and Eos form an active transcriptional complex on the chromatin to regulate the expression of the endogenous Myh7b/miR-499 gene in muscle cells. We also provide the first evidence that Eos can regulate expression of additional myosin genes (Myosin 1 and β-Myosin) via the miR-499/Sox6 pathway. Therefore, our results indicate a novel role for Eos in the regulation of the myofiber gene program. PMID:22638570

  10. IUE observations of circumstellar emission from the late type variable R Aquarii /M7 + pec/

    NASA Technical Reports Server (NTRS)

    Michalitsianos, A. G.; Hobbs, R. W.; Kafatos, M.

    1980-01-01

    IUE observations of R Aquarii (M7 + pec) have been obtained in low dispersion in order to study its circumstellar emission. Strong permitted, semiforbidden, and forbidden emission lines are identified that are superposed on a bright ultraviolet continuum. From the analysis it is deduced that the strong emission-line spectrum that involves semiforbidden C III, C IV, semiforbidden Si III, forbidden O II, and forbidden O III probably arises from a dense compact nebula the size of which is comparable to the binary system of which R Aqr is the primary star. Low-excitation emission lines of Fe II, Mg II, O I, and Si II suggest the presence of a warm chromosphere (T less than about 10,000 K) in the primary M7 late type giant. The secondary is identified as a white dwarf, comparable to or somewhat brighter than the sun, since such a star can produce enough ionizing photons to excite the continuum and emission-line spectrum and yet be sufficiently faint to escape detection by direct observation. The UV continuum observed is attributed to Balmer recombination and not to blackbody emission from the hot companion. The general spectral properties of R Aqr between 1200 A and 3200 A are discussed in the context of the model for the circumstellar nebula, the companion, and the mass-loss rate of the primary star.

  11. L'Aventure du LHC

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    None

    2010-06-11

    Cette présentation s’adressera principalement aux personnes qui ont construit le LHC. La construction du LHC fut longue et difficile. De nombreux problèmes sont apparus en cours de route. Tous ont été résolus grâce au dévouement et à l’engagement du personnel et des collaborateurs. Je reviendrai sur les coups durs et les réussites qui ont marqués ces 15 dernières années et je vous montrerai combien cette machine, le fruit de vos efforts, est extraordinaire.

  12. Profil bactériologique du pied diabétique et son impact sur le choix des antibiotiques

    PubMed Central

    Zemmouri, Adil; Tarchouli, Mohamed; Benbouha, Abdellatif; Lamkinsi, Tarik; Bensghir, Mustapha; Elouennass, Mostafa; Haimeur, Cherqui

    2015-01-01

    Introduction Analyse du profil bactériologique des pieds diabétiques pris en charge à l'hôpital militaire de Rabat et son influence sur l'antibiothérapie de première intention. Méthodes Etude prospective non randomisée étalée sur 18 mois, ayant concerné 105 patients. Après recueil des données et en attente des résultats bactériologiques nos patients ont été divisés en deux groupes: un groupe a été mis sous Amoxicilline + Acide clavulanique + Gentamycine (59 patients) et un groupe sous Ertapénème±Gentamycine (46 patients). Résultats L’étude a regroupé 85 hommes et 20 femmes (sexe ratio = 4.26). L’âge moyen est de 64.4 ans. La gangrène a été observée chez 79% des malades; elle était humide-donc surinfectée en principe- dans 43% des cas. Par ailleurs, 67% des malades ont un chiffre de globules blancs 12000 définissant une infection sévère. L'ostéolyse a été mise en évidence chez 27% de nos patients. Parmi les différentes techniques de prélèvements: 81% ont été profonds dont 21% de biopsie osseuse per opératoire et 14% de prélèvements combinés. 42% de ces prélèvements sont poly microbiens et 21% sont stériles. Les résultats bactériologiques viennent confirmer la prédominance des bactéries aérobies à Gram positif. Le taux de remplacement de l'Ertapénème est de 22% contre un taux de 50% pour l'Amoxiclav. Conclusion L'antibiothérapie ne doit être instaurée qu'en cas d'infection du pied diabétique diagnostiquée sur les critères cliniques établis par les consensus internationaux récents. Le respect des mesures de lutte contre la diffusion de la résistance bactérienne s'avère primordiale. PMID:27386024

  13. MR imaging of the temporomandibular joint: comparison between acquisitions at 7.0 T using dielectric pads and 3.0 T

    PubMed Central

    Kuhn, Felix P; Spinner, Georg; Del Grande, Filippo; Wyss, Michael; Piccirelli, Marco; Erni, Stefan; Pfister, Pascal; Ho, Michael; Sah, Bert-Ram; Filli, Lukas; Ettlin, Dominik A; Gallo, Luigi M; Andreisek, Gustav

    2017-01-01

    Objectives: To qualitatively and quantitatively compare MRI of the temporomandibular joint (TMJ) at 7.0 T using high-permittivity dielectric pads and 3.0 T using a clinical high-resolution protocol. Methods: Institutional review board-approved study with written informed consent. 12 asymptomatic volunteers were imaged at 7.0 and 3.0 T using 32-channel head coils. High-permittivity dielectric pads consisting of barium titanate in deuterated suspension were used for imaging at 7.0 T. Imaging protocol consisted of oblique sagittal proton density weighted turbo spin echo sequences. For quantitative analysis, pixelwise signal-to-noise ratio maps of the TMJ were calculated. For qualitative analysis, images were evaluated by two independent readers using 5-point Likert scales. Quantitative and qualitative results were compared using t-tests and Wilcoxon signed-rank tests, respectively. Results: TMJ imaging at 7.0 T using high-permittivity dielectric pads was feasible in all volunteers. Quantitative analysis showed similar signal-to-noise ratio for both field strengths (mean ± SD; 7.0 T, 13.02 ± 3.92; 3.0 T, 14.02 ± 3.41; two-sample t-tests, p = 0.188). At 7.0 T, qualitative analysis yielded better visibility of all anatomical subregions of the temporomandibular disc (anterior band, intermediate zone and posterior band) than 3.0 T (Wilcoxon signed-rank tests, p < 0.05, corrected for multiple comparisons). Conclusions: MRI of the TMJ at 7.0 T using high-permittivity dielectric pads yields superior visibility of the temporomandibular disc compared with 3.0 T. PMID:27704872

  14. MR imaging of the temporomandibular joint: comparison between acquisitions at 7.0 T using dielectric pads and 3.0 T.

    PubMed

    Kuhn, Felix P; Spinner, Georg; Del Grande, Filippo; Wyss, Michael; Piccirelli, Marco; Erni, Stefan; Pfister, Pascal; Ho, Michael; Sah, Bert-Ram; Filli, Lukas; Ettlin, Dominik A; Gallo, Luigi M; Andreisek, Gustav; Manoliu, Andrei

    2017-01-01

    To qualitatively and quantitatively compare MRI of the temporomandibular joint (TMJ) at 7.0 T using high-permittivity dielectric pads and 3.0 T using a clinical high-resolution protocol. Institutional review board-approved study with written informed consent. 12 asymptomatic volunteers were imaged at 7.0 and 3.0 T using 32-channel head coils. High-permittivity dielectric pads consisting of barium titanate in deuterated suspension were used for imaging at 7.0 T. Imaging protocol consisted of oblique sagittal proton density weighted turbo spin echo sequences. For quantitative analysis, pixelwise signal-to-noise ratio maps of the TMJ were calculated. For qualitative analysis, images were evaluated by two independent readers using 5-point Likert scales. Quantitative and qualitative results were compared using t-tests and Wilcoxon signed-rank tests, respectively. TMJ imaging at 7.0 T using high-permittivity dielectric pads was feasible in all volunteers. Quantitative analysis showed similar signal-to-noise ratio for both field strengths (mean ± SD; 7.0 T, 13.02 ± 3.92; 3.0 T, 14.02 ± 3.41; two-sample t-tests, p = 0.188). At 7.0 T, qualitative analysis yielded better visibility of all anatomical subregions of the temporomandibular disc (anterior band, intermediate zone and posterior band) than 3.0 T (Wilcoxon signed-rank tests, p < 0.05, corrected for multiple comparisons). MRI of the TMJ at 7.0 T using high-permittivity dielectric pads yields superior visibility of the temporomandibular disc compared with 3.0 T.

  15. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study.

    PubMed

    Lee, Sung Won; Lee, Shin Seok; Oh, Dong Ho; Park, Dong Jin; Kim, Hyun Sook; Choi, Jung Ran; Chae, Soo Cheon; Yun, Ki Jung; Chung, Won Tae; Choe, Jung Yoon; Kim, Seong Kyu

    2016-10-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.

  16. Homeostatic Proliferation and IL-7R Alpha Expression Do Not Correlate with Enhanced T Cell Proliferation and Protection in Chronic Mouse Malaria

    PubMed Central

    Stephens, Robin; Seddon, Benedict; Langhorne, Jean

    2011-01-01

    While chronic infection has been shown to enhance protection from disease caused by several pathogens, the mechanisms are not known. The gamma-c family of cytokines IL-7, IL-2, and IL-15 are implicated in homeostatic proliferation, which is thought to maintain T cell memory. However in chronic infection, prolonged antigen exposure itself may contribute to lymphocyte survival. We have previously observed that chronic malaria infection enhances protection to re-infection, as well as enhancing B cell responses. Here, we show that chronic Plasmodium chabaudi malaria infection in mice enhances the expansion of CD4+ T cells in a second infection, and that this correlates with increased expression of the IL-2/15 Receptor beta (CD122) on memory T cells, as well as increasing IL-2 producers on re-infection. IL-2 has been recently linked to improved secondary proliferation, while the role of IL-7 in maintenance of CD4+ memory cells has been demonstrated in homeostatic proliferation, but its role in protective memory populations in infectious disease protective has not been fully investigated. Increased IL-7Rα (CD127) expression correlated, as previously reported with increased turnover of CD4 memory cells, however, this was not linked to protection or enhanced response to rechallenge, These data support the idea that antigen or IL-2 production resulting from chronic stimulation may play a role in an enhanced secondary T cell response. PMID:22039531

  17. Mechanism of T7 RNAP pausing and termination at the T7 concatemer junction: a local change in transcription bubble structure drives a large change in transcription complex architecture.

    PubMed

    Nayak, Dhananjaya; Siller, Sylvester; Guo, Qing; Sousa, Rui

    2008-02-15

    The T7RNA polymerase (RNAP) elongation complex (EC) pauses and is destabilized at a unique 8 nucleotide (nt) sequence found at the junction of the head-to-tail concatemers of T7 genomic DNA generated during T7 DNA replication. The paused EC may recruit the T7 DNA processing machinery, which cleaves the concatemerized DNA within this 8 nt concatemer junction (CJ). Pausing of the EC at the CJ involves structural changes in both the RNAP and transcription bubble. However, these structural changes have not been fully defined, nor is it understood how the CJ sequence itself causes the EC to change its structure, to pause, and to become less stable. Here we use solution and RNAP-tethered chemical nucleases to probe the CJ transcript and changes in the EC structure as the polymerase pauses and terminates at the CJ. Together with extensive mutational scanning of regions of the polymerase that are likely to be involved in recognition of the CJ, we are able to develop a description of the events that occur as the EC transcribes through the CJ and subsequently pauses. In this process, a local change in the structure of the transcription bubble drives a large change in the architecture of the EC. This altered EC structure may then serve as the signal that recruits the processing machinery to the CJ.

  18. J-Refocused Coherence Transfer Spectroscopic Imaging at 7 T in Human Brain

    PubMed Central

    Pan, J.W.; Avdievich, N.; Hetherington, H.P.

    2013-01-01

    Short echo spectroscopy is commonly used to minimize signal modulation due to J-evolution of the cerebral amino acids. However, short echo acquisitions suffer from high sensitivity to macromolecules which make accurate baseline determination difficult. In this report, we describe implementation at 7 T of a double echo J-refocused coherence transfer sequence at echo time (TE) of 34 msec to minimize J-modulation of amino acids while also decreasing interfering macromolecule signals. Simulation of the pulse sequence at 7 T shows excellent resolution of glutamate, glutamine, and N-acetyl aspartate. B1 sufficiency at 7 T for the double echo acquisition is achieved using a transceiver array with radiofrequency (RF) shimming. Using an alternate RF distribution to minimize receiver phase cancellation in the transceiver, accurate phase determination for the coherence transfer is achieved with rapid single scan calibration. This method is demonstrated in spectroscopic imaging mode with n = 5 healthy volunteers resulting in metabolite values consistent with literature and in a patient with epilepsy. PMID:20648684

  19. Paired box 7 inhibits differentiation in 3T3-L1 preadipocytes.

    PubMed

    Izumi, Wakana; Takuma, Yuko; Ebihara, Ryo; Mizunoya, Wataru; Tatsumi, Ryuichi; Nakamura, Mako

    2018-06-13

    Myogenesis is precisely proceeded by myogenic regulatory factors. Myogenic stem cells are activated, proliferated and fused into a multinuclear myofiber. Pax7, paired box 7, one of the earliest markers during myogenesis. It has been reported that Pax7 regulates the muscle marker genes, Myf5 and MyoD toward differentiation. The possible roles of Pax7 in myogenic cells have been well researched. However, it has not yet been clarified if Pax7 itself is able to induce myogenic fate in nonmyogenic lineage cells. In this study, we performed experiments using stably expressed Pax7 in 3T3-L1 preadipocytes to elucidate if Pax7 inhibits adipogenesis. We found that Pax7 represses adipogenic markers and prevents differentiation. These cells showed decreased expression of PDGFRα, PPARγ and Fabp4 and inhibited forming lipid droplets. © 2018 Japanese Society of Animal Science.

  20. LncRNA uc.48+ is involved in the diabetic immune and inflammatory responses mediated by P2X7 receptor in RAW264.7 macrophages.

    PubMed

    Wu, Hong; Wen, Fang; Jiang, Mei; Liu, Qiang; Nie, Yijun

    2018-08-01

    High glucose combined with high FFAs can contribute to the unfavorable development of type 2 diabetes mellitus (T2DM) and monocytes/macrophages are important in the occurrence and development of T2DM, which is regarded as a type of low‑grade inflammation. Although our previous study demonstrated that increased expression of P2X7 receptor (P2X7R) in peripheral blood monocytes may alter the innate immune system and that long non‑coding (lnc)RNA uc.48+ was involved in diabetic neuropathic pain, the involvement of uc.48+ mediated by the P2X7R in monocyte/macrophages during T2DM has not been reported. In the present study, the effectsof uc.48+ small interference RNA (siRNA) on factors, including the mRNA and protein expression of P2X7R, apoptosis and proliferation, levels of reactive oxygen species (ROS), cytokine levels, and expression of phosphorylated (p‑) extracellular signal‑regulated kinase (ERK)1/2, were examined in RAW264.7 macrophages following exposure to high glucose and high plasma free fatty acids (FFAs). After RAW264.7 cells were transfected with uc.48+ siRNA under high glucose conditions and FFAs treatment, the mRNA expression levels of uc.48+ and P2X7 receptor were detected by reverse transcription‑polymerase chain reaction. The protein mass of P2X7 receptor and ERK signaling pathway were assessed by western blotting. ROS and calcium concentrations, and culture supernatant cytokine content [tumor necrosis factor‑α, interleukin (IL)‑10, IL‑1β] were detected by fluorescent probes and ELISA respectively. Cell viability and apoptosis were determined by MTS test and flow cytometry, respectively. It was found that treatment of RAW264.7 cells with high glucose and FFAs, which exhibited increased expression of uc.48+, evoked P2X7R‑mediated immune and inflammatory responses through several means, including cytokine secretion, ROS formation, and activation of the ERK signaling pathway. The uc.48+ siRNA regulated these factors and thus

  1. Mise à jour sur le nouveau vaccin 9-valent pour la prévention du virus du papillome humain

    PubMed Central

    Yang, David Yi; Bracken, Keyna

    2016-01-01

    Résumé Objectif Informer les médecins de famille quant à l’efficacité, à l’innocuité, aux effets sur la santé publique et à la rentabilité du vaccin 9-valent contre le virus du papillome humain (VPH). Qualité des données Des articles pertinents publiés dans PubMed jusqu’en mai 2015 ont été examinés et analysés. La plupart des données citées sont de niveau I (essais randomisés et contrôlés et méta-analyses) ou de niveau II (études transversales, cas-témoins et épidémiologiques). Des rapports et recommandations du gouvernement sont aussi cités en référence. Message principal Le vaccin 9-valent contre le VPH, qui offre une protection contre les types 6, 11, 16, 18, 31, 33, 45, 52 et 58 du VPH, est sûr et efficace et réduira encore plus l’incidence des infections à VPH, de même que les cas de cancer lié au VPH. Il peut également protéger indirectement les personnes non immunisées par l’entremise du phénomène d’immunité collective. Un programme d’immunisation efficace peut prévenir la plupart des cancers du col de l’utérus. Les analyses montrent que la rentabilité du vaccin 9-valent chez les femmes est comparable à celle du vaccin quadrivalent original contre le VPH (qui protège contre les types 6, 11, 16 et 18 du VPH) en usage à l’heure actuelle. Toutefois, il faut investiguer plus en profondeur l’utilité d’immuniser les garçons avec le vaccin 9-valent contre le VPH. Conclusion en plus d’être sûr, le vaccin 9-valent protège mieux contre le VPH que le vaccin quadrivalent. Une analyse coûtefficacité en favorise l’emploi, du moins chez les adolescentes. Ainsi, les médecins devraient recommander le vaccin 9-valent à leurs patients plutôt que le vaccin quadrivalent contre le VPH.

  2. MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

    PubMed

    Zhou, Nan; Hao, Shuang; Huang, Zongqiang; Wang, Weiwei; Yan, Penghui; Zhou, Wei; Zhu, Qihang; Liu, Xiaokang

    2018-01-01

    Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed with a gelatin hydrogel conduit containing neural stem cells inserted into the sciatic nerve injury mice. The Sciatic Function Index was used to quantify sciatic nerve functional recovery in the mice. The messenger RNA and protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. Luciferase reporter assay was used to confirm the binding between miR-7 and the 3'UTR of cell division cycle protein 42 (cdc42). The neural stem cells migration and proliferation were analyzed by transwell assay and a Cell-LightTM EdU DNA Cell Proliferation kit, respectively. Results Neural stem cells treatment significantly promoted nerve repair in sciatic nerve injury mice. MiR-7 expression was decreased in sciatic nerve injury mice with neural stem cells treatment, and miR-7 mimic transfected into neural stem cells suppressed migration and proliferation, while miR-7 inhibitor promoted migration and proliferation. The expression level and effect of cdc42 on neural stem cells migration and proliferation were opposite to miR-7, and the luciferase reporter assay proved that cdc42 was a target of miR-7. Using co-transfection into neural stem cells, we found pcDNA3.1-cdc42 and si-cdc42 could reverse respectively the role of miR-7 mimic and miR-7 inhibitor on neural stem cells migration and proliferation. In addition, miR-7 mimic-transfected neural stem cells could abolish the protective role of neural stem cells on peripheral nerve injury

  3. Bypass of a nick by the replisome of bacteriophage T7.

    PubMed

    Zhu, Bin; Lee, Seung-Joo; Richardson, Charles C

    2011-08-12

    DNA polymerase and DNA helicase are essential components of DNA replication. The helicase unwinds duplex DNA to provide single-stranded templates for DNA synthesis by the DNA polymerase. In bacteriophage T7, movement of either the DNA helicase or the DNA polymerase alone terminates upon encountering a nick in duplex DNA. Using a minicircular DNA, we show that the helicase · polymerase complex can bypass a nick, albeit at reduced efficiency of 7%, on the non-template strand to continue rolling circle DNA synthesis. A gap in the non-template strand cannot be bypassed. The efficiency of bypass synthesis depends on the DNA sequence downstream of the nick. A nick on the template strand cannot be bypassed. Addition of T7 single-stranded DNA-binding protein to the complex stimulates nick bypass 2-fold. We propose that the association of helicase with the polymerase prevents dissociation of the helicase upon encountering a nick, allowing the helicase to continue unwinding of the duplex downstream of the nick.

  4. The Class III Kinase Vps34 Promotes T Lymphocyte Survival through Regulating IL-7Rα Surface Expression

    PubMed Central

    McLeod, Ian X.; Zhou, Xiang; Li, Qi-Jing; Wang, Fan; He, You-Wen

    2011-01-01

    IL-7Rα mediated signals are essential for naive T lymphocyte survival. Recent studies show that IL-7Rα is internalized and either recycled to cell surface or degraded. However, how the intracellular process of IL-7Rα trafficking is regulated is unclear. Here we show that Vps34, the class III phosphatidylinositol 3-kinase, plays a critical role in proper IL-7Rα intracellular trafficking. Mice lacking Vps34 in T lymphocytes had a severely reduced T lymphocyte compartment. Vps34-deficient T lymphocytes exhibit increased death and reduced IL-7Rα surface expression, though three major forms of autophagy remain intact. Intracellular IL-7Rα in normal T lymphocytes at steady-state is trafficked through either early endosome/multivesicular bodies (MVB) to the late endosome-Golgi for surface expression or to the lysosome for degradation. However, Vps34-deficient T cells have mislocalized intracellular Eea1, HRS, and Vps36 protein levels, the combined consequence of which is the inability to mobilize internalized IL-7Rα into the retromer pathway for surface display. Our studies reveal that Vps34, though dispensible for autophagy induction, is a critical regulator of naïve T cell homeostasis, modulating IL-7Rα trafficking, signaling, and recycling. PMID:22021616

  5. Development of a Small Molecule P2X7R Antagonist as a Treatment for Acute SCI

    DTIC Science & Technology

    2012-10-01

    in isolated spinal astrocytes and microglia, concentrating on P2X7R activity -dependent transcription. In year 1, we established the injury...astroglia and microglia in response to SCI. Besides defining the effects of P2X7R activation and its blockade on phenotype-specific gene expression...injury (SCI) in isolated spinal astrocytes and microglia, concentrating on P2X7R activity - dependent transcription. In year 1, we established the injury

  6. LEED STUDY OF Ag(111)-(√ 7×√ 7)R19.1^o-4Ar

    NASA Astrophysics Data System (ADS)

    Caragiu, Mellita; Diehl, Renee D.; Leatherman, Gerry S.

    2000-03-01

    Recent LEED studies of the adsorption geometries of Xe and Kr on metal surfaces have indicated that, contrary to expectations, the low-coordination adsorption sites are generally preferred, even on relatively corrugated surfaces such as Cu(1\\overline 1 0). This study extends the range of this phenomenon to include Ar. On Ag(111), Ar can form a commensurate structure, Ag(111)-(√ 7×√ 7)R19.1^o-4Ar, if the step sites are first blocked by preadsorbing another species such as CO. A dynamical LEED analysis of this structure at 33K indicates that the structure includes one atom per unit cell on a top site and the remaining three on bridge sites. This structure is clearly preferred over ones in which hollow sites are occupied, providing evidence that the preference of noble gases atoms for low-coordination sites on metals extends to Ar.

  7. Information non précise sur la taille du pénis en République Démocratique du Congo: à propos de 21 sources

    PubMed Central

    Mulenga, Philippe Cilundika; Kazadi, Alex Bukasa

    2016-01-01

    Introduction La taille du pénis constitue une préoccupation de beaucoup des gens actuellement et certains ne sont pas satisfaits de la dimension de leur pénis comme le montre l’étude de Tiggemann en 2008. Il existe relativement peu d'études sur le pénis en érection. Cela peut refléter les tabous culturels des chercheurs ou des médecins en interaction avec les hommes qui sont dans un état d’excitation sexuelle. Toutes fois, il est important pour les personnes qui annoncent des détails sur la taille du pénis d’annoncer d’abord les repères de la mesure du pénis puis ensuite donner les chiffres que proposent les chercheurs. Méthodes Notre enquête de type descriptif transversale s’est effectuée dans les deux grandes villes de la République Démocratique du Congo à savoir la ville de Kinshasa et la ville de Lubumbashi, pendant une période de deux ans soit de Mai 2014 à Mai 2016. Au total, 21 sources d’information ont constitué notre échantillon dont 8 à Kinshasa et 13 à Lubumbashi et nous avons trouvé cela suffisant car les sujets à caractère sexuel sont souvent rares chez nous. Les paramètres étudiés étaient: la nature de la source, la précision de la technique de la mesure, la présence de référence bibliographique, la longueur annoncée du pénis. Résultats La majorité des sources d’information sont faites des émissions de radio et de télévision (23,8%), ceci pourra s’expliquer par le fait que dans notre milieu il y a de plus en plus des chaines de radio et télévision et surtout dans les grandes villes. Concernant la précision de la technique de la mesure du pénis lors du partage du message sur la taille du pénis, l’étude nous montre que la majorité des sources d’information ne signale pas cela lorsqu’elles annoncent la taille du pénis au public soit 85,7%. Plusieurs sources ne déclarent pas les références bibliographiques (57,1%). Lorsqu’on regarde même les chiffres de la taille du p

  8. A promoter recognition mechanism common to yeast mitochondrial and phage t7 RNA polymerases.

    PubMed

    Nayak, Dhananjaya; Guo, Qing; Sousa, Rui

    2009-05-15

    Yeast mitochondrial (YMt) and phage T7 RNA polymerases (RNAPs) are two divergent representatives of a large family of single subunit RNAPs that are also found in the mitochondria and chloroplasts of higher eukaryotes, mammalian nuclei, and many other bacteriophage. YMt and phage T7 promoters differ greatly in sequence and length, and the YMt RNAP uses an accessory factor for initiation, whereas T7 RNAP does not. We obtain evidence here that, despite these apparent differences, both the YMt and T7 RNAPs utilize a similar promoter recognition loop to bind their respective promoters. Mutations in this element in YMt RNAP specifically disrupt mitochondrial promoter utilization, and experiments with site-specifically tethered chemical nucleases indicate that this element binds the mitochondrial promoter almost identically to how the promoter recognition loop from the phage RNAP binds its promoter. Sequence comparisons reveal that the other members of the single subunit RNAP family display loops of variable sequence and size at a position corresponding to the YMt and T7 RNAP promoter recognition loops. We speculate that these elements may be involved in promoter recognition in most or all of these enzymes and that this element's structure allows it to accommodate significant sequence and length variation to provide a mechanism for rapid evolution of new promoter specificities in this RNAP family.

  9. Automated detection of periventricular veins on 7 T brain MRI

    NASA Astrophysics Data System (ADS)

    Kuijf, Hugo J.; Bouvy, Willem H.; Zwanenburg, Jaco J. M.; Viergever, Max A.; Biessels, Geert Jan; Vincken, Koen L.

    2015-03-01

    Cerebral small vessel disease is common in elderly persons and a leading cause of cognitive decline, dementia, and acute stroke. With the introduction of ultra-high field strength 7.0T MRI, it is possible to visualize small vessels in the brain. In this work, a proof-of-principle study is conducted to assess the feasibility of automatically detecting periventricular veins. Periventricular veins are organized in a fan-pattern and drain venous blood from the brain towards the caudate vein of Schlesinger, which is situated along the lateral ventricles. Just outside this vein, a region-of- interest (ROI) through which all periventricular veins must cross is defined. Within this ROI, a combination of the vesselness filter, tubular tracking, and hysteresis thresholding is applied to locate periventricular veins. All detected locations were evaluated by an expert human observer. The results showed a positive predictive value of 88% and a sensitivity of 95% for detecting periventricular veins. The proposed method shows good results in detecting periventricular veins in the brain on 7.0T MR images. Compared to previous works, that only use a 1D or 2D ROI and limited image processing, our work presents a more comprehensive definition of the ROI, advanced image processing techniques to detect periventricular veins, and a quantitative analysis of the performance. The results of this proof-of-principle study are promising and will be used to assess periventricular veins on 7.0T brain MRI.

  10. DNA damage under simulated extraterrestrial conditions in bacteriophage T7

    NASA Astrophysics Data System (ADS)

    Fekete, A.; Módos, K.; Hegedüs, M.; Kovács, G.; Rontó, Gy.; Péter, Á.; Lammer, H.; Panitz, C.

    The experiment "Phage and Uracil response" will be accommodated in the EXPOSE facility of the International Space Station. Its objective is to examine and quantify the effect of specific space conditions on nucleic acid models, especially on bacteriophage T7 and isolated T7 DNA thin films. In order to define the environmental and technical requirements of the EXPOSE, the samples were subjected to the experiment verification test (EVT). During EVT, the samples were exposed to vacuum (10 -4-10 -6 Pa) and polychromatic UV-radiation (200-400 nm) in air, in inert atmosphere, as well as in simulated space vacuum. The effect of extreme temperature in vacuum and the influence of temperature fluctuations around 0 °C were also studied. The total intraphage/isolated DNA damage was determined by quantitative PCR using 555 and 3826 bp fragments of T7 DNA. The type of the damage was resolved using a combination of enzymatic probes and neutral and alkaline agarose gel electrophoresis; the structural/chemical effects were analyzed by spectroscopic and microscopical methods. We obtained substantial evidence that DNA lesions accumulate throughout exposure, but the amount of damage depends on the thickness of the layers. According to our preliminary results, the damages by exposure to conditions of dehydration and UV-irradiation are larger than the sum of vacuum alone, or radiation alone case, suggesting a synergistic action of space vacuum and UV radiation with DNA being the critical target.

  11. Miniature low-pass filter in low-loss 9k7 LTCC

    DOE PAGES

    Dai, Steve Xunhu; Hsieh, Lung -Hwa

    2015-09-30

    DuPont 9k7 low-temperature cofired ceramic (LTCC) is a low-loss, or high-quality-factor Q, tape system targeting at radio frequency (RF) applications. This paper reports on the effect of a critical process parameter, the heating rate, on the densification and dielectric properties of the 9k7 LTCC. The role of competing densification and crystallization during the sintering of 9k7 is discussed. The high Q of DuPont 9K7 can be used to improve RF system performance, for example a better receiver noise figure, by designing embedded passive RF components such as inductors, capacitors and filters. Furthermore, miniaturized multilayer low-pass filters (LPF) with a widemore » stopband were fabricated to showcase the technology.« less

  12. MiR-9 is involved in TGF-β1-induced lung cancer cell invasion and adhesion by targeting SOX7.

    PubMed

    Han, Lichun; Wang, Wei; Ding, Wei; Zhang, Lijian

    2017-09-01

    MicroRNA (miR)-9 plays different roles in different cancer types. Here, we investigated the role of miR-9 in non-small-cell lung cancer (NSCLC) cell invasion and adhesion in vitro and explored whether miR-9 was involved in transforming growth factor-beta 1 (TGF-β1)-induced NSCLC cell invasion and adhesion by targeting SOX7. The expression of miR-9 and SOX7 in human NSCLC tissues and cell lines was examined by reverse transcription-quantitative polymerase chain reaction. Gain-of-function and loss-of-function experiments were performed on A549 and HCC827 cells to investigate the effect of miR-9 and SOX7 on NSCLC cell invasion and adhesion in the presence or absence of TGF-β1. Transwell-Matrigel assay and cell adhesion assay were used to examine cell invasion and adhesion abilities. Luciferase reporter assay was performed to determine whether SOX7 was a direct target of miR-9. We found miR-9 was up-regulated and SOX7 was down-regulated in human NSCLC tissues and cell lines. Moreover, SOX7 expression was negatively correlated with miR-9 expression. miR-9 knockdown or SOX7 overexpression could suppress TGF-β1-induced NSCLC cell invasion and adhesion. miR-9 directly targets the 3' untranslated region of SOX7, and SOX7 protein expression was down-regulated by miR-9. TGF-β1 induced miR-9 expression in NSCLC cells. miR-9 up-regulation led to enhanced NSCLC cell invasion and adhesion; however, these effects could be attenuated by SOX7 overexpression. We concluded that miR-9 expression was negatively correlated with SOX7 expression in human NSCLC. miR-9 was up-regulated by TGF-β1 and contributed to TGF-β1-induced NSCLC cell invasion and adhesion by directly targeting SOX7. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons.

    PubMed

    Briese, Michael; Saal-Bauernschubert, Lena; Ji, Changhe; Moradi, Mehri; Ghanawi, Hanaa; Uhl, Michael; Appenzeller, Silke; Backofen, Rolf; Sendtner, Michael

    2018-03-20

    Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein R (hnRNP R) interacts with several proteins involved in motoneuron diseases. It is located in axons of developing motoneurons, and its depletion causes defects in axon growth. Here, we used individual nucleotide-resolution cross-linking and immunoprecipitation (iCLIP) to determine the RNA interactome of hnRNP R in motoneurons. We identified ∼3,500 RNA targets, predominantly with functions in synaptic transmission and axon guidance. Among the RNA targets identified by iCLIP, the noncoding RNA 7SK was the top interactor of hnRNP R. We detected 7SK in the nucleus and also in the cytosol of motoneurons. In axons, 7SK localized in close proximity to hnRNP R, and depletion of hnRNP R reduced axonal 7SK. Furthermore, suppression of 7SK led to defective axon growth that was accompanied by axonal transcriptome alterations similar to those caused by hnRNP R depletion. Using a series of 7SK-deletion mutants, we show that the function of 7SK in axon elongation depends on its interaction with hnRNP R but not with the PTEF-B complex involved in transcriptional regulation. These results propose a role for 7SK as an essential interactor of hnRNP R to regulate its function in axon maintenance. Copyright © 2018 the Author(s). Published by PNAS.

  14. CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5-7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses.

    PubMed

    Neves, Patrícia C C; Rudersdorf, Richard A; Galler, Ricardo; Bonaldo, Myrna C; de Santana, Marlon Gilsepp Veloso; Mudd, Philip A; Martins, Maurício A; Rakasz, Eva G; Wilson, Nancy A; Watkins, David I

    2010-11-29

    The yellow fever 17D (YF-17D) vaccine is one of the most efficacious vaccines developed to date. Interestingly, vaccination with YF-17D induces IFN-γ production early after vaccination (days 5-7) before the development of classical antigen-specific CD8(+) and CD4(+) T cell responses. Here we investigated the cellular source of this early IFN-γ production. At days 5 and 7 post-vaccination activated CD8(+) gamma-delta TCR T cells produced IFN-γ and TNF-α. Activated CD4(+) T cells produced IFN-γ and TNF-α at day 7 post-vaccination. This early IFN-γ production was also induced after vaccination with recombinant YF-17D (rYF-17D), but was not observed after recombinant Adenovirus type 5 (rAd5) vaccination. Early IFN-γ production, therefore, might be an important aspect of yellow fever vaccination. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Expression Levels and Clinical Significance of miR-21-5p, miR-let-7a, and miR-34c-5p in Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Gioacchini, Federico M.; Çeka, Artan; Rubini, Corrado; Ferrante, Luigi; Procopio, Antonio D.; Olivieri, Fabiola

    2017-01-01

    Objective Altered microRNAs (miRNAs) expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). The aim of this study was to determine the role and clinical value of three LSCC-related miRs, such as miR-21-5p, miR-let-7a, and miR-34c-5p in a homogeneous cohort of patients with primary LSCC treated by primary surgery. Methods Expression levels of miR-21-5p, miR-let-7a, and miR-34c-5p were detected in 43 pairs of LSCC and adjacent normal tissues by reverse-transcription quantitative PCR. Overall survival and disease-free survival were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results miR-21-5p is significantly upregulated, while miR-let-7a is significantly downregulated in LSCC tumor tissues compared with the corresponding adjacent normal tissues. The downregulation of miR-34c-5p expression significantly correlated with a shorter disease-free survival and, in the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. Conclusions miR-21-5p, miR-let-7a, and miR-34c-5p seem to play a critical role in LSCC carcinogenesis and might have a diagnostic and prognostic clinical value. The miR-let-7a levels could have a predictive role for lymph node metastases and miR-34c-5p might be a promising biomarker of patient outcome. PMID:29082244

  16. Clinical applications at ultrahigh field (7  T). Where does it make the difference?

    PubMed

    Trattnig, Siegfried; Bogner, Wolfgang; Gruber, Stephan; Szomolanyi, Pavol; Juras, Vladimir; Robinson, Simon; Zbýň, Štefan; Haneder, Stefan

    2016-09-01

    Presently, three major MR vendors provide commercial 7-T units for clinical research under ethical permission, with the number of operating 7-T systems having increased to over 50. This rapid increase indicates the growing interest in ultrahigh-field MRI because of improved clinical results with regard to morphological as well as functional and metabolic capabilities. As the signal-to-noise ratio scales linearly with the field strength (B0 ) of the scanner, the most obvious application at 7T is to obtain higher spatial resolution in the brain, musculoskeletal system and breast. Of specific clinical interest for neuro-applications is the cerebral cortex at 7T, for the detection of changes in cortical structure as a sign of early dementia, as well as for the visualization of cortical microinfarcts and cortical plaques in multiple sclerosis. In the imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology can be visualized with excellent resolution. The dynamic and static blood oxygenation level-dependent contrast increases linearly with the field strength, which significantly improves the pre-surgical evaluation of eloquent areas before tumor removal. Using susceptibility-weighted imaging, the plaque-vessel relationship and iron accumulation in multiple sclerosis can be visualized for the first time. Multi-nuclear clinical applications, such as sodium imaging for the evaluation of repair tissue quality after cartilage transplantation and (31) P spectroscopy for the differentiation between non-alcoholic benign liver disease and potentially progressive steatohepatitis, are only possible at ultrahigh fields. Although neuro- and musculoskeletal imaging have already demonstrated the clinical superiority of ultrahigh fields, whole-body clinical applications at 7T are still limited, mainly because of the lack of suitable coils. The purpose of this article was therefore to review the clinical studies that have been performed thus

  17. Comparison of 7.0- and 3.0-T MRI and MRA in ischemic-type moyamoya disease: preliminary experience.

    PubMed

    Deng, Xiaofeng; Zhang, Zihao; Zhang, Yan; Zhang, Dong; Wang, Rong; Ye, Xun; Xu, Long; Wang, Bo; Wang, Kai; Zhao, Jizong

    2016-06-01

    OBJECT The authors compared the image quality and diagnostic sensitivity and specificity of 7.0-T and 3.0-T MRI and time-of-flight (TOF) MR angiography (MRA) in patients with moyamoya disease (MMD). METHODS MR images of 15 patients with ischemic-type MMD (8 males, 7 females; age 13-48 years) and 13 healthy controls (7 males, 6 females; age 19-28 years) who underwent both 7.0-T and 3.0-T MRI and MRA were studied retrospectively. The main intracranial arteries were assessed by using the modified Houkin's grading system (MRA score). Moyamoya vessels (MMVs) were evaluated by 2 grading systems: the MMV quality score and the MMV area score. Two diagnostic criteria for MMD were used: the T2 criteria, which used flow voids in the basal ganglion on T2-weighted images, and the TOF criteria, which used the high-intensity areas in the basal ganglion on source images from TOF MRA. All data were evaluated by 2 independent readers who were blinded to the strength field and presence or absence of MMD. Using conventional angiography as the gold standard, the sensitivity and specificity of 7.0-T and 3.0-T MRI/MRA in the diagnosis of MMD were calculated. The differences between 7.0-T and 3.0-T MRI and MRA were statistically compared. RESULTS No significant differences were observed between 7.0-T and 3.0-T MRA in MRA score (p = 0.317) or MRA grade (p = 0.317). There was a strong correlation between the Suzuki's stage and MRA grade in both 3.0-T (rs = 0.930; p < 0.001) and 7.0-T (rs = 0.966; p < 0.001) MRA. However, MMVs were visualized significantly better on 7.0-T than on 3.0-T MRA, suggested by both the MMV quality score (p = 0.001) and the MMV area score (p = 0.001). The correlation between the Suzuki's stage and the MMV area score was moderate in 3.0-T MRA (rs = 0.738; p = 0.002) and strong in 7.0-T MRA (rs = 0.908; p < 0.001). Moreover, 7.0-T MR images showed a greater capacity for detecting flow voids in the basal ganglion on both T2-weighted MR images (p < 0.001) and TOF source

  18. Qualitative and quantitative detection of T7 bacteriophages using paper based sandwich ELISA.

    PubMed

    Khan, Mohidus Samad; Pande, Tripti; van de Ven, Theo G M

    2015-08-01

    Viruses cause many infectious diseases and consequently epidemic health threats. Paper based diagnostics and filters can offer attractive options for detecting and deactivating pathogens. However, due to their infectious characteristics, virus detection using paper diagnostics is more challenging compared to the detection of bacteria, enzymes, DNA or antigens. The major objective of this study was to prepare reliable, degradable and low cost paper diagnostics to detect viruses, without using sophisticated optical or microfluidic analytical instruments. T7 bacteriophage was used as a model virus. A paper based sandwich ELISA technique was developed to detect and quantify the T7 phages in solution. The paper based sandwich ELISA detected T7 phage concentrations as low as 100 pfu/mL to as high as 10(9) pfu/mL. The compatibility of paper based sandwich ELISA with the conventional titre count was tested using T7 phage solutions of unknown concentrations. The paper based sandwich ELISA technique is faster and economical compared to the traditional detection techniques. Therefore, with proper calibration and right reagents, and by following the biosafety regulations, the paper based technique can be said to be compatible and economical to the sophisticated laboratory diagnostic techniques applied to detect pathogenic viruses and other microorganisms. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Protein Interactions in T7 DNA Replisome Facilitate DNA Damage Bypass.

    PubMed

    Zou, Zhenyu; Chen, Ze; Xue, Qizhen; Xu, Ying; Xiong, Jingyuan; Yang, Ping; Le, Shuai; Zhang, Huidong

    2018-06-14

    DNA replisome inevitably encounters DNA damage during DNA replication. T7 DNA replisome contains DNA polymerase (gp5), the processivity factor thioredoxin (trx), helicase-primase (gp4), and ssDNA binding protein (gp2.5). T7 protein interactions mediate this DNA replication. However, whether the protein interactions could promote DNA damage bypass is still little addressed. In this study, we investigated the strand-displacement DNA synthesis past 8-oxoG or O6-MeG at the synthetic DNA fork by T7 DNA replisome. DNA damage does not obviously affect the binding affinities among helicase, polymerase, and DNA fork. Relative to unmodified G, both 8-oxoG and O6-MeG, as well as GC-rich template sequence clusters, inhibit the strand-displacement DNA synthesis and produce partial extension products. Relative to gp4 ΔC-tail, gp4 promotes the DNA damage bypass. The presence of gp2.5 further promotes this bypass. Thus, the interactions of polymerase with helicase and ssDNA binidng protein faciliate the DNA damage bypass. Similarly, accessory proteins in other complicated DNA replisomes also facilitate the DNA damage bypass. This work provides the novel mechanism information of DNA damage bypass by DNA replisome. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 7. View to northwest showing (from L to R) ends ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. View to northwest showing (from L to R) ends of 1941 NW wing, original NW ward wing, and original SE ward wing, with ends of Medical Wards C and B (HABS Nos. VA-1287-I and -H) at left - Portsmouth Naval Hospital, Hospital Building, Rixey Place, bounded by Williamson Drive, Holcomb Road, & The Circle, Portsmouth, Portsmouth, VA

  1. Anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract in mice and humans

    PubMed Central

    Kim, Tae-Su; Choi, Ehn-Kyoung; Kim, Jihyun; Shin, Kyungha; Lee, Sung-Pyo; Choi, Youngjin; Jeon, Joseph H.

    2014-01-01

    Helicobacter pylori-eliminating effects of FEMY-R7, composed of fucoidan and evening primrose extract, were investigated in mice and humans. Male C57BL/6 mice were infected with the bacteria by intragastric inoculation (1×109 CFU/mouse) 3 times at 2-day intervals, and simultaneously, orally treated twice a day with 10 or 100 mg/kg FEMY-R7 for 2 weeks. In Campylobcter-like organism-detection test, FEMY-R7 markedly reduced the urease-positive reactivity. In a clinical sudy, human subjects, confirmed to be infected with Helicobacter pylori, were orally administered twice a day with a capsule containing 150 mg FEMY-R7 for 8 weeks. FEMY-R7 significantly decreased both the Delta over baseline-value in urea breath test and the serum pepsinogens I and II levels. The results indicate that FEMY-R7 not only eliminates H. pylori from gastric mucosa of animals and humans, but also improves gastric function. PMID:25324874

  2. Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

    PubMed Central

    Leiva-Salcedo, Elias; Coddou, Claudio; Rodríguez, Felipe E.; Penna, Antonello; Lopez, Ximena; Neira, Tanya; Fernández, Ricardo; Imarai, Mónica; Rios, Miguel; Escobar, Jorge; Montoya, Margarita; Huidobro-Toro, J. Pablo; Escobar, Alejandro; Acuña-Castillo, Claudio

    2011-01-01

    The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance. PMID:21941410

  3. Telomerase Is Involved in IL-7-Mediated Differential Survival of Naive and Memory CD4+ T Cells1

    PubMed Central

    Yang, Yinhua; An, Jie; Weng, Nan-ping

    2008-01-01

    IL-7 plays an essential role in T cell maintenance and survival. The survival effect of IL-7 is thought to be mediated through regulation of Bcl2 family proteins. After a comparative analysis of IL-7-induced growth and cell death of human naive and memory CD4+ T cells, we observed that more memory CD4+ T cells underwent cell division and proceeded to apoptosis than naive cells in response to IL-7. However, IL-7-induced expressions of Bcl2 family members (Bcl2, Bcl-xL, Bax, and Bad) were similar between naive and memory cells. Instead, we found that IL-7 induced higher levels of telomerase activity in naive cells than in memory cells, and the levels of IL-7-induced telomerase activity had a significant inverse correlation with cell death in CD4+ T cells. Furthermore, we showed that reducing expression of telomerase reverse transcriptase and telomerase activity significantly increased cell death of IL-7-cultured CD4+ T cells. Together, these findings demonstrate that telomerase is involved in IL-7-mediated differential survival of naive and memory CD4+ T cells. PMID:18322183

  4. Codon Optimization of the Human Papillomavirus E7 Oncogene Induces a CD8+ T Cell Response to a Cryptic Epitope Not Harbored by Wild-Type E7

    PubMed Central

    Lorenz, Felix K. M.; Wilde, Susanne; Voigt, Katrin; Kieback, Elisa; Mosetter, Barbara; Schendel, Dolores J.; Uckert, Wolfgang

    2015-01-01

    Codon optimization of nucleotide sequences is a widely used method to achieve high levels of transgene expression for basic and clinical research. Until now, immunological side effects have not been described. To trigger T cell responses against human papillomavirus, we incubated T cells with dendritic cells that were pulsed with RNA encoding the codon-optimized E7 oncogene. All T cell receptors isolated from responding T cell clones recognized target cells expressing the codon-optimized E7 gene but not the wild type E7 sequence. Epitope mapping revealed recognition of a cryptic epitope from the +3 alternative reading frame of codon-optimized E7, which is not encoded by the wild type E7 sequence. The introduction of a stop codon into the +3 alternative reading frame protected the transgene product from recognition by T cell receptor gene-modified T cells. This is the first experimental study demonstrating that codon optimization can render a transgene artificially immunogenic through generation of a dominant cryptic epitope. This finding may be of great importance for the clinical field of gene therapy to avoid rejection of gene-corrected cells and for the design of DNA- and RNA-based vaccines, where codon optimization may artificially add a strong immunogenic component to the vaccine. PMID:25799237

  5. Rapid desensitization of the rat α7 nAChR is facilitated by the presence of a proline residue in the outer β-sheet

    PubMed Central

    McCormack, Thomas J; Melis, Claudio; Colón, José; Gay, Elaine A; Mike, Arpad; Karoly, Robert; Lamb, Patricia W; Molteni, Carla; Yakel, Jerrel L

    2010-01-01

    The rat α7 nicotinic acetylcholine receptor (nAChR) has a proline residue near the middle of the β9 strand. The replacement of this proline residue at position 180 (P180) by either threonine (α7-P180T) or serine (α7-P180S) slowed the onset of desensitization dramatically, with half-times of ∼930 and 700 ms, respectively, compared to 90 ms for the wild-type receptor. To investigate the importance of the hydroxyl group on the position 180 side-chains, the mutant receptors α7-P180Y and α7-P180F were studied and showed half-times of desensitization of 650 and 160 ms, respectively. While a position 180 side-chain OH group may contribute to the slow desensitization rates, α7-P180S and α7-P180V resulted in receptors with similar desensitization rates, suggesting that increased backbone to backbone H bonding expected in the absence of proline at position 180 would likely exert a great effect on desensitization. Single channel recordings indicated that for the α7-P180T receptor there was a significantly reduced closed time without any change in single channel conductance (as compared to wild-type). Kinetic simulations indicated that all changes observed for the mutant channel behaviour were reproduced by decreasing the rate of desensitization, and increasing the microscopic affinity to resting receptors. Molecular dynamics (MD) simulations on a homology model were used to provide insight into likely H bond interactions within the outer β-sheet that occur when the P180 residue is mutated. All mutations analysed increased about twofold the predicted number of H bonds between the residue at position 180 and the backbone of the β10 strand. Moreover, the α7-P180T and α7-P180S mutations also formed some intrastrand H bonds along the β9 strand, although H bonding of the OH groups of the threonine or serine side-chains was predicted to be infrequent. Our results indicate that rapid desensitization of the wild-type rat α7 nAChR is facilitated by the presence of the

  6. Rapid desensitization of the rat α7 nAChR is facilitated by the presence of a proline residue in the outer β-sheet.

    PubMed

    McCormack, Thomas J; Melis, Claudio; Colón, José; Gay, Elaine A; Mike, Arpad; Karoly, Robert; Lamb, Patricia W; Molteni, Carla; Yakel, Jerrel L

    2010-11-15

    The rat α7 nicotinic acetylcholine receptor (nAChR) has a proline residue near the middle of the β9 strand. The replacement of this proline residue at position 180 (P180) by either threonine (α7-P180T) or serine (α7-P180S) slowed the onset of desensitization dramatically, with half-times of ~930 and 700 ms, respectively, compared to 90 ms for the wild-type receptor. To investigate the importance of the hydroxyl group on the position 180 side-chains, the mutant receptors α7-P180Y and α7-P180F were studied and showed half-times of desensitization of 650 and 160 ms, respectively. While a position 180 side-chain OH group may contribute to the slow desensitization rates, α7-P180S and α7-P180V resulted in receptors with similar desensitization rates, suggesting that increased backbone to backbone H bonding expected in the absence of proline at position 180 would likely exert a great effect on desensitization. Single channel recordings indicated that for the α7-P180T receptor there was a significantly reduced closed time without any change in single channel conductance (as compared to wild-type). Kinetic simulations indicated that all changes observed for the mutant channel behaviour were reproduced by decreasing the rate of desensitization, and increasing the microscopic affinity to resting receptors. Molecular dynamics (MD) simulations on a homology model were used to provide insight into likely H bond interactions within the outer β-sheet that occur when the P180 residue is mutated. All mutations analysed increased about twofold the predicted number of H bonds between the residue at position 180 and the backbone of the β10 strand. Moreover, the α7-P180T and α7-P180S mutations also formed some intrastrand H bonds along the β9 strand, although H bonding of the OH groups of the threonine or serine side-chains was predicted to be infrequent. Our results indicate that rapid desensitization of the wild-type rat α7 nAChR is facilitated by the presence of the

  7. α7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile-Duct Ligated Mice.

    PubMed

    Ehrlich, Laurent; O'Brien, April; Hall, Chad; White, Tori; Chen, Lixian; Wu, Nan; Venter, Julie; Scrushy, Marinda; Mubarak, Muhammad; Meng, Fanyin; Dostal, David; Wu, Chaodong; Lairmore, Terry C; Alpini, Gianfranco; Glaser, Shannon

    2018-03-26

    α7-nAChR is a nicotinic acetylcholine receptor (specifically expressed on hepatic stellate cells, Kupffer cells, and cholangiocytes) that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile-duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile-duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess co-localization of α7-nAChR with bile ducts (co-stained with CK-19) and hepatic stellate cells (HSCs) (co-stained with desmin). The mRNA expression of α7-nAChR, Ki67/PCNA (proliferation), fibrosis genes (TGF-β1, Fibronectin-1, Col1α1, and α-SMA), and inflammatory markers (IL-6, IL-1β, and TNFα) was measured by real-time PCR. Biliary TGF-β1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. α7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. α7-nAChR-/- BDL mice exhibited decreased: (i) bile duct mass, liver fibrosis, and inflammation; and (ii) immunoreactivity of TGF-1 as well as expression of fibrosis genes compared to WT BDL mice. α7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extra-hepatic biliary obstruction.

  8. Optimized cartilage visualization using 7-T sodium ((23)Na) imaging after patella dislocation.

    PubMed

    Widhalm, Harald K; Apprich, Sebastian; Welsch, Goetz H; Zbyn, Stefan; Sadoghi, Patrick; Vekszler, György; Hamböck, Martina; Weber, Michael; Hajdu, Stefan; Trattnig, Siegfried

    2016-05-01

    Retropatellar cartilage lesions often occur in the course of recurrent patella dislocation. Aim of this study was to develop a more detailed method for examining cartilage tissue, in order to reduce patient discomfort and time of care. For detailed diagnosing, a 7-T MRI of the knee joint and patella was performed in nine patients, with mean age of 26.4 years, after patella dislocation to measure the cartilage content in three different regions of interest of the patella. Axial sodium ((23)Na) images were derived from an optimized 3D GRE sequence on a 7-T MR scanner. Morphological cartilage grading was performed, and sodium signal-to-noise ratio (SNR) values were calculated. Mean global sodium values and SNR were compared between patients and volunteers. Two out of nine patients showed a maximum cartilage defect of International Cartilage Repair Society (ICRS) grade 3, three of grade 2, three of  grade 1, and one patient showed no cartilage defect. The mean SNR in sodium images for cartilage was 13.4 ± 2.5 in patients and 14.6 ± 3.7 in volunteers (n.s.). A significant negative correlation between age and global sodium SNR for cartilage was found in the medial facet (R = -0.512; R (2) = 0.26; p = 0.030). Mixed-model ANOVA yielded a marked decrease of the sodium SNR, with increasing grade of cartilage lesions (p < 0.001). Utilization of the (23)Na MR imaging will make earlier detection of alterations to the patella cartilage after dislocation possible and will help prevent subsequent disease due to start adequate therapy earlier in the rehabilitation process. II.

  9. Electronic and optical properties of La-doped S r3I r2O7 epitaxial thin films

    NASA Astrophysics Data System (ADS)

    Souri, M.; Terzic, J.; Johnson, J. M.; Connell, J. G.; Gruenewald, J. H.; Thompson, J.; Brill, J. W.; Hwang, J.; Cao, G.; Seo, A.

    2018-02-01

    We have investigated structural, transport, and optical properties of tensile strained (Sr1-xL ax ) 3I r2O7 (x =0 , 0.025, 0.05) epitaxial thin films. While high-Tc superconductivity is predicted theoretically in the system, we have observed that all of the samples remain insulating with finite optical gap energies and Mott variable-range hopping characteristics in transport. Cross-sectional scanning transmission electron microscopy indicates that structural defects such as stacking faults appear in this system. The insulating behavior of the La-doped S r3I r2O7 thin films is presumably due to disorder-induced localization and ineffective electron doping of La, which brings to light the intriguing difference between epitaxial thin films and bulk single crystals of the iridates.

  10. High-resolution T2-weighted cervical cancer imaging: a feasibility study on ultra-high-field 7.0-T MRI with an endorectal monopole antenna.

    PubMed

    Hoogendam, Jacob P; Kalleveen, Irene M L; de Castro, Catalina S Arteaga; Raaijmakers, Alexander J E; Verheijen, René H M; van den Bosch, Maurice A A J; Klomp, Dennis W J; Zweemer, Ronald P; Veldhuis, Wouter B

    2017-03-01

    We studied the feasibility of high-resolution T 2 -weighted cervical cancer imaging on an ultra-high-field 7.0-T magnetic resonance imaging (MRI) system using an endorectal antenna of 4.7-mm thickness. A feasibility study on 20 stage IB1-IIB cervical cancer patients was conducted. All underwent pre-treatment 1.5-T MRI. At 7.0-T MRI, an external transmit/receive array with seven dipole antennae and a single endorectal monopole receive antenna were used. Discomfort levels were assessed. Following individualised phase-based B 1 + shimming, T 2 -weighted turbo spin echo sequences were completed. Patients had stage IB1 (n = 9), IB2 (n = 4), IIA1 (n = 1) or IIB (n = 6) cervical cancer. Discomfort (ten-point scale) was minimal at placement and removal of the endorectal antenna with a median score of 1 (range, 0-5) and 0 (range, 0-2) respectively. Its use did not result in adverse events or pre-term session discontinuation. To demonstrate feasibility, T 2 -weighted acquisitions from 7.0-T MRI are presented in comparison to 1.5-T MRI. Artefacts on 7.0-T MRI were due to motion, locally destructive B 1 interference, excessive B 1 under the external antennae and SENSE reconstruction. High-resolution T 2 -weighted 7.0-T MRI of stage IB1-IIB cervical cancer is feasible. The addition of an endorectal antenna is well tolerated by patients. • High resolution T 2 -weighted 7.0-T MRI of the inner female pelvis is challenging • We demonstrate a feasible approach for T 2 -weighted 7.0-T MRI of cervical cancer • An endorectal monopole receive antenna is well tolerated by participants • The endorectal antenna did not lead to adverse events or session discontinuation.

  11. Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

    PubMed Central

    Di Giovangiulio, Martina; Bosmans, Goele; Meroni, Elisa; Stakenborg, Nathalie; Florens, Morgane; Farro, Giovanna; Gomez-Pinilla, Pedro J; Matteoli, Gianluca; Boeckxstaens, Guy E

    2016-01-01

    Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR-/- mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in the lamina propria and mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR-/- mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR. PMID:27341335

  12. Epidémiologie et prise en charge des infections du per-partum à la maternité du centre hospitalier départemental de l'Ouémé-Plateau au Bénin

    PubMed Central

    Saizonou, Jacques; Ouédraogo, Laurent; Paraiso, Moussiliou Noël; Ayélo, Paul; Kpozèhouen, Alphonse; Daraté, René; Traoré, Esther

    2014-01-01

    Introduction La présente étude avait pour objectif de mesurer l'ampleur des infections du per-partum à la maternité du Centre Hospitalier Départemental de l'Ouémé-Plateau d'analyser les conditions de survenue et de prise en charge dans la perspective de l'amélioration des soins et services maternels et néonataux. Méthodes Une étude descriptive et analytique a été conduite de Août 2009 à Février 2010 et a impliqué 110 mères victimes d'infections du per-partum; elles ont été soumises à un questionnaire durant tout leur séjour hospitalier; des observations des pratiques de prise en charge des prestataires de soins ont été menées et des registres et autres supports de données sanitaires ont été exploités. L'analyse des données a été effectuée à l'aide du logiciel Epi Info 6.4 dans sa version française. Résultats L'incidence des infections du per-partum était de 5,9 pour 100 accouchements (110/ 1875); les types d'infections les plus incriminés étaient les endométrites (27,3%), les chorioamniotites (18,2%), les infections du site opératoire (12,7%) et les infections urinaires (2,7%). Les examens cliniques ont été relativement acceptables. En revanche, les examens biologiques ont été très insuffisants expliquant l'imprécision importante au niveau des diagnostics. L'antibiothérapie a été instaurée systématiquement. Le taux de mortinaissance était de 25,6% et les enfants de petit poids représentaient 23,2%. Conclusion L'incidence des infections du per-partum dans la présente étude était assez élevée. Des efforts de préventions et de dépistage de ces infections sont nécessaire afin d'améliorer la qualité des soins PMID:25120854

  13. Structures and phase transitions of the A7PSe6 (A = ag, Cu) argyrodite-type ionic conductors. III. alpha-Cu7PSe6

    PubMed

    Gaudin; Petricek; Boucher; Taulelle; Evain

    2000-12-01

    The crystal structure of the third polymorph of the Cu(7)PSe(6) argyrodite compound, alpha-Cu(7)PSe(6), heptacopper phosphorus hexaselenide, is determined by means of single-crystal diffraction from twinned crystals and X-ray powder diffraction, with the help of extensive NMR measurements. In the low-temperature form, i.e. below the last phase transition, alpha-Cu(7)PSe(6) crystallizes in orthorhombic symmetry, space group Pna2(1), with a = 14.3179 (4), b = 7.1112 (2), c = 10.1023 (3) A, V = 1028.590 (9) A(3) (deduced from powder data, T = 173 K) and Z = 4. Taking into account a twinning by reticular merohedry, the refinement of the alpha-Cu(7)PSe(6) structure leads to the residual factors R = 0.0466 and wR = 0.0486 for 127 parameters and 3714 observed, independent reflections (single-crystal data, T = 173 K). A full localization of the Cu(+)d(10) element is reached with one twofold-, one threefold- and five fourfold-coordinated Cu atoms. The observation of two phase transitions for Cu(7)PSe(6), to be compared with only one for Ag(7)PSe(6), is attributed to the d(10) element stability in a low coordination environment, copper being less prone to lower coordination sites than silver, especially at low temperature.

  14. Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p.

    PubMed

    Huang, Xiaojing; Zhu, Hongwen; Gao, Zemin; Li, Junzun; Zhuang, Junlong; Dong, Yu; Shen, Bing; Li, Meiqian; Zhou, Hu; Guo, Hongqian; Huang, Ruimin; Yan, Jun

    2018-05-04

    Once urinary bladder cancer (UBC) develops into muscle-invasive bladder cancer, its mortality rate increases dramatically. However, the molecular mechanisms of UBC invasion and metastasis remain largely unknown. Herein, using 5637 UBC cells, we generated two sublines with low (5637 NMI) and high (5637 HMI) invasive capabilities. Mass spectrum analyses revealed that the Wnt family protein Wnt7a is more highly expressed in 5637 HMI cells than in 5637 NMI cells. We also found that increased Wnt7a expression is associated with UBC metastasis and predicted worse clinical outcome in UBC patients. Wnt7a depletion in 5637 HMI and T24 cells reduced UBC cell invasion and decreased levels of active β-catenin and its downstream target genes involved in the epithelial-to-mesenchymal transition (EMT) and extracellular matrix (ECM) degradation. Consistently, treating 5637 NMI and J82 cells with recombinant Wnt7a induced cell invasion, EMT, and expression of ECM degradation-associated genes. Moreover, TOP/FOPflash luciferase assays indicated that Wnt7a activated canonical β-catenin signaling in UBC cells, and increased Wnt7a expression was associated with nuclear β-catenin in UBC samples. Wnt7a ablation suppressed matrix metalloproteinase 10 (MMP10) expression, and Wnt7a overexpression increased MMP10 promoter activity through two TCF/LEF promoter sites, confirming that Wnt7a-mediated MMP10 activation is mediated by the canonical Wnt/β-catenin pathway. Of note, the microRNA miR-370-3p directly repressed Wnt7a expression and thereby suppressed UBC cell invasion, which was partially restored by Wnt7a overexpression. Our results have identified an miR-370-3p/Wnt7a axis that controls UBC invasion through canonical Wnt/β-catenin signaling, which may offer prognostic and therapeutic opportunities. © 2018 Huang et al.

  15. Bypass of a Nick by the Replisome of Bacteriophage T7*

    PubMed Central

    Zhu, Bin; Lee, Seung-Joo; Richardson, Charles C.

    2011-01-01

    DNA polymerase and DNA helicase are essential components of DNA replication. The helicase unwinds duplex DNA to provide single-stranded templates for DNA synthesis by the DNA polymerase. In bacteriophage T7, movement of either the DNA helicase or the DNA polymerase alone terminates upon encountering a nick in duplex DNA. Using a minicircular DNA, we show that the helicase·polymerase complex can bypass a nick, albeit at reduced efficiency of 7%, on the non-template strand to continue rolling circle DNA synthesis. A gap in the non-template strand cannot be bypassed. The efficiency of bypass synthesis depends on the DNA sequence downstream of the nick. A nick on the template strand cannot be bypassed. Addition of T7 single-stranded DNA-binding protein to the complex stimulates nick bypass 2-fold. We propose that the association of helicase with the polymerase prevents dissociation of the helicase upon encountering a nick, allowing the helicase to continue unwinding of the duplex downstream of the nick. PMID:21701044

  16. DNA damage under simulated extraterrestrial conditions in bacteriophage T7

    NASA Astrophysics Data System (ADS)

    Fekete, A.; Kovács, G.; Hegedüs, M.; Módos, K.; Rontó, Gy.; Lammer, H.; Panitz, C.

    The experiment ``Phage and uracil response'' (PUR) will be accommodated in the EXPOSE facility of the ISS aiming to examine and quantify the effect of specific space conditions on bacteriophage T7 and isolated T7 DNA thin films. To achieve this new method was elaborated for the preparation of DNA and nucleoprotein thin films (1). During the EXPOSE Experiment Verification Tests (EVT) the samples were exposed to vacuum (10 -6 Pa), to monochromatic (254 nm) and polychromatic (200-400 nm) UV radiation in air as well in simulated space vacuum. Using neutral density (ND) filters dose-effect curves were performed in order to define the maximum doses tolerated, and we also studied the effect of temperature in vacuum as well as the influence of temperature fluctuations. We obtained substantial evidence that DNA lesions (e.g. strand breaks, DNA-protein cross-links, DNA-DNA cross-links) accumulate throughout exposure. DNA damage was determined by quantitative PCR using 555 bp and 3826 bp fragments of T7 DNA (2) and by neutral and alkaline agarose gel electrophoresis; the structural/chemical effects were analyzed by spectroscopic and microscopical methods. Characteristic changes in the absorption spectrum, in the electrophoretic pattern of DNA and the decrease of the amount of the PCR products have been detected indicating the damage of isolated and intraphage DNA. Preliminary results suggest a synergistic action of space vacuum and UV radiation with DNA being the critical target. Fekete et al. J. Luminescence 102-103, 469-475, 2003 Hegedüs et al. Photochem. Photobiol. 78, 213-219, 2003

  17. Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

    PubMed Central

    Moaddel, Ruin; Abdrakhmanova, Galia; Kozak, Joanna; Jozwiak, Krzysztof; Toll, Lawrence; Jimenez, Lucita; Rosenberg, Avraham; Tran, Thao; Xiao, Yingxian; Zarate, Carlos A.; Wainer, Irving W.

    2012-01-01

    The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)- hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC50 = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤1μM, while (R,S)-ketamine was inactive at these concentrations. The inhibitory effect of (R,S)-dehydronorketamine was voltage-independent and the compound did not competitively displace selective α7-nicotinic acetylcholine receptor ligands [125I]-α-bungarotoxin and [3H]-epibatidine indicating that (R,S)-dehydronorketamine is a negative allosteric modulator of the α7-nicotinic acetylcholine receptor. (R,S)-Ketamine and (R,S)-norketamine inhibited (S)-nicotine-induced whole-cell currents in cells expressing α3β4-nicotinic acetylcholine receptor, IC50 3.1 and 9.1μM, respectively, while (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine were weak inhibitors, IC50 >100μM. The binding affinities of (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine at the NMDA receptor were also determined using rat brain membranes and the selective NMDA receptor antagonist [3H]-MK-801. The calculated Ki values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and > 100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug. PMID:23183107

  18. Crystal structure and absolute configuration of (3aR,3′aR,7aS,7′aS)-2,2,2′,2′-tetra­methyl-3a,6,7,7a,3′a,6′,7′,7′a-octa­hydro-4,4′-bi[1,3-benzodioxol­yl], obtained from a Pd-catalyzed homocoupling reaction

    PubMed Central

    Macías, Mario A.; Pandolfi, Enrique; Schapiro, Valeria; Silveira, Gustavo P.; Vilela, Guilherme D.; Suescun, Leopoldo

    2017-01-01

    The absolute configuration, i.e. (3aR,3′aR,7aS,7′aS), of the title compound, C18H26O4, synthesized via a palladium-catalyzed homocoupling reaction, was determined on the basis of the synthetic pathway and was confirmed by X-ray diffraction. The homocoupled mol­ecule is formed by two chemically identical moieties built up from two five- and six-membered fused rings. The supra­molecular assembly is controlled mainly by C—H⋯O inter­actions that lead to the formation of hydrogen-bonded chains of mol­ecules along the [001] direction, while weak dipolar inter­actions and van der Waals forces hold the chains together in the crystal structure. PMID:28083142

  19. Computation, prediction, and experimental tests of fitness for bacteriophage T7 mutants with permuted genomes

    NASA Astrophysics Data System (ADS)

    Endy, Drew; You, Lingchong; Yin, John; Molineux, Ian J.

    2000-05-01

    We created a simulation based on experimental data from bacteriophage T7 that computes the developmental cycle of the wild-type phage and also of mutants that have an altered genome order. We used the simulation to compute the fitness of more than 105 mutants. We tested these computations by constructing and experimentally characterizing T7 mutants in which we repositioned gene 1, coding for T7 RNA polymerase. Computed protein synthesis rates for ectopic gene 1 strains were in moderate agreement with observed rates. Computed phage-doubling rates were close to observations for two of four strains, but significantly overestimated those of the other two. Computations indicate that the genome organization of wild-type T7 is nearly optimal for growth: only 2.8% of random genome permutations were computed to grow faster, the highest 31% faster, than wild type. Specific discrepancies between computations and observations suggest that a better understanding of the translation efficiency of individual mRNAs and the functions of qualitatively "nonessential" genes will be needed to improve the T7 simulation. In silico representations of biological systems can serve to assess and advance our understanding of the underlying biology. Iteration between computation, prediction, and observation should increase the rate at which biological hypotheses are formulated and tested.

  20. Experimental and Theoretical Approaches To Investigate the Immunogenicity of Taenia solium-Derived KE7 Antigen

    PubMed Central

    Bobes, Raúl J.; Navarrete-Perea, José; Ochoa-Leyva, Adrián; Anaya, Víctor Hugo; Hernández, Marisela; Cervantes-Torres, Jacquelynne; Estrada, Karel; Sánchez-Lopez, Filiberto; Soberón, Xavier; Rosas, Gabriela; Nunes, Cáris Maroni; García-Varela, Martín; Sotelo-Mundo, Rogerio Rafael; López-Zavala, Alonso Alexis; Gevorkian, Goar; Acero, Gonzalo; Laclette, Juan P.; Fragoso, Gladis

    2017-01-01

    ABSTRACT Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps. Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways. The aim of this study was to identify the T. solium KE7 (TsKE7) full-length protein and to determine its immunogenic properties. Recombinant TsKE7 (rTsKE7) was expressed in Escherichia coli Rosetta2 cells and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from T. solium cyst vesicular fluid in a mass spectrometry-coupled immune proteomic analysis. These antibodies were then used to screen a phage-displayed 7-random-peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides, with the consensus motif Y(F/Y)PS sequence, which includes YYYPS (named GK-1M, for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of serum samples from cysticercotic pigs with 100% specificity but induced weak protection against murine cysticercosis. In silico analysis revealed a universal T-cell epitope(s) in native TsKE7 potentially capable of stimulating cytotoxic T lymphocytes and helper T lymphocytes under different major histocompatibility complex class I and class II mouse haplotypes. Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines. PMID:28923896

  1. Effet paradoxal du type d’excision sur la prise et le délai de cicatrisation des greffes expansées pour le traitement des brûlures aiguës: a propos de 1129 cas

    PubMed Central

    Guibert, M.; Chaouat, M.; Boccara, D.; Marco, O.; Lavocat, R.; Alameri, O.; Deslandes, E.; Montlahuc, C.; Mimoun, M.

    2016-01-01

    Summary La greffe de peau mince expansée est très employée dans le traitement des brûlures aiguës. Nous avons étudié l’influence de la préparation du sous-sol sur le taux de prise et le délai de cicatrisation des greffes expansées. Nous avons analysé rétrospectivement les 1 129 greffes expansées réalisées dans notre service entre 1995 et 2005 pour le traitement des brûlures aiguës. Leur taux de prise a été significativement meilleur après une préparation du sous-sol par avulsion (82%) par rapport à une préparation du sous-sol par excision tangentielle (75%). Ce taux était meilleur lorsque l’avulsion était pratiquée dans les 7 jours suivant la brûlure (83% vs 73%). Pour une prise en charge entre 7 et 21 jours, ce taux a semblé être meilleur après excision tangentielle, mais de façon non significative. La durée d’évolution jusqu’à cicatrisation était significativement raccourcie pour une préparation du sous-sol par excision tangentielle par rapport à une préparation du sous-sol par avulsion. Ces résultats montrent, paradoxalement, qu’une préparation du sous-sol par avulsion favorise la prise des greffes expansées mais rallonge leur délai de cicatrisation au contraire de l’excision tangentielle. PMID:28149235

  2. Quantification of M13 and T7 bacteriophages by TaqMan and SYBR green qPCR.

    PubMed

    Peng, Xiujuan; Nguyen, Alex; Ghosh, Debadyuti

    2018-02-01

    TaqMan and SYBR Green quantitative PCR (qPCR) methods were developed as DNA-based approaches to reproducibly enumerate M13 and T7 phages from phage display selection experiments individually and simultaneously. The genome copies of M13 and T7 phages were quantified by TaqMan or SYBR Green qPCR referenced against M13 and T7 DNA standard curves of known concentrations. TaqMan qPCR was capable of quantifying M13 and T7 phage DNA simultaneously with a detection range of 2.75*10 1 -2.75*10 8 genome copies(gc)/μL and 2.66*10 1 -2.66*10 8 genome copies(gc)/μL respectively. TaqMan qPCR demonstrated an efficient amplification efficiency (E s ) of 0.97 and 0.90 for M13 and T7 phage DNA, respectively. SYBR Green qPCR was ten-fold more sensitive than TaqMan qPCR, able to quantify 2.75-2.75*10 7 gc/μL and 2.66*10 1 -2.66*10 7 gc/μL of M13 and T7 phage DNA, with an amplification efficiency E s of 1.06 and 0.78, respectively. Due to its superior sensitivity, SYBR Green qPCR was used to enumerate M13 and T7 phage display clones selected against a cell line, and quantified titers demonstrated accuracy comparable to titers from traditional double-layer plaque assay. Compared to enzyme linked immunosorbent assay, both qPCR methods exhibited increased detection sensitivity and reproducibility. These qPCR methods are reproducible, sensitive, and time-saving to determine their titers and to quantify a large number of phage samples individually or simultaneously, thus avoiding the need for time-intensive double-layer plaque assay. These findings highlight the attractiveness of qPCR for phage enumeration for applications ranging from selection to next-generation sequencing (NGS). Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Étude ethnobotanique des plantes utilisées dans le traitement du diabète dans la médecine traditionnelle de la région Maritime du Togo

    PubMed Central

    Holaly, Gbekley Efui; Simplice, Karou Damintoti; Charlemagne, Gnoula; Kodjovi, Agbodeka; Kokou, Anani; Tchadjobo, Tchacondo; Amegnona, Agbonon; Komlan, Batawila; Jacques, Simpore

    2015-01-01

    Introduction Les plantes constituent une grande source de principes actifs qui peuvent être utilisés pour traiter de nombreuses maladies, dont le diabète. L'objectif de cette étude était de recenser les plantes utilisées en médecine traditionnelle pour traiter le diabète dans la région Maritime du Togo. Méthodes De janvier 2013 à juin 2014, une enquête ethnobotanique a été réalisée auprès de 164 guérisseurs traditionnels dans la région Maritime par des interviews directes à l'aide d'un questionnaire semi structuré. Résultats Les données recueillies ont permis d'identifier 112 espèces végétales appartenant à 51 familles. Les familles les plus représentées ont été les Caesalpiniaceae / Fabaceae avec 9 espèces, suivie des Euphorbiaceae et des Compositae avec 8 espèces chacune. Les espèces les plus citées ont été Allium sativum, Alium cepa, Guilandina bonduc, Moringa oleifera et de Picralima nitida qui ont eu une valeur usuelle de 0,05. En termes de recettes, 132 recettes sont préparées à partir des 112 espèces de plantes. Les recettes à plantes uniques ont été au nombre de 78, tandis que 54 recettes sont obtenues par des associations de plantes. Les parties de plantes les plus utilisées ont été les feuilles suivies par les racines. La principale méthode de préparation reste la décoction. Conclusion La région maritime du Togo dispose d'une biodiversité floristique importante en matière de plantes antidiabétiques. Ces résultats constituent une bonne base de données pour le criblage biologique dans la recherche de molécules antidiabétiques à base des plantes. PMID:26309469

  4. Subjective perception of safety in healthy individuals working with 7 T MRI scanners: a retrospective multicenter survey.

    PubMed

    Fatahi, Mahsa; Demenescu, Liliana Ramona; Speck, Oliver

    2016-06-01

    To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla (T) magnetic resonance imaging (MRI) scanners. A total of 66 healthy individuals with a mean age of 31 ± 7 years participated in this retrospective multicentre survey study. Nonparametric correlation analysis was conducted to evaluate the relation between self-reported perception of safety and prevalence of sensory effects while working with 7 T MRI scanners for an average 47 months. The results indicated that 98.5 % of the study participants had a neutral or positive feeling about safety aspects at 7 T MRI scanners. 45.5 % reported that they feel very safe and none of the participants stated that they feel moderately or very unsafe while working with 7 T MRI scanners. Perception of safety was not affected by the number of hours per week spent in the vicinity of the 7 T MRI scanner or the duration of experience with 7 T MRI. More than 50 % of individuals experienced vertigo and metallic taste while working with 7 T MRI scanners. However, participants' perceptions of safety were not affected by the prevalence of MR-related symptoms. The overall data indicated an average perception of a moderately safe work environment. To our knowledge, this study delineates the first attempt to assess the subjective safety perception among 7 T MRI workers and suggests further investigations are indicated.

  5. Long-range magnetic order in the Heisenberg pyrochlore antiferromagnets G d2G e2O7 and G d2P t2O7 synthesized under high pressure

    NASA Astrophysics Data System (ADS)

    Li, X.; Cai, Y. Q.; Cui, Q.; Lin, C. J.; Dun, Z. L.; Matsubayashi, K.; Uwatoko, Y.; Sato, Y.; Kawae, T.; Lv, S. J.; Jin, C. Q.; Zhou, J.-S.; Goodenough, J. B.; Zhou, H. D.; Cheng, J.-G.

    2016-12-01

    G d2S n2O7 and G d2T i2O7 have been regarded as good experimental realizations of the classical Heisenberg pyrochlore antiferromagnet with dipolar interaction. The former was found to adopt the Palmer-Chalker state via a single, first-order transition at TN≈1 K , while the latter enters a distinct, partially ordered state through two successive transitions at TN 1≈1 K and TN 2= 0.75 K . To shed more light on their distinct magnetic ground states, we have synthesized two more gadolinium-based pyrochlore oxides, G d2G e2O7 and G d2P t2O7 , under high-pressure conditions and performed detailed characterizations via x-ray powder diffraction, dc and ac magnetic susceptibility, and specific heat measurements down to 100 mK. We found that both compounds enter a long-range antiferromagnetically ordered state through a single, first-order transition at TN= 1.4 K for G d2G e2O7 and TN= 1.56 K for G d2P t2O7 , with the specific heat anomaly similar to that of G d2S n2O7 rather than G d2T i2O7 . Interestingly, the low-temperature magnetic specific heat values of both G d2G e2O7 and G d2P t2O7 were found to follow nicely the T3 dependence as expected for a three-dimensional antiferromagnet with gapless spin-wave excitations. We have rationalized the enhancement of TN in terms of the reduced Gd-Gd distances for the chemically pressurized G d2G e2O7 and the addition of extra superexchange pathways through the empty Pt -eg orbitals for G d2P t2O7 . Our current study has expanded the family of gadolinium-based pyrochlores and permits us to achieve a better understanding of their distinct magnetic properties in a more comprehensive perspective.

  6. The 5.5 protein of phage T7 inhibits H-NS through interactions with the central oligomerization domain.

    PubMed

    Ali, Sabrina S; Beckett, Emily; Bae, Sandy Jeehoon; Navarre, William Wiley

    2011-09-01

    The 5.5 protein (T7p32) of coliphage T7 (5.5(T7)) was shown to bind and inhibit gene silencing by the nucleoid-associated protein H-NS, but the mechanism by which it acts was not understood. The 5.5(T7) protein is insoluble when expressed in Escherichia coli, but we find that 5.5(T7) can be isolated in a soluble form when coexpressed with a truncated version of H-NS followed by subsequent disruption of the complex during anion-exchange chromatography. Association studies reveal that 5.5(T7) binds a region of H-NS (residues 60 to 80) recently found to contain a distinct domain necessary for higher-order H-NS oligomerization. Accordingly, we find that purified 5.5(T7) can disrupt higher-order H-NS-DNA complexes in vitro but does not abolish DNA binding by H-NS per se. Homologues of the 5.5(T7) protein are found exclusively among members of the Autographivirinae that infect enteric bacteria, and despite fairly low sequence conservation, the H-NS binding properties of these proteins are largely conserved. Unexpectedly, we find that the 5.5(T7) protein copurifies with heterogeneous low-molecular-weight RNA, likely tRNA, through several chromatography steps and that this interaction does not require the DNA binding domain of H-NS. The 5.5 proteins utilize a previously undescribed mechanism of H-NS antagonism that further highlights the critical importance that higher-order oligomerization plays in H-NS-mediated gene repression. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

  7. Design and Simulation of a Birdcage Coil using CST Studio Suite for Application at 7T

    NASA Astrophysics Data System (ADS)

    Palau Tomas, Bernat; Li, Houmin; Anjum, M. R.

    2013-12-01

    This work describes the study of coils for Magnetic Resonance Imaging (MRI) applications. The principal objective is the design of a birdcage Radio Frequency (RF) coil to use in a 7 Tesla (7T) scanner. Higher strength field generates a better SNR and increased chemical shift effect, improving spectral fat suppression and spectroscopy. Moreover, a better SNR increases the spatial resolution or reduces the imaging time. This research work presented recent developments based on high field 7T design using CST studio. The birdcage coil achieves circular polarization and generates a high homogeneous radio frequency magnetic field under many conditions. Design of a Birdcage coil for a 7T to obtain the images from s mall animals (i.e. mouse). It opens the door to design and construct a Birdcage coil for a 7T to obtain human brain images. Firstly we design a birdcage coil then the results are obtained with simulator CST Wave Studio, creating a 3D model and generating a simulation. Finally the parameters are re adjusted to obtain our desired Larmor frequency 298.2 MHz for a correct operation in 7T. This research work demonstrates the theoretical results from our design and shows the designed antenna behavior.

  8. Autoimmune manifestations in SCID due to IL7R mutations: Omenn syndrome and cytopenias.

    PubMed

    Zago, Claudia Augusta; Jacob, Cristina Miuki Abe; de Albuquerque Diniz, Edna Maria; Lovisolo, Silvana Maria; Zerbini, Maria Claudia Nogueira; Dorna, Mayra; Watanabe, Letícia; Fernandes, Juliana Folloni; Rocha, Vanderson; Oliveira, João Bosco; Carneiro-Sampaio, Magda

    2014-07-01

    B+NK+SCID (severe combined immunodeficiency) due to IL7Rα deficiency represents approximately 10% of American SCID cases. To better understand the spectrum of autoimmune disorders associated with IL7Rα deficiency, we describe two unrelated IL7Rα-deficient female SCID infants whose clinical picture was dominated by autoimmune manifestations: one with intrauterine Omenn syndrome (OS) and another with persistent thrombocytopenic purpura since 4months of age. The OS baby harbored a homozygous p.C118Y mutation in IL7R. She presented dense eosinophilic infiltrates in several organs, including pancarditis, which may have contributed to her death (on the 2nd day of life). B cells were observed in lymph nodes, spleen, bone marrow and thymus. The second patient harbored compound heterozygous p.C118Y and p.I121NfsX8 mutations. She underwent a successful unrelated cord blood transplant. In conclusion, early OS can be observed in patients with IL7R mutations, and autoimmune cytopenias could also complicate the clinical course of SCID babies with this type of defect. Copyright © 2014. Published by Elsevier Inc.

  9. Inherited pain: sodium channel Nav1.7 A1632T mutation causes erythromelalgia due to a shift of fast inactivation.

    PubMed

    Eberhardt, Mirjam; Nakajima, Julika; Klinger, Alexandra B; Neacsu, Cristian; Hühne, Kathrin; O'Reilly, Andrias O; Kist, Andreas M; Lampe, Anne K; Fischer, Kerstin; Gibson, Jane; Nau, Carla; Winterpacht, Andreas; Lampert, Angelika

    2014-01-24

    Inherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain characterized by burning in the extremities. Inherited "paroxysmal extreme pain disorder" (PEPD) differs in its clinical picture and affects proximal body areas like the rectal, ocular, or jaw regions. Both pain syndromes have been linked to mutations in the voltage-gated sodium channel Nav1.7. Electrophysiological characterization shows that IEM-causing mutations generally enhance activation, whereas mutations leading to PEPD alter fast inactivation. Previously, an A1632E mutation of a patient with overlapping symptoms of IEM and PEPD was reported (Estacion, M., Dib-Hajj, S. D., Benke, P. J., Te Morsche, R. H., Eastman, E. M., Macala, L. J., Drenth, J. P., and Waxman, S. G. (2008) NaV1.7 Gain-of-function mutations as a continuum. A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J. Neurosci. 28, 11079-11088), displaying a shift of both activation and fast inactivation. Here, we characterize a new mutation of Nav1.7, A1632T, found in a patient suffering from IEM. Although transfection of A1632T in sensory neurons resulted in hyperexcitability and spontaneous firing of dorsal root ganglia (DRG) neurons, whole-cell patch clamp of transfected HEK cells revealed that Nav1.7 activation was unaltered by the A1632T mutation but that steady-state fast inactivation was shifted to more depolarized potentials. This is a characteristic normally attributed to PEPD-causing mutations. In contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to slow current decay (i.e. open-state inactivation) and did not increase resurgent currents, which have been suggested to contribute to high-frequency firing in physiological and pathological conditions. Reduced fast inactivation without increased resurgent currents induces symptoms of IEM, not PEPD, in the new Nav1.7 mutation, A1632T. Therefore

  10. The HMGA1 Pseudogene 7 Induces miR-483 and miR-675 Upregulation by Activating Egr1 through a ceRNA Mechanism

    PubMed Central

    De Martino, Marco; Azzariti, Amalia; Arra, Claudio; Fusco, Alfredo; Esposito, Francesco

    2017-01-01

    Several studies have established that pseudogene mRNAs can work as competing endogenous RNAs and, when deregulated, play a key role in the onset of human neoplasias. Recently, we have isolated two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7. These pseudogenes have a critical role in cancer progression, acting as micro RNA (miRNA) sponges for HMGA1 and other cancer-related genes. HMGA1 pseudogenes were found overexpressed in several human carcinomas, and their expression levels positively correlate with an advanced cancer stage and a poor prognosis. In order to investigate the molecular alterations following HMGA1 pseudogene 7 overexpression, we carried out miRNA sequencing analysis on HMGA1P7 overexpressing mouse embryonic fibroblasts. Intriguingly, the most upregulated miRNAs were miR-483 and miR-675 that have been described as key regulators in cancer progression. Here, we report that HMGA1P7 upregulates miR-483 and miR-675 through a competing endogenous RNA mechanism with Egr1, a transcriptional factor that positively regulates miR-483 and miR-675 expression. PMID:29149041

  11. MicroRNA-7a regulates Müller glia differentiation by attenuating Notch3 expression.

    PubMed

    Baba, Yukihiro; Aihara, Yuko; Watanabe, Sumiko

    2015-09-01

    miRNA-7a plays critical roles in various biological aspects in health and disease. We aimed to reveal roles of miR-7a in mouse retinal development by loss- and gain-of-function analyses of miR-7a. Plasmids encoding miR-7a or miR-7a-decoy (anti-sense miR-7a) were introduced into mouse retina at P0, and the retina was cultured as explant. Then, proliferation of retinal progenitors and differentiation of retinal subtypes were examined by immunostaining. miR-7a had no apparent effect on the proliferation of retinal progenitor cells. However, the expression of Müller glia marker, cyclin D3, was reduced by miR-7a overexpression and up-regulated by miR-7a decoy, suggesting that miR-7a negatively regulates differentiation of Müller glia. Targets of miR-7a, which were predicted by using a public program miRNA.org, and Notch3 was suggested to be one of candidate genes of miR-7a target. Notch3 3' UTR appeared to contain complementary sequence to the seed sequence of miR-7a. A reporter assay in NIH3T3 cells using a plasmid containing multiple repeats of potential target sequence of 3' Notch UTR showed that miR-7a suppress expression of reporter EGFP through 3'UTR region. Expression of sh-Notch3 and over-expression of NICD3 in retina suggested that miR-7a regulates Müller glia differentiation through attenuation of Notch3 expression. Taken together, we revealed that the miR-7a regulates the differentiation of Müller glia through the suppression of Notch3 expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. [Antitumor effect of recombinant T7 phage vaccine expressing xenogenic vascular endothelial growth factor on Lewis lung cancer in mice].

    PubMed

    Li, Xiao-Hui; Tang, Liang; Liu, Dong; Sun, Hong-Mei; Zhou, Cai-Cun; Tan, Li-Song; Wang, Li-Ping; Zhang, Pei-De; Zhang, Shang-Quan

    2006-10-01

    Angiogenesis plays an important role in growth and metastasis of tumors. Vascular endothelial growth factor (VEGF) is considered as a fundamental regulator for angiogenesis. This study was to construct a recombinant T7 phage vaccine expressing xenogenic VEGF on the capsid, and test its inhibitory effect on Lewis lung cancer cells in mice. VEGF gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR) from human lung cancer tissues, and inserted into phage using T7 Select10-3b kit to construct T7 Select10-3b_VEGF vaccine. The titer of prepared phage reached 1x10(13) pfu/ml. C57BL/6J mice were randomly divided into 3 groups: T7 Select10-3b_VEGF vaccine group (T7-VEGF), T7 phage (T7) group, normal saline (NS) group (10 mice/group). Each mouse was injected with Freundos adjuvant mixed with 1x10(12) pfu/200 microl T7 Select10-3b_VEGF, or T7, or normal saline once a week for 4 weeks. Lewis lung carcinoma model (LL/2) was established in C57BL/6J mice after 4-week immunization. Tumor growth and mouse's physical status were observed during immunization. Tumor weight and serum level of specific anti-VEGF antibody were measured by enzyme-linked immunosorbent assay (ELISA). Microvessel density (MVD) of tumors was detected by immunohistochemistry 14 days after the inoculation of tumor cells. Tumor weight of T7-VEGF vaccine group,T7 group, and NS group were (0.543+/-0.259)g, (0.982+/-0.359)g, (1.169+/-0.460)g, respectively. Tumor weight of T7-VEGF vaccine group was significantly lower than that of NS group (P<0.01). Serum anti-VEGF antibody level in T7-VEGF vaccine group was 1:1,000. MVD was significantly lower in T7-VEGF vaccine group than in NS group (8.5+/-0.8 vs 18.5+/-1.6, P<0.05). MVD in T7 group was 16.4+/-1.3. Recombinant T7 phage vaccine expressing xenogenic VEGF can break immunologic tolerance against self-VEGF and inhibit the growth of Lewis lung cancer cells.

  13. T7 lytic phage-displayed peptide libraries exhibit less sequence bias than M13 filamentous phage-displayed peptide libraries.

    PubMed

    Krumpe, Lauren R H; Atkinson, Andrew J; Smythers, Gary W; Kandel, Andrea; Schumacher, Kathryn M; McMahon, James B; Makowski, Lee; Mori, Toshiyuki

    2006-08-01

    We investigated whether the T7 system of phage display could produce peptide libraries of greater diversity than the M13 system of phage display due to the differing processes of lytic and filamentous phage morphogenesis. Using a bioinformatics-assisted computational approach, collections of random peptide sequences obtained from a T7 12-mer library (X(12)) and a T7 7-mer disulfide-constrained library (CX(7)C) were analyzed and compared with peptide populations obtained from New England BioLabs' M13 Ph.D.-12 and Ph.D.-C7C libraries. Based on this analysis, peptide libraries constructed with the T7 system have fewer amino acid biases, increased peptide diversity, and more normal distributions of peptide net charge and hydropathy than the M13 libraries. The greater diversity of T7-displayed libraries provides a potential resource of novel binding peptides for new as well as previously studied molecular targets. To demonstrate their utility, several of the T7-displayed peptide libraries were screened for streptavidin- and neutravidin-binding phage. Novel binding motifs were identified for each protein.

  14. New design concept of monopole antenna array for UHF 7T MRI.

    PubMed

    Hong, Suk-Min; Park, Joshua Haekyun; Woo, Myung-Kyun; Kim, Young-Bo; Cho, Zang-Hee

    2014-05-01

    We have developed and evaluated a monopole antenna array that can increase sensitivity at the center of the brain for 7T MRI applications. We have developed a monopole antenna array that has half the length of a conventional dipole antenna with eight channels for brain imaging with a 7T MRI. The eight-channel monopole antenna array and conventional eight-channel transceiver surface coil array were evaluated and compared in terms of transmit properties, specific absorption ratio (SAR), and sensitivity. The sensitivity maps were generated by dividing the SNR map by the flip angle distribution. A single surface coil provides asymmetric sensitivity resulting in reduced sensitivity at the center of the brain. In contrast, a single monopole antenna provides higher sensitivity at the center of the brain. Moreover, the monopole antenna array provides uniform sensitivity over the entire brain, and the sensitivity gain was 1.5 times higher at the center of the brain compared with the surface coil array. The monopole antenna array is a promising candidate for MRI applications, especially for brain imaging in a 7T MRI because it provides increased sensitivity at the center of the brain. Copyright © 2013 Wiley Periodicals, Inc.

  15. Computational Assay of H7N9 Influenza Neuraminidase Reveals R292K Mutation Reduces Drug Binding Affinity

    NASA Astrophysics Data System (ADS)

    Woods, Christopher J.; Malaisree, Maturos; Long, Ben; McIntosh-Smith, Simon; Mulholland, Adrian J.

    2013-12-01

    The emergence of a novel H7N9 avian influenza that infects humans is a serious cause for concern. Of the genome sequences of H7N9 neuraminidase available, one contains a substitution of arginine to lysine at position 292, suggesting a potential for reduced drug binding efficacy. We have performed molecular dynamics simulations of oseltamivir, zanamivir and peramivir bound to H7N9, H7N9-R292K, and a structurally related H11N9 neuraminidase. They show that H7N9 neuraminidase is structurally homologous to H11N9, binding the drugs in identical modes. The simulations reveal that the R292K mutation disrupts drug binding in H7N9 in a comparable manner to that observed experimentally for H11N9-R292K. Absolute binding free energy calculations with the WaterSwap method confirm a reduction in binding affinity. This indicates that the efficacy of antiviral drugs against H7N9-R292K will be reduced. Simulations can assist in predicting disruption of binding caused by mutations in neuraminidase, thereby providing a computational `assay.'

  16. IL-7 Promotes T Cell Viability, Trafficking, and Functionality and Improves Survival in Sepsis

    PubMed Central

    Unsinger, Jacqueline; McGlynn, Margaret; Kasten, Kevin R.; Hoekzema, Andrew S.; Watanabe, Eizo; Muenzer, Jared T.; McDonough, Jacquelyn S.; Tschoep, Johannes; Ferguson, Thomas A.; McDunn, Jonathan E.; Morre, Michel; Hildeman, David A.; Caldwell, Charles C.; Hotchkiss, Richard S.

    2010-01-01

    Sepsis is a highly lethal disorder characterized by widespread apoptosis-induced depletion of immune cells and the development of a profound immunosuppressive state. IL-7 is a potent antiapoptotic cytokine that enhances immune effector cell function and is essential for lymphocyte survival. In this study, recombinant human IL-7 (rhIL-7) efficacy and potential mechanisms of action were tested in a murine peritonitis model. Studies at two independent laboratories showed that rhIL-7 markedly improved host survival, blocked apoptosis of CD4 and CD8 T cells, restored IFN-γ production, and improved immune effector cell recruitment to the infected site. Importantly, rhIL-7 also prevented a hallmark of sepsis (i.e., the loss of delayed-type hypersensitivity), which is an IFN-γ– and T cell-dependent response. Mechanistically, rhIL-7 significantly increased the expression of the leukocyte adhesion markers LFA-1 and VLA-4, consistent with its ability to improve leukocyte function and trafficking to the infectious focus. rhIL-7 also increased the expression of CD8. The potent antiapoptotic effect of rhIL-7 was due to increased Bcl-2, as well as to a dramatic decrease in sepsis-induced PUMA, a heretofore unreported effect of IL-7. If additional animal studies support its efficacy in sepsis and if current clinical trials continue to confirm its safety in diverse settings, rhIL-7 should be strongly considered for clinical trials in sepsis. PMID:20200277

  17. Etude de pratiques d'enseignement relatives a la modelisation en sciences et technologies avec des enseignants du secondaire

    NASA Astrophysics Data System (ADS)

    Aurousseau, Emmanuelle

    Les modeles sont des outils amplement utilises en sciences et technologies (S&T) afin de representer et d’expliquer un phenomene difficilement accessible, voire abstrait. La demarche de modelisation est presentee de maniere explicite dans le programme de formation de l’ecole quebecoise (PFEQ), notamment au 2eme cycle du secondaire (Quebec. Ministere de l'Education du Loisir et du Sport, 2007a). Elle fait ainsi partie des sept demarches auxquelles eleves et enseignants sont censes recourir. Cependant, de nombreuses recherches mettent en avant la difficulte des enseignants a structurer leurs pratiques d’enseignement autour des modeles et de la demarche de modelisation qui sont pourtant reconnus comme indispensables. En effet, les modeles favorisent la conciliation des champs concrets et abstraits entre lesquels le scientifique, meme en herbe, effectue des allers-retours afin de concilier le champ experimental de reference qu’il manipule et observe au champ theorique relie qu’il construit. L’objectif de cette recherche est donc de comprendre comment les modeles et la demarche de modelisation contribuent a faciliter l’articulation du concret et de l’abstrait dans l’enseignement des sciences et des technologies (S&T) au 2eme cycle du secondaire. Pour repondre a cette question, nous avons travaille avec les enseignants dans une perspective collaborative lors de groupes focalises et d’observation en classe. Ces dispositifs ont permis d’examiner les pratiques d’enseignement que quatre enseignants mettent en oeuvre en utilisant des modeles et des demarches de modelisation. L’analyse des pratiques d’enseignement et des ajustements que les enseignants envisagent dans leur pratique nous permet de degager des connaissances a la fois pour la recherche et pour la pratique des enseignants, au regard de l’utilisation des modeles et de la demarche de modelisation en S&T au secondaire.

  18. γδT Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway

    PubMed Central

    Chen, Wanbing; Zhang, Gaofu; Wang, Mo; Yang, Haiping

    2018-01-01

    Primary nephrotic syndrome (PNS) is a devastating pediatric disorder. However, its mechanism remains unclear. Previous studies detected B7-1 in podocytes; meanwhile, γδT cells play pivotal roles in immune diseases. Therefore, this study aimed to assess whether and how γδT cells impact podocytes via the CD28/B7-1 pathway. WT and TCRδ−/− mice were assessed. LPS was used to induce nephropathy. Total γδT and CD28+γδT cells were quantitated in mouse spleen and kidney samples. B7-1 and phosphor-SRC levels in the kidney were detected as well. In vitro, γδT cells from the mouse spleen were cocultured with mouse podocytes, and apoptosis rate and phosphor-SRC expression in podocytes were assessed. Compared with control mice, WT mice with LPS nephropathy showed increased amounts of γδT cells in the kidney. Kidney injury was alleviated in TCRδ−/− mice. Meanwhile, B7-1 and phosphor-SRC levels were increased in the kidney from WT mice with LPS nephropathy. CD28+γδT cells were decreased, indicating CD28 may play a role in LPS nephropathy. Immunofluorescence colocalization analysis revealed a tight association of γδT cells with B7-1 in the kidney. High B7-1 expression was detected in podocytes treated with LPS. Podocytes cocultured with γδT cells showed higher phosphor-SRC and apoptosis rate than other cell groups. Furthermore, CD28/B7-1 blockage with CTLA4-Ig in vitro relieved podocyte injury. γδT cells exacerbate podocyte injury via CD28/B7-1 signaling, with downstream involvement of phosphor-SRC. The CD28/B7-1 blocker CTLA4-Ig prevented progressive podocyte injury, providing a potential therapeutic tool for PNS. PMID:29862277

  19. Co-Requirement of PICK1 Binding and PKC Phosphorylation for Stable Surface Expression of the Metabotropic Glutamate Receptor mGluR7

    PubMed Central

    Suh, Young Ho; Pelkey, Kenneth A.; Lavezzari, Gabriela; Roche, Paul A.; Huganir, Richard L.; McBain, Chris J.; Roche, Katherine W.

    2008-01-01

    SUMMARY The presynaptic metabotropic glutamate receptor (mGluR) mGluR7 modulates excitatory neurotransmission by regulating neurotransmitter release, and plays a critical role in certain forms of synaptic plasticity. Although the dynamic regulation of mGluR7 surface expression governs a novel form of metaplasticity in the hippocampus, little is known about the molecular mechanisms regulating mGluR7 trafficking. We now show that mGluR7 surface expression is stabilized by both PKC phosphorylation and by receptor binding to the PDZ domain-containing protein PICK1. Phosphorylation of mGluR7 on serine 862 (S862) inhibits CaM binding thereby increasing mGluR7 surface expression and receptor binding to PICK1. Furthermore, in mice lacking PICK1, PKC-dependent increases in mGluR7 phosphorylation and surface expression are diminished, and mGluR7-dependent plasticity at mossy fiber-interneuron hippocampal synapses is impaired. These data support a model in which PICK1 binding and PKC phosphorylation act together to stabilize mGluR7 on the cell surface in vivo. PMID:18549785

  20. Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer.

    PubMed

    Hu, Jianguo; Zhang, Luo; Mei, Zhiqiang; Jiang, Yuan; Yi, Yuan; Liu, Li; Meng, Ying; Zhou, Lili; Zeng, Jianhua; Wu, Huan; Jiang, Xingwei

    2018-05-22

    Ubiquitin E3 ligase MARCH7 plays an important role in T cell proliferation and neuronal development. But its role in ovarian cancer remains unclear. This study aimed to investigate the role of Ubiquitin E3 ligase MARCH7 in ovarian cancer. Real-time PCR, immunohistochemistry and western blotting analysis were performed to determine the expression of MARCH7, MALAT1 and ATG7 in ovarian cancer cell lines and clinical specimens. The role of MARCH7 in maintaining ovarian cancer malignant phenotype was examined by Wound healing assay, Matrigel invasion assays and Mouse orthotopic xenograft model. Luciferase reporter assay, western blot analysis and ChIP assay were used to determine whether MARCH7 activates TGF-β-smad2/3 pathway by interacting with TGFβR2. MARCH7 interacted with MALAT1 by miR-200a (microRNA-200a). MARCH7 may function as a competing endogenous RNA (ceRNA) to regulate the expression of ATG7 by competing with miR-200a. MARCH7 regulated TGF-β-smad2/3 pathway by interacting with TGFβR2. Inhibition of TGF-β-smad2/3 pathway downregulated MARCH7, MALAT1 and ATG7. MiR-200a regulated TGF-β induced autophagy, invasion and metastasis of SKOV3 cells by targeting MARCH7. MARCH7 silencing inhibited autophagy invasion and metastasis of SKOV3 cells both in vitro and in vivo. In contrast, MARCH7 overexpression promoted TGF-β induced autophagy, invasion and metastasis of A2780 cells in vitro by depending on MALAT1 and ATG7. We also found that TGF-β-smad2/3 pathway regulated MARCH7 and ATG7 through MALAT1. These findings suggested that TGFβR2-Smad2/3-MALAT1/MARCH7/ATG7 feedback loop mediated autophagy, migration and invasion in ovarian cancer. © 2018 The Author(s). Published by S. Karger AG, Basel.

  1. Transient state kinetics of transcription elongation by T7 RNA polymerase.

    PubMed

    Anand, Vasanti Subramanian; Patel, Smita S

    2006-11-24

    The single subunit DNA-dependent RNA polymerase (RNAP) from bacteriophage T7 catalyzes both promoter-dependent transcription initiation and promoter-independent elongation. Using a promoter-free substrate, we have dissected the kinetic pathway of single nucleotide incorporation during elongation. We show that T7 RNAP undergoes a slow conformational change (0.01-0.03 s(-1)) to form an elongation competent complex with the promoter-free substrate (dissociation constant (Kd) of 96 nM). The complex binds to a correct NTP (Kd of 80 microM) and incorporates the nucleoside monophosphate (NMP) into RNA primer very efficiently (220 s(-1) at 25 degrees C). An overall free energy change (-5.5 kcal/mol) and internal free energy change (-3.7 kcal/mol) of single NMP incorporation was calculated from the measured equilibrium constants. In the presence of inorganic pyrophosphate (PPi), the elongation complex catalyzes the reverse pyrophosphorolysis reaction at a maximum rate of 0.8 s(-1) with PPi Kd of 1.2 mM. Several experiments were designed to investigate the rate-limiting step in the pathway of single nucleotide addition. Acid-quench and pulse-chase kinetics indicated that an isomerization step before chemistry is rate-limiting. The very similar rate constants of sequential incorporation of two nucleotides indicated that the steps after chemistry are fast. Based on available data, we propose that the preinsertion to insertion isomerization of NTP observed in the crystallographic studies of T7 RNAP is a likely candidate for the rate-limiting step. The studies here provide a kinetic framework to investigate structure-function and fidelity of RNA synthesis and to further explore the role of the conformational change in nucleotide selection during RNA synthesis.

  2. Ultra high spatial and temporal resolution breast imaging at 7T.

    PubMed

    van de Bank, B L; Voogt, I J; Italiaander, M; Stehouwer, B L; Boer, V O; Luijten, P R; Klomp, D W J

    2013-04-01

    There is a need to obtain higher specificity in the detection of breast lesions using MRI. To address this need, Dynamic Contrast-Enhanced (DCE) MRI has been combined with other structural and functional MRI techniques. Unfortunately, owing to time constraints structural images at ultra-high spatial resolution can generally not be obtained during contrast uptake, whereas the relatively low spatial resolution of functional imaging (e.g. diffusion and perfusion) limits the detection of small lesions. To be able to increase spatial as well as temporal resolution simultaneously, the sensitivity of MR detection needs to increase as well as the ability to effectively accelerate the acquisition. The required gain in signal-to-noise ratio (SNR) can be obtained at 7T, whereas acceleration can be obtained with high-density receiver coil arrays. In this case, morphological imaging can be merged with DCE-MRI, and other functional techniques can be obtained at higher spatial resolution, and with less distortion [e.g. Diffusion Weighted Imaging (DWI)]. To test the feasibility of this concept, we developed a unilateral breast coil for 7T. It comprises a volume optimized dual-channel transmit coil combined with a 30-channel receive array coil. The high density of small coil elements enabled efficient acceleration in any direction to acquire ultra high spatial resolution MRI of close to 0.6 mm isotropic detail within a temporal resolution of 69 s, high spatial resolution MRI of 1.5 mm isotropic within an ultra high temporal resolution of 6.7 s and low distortion DWI at 7T, all validated in phantoms, healthy volunteers and a patient with a lesion in the right breast classified as Breast Imaging Reporting and Data System (BI-RADS) IV. Copyright © 2012 John Wiley & Sons, Ltd.

  3. EURAMET.T-K7 Key Comparison of Water Triple-Point Cells

    NASA Astrophysics Data System (ADS)

    Peruzzi, A.; Bosma, R.; Kerkhof, O.; Rosenkranz, P.; Del Campo Maldonado, M. D.; Strnad, R.; Nielsen, J.; Anagnostou, M.; Veliki, T.; Zvizdic, D.; Grudnewicz, E.; Nedea, M.; Neagu, D. M.; Steur, P.; Filipe, E.; Lobo, I.; Antonsen, I.; Renaot, E.; Heinonen, M.; Weckstrom, T.; Bojkovski, J.; Turzo-Andras, E.; Nemeth, S.; White, M.; Tegeler, E.; Dobre, M.; Duris, S.; Kartal Dogan, A.; Uytun, A.; Augevicius, V.; Pauzha, A.; Pokhodun, A.; Simic, S.

    2011-12-01

    The results of a EURAMET key comparison of water triple-point cells (EURAMET.T-K7) are reported. The equipment used, the measuring conditions applied, and the procedures adopted for the water triple-point measurement at the participating laboratories are synthetically presented. The definitions of the national reference for the water triple-point temperature adopted by each laboratory are disclosed. The multiplicity of degrees of equivalence arising for the linking laboratories with respect to the "mother" comparison CCT-K7 is discussed in detail.

  4. Visualization of human inner ear anatomy with high-resolution MR imaging at 7T: initial clinical assessment.

    PubMed

    van der Jagt, M A; Brink, W M; Versluis, M J; Steens, S C A; Briaire, J J; Webb, A G; Frijns, J H M; Verbist, B M

    2015-02-01

    In many centers, MR imaging of the inner ear and auditory pathway performed on 1.5T or 3T systems is part of the preoperative work-up of cochlear implants. We investigated the applicability of clinical inner ear MR imaging at 7T and compared the visibility of inner ear structures and nerves within the internal auditory canal with images acquired at 3T. Thirteen patients with sensorineural hearing loss eligible for cochlear implantation underwent examinations on 3T and 7T scanners. Two experienced head and neck radiologists evaluated the 52 inner ear datasets. Twenty-four anatomic structures of the inner ear and 1 overall score for image quality were assessed by using a 4-point grading scale for the degree of visibility. The visibility of 11 of the 24 anatomic structures was rated higher on the 7T images. There was no significant difference in the visibility of 13 anatomic structures and the overall quality rating. A higher incidence of artifacts was observed in the 7T images. The gain in SNR at 7T yielded a more detailed visualization of many anatomic structures, especially delicate ones, despite the challenges accompanying MR imaging at a high magnetic field. © 2015 by American Journal of Neuroradiology.

  5. Synthesis of 13(R)-Hydroxy-7Z,10Z,13R,14E,16Z,19Z Docosapentaenoic Acid (13R-HDPA) and Its Biosynthetic Conversion to the 13-Series Resolvins

    PubMed Central

    2016-01-01

    Specialized pro-resolving lipid mediators are biosynthesized during the resolution phase of acute inflammation from n-3 polyunsaturated fatty acids. Recently, the isolation and identification of the four novel mediators denoted 13-series resolvins, namely, RvT1 (1), RvT2 (2), RvT3 (3) and RvT4 (4), were reported, which showed potent bioactions characteristic for specialized pro-resolving lipid mediators. Herein, based on results from LC/MS-MS metabololipidomics and the stereoselective synthesis of 13(R)-hydroxy-7Z,10Z,13R,14E,16Z,19Z docosapentaenoic acid (13R-HDPA, 5), we provide direct evidence that the four novel mediators 1–4 are all biosynthesized from the pivotal intermediate 5. The UV and LC/MS-MS results from synthetic 13R-HDPA (5) matched those from endogenously and biosynthetically produced material obtained from in vivo infectious exudates, endothelial cells, and human recombinant COX-2 enzyme. Stereochemically pure 5 was obtained with the use of a chiral pool starting material that installed the configuration at the C-13 atom as R. Two stereoselective Z-Wittig reactions and two Z-selective reductions of internal alkynes afforded the geometrically pure alkene moieties in 5. Incubation of 5 with isolated human neutrophils gave all four RvTs. The results presented herein provide new knowledge on the biosynthetic pathways and the enzymatic origin of RvTs 1–4. PMID:27704804

  6. CCR7 Plays No Appreciable Role in Trafficking of Central Memory CD4 T Cells to Lymph Nodes

    PubMed Central

    Lugt, Bryan Vander; Tubo, Noah J.; Nizza, Suzanne T.; Boes, Marianne; Malissen, Bernard; Fuhlbrigge, Robert C.; Kupper, Thomas S.; Campbell, James J.

    2013-01-01

    CCR7−/− mice exhibit profound anomalies in LN and spleen architecture, which complicates the study of CCR7-mediated T cell trafficking in vivo. To circumvent this problem, we established in vivo models in which WT and CCR7−/− populations coexist within mice possessing normal lymphoid organs, and must compete for developmental niches within the tissues of these mice. Under the conditions we have created in vivo, we find the entry of memory CD4 T cells into LN from the blood to be independent of CCR7. Thus, the central memory CD4 T cells that traffic though LN, which are often defined by their expression of CCR7, do not appear to gain any competitive homing advantage by expressing this receptor. Furthermore, in contrast to cutaneous DC populations, we found that CCR7 deficiency had no appreciable effect on the exit of CD4 T cells from inflamed skin. Finally, we found that WT and CCR7−/− precursors were equally represented within the major thymic subpopulations, despite previous findings that CCR7 plays a role in seeding the thymus from bone marrow-derived T cell precursors. PMID:23935190

  7. TRAV7-2*02 Expressing CD8⁺ T Cells Are Responsible for Palladium Allergy.

    PubMed

    Takeda, Yuri; Suto, Yoshiko; Ito, Koyu; Hashimoto, Wataru; Nishiya, Tadashi; Ueda, Kyosuke; Narushima, Takayuki; Takahashi, Tetsu; Ogasawara, Kouetsu

    2017-05-31

    While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8⁺ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8⁺ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8⁺ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy.

  8. Significance Assessment of Site 16SC61, Luling Revetment, Mississippi River M-116.7-R

    DTIC Science & Technology

    1993-03-01

    16SC61, LULING REVETMENT , MISSISSIPPI RIVER M-1 16.7-R DTIC ELECTE Final Report AUG 0 4 1993 I_ March 1993A EARTH SEARCH, IN, . P.O. Box 850319 New...Classification) Significance Assessment of Site 16SC61, Luling Revetment , Mississippi River M-116.7-R 12. PERSONAL AUTHOR(S) Herschel A. Franks and...by block number) FIELD GROUP SUB-GROUP Archeology, historic archeology, sugar plantation,I Islave quarters, nineteenth century, St. Charles Parish

  9. PICK1 uncoupling from mGluR7a causes absence-like seizures

    PubMed Central

    Bertaso, Federica; Zhang, Chuansheng; Scheschonka, Astrid; de Bock, Frédéric; Fontanaud, Pierre; Marin, Philippe; Huganir, Richard L; Betz, Heinrich; Bockaert, Joël; Fagni, Laurent; Lerner-Natoli, Mireille

    2009-01-01

    Absence epilepsy is a neurological disorder that causes a recurrent loss of consciousness and generalized spike-and-wave discharges on an electroencephalogram (EEG). The role of metabotropic glutamate receptors (mGluRs) and associated scaffolding proteins in absence epilepsy has been unclear to date. We investigated a possible role for these proteins in absence epilepsy, focusing on the mGluR7a receptor and its PDZ-interacting protein, protein interacting with C kinase 1 (PICK1), in rats and mice. Injection of a cell-permeant dominant-negative peptide or targeted mutation of the mGluR7a C terminus, both of which disrupt the interaction between the receptor and PDZ proteins, caused behavioral symptoms and EEG discharges that are characteristic of absence epilepsy. Inactivation of the Pick1 gene also facilitated pharmacological induction of the absence epilepsy phenotype. The cortex and thalamus, which are known to participate in absence epilepsy, were involved, but the hippocampus was not. Our results indicate that disruption of the mGluR7a-PICK1 complex is sufficient to induce absence epilepsy—like seizures in rats and mice, thus providing, to the best of our knowledge, the first animal model of metabotropic glutamate receptor—PDZ protein interaction in absence epilepsy. PMID:18641645

  10. Weyerhaeuser Export Facility at DuPont. Volume III. Appendices R - T.

    DTIC Science & Technology

    1982-05-01

    o 1 0N. u 𔃺-43-.Ell. in- All~ 4E-W -Sl >.41 03..l 0 -. 0.El El4 -0 00. ElE w wo El0 0 E.W a A44 l iV t 4 r A - - . 1 %9C 4 U. o U 10 ).- 3W 4 aQ 4...8217 , u =1 0.H, a t 0𔃺 El4 2-0.4 4 00 LI 40. -0 f.. N . .2 C 44 04 >, . 00 a 10 0 ~ 01 020 0 *. 20A 3. 40 04 .4 a,4 - 44 4 E 0 A2. U.~E4 Q 4 4.0 0 6.a

  11. A let-7-to-miR-125 MicroRNA Switch Regulates Neuronal Integrity and Lifespan in Drosophila

    PubMed Central

    Chawla, Geetanjali; Deosthale, Padmini; Childress, Sue; Wu, Yen-chi; Sokol, Nicholas S.

    2016-01-01

    Messenger RNAs (mRNAs) often contain binding sites for multiple, different microRNAs (miRNAs). However, the biological significance of this feature is unclear, since such co-targeting miRNAs could function coordinately, independently, or redundantly with one another. Here, we show that two co-transcribed Drosophila miRNAs, let-7 and miR-125, non-redundantly regulate a common target, the transcription factor Chronologically Inappropriate Morphogenesis (Chinmo). We first characterize novel adult phenotypes associated with loss of both let-7 and miR-125, which are derived from a common, polycistronic transcript that also encodes a third miRNA, miR-100. Consistent with the coordinate upregulation of all three miRNAs in aging flies, these phenotypes include brain degeneration and shortened lifespan. However, transgenic rescue analysis reveal separable roles for these miRNAs: adult miR-125 but not let-7 mutant phenotypes are associated with ectopic Chinmo expression in adult brains and are suppressed by chinmo reduction. In contrast, let-7 is predominantly responsible for regulating chinmo during nervous system formation. These results indicate that let-7 and miR-125 function during two distinct stages, development and adulthood, rather than acting at the same time. These different activities are facilitated by an increased rate of processing of let-7 during development and a lower rate of decay of the accumulated miR-125 in the adult nervous system. Thus, this work not only establishes a key role for the highly conserved miR-125 in aging. It also demonstrates that two co-transcribed miRNAs function independently during distinct stages to regulate a common target, raising the possibility that such biphasic control may be a general feature of clustered miRNAs. PMID:27508495

  12. Suivi après le traitement du cancer du sein

    PubMed Central

    Sisler, Jeffrey; Chaput, Geneviève; Sussman, Jonathan; Ozokwelu, Emmanuel

    2016-01-01

    Résumé Objectif Offrir aux médecins de famille un résumé des recommandations fondées sur les données probantes pour guider les soins aux survivantes traitées pour le cancer du sein. Qualité des données Une recherche documentaire a été effectuée dans MEDLINE entre 2000 et 2016 à l’aide des mots-clés anglais suivants : breast cancer, survivorship, follow-up care, aftercare, guidelines et survivorship care plans, en se concentrant sur la revue des lignes directrices publiées récemment par les organismes nationaux de cancérologie. Les données étaient de niveaux I à III. Message principal Les soins aux survivantes comportent 4 facettes : surveillance et dépistage, prise en charge des effets à long terme, promotion de la santé et coordination des soins. La surveillance des récidives ne se traduit que par une mammographie annuelle, et le dépistage d’autres cancers doit suivre les lignes directrices basées sur la population. La prise en charge des effets à long terme du cancer et de son traitement aborde des problèmes courants tels la douleur, la fatigue, le lymphœdème, la détresse et les effets indésirables des médicaments, de même que les préoccupations à long terme comme la santé du cœur et des os. La promotion de la santé met en relief les bienfaits de l’activité chez les survivantes du cancer, avec l’accent mis sur l’activité physique. Les soins aux survivantes sont de meilleure qualité lorsque divers services et professionnels de la santé participent aux soins, et le médecin de famille joue un rôle important dans la coordination des soins. Conclusion Les médecins de famille sont de plus en plus souvent les principaux fournisseurs de soins de suivi après le traitement du cancer du sein. Le cancer du sein doit être considéré comme une affection médicale chronique, même chez les femmes en rémission, et les patientes profitent de la même approche que celle utilisée pour les autres affections chroniques en

  13. An Asymmetric Birdcage Coil for Small-animal MR Imaging at 7T

    PubMed Central

    Kim, Kyoung-Nam; Han, Sang-Doc; Seo, Jeung-Hoon; Heo, Phil; Yoo, Dongkyeom; Im, Geun Ho; Lee, Jung Hee

    2017-01-01

    The birdcage (BC) coil is currently being utilized for uniform radiofrequency (RF) transmit/receive (Tx/Rx) or Tx-only configuration in many magnetic resonance (MR) imaging applications, but insufficient magnetic flux (|B1|) density and their non-uniform distribution still exists in high-field (HF) environments. We demonstrate that the asymmetric birdcage (ABC) transmit/receive (Tx/Rx) volume coil, which is a modified standard birdcage (SBC) coil with the end ring split into two halves, is suitable for improving the |B1| sensitivity in 7T small-animal MR imaging. Cylindrical SBC and ABC coils with 35 mm diameter were constructed and bench tested for mouse body MR imaging at 300 MHz using a 7T scanner. To assess the ABC coil performance, computational electromagnetic (EM) simulation and 7T MR experiment were performed by using a cylindrical phantom and in vivo mouse body and quantitatively compared with the SBC coil in terms of |B1| distribution, RF transmit (|B1+|) field, and signal-to-noise ratio (SNR). The bench measurements of the two BC coils are similar, yielding a quality value (Q-value) of 74.42 for the SBC coil and 77.06 for the ABC coil. The computational calculation results clearly show that the proposed ABC coil offers superior |B1| field and |B1+| field sensitivity in the central axial slice compared with the SBC coil. There was also high SNR and uniformly distributed flip angle (FA) under the loaded condition of mouse body in the 7T experiment. Although ABC geometry allows a further increase in the |B1| field and |B1+| field sensitivity in only the central axial slice, the geometrical modification of the SBC coil can make a high performance RF coil feasible in the central axial slice and also make target imaging possible in the diagonal direction. PMID:27725573

  14. Molecular analysis of congenital goitres with hypothyroidism caused by defective thyroglobulin synthesis. Identification of a novel c.7006C>T [p.R2317X] mutation and expression of minigenes containing nonsense mutations in exon 7.

    PubMed

    Machiavelli, Gloria A; Caputo, Mariela; Rivolta, Carina M; Olcese, María C; Gruñeiro-Papendieck, Laura; Chiesa, Ana; González-Sarmiento, Rogelio; Targovnik, Héctor M

    2010-01-01

    Thyroglobulin (TG) deficiency is an autosomal-recessive disorder that results in thyroid dyshormonogenesis. A number of distinct mutations have been identified as causing human hypothyroid goitre. The purpose of this study was to identify and characterize new mutations in the TG gene in an attempt to increase the understanding of the genetic mechanism responsible for this disorder. A total of six patients from four nonconsanguineous families with marked impairment of TG synthesis were studied. Single-strand conformation polymorphism (SSCP) analysis, sequencing of DNA, genotyping, expression of chimeric minigenes and bioinformatic analysis were performed. Four different inactivating TG mutations were identified: one novel mutation (c.7006C>T [p.R2317X]) and three previously reported (c.886C>T [p.R277X], c.6701C>A [p.A2215D] and c.6725G>A [p.R2223H]). Consequently, one patient carried a compound heterozygous for p.R2223H/p.R2317X mutations; two brothers showed a homozygous p.A2215D substitution and the remaining three patients, from two families with typical phenotype, had a single p.R277X mutated allele. We also showed functional evidences that premature stop codons inserted at different positions in exon 7, which disrupt exonic splicing enhancer (ESE) sequences, do not interfere with exon definition and processing. In this study, we have identified a novel nonsense mutation p.R2317X in the acetylcholinesterase homology domain of TG. We have also observed that nonsense mutations do not interfere with the pre-mRNA splicing of exon 7. The results are in accordance with previous observations confirming the genetic heterogeneity of TG defects.

  15. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    PubMed

    Gizewski, Elke R; Maderwald, Stefan; Linn, Jennifer; Dassinger, Benjamin; Bochmann, Katja; Forsting, Michael; Ladd, Mark E

    2014-03-01

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures.

  16. High-pressure synthesis and characterizations of the R2Pt2O7 pyrochlores.

    NASA Astrophysics Data System (ADS)

    Cai, Yunqi; Cui, Qi; Cheng, Jinguang; Dun, Zhiling; Zhou, Haidong; Ma, Jie; Cruz, C. Dela; Yan, Jiaqiang; Li, Xiang; Zhou, Jianshi

    Pyrochlore R2B2O7 where R3 + stands for rear-earth ion and B4 + for a nonmagnetic cation such as Sn4 +or Ti4 +consist of an important family of geometrically frustrated magnets, which have been the focus of extensive investigations over last decades. To further enlarge the R2B2O7, we have chosen to stabilize the Pt-based cubic pyrochlores under HPHT conditions for two reasons: (1) Pt4 + is in a low-spin state which ionic radius is located in between Ti4 + (0.605\\x85) and Sn4 + (0.69\\x85), and (2) Pt4 + has a spatially much more extended 5d orbitals and thus enhanced Pt 5d-O 2p hybridizations that might modify the local anisotropic exchange interactions. Such an effect has never been taken into account in the previous studies. In this work, we will present the detailed characterizations on the pyrochlores R2Pt2O7 obtained under HPHT conditions. This work is supported by the National Science Foundation of China (Grant Nos.11304371, 11574377), part of the work was supported by the CEM, and NSF MRSEC, under Grant DMR-1420451, and Grant No. NSF-DMR-1350002.

  17. Fragile singlet ground-state magnetism in the pyrochlore osmates R 2 Os 2 O 7 ( R = Y and Ho)

    DOE PAGES

    Zhao, Z. Y.; Calder, S.; Aczel, A. A.; ...

    2016-04-25

    The singlet ground state magnetism in pyrochlore osmates Y 2Os 2O 7 and Ho 2Os 2O 7 is studied by DC and AC susceptibility, specific heat, and neutron powder diffraction measurements. Despite the expected non-magnetic singlet in the strong spin-orbit coupling (SOC) limit for Os 4+ (5d 4), Y 2Os 2O 7 exhibits a spin-glass (SG) ground state below 4 K with weak magnetism, suggesting possible proximity to a quantum phase transition between the non-magnetic state in the strong SOC limit and the magnetic state in the strong superexchange limit. Ho 2Os 2O 7 has the same structural distortion asmore » occurs in Y 2Os 2O 7. However, the Os sublattice in Ho 2Os 2O 7 shows long- range magnetic ordering below 36 K. We find that the sharp difference of the magnetic ground state between Y 2Os 2O 7 and Ho 2Os 2O 7 signals the singlet ground state magnetism in R 2 Os 2 O 7 is fragile and can be disturbed by the weak 4f—5d interactions.« less

  18. Fragile singlet ground-state magnetism in the pyrochlore osmates R 2 Os 2 O 7 ( R = Y and Ho)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Z. Y.; Calder, S.; Aczel, A. A.

    The singlet ground state magnetism in pyrochlore osmates Y 2Os 2O 7 and Ho 2Os 2O 7 is studied by DC and AC susceptibility, specific heat, and neutron powder diffraction measurements. Despite the expected non-magnetic singlet in the strong spin-orbit coupling (SOC) limit for Os 4+ (5d 4), Y 2Os 2O 7 exhibits a spin-glass (SG) ground state below 4 K with weak magnetism, suggesting possible proximity to a quantum phase transition between the non-magnetic state in the strong SOC limit and the magnetic state in the strong superexchange limit. Ho 2Os 2O 7 has the same structural distortion asmore » occurs in Y 2Os 2O 7. However, the Os sublattice in Ho 2Os 2O 7 shows long- range magnetic ordering below 36 K. We find that the sharp difference of the magnetic ground state between Y 2Os 2O 7 and Ho 2Os 2O 7 signals the singlet ground state magnetism in R 2 Os 2 O 7 is fragile and can be disturbed by the weak 4f—5d interactions.« less

  19. CCR7 directs the recruitment of T cells into inflamed pancreatic islets of nonobese diabetic (NOD) mice.

    PubMed

    Shan, Zhongyan; Xu, Baohui; Mikulowska-Mennis, Anna; Michie, Sara A

    2014-05-01

    Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of insulin-producing β cells in the pancreatic islets. The migration of T cells from blood vessels into pancreas is critical for the development of islet inflammation and β cell destruction in T1D. To define the roles of C-C chemokine receptor type 7 (CCR7) in recruitment of T cells into islets, we used laser capture microdissection to isolate tissue from inflamed islets of nonobese diabetic (NOD) mice and uninflamed islets of BALB/c and young NOD mice. RT-PCR analyses detected mRNAs for CCR7 and its chemokine ligands CCL19 (ELC; MIP-3β) and CCL21 (SLC) in captures from inflamed, but not from uninflamed, islets. Immunohistology studies revealed that high endothelial venules in inflamed islets co-express CCL21 protein and MAdCAM-1 (an adhesion molecule that recruits lymphocytes into islets). Desensitization of lymphocyte CCR7 blocked about 75 % of T cell migration from the bloodstream into inflamed islets, but had no effect on B cell migration into islets. These results indicate that CCR7 and its ligands are important in the recruitment of T cells into inflamed islets and thus in the pathogenesis of T1D.

  20. Croissance de couches de Si{1-x}Ge{x} par réaction chimique a partir d'une phase gazeuse : étude thermodynamique et analyse du transfert de matière

    NASA Astrophysics Data System (ADS)

    Rouch, H.; Pons, M.; Bernard, C.; Madar, R.

    1995-06-01

    The growth of Si{1-x}Gex layers at a high temperature (1300 K) and low pressure (315 Pa) (by chemical vapour deposition) was studied by a thermodynamic approach and a mass transport analysis using simplifying assumptions. The results showed that the thermodynamic analysis does not permit alone to explain the experimental measurements concerning the composition of the layer. The mass transport analysis showed that thermodiffusion would be of importance on layer composition and uniformity for large substrates. La croissance de couches de Si{1-x}Gex à haute température (1300 K) et basse pression (315 Pa) par réaction chimique à partir d'une phase gazeuse a été étudiée à l'aide d'une approche thermodynamique et de l'analyse du transfert de matière pour laquelle des hypothèses très simplificatrices ont été émises. Les résultats ont montré que l'analyse thermodynamique, seule, ne permet pas d'interpréter les mesures concernant la composition du matériau déposé. Quant à l'étude du transfert de matière, elle a montré que la thermodiffusion jouait un rôle important sur la composition du matériau déposé ainsi que sur l'uniformité du dépôt sur des substrats de grandes dimensions.

  1. Restauration fonctionnelle du rachis : effet du niveau initial de douleur sur les performances des sujets lombalgiques chroniques

    PubMed Central

    Caby, Isabelle; Olivier, N; Mendelek, F; Kheir, R Bou; Vanvelcenaher, J; Pelayo, P

    2014-01-01

    HISTORIQUE : La lombalgie chronique est une douleur lombaire persistante d’origine multifactorielle. Le niveau de douleur initial reste faiblement utilisé pour analyser et comparer les réponses des patients lombalgiques au programme de reconditionnement. OBJECTIFS : Apprécier et évaluer les réponses des sujets lombalgiques chroniques très douloureux à une prise en charge dynamique et intensive. MÉTHODOLOGIE : 144 sujets atteints de lombalgie chronique ont été inclus dans un programme de restauration fonctionnelle du rachis de 5 semaines. Les sujets ont été classés en deux groupes de niveau de douleur: un groupe atteint de douleur sévère (n = 28) et un groupe atteint de douleur légère à modérée (n = 106). L’ensemble des sujets ont bénéficié d’une prise en charge identique comprenant principalement de la kinésithérapie, de l’ergothérapie, du reconditionnement musculaire et cardio-vasculaire ainsi qu’un suivi psychologique. Les paramètres physiques (flexibilité, force musculaire) et psychologiques (qualité de vie) ont été mesurés avant (T0) et après le programme (T5sem). RÉSULTATS : L’ensemble des performances physiques et fonctionnelles des sujets très douloureux sont moins bonnes et le retentissement de la lombalgie sur la qualité de vie, pour ces mêmes sujets, est majoré à T0. Toutes les différences significatives constatées à T0 entre les deux groupes s’effacent à T5sem. CONCLUSIONS : Les sujets lombalgiques chroniques très douloureux répondent favorablement au programme dynamique et intensif. L’intensité douloureuse de la lombalgie n’aurait pas d’effet sur les réponses au programme. La restauration fonctionnelle du rachis apporterait aux sujets la possibilité de mieux gérer leur douleur quel que soit son niveau. PMID:25299476

  2. Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice

    PubMed Central

    Higa, K. K.; Grim, A.; Kamenski, M. E.; van Enkhuizen, J.; Zhou, X.; Li, K.; Naviaux, J. C.; Wang, L.; Naviaux, R. K.; Geyer, M. A.; Markou, A.; Young, J. W.

    2017-01-01

    Rationale Smoking is the leading cause of preventable death in the U.S., but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. Objectives We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the 5-choice continuous performance test (5C-CPT). Methods Mice were trained in the 5C-CPT prior to osmotic minipump implantation containing saline or nicotine. Experiment 1 used 40 mg/kg/day nicotine treatment and tested C57BL/6 mice 4, 28, and 52 h after pump removal. Experiment 2 used 14 and 40 mg/kg/day nicotine treatment in α7 nAChR knockout (KO) and wildtype (WT) littermates tested 4 h after pump removal. Subsets of WT mice were sacrificed before and after pump removal to assess changes in receptor expression associated with nicotine administration and withdrawal. Results Nicotine withdrawal impaired attention in the 5C-CPT, driven by response inhibition and target detection deficits. The overall attentional deficit was absent in α7 nAChR KO mice despite response disinhibition in these mice. Synaptosomal glutamate mGluR5 and dopamine D4 receptor expression were reduced during chronic nicotine but increased during withdrawal, potentially contributing to cognitive deficits. Conclusions The α7 nAChR may underlie nicotine withdrawal-induced deficits in target detection but is not required for response disinhibition deficits. Alterations to the glutamatergic and dopaminergic pathways may also contribute to withdrawal-induced attentional deficits, providing novel targets to alleviate the cognitive symptoms of withdrawal during quit attempts. PMID:28243714

  3. VizieR Online Data Catalog: Kinematic analysis of M7-L8 dwarfs (Faherty+, 2016)

    NASA Astrophysics Data System (ADS)

    Faherty, J. K.; Riedel, A. R.; Cruz, K. L.; Gagne, J.; Filippazzo, J. C.; Lambrides, E.; Fica, H.; Weinberger, A.; Thorstensen, J. R.; Tinney, C. G.; Baldassare, V.; Lemonier, E.; Rice, E. L.

    2017-08-01

    The sample of 152 M7-L8 ultra-cool dwarfs comprising our sample (see table 1) were placed on follow-up programs --either imaging (parallax, proper motion), spectroscopy (radial velocity), or both-- to determine kinematic membership in a nearby moving group. For Northern Hemisphere astrometry targets, we obtained I-band images with the MDM Observatory 2.4m Hiltner telescope on Kitt Peak, Arizona. We also observed 16 of the most southern targets with the Carnegie Astrometric Planet Search Camera (CAPSCam) on the 100 inch du Pont telescope and 5 with the FourStar imaging camera on the Magellan Baade Telescope. Table 2 gives the pertinent astrometric information; Table 3 lists our measured parallaxes and proper motions. New proper-motion measurements are listed in Table 5. See also section 3.1. We used the 6.5m Baade Magellan telescope and the FIRE spectrograph to obtain near-infrared spectra of 36 sources. Observations were made over seven runs between 2013 July and 2014 September. All observations (resolution R~6000) cover the full 0.8-2.5um band with a spatial resolution of 0.18"/pixel. We used the 3m NASA IRTF to obtain low-resolution near-infrared spectroscopy for 10 targets. All of the observations were aligned to the parallactic angle to obtain R~120 spectral data over the wavelength range of 0.7-2.5um. We used the Triple Spectrograph (TSpec) at the 5m Hale Telescope at Palomar Observatory to obtain near-infrared spectra of two targets. TSpec covers simultaneously the range from 1.0 to 2.45um and achieves a resolution of ~2500. Exposure times for each source and the number of images acquired are listed in Table 6; see also section 3.2. Multiple observations of 17 sources were taken in high-resolution mode on Keck II on 2008 September 14-16, using the NIRSPEC-5 filter to obtain H-band spectra in Order 49 (1.545-1.570um ). Observations of 18 sources were taken during semesters 2007B and 2009B using the H6420 filter of the Phoenix instrument (previously on Gemini

  4. α7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way.

    PubMed

    Grandi, Andrea; Zini, Irene; Flammini, Lisa; Cantoni, Anna M; Vivo, Valentina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bertoni, Simona

    2017-01-01

    The existence of a cholinergic anti-inflammatory pathway negatively modulating the inflammatory and immune responses in various clinical conditions and experimental models has long been postulated. In particular, the protective involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs) has been proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS-induced colitis. However, the role of α 7 nAChRs stimulation is still controversial and the potential contribution of α 4 β 2 nAChRs has never been explored in this experimental condition. Our aims were therefore to pharmacologically investigate the role played by both α 7 and α 4 β 2 nAChRs in the modulation of the local and systemic inflammatory responses activated in TNBS-induced colitis in mice and to assess the involvement of the spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely treated with various subcutaneous doses of highly selective agonists (AR-R17779 and TC-2403) and antagonists (methyllycaconitine and dihydro-β-erythroidine) of α 7 and α 4 β 2 nAChRs, respectively, or with sulfasalazine 50 mg/kg per os and clinical and inflammatory responses were evaluated by means of biochemical, histological and flow cytometry assays. α 4 β 2 ligands evoked weak and contradictory effects, while α 7 nAChR agonist AR-R17779 emerged as the most beneficial treatment, able to attenuate several local markers of colitis severity and to revert the rise in splenic T-cells and in colonic inflammatory cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its protective effects, demonstrating for the first time that, in TNBS-model of experimental colitis, the anti-inflammatory effect of exogenous α 7 nAChR stimulation is strictly spleen-dependent. Our findings showed that the selective α 7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of intestinal inflammation characterized by activation of the adaptive immune

  5. Inhibition of biofilm formation by T7 bacteriophages producing quorum-quenching enzymes.

    PubMed

    Pei, Ruoting; Lamas-Samanamud, Gisella R

    2014-09-01

    Bacterial growth in biofilms is the major cause of recalcitrant biofouling in industrial processes and of persistent infections in clinical settings. The use of bacteriophage treatment to lyse bacteria in biofilms has attracted growing interest. In particular, many natural or engineered phages produce depolymerases to degrade polysaccharides in the biofilm matrix and allow access to host bacteria. However, the phage-produced depolymerases are highly specific for only the host-derived polysaccharides and may have limited effects on natural multispecies biofilms. In this study, an engineered T7 bacteriophage was constructed to encode a lactonase enzyme with broad-range activity for quenching of quorum sensing, a form of bacterial cell-cell communication via small chemical molecules (acyl homoserine lactones [AHLs]) that is necessary for biofilm formation. Our results demonstrated that the engineered T7 phage expressed the AiiA lactonase to effectively degrade AHLs from many bacteria. Addition of the engineered T7 phage to mixed-species biofilms containing Pseudomonas aeruginosa and Escherichia coli resulted in inhibition of biofilm formation. Such quorum-quenching phages that can lyse host bacteria and express quorum-quenching enzymes to affect diverse bacteria in biofilm communities may become novel antifouling and antibiofilm agents in industrial and clinical settings. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Inhibition of Biofilm Formation by T7 Bacteriophages Producing Quorum-Quenching Enzymes

    PubMed Central

    Lamas-Samanamud, Gisella R.

    2014-01-01

    Bacterial growth in biofilms is the major cause of recalcitrant biofouling in industrial processes and of persistent infections in clinical settings. The use of bacteriophage treatment to lyse bacteria in biofilms has attracted growing interest. In particular, many natural or engineered phages produce depolymerases to degrade polysaccharides in the biofilm matrix and allow access to host bacteria. However, the phage-produced depolymerases are highly specific for only the host-derived polysaccharides and may have limited effects on natural multispecies biofilms. In this study, an engineered T7 bacteriophage was constructed to encode a lactonase enzyme with broad-range activity for quenching of quorum sensing, a form of bacterial cell-cell communication via small chemical molecules (acyl homoserine lactones [AHLs]) that is necessary for biofilm formation. Our results demonstrated that the engineered T7 phage expressed the AiiA lactonase to effectively degrade AHLs from many bacteria. Addition of the engineered T7 phage to mixed-species biofilms containing Pseudomonas aeruginosa and Escherichia coli resulted in inhibition of biofilm formation. Such quorum-quenching phages that can lyse host bacteria and express quorum-quenching enzymes to affect diverse bacteria in biofilm communities may become novel antifouling and antibiofilm agents in industrial and clinical settings. PMID:24951790

  7. Multidimensional analysis of intracellular bacteriophage T7 DNA: effects of amber mutations in genes 3 and 19.

    PubMed Central

    Serwer, P; Watson, R H; Hayes, S J

    1987-01-01

    By use of rate-zonal centrifugation, followed by either one- or two-dimensional agarose gel electrophoresis, the forms of intracellular bacteriophage T7 DNA produced by replication, recombination, and packaging have been analyzed. Previous studies had shown that at least some intracellular DNA with sedimentation coefficients between 32S (the S value of mature T7 DNA) and 100S is concatemeric, i.e., linear and longer than mature T7 DNA. The analysis presented here confirmed that most of this DNA is linear, but also revealed a significant amount of circular DNA. The data suggest that these circles are produced during DNA packaging. It is proposed that circles are produced after a capsid has bound two sequential genomes in a concatemer. The size distribution of the linear, concatemeric DNA had peaks at the positions of dimeric and trimeric concatemers. Restriction endonuclease analysis revealed that most of the mature T7 DNA subunits of concatemers were joined left end to right end. However, these data also suggest that a comparatively small amount of left-end to left-end joining occurs, possibly by blunt-end ligation. A replicating form of T7 DNA that had an S value greater than 100 (100S+ DNA) was also found to contain concatemers. However, some of the 100S+ DNA, probably the most branched component, remained associated with the origin after agarose gel electrophoresis. It has been found that T7 protein 19, known to be required for DNA packaging, was also required to prevent loss, probably by nucleolytic degradation, of the right end of all forms of intracellular T7 DNA. T7 gene 3 endonuclease, whose activity is required for both recombination of T7 DNA and degradation of host DNA, was required for the formation of the 32S to 100S molecules that behaved as concatemers during gel electrophoresis. In the absence of gene 3 endonuclease, the primary accumulation product was origin-associated 100S+ DNA with properties that suggest the accumulation of branches, primarily

  8. Nonlinear Filtering and Approximation Techniques

    DTIC Science & Technology

    1991-09-01

    filtering. UNIT8 Q RECERCE**No 1223 Programme 5 A utomatique, Productique, Traitement dui Signal et des Donnc~es CONSISTENT PARAMETER ESTIMATION FOR...ue’e[71 E C 2.’(Rm x [0,7]; R) is the unique solution of the Hamilton-Jacobi-Bellman equation 9u,’[7](x, t) - EAu "’[ 7](x,t) + He,’[ 7](x,t,Du,[ 7](x,t

  9. Functional contribution of coenzyme specificity-determining sites of 7α-hydroxysteroid dehydrogenase from Clostridium absonum.

    PubMed

    Lou, Deshuai; Wang, Yue; Tan, Jun; Zhu, Liancai; Ji, Shunlin; Wang, Bochu

    2017-10-01

    Studies of the molecular determinants of coenzyme specificity help to reveal the structure-function relationship of enzymes, especially with regards to coenzyme specificity-determining sites (CSDSs) that usually mediate complex interactions. NADP(H)-dependent 7α-hydroxysteroid dehydrogenase from Clostridium absonum (CA 7α-HSDH), a member of the short-chain dehydrogenase/reductase superfamily (SDRs), possesses positively charged CSDSs that mainly contain T15, R16, R38, and R194, forming complicated polar interactions with the adenosine ribose C2 phosphate group of NADP(H). The R38 residue is crucial for coenzyme anchoring, but the influence of the other residues on coenzyme utilization is still not clear. Hence, we performed alanine scanning mutagenesis and molecular dynamic (MD) simulations. The results suggest that the natural CSDSs have the greatest NADP(H)-binding affinity, but not the best activity (k cat ) toward NADP + . Compared with the wild type and other mutants, the mutant R194A showed the highest catalytic efficiency (k cat /K m ), which was more than three-times that of the wild type. MD simulation and kinetics analysis suggested that the importance of the CSDSs of CA 7α-HSDH should be in accordance with the following order R38>T15>R16>R194, and S39 may have a supporting role in NADP(H) anchoring for mutants R16A/T194A and T15A/R16A/T194A. Copyright © 2017. Published by Elsevier Ltd.

  10. Experimental and Theoretical Approaches To Investigate the Immunogenicity of Taenia solium-Derived KE7 Antigen.

    PubMed

    Bobes, Raúl J; Navarrete-Perea, José; Ochoa-Leyva, Adrián; Anaya, Víctor Hugo; Hernández, Marisela; Cervantes-Torres, Jacquelynne; Estrada, Karel; Sánchez-Lopez, Filiberto; Soberón, Xavier; Rosas, Gabriela; Nunes, Cáris Maroni; García-Varela, Martín; Sotelo-Mundo, Rogerio Rafael; López-Zavala, Alonso Alexis; Gevorkian, Goar; Acero, Gonzalo; Laclette, Juan P; Fragoso, Gladis; Sciutto, Edda

    2017-12-01

    Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways. The aim of this study was to identify the T. solium KE7 (TsKE7) full-length protein and to determine its immunogenic properties. Recombinant TsKE7 (rTsKE7) was expressed in Escherichia coli Rosetta2 cells and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from T. solium cyst vesicular fluid in a mass spectrometry-coupled immune proteomic analysis. These antibodies were then used to screen a phage-displayed 7-random-peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides, with the consensus motif Y(F/Y)PS sequence, which includes YYYPS (named GK-1M, for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of serum samples from cysticercotic pigs with 100% specificity but induced weak protection against murine cysticercosis. In silico analysis revealed a universal T-cell epitope(s) in native TsKE7 potentially capable of stimulating cytotoxic T lymphocytes and helper T lymphocytes under different major histocompatibility complex class I and class II mouse haplotypes. Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines. Copyright © 2017 American Society for Microbiology.

  11. [Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms].

    PubMed

    Isakova, Zh T; Talaibekova, E T; Asambaeva, D A; Kerimkulova, A S; Lunegova, O S; Aldasheva, N M; Aldashev, A A

    To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T

  12. 7. Exterior view of Components Test Laboratory (T27), looking south. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Exterior view of Components Test Laboratory (T-27), looking south. The wing in the immediate foreground houses the equipment room. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  13. High-resolution whole-brain diffusion MRI at 7T using radiofrequency parallel transmission.

    PubMed

    Wu, Xiaoping; Auerbach, Edward J; Vu, An T; Moeller, Steen; Lenglet, Christophe; Schmitter, Sebastian; Van de Moortele, Pierre-François; Yacoub, Essa; Uğurbil, Kâmil

    2018-03-30

    Investigating the utility of RF parallel transmission (pTx) for Human Connectome Project (HCP)-style whole-brain diffusion MRI (dMRI) data at 7 Tesla (7T). Healthy subjects were scanned in pTx and single-transmit (1Tx) modes. Multiband (MB), single-spoke pTx pulses were designed to image sagittal slices. HCP-style dMRI data (i.e., 1.05-mm resolutions, MB2, b-values = 1000/2000 s/mm 2 , 286 images and 40-min scan) and data with higher accelerations (MB3 and MB4) were acquired with pTx. pTx significantly improved flip-angle detected signal uniformity across the brain, yielding ∼19% increase in temporal SNR (tSNR) averaged over the brain relative to 1Tx. This allowed significantly enhanced estimation of multiple fiber orientations (with ∼21% decrease in dispersion) in HCP-style 7T dMRI datasets. Additionally, pTx pulses achieved substantially lower power deposition, permitting higher accelerations, enabling collection of the same data in 2/3 and 1/2 the scan time or of more data in the same scan time. pTx provides a solution to two major limitations for slice-accelerated high-resolution whole-brain dMRI at 7T; it improves flip-angle uniformity, and enables higher slice acceleration relative to current state-of-the-art. As such, pTx provides significant advantages for rapid acquisition of high-quality, high-resolution truly whole-brain dMRI data. © 2018 International Society for Magnetic Resonance in Medicine.

  14. Traitement des séquelles de brûlures de la main dans les pays à ressources limitées ; notre expérience en république démocratique du Congo

    PubMed Central

    Kibadi, K.; Moutet, F.

    2015-01-01

    Summary Les séquelles de brûlures de la main sont encore fréquentes dans les pays à ressources limitées. Trente-deux patients, représentant 38 mains, ont été admis et traités, entre le 1er décembre 2010 et le 1er mai 2014 aux Cliniques Universitaires de Kinshasa en République Démocratique du Congo (RDC). nous avons observé 22 patients (69 %) dans le groupe de jeunes (patients âgés de moins de 18 ans), et 10 patients (31 %) chez les adultes (18 à 59 ans). Aucun patient dans le groupe de seniors (60 ans et plus) n’a été observé. Dans le groupe de jeunes, la tranche d’âge de 1 à 5 ans a été la plus atteinte avec 13 malades (40 %). l’accident à la maison était le plus fréquent (72 %). le mécanisme de la brûlure était le plus souvent thermique par flammes (51 %) ou par liquide chaud (34 %). les rétractions et brides sont les lésions le plus observées (84 %). la rétraction dorsale globale « main en griffe» est observée chez 40 % de patients traités, associée à des cicatrices hypertrophiques et chéloïdiennes dans 84 % de cas. Chez les 32 mains traitées chirurgicalement, des excision-greffes ont été réalisées dans 43,7 %, des lambeaux locaux dans 43,7 % et des lambeaux à distance dans 12,5 % de cas. A la sortie de l’hôpital, 84 % de « bons » résultats ont été observés. le suivi a été de 18 mois. le traitement des séquelles de brûlures de la main est possible dans ces pays, exemple de la rDC. Mais les défis à surmonter dans ces pays sont nombreux : la faible accessibilité aux techniques actuelles de la chirurgie plastique, la prise en charge initiale inadéquate des brûlures, la pauvreté. PMID:26668560

  15. Le kyste hydatique du cordon spermatique: une localisation exceptionnelle

    PubMed Central

    Hamdane, Mohamed Moncef; Bougrine, Fethi; Msakni, Issam; Dhaoui-Ghozzi, Amen; Bouziani, Ammar

    2011-01-01

    L’ hydatidose est une anthropo-zoonose due au développement chez l'homme de la forme larvaire du taenia Echinococcus granulosis. La plupart des kystes hydatiques se localisent dans le foie et les poumons. Le kyste hydatique du cordon spermatique est extrêmement rare avec seulement 4 cas rapportés dans la littérature. Les auteurs rapportent dans cet article un nouveau cas d'hydatidose du cordon spermatique. Il s'agissait d'un homme de 40 ans qui consultait pour des douleurs scrotales évoluant depuis huit mois. L'examen clinique a mis en évidence une tuméfaction mobile, inguino-scrotale, droite. L’échographie testiculaire a objectivé une hernie inguinale droite associée à deux kystes épididymaires bilatéraux. Le patient a été opéré pour cure de son hernie avec découverte en per-opératoire d'un kyste du cordon spermatique qui a été réséqué. L'examen anatomopathologique a conclu à une hydatidose du cordon spermatique. PMID:22384304

  16. First-principles studies of the v7×v7R19.1° structure of sulfur on the Pd(1 1 1) surface

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alfonso, D.R.

    2007-11-01

    Density functional theory is used to investigate the v7×v7R19.1° structure of sulfur on the Pd(111) surface. Among the different models that were considered, the densely packed mixed sulfur-metal overlayer structure proposed by Liu et al. [W. Liu, K.A.R. Mitchell, W. Berndt, Surf. Sci. 393 (1997) L119] was found to be the most energetically favorable. This model consists of arrangement of Pd triangles and pentagons on top of Pd(111) with the sulfur atoms at 3/7 monolayer coverage. The dominant mechanism for sulfur interaction with Pd in the overlayer region is the rehybridization of sulfur 3p and metal 4d bands. Simulated scanningmore » tunneling microscopy image for this structure shows some similarity with that obtained from experiment. Our study confirms that surface sulfide with no structural resemblance to its bulk counterparts can form on Pd(111).« less

  17. Quadrennial Review of Military Compensation (7TH). Global Subject Papers

    DTIC Science & Technology

    1992-08-01

    the added result of reducing officers’ retired pay via a reduction in Basic Pay. The draft report recommends the continuous payment of BAS to all...being eligible for VHA is unfair. However, we also believe a minimum eligibility period is needed. The draft report recommends payment of full housing...93-12040 JOIN form Approved REPORT DOCUMENTATION PACE J No0 *flcrr t 0 datA .,-Vtr A’d :,r.¶tq. ~.-- r’ ~ (F. 0 ’ ~ ~ t’-e’,’ -o..t,7d’ A-t’trt I

  18. The technological future of 7T MRI hardware.

    PubMed

    Webb, A G; Van de Moortele, P F

    2016-09-01

    In this article we present our projections of future hardware developments on 7T human MRI systems. These include compact cryogen-light magnets, improved gradient performance, integrated RF-receive and direct current shimming coil arrays, new RF technology with adaptive impedance matching, patient-specific specific absorption rate estimation and monitoring, and increased integration of physiological monitoring systems. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  19. The Roles of Tidal Evolution and Evaporative Mass Loss in the Origin of CoRoT-7 b

    NASA Technical Reports Server (NTRS)

    Jackson, Brian; Miller, Neil; Barnes, Rory; Raymond, Sean N.; Fortney, Jonathan J.; Greenberg, Richard

    2010-01-01

    CoRoT-7 b is the first confirmed rocky exoplanet, but, with an orbital semimajor axis of 0.0172 au, its origins may be unlike any rocky planet in our Solar System. In this study, we consider the roles of tidal evolution and evaporative mass loss in CoRoT-7 b's history, which together have modified the planet's mass and orbit. If CoRoT-7 b has always been a rocky body, evaporation may have driven off almost half its original mass, but the mass loss may depend sensitively on the extent of tidal decay of its orbit. As tides caused CoRoT-7 b's orbit to decay, they brought the planet closer to its host star, thereby enhancing the mass loss rate. Such a large mass loss also suggests the possibility that CoRoT-7 b began as a gas giant planet and had its original atmosphere completely evaporated. In this case, we find that CoRoT-7 b's original mass probably did not exceed 200 Earth masses (about two-third of a Jupiter mass). Tides raised on the host star by the planet may have significantly reduced the orbital semimajor axis, perhaps causing the planet to migrate through mean-motion resonances with the other planet in the system, CoRoT-7 c. The coupling between tidal evolution and mass loss may be important not only for CoRoT-7 b but also for other close-in exoplanets, and future studies of mass loss and orbital evolution may provide insight into the origin and fate of close-in planets, both rocky and gaseous.

  20. Etude de l'amelioration de la qualite des anodes par la modification des proprietes du brai

    NASA Astrophysics Data System (ADS)

    Bureau, Julie

    La qualite des anodes produites se doit d'etre bonne afin d'obtenir de l'aluminium primaire tout en reduisant le cout de production du metal, la consommation d'energie et les emissions environnementales. Or, l'obtention des proprietes finales de l'anode necessite une liaison satisfaisante entre le coke et le brai. Toutefois, la matiere premiere actuelle n'assure pas forcement la compatibilite entre le coke et le brai. Une des solutions les plus prometteuses, pour ameliorer la cohesion entre ces deux materiaux, est la modification des proprietes du brai. L'objectif de ce travail consiste a modifier les proprietes du brai par l'ajout d'additifs chimiques afin d'ameliorer la mouillabilite du coke par le brai modifie pour produire des anodes de meilleure qualite. La composition chimique du brai est modifiee en utilisant des tensioactifs ou agents de modification de surface choisis dans le but d'enrichir les groupements fonctionnels susceptibles d'ameliorer la mouillabilite. L'aspect economique, l'empreinte environnementale et l'impact sur la production sont consideres dans la selection des additifs chimiques. Afin de realiser ce travail, la methodologie consiste a d'abord caracteriser les brais non modifies, les additifs chimiques et les cokes par la spectroscopie infrarouge a transformee de Fourier (FTIR) afin d'identifier les groupements chimiques presents. Puis, les brais sont modifies en ajoutant un additif chimique afin de possiblement modifier ses proprietes. Differentes quantites d'additif sont ajoutees afin d'examiner l'effet de la variation de la concentration sur les proprietes du brai modifie. La methode FTIR permet d'evaluer la composition chimique des brais modifies afin de constater si l'augmentation de la concentration d'additif enrichit les groupements fonctionnels favorisant l'adhesion coke/brai. Ensuite, la mouillabilite du coke par le brai est observee par la methode goutte- sessile. Une amelioration de la mouillabilite par la modification a l'aide d

  1. L'Aventure du LHC

    ScienceCinema

    None

    2018-05-16

    Cette présentation s’adressera principalement aux personnes qui ont construit le LHC. La construction du LHC fut longue et difficile. De nombreux problèmes sont apparus en cours de route. Tous ont été résolus grâce au dévouement et à l’engagement du personnel et des collaborateurs. Je reviendrai sur les coups durs et les réussites qui ont marqués ces 15 dernières années et je vous montrerai combien cette machine, le fruit de vos efforts, est extraordinaire.

  2. On the role of mobile nanoclusters in 2D island nucleation on Si(111)-(7 × 7) surface

    NASA Astrophysics Data System (ADS)

    Rogilo, D. I.; Fedina, L. I.; Kosolobov, S. S.; Latyshev, A. V.

    2018-01-01

    Two-dimensional (2D) Si island nucleation has been studied by in situ reflection electron microscopy within a wide temperature range (650-1090 °C ) on large-scale (∼10-100 μm) terraces to exclude the impact of step permeability and adatom sink to steps. The dependence of 2D island concentration N2D on substrate temperature T and Si deposition rate R displays N2D∝Rχexp (E2D/kT) scaling which parameters change from χ≈0.81, E2D≈1.02 eV to χ≈0.5, E2D≈1.8 eV when Si(111) surface converts from (1 × 1) structure to (7 × 7) reconstruction. We propose that this strong E2D rise accompanied by χ reduction is caused by the change of dominating diffusing particles from adatoms to reconstruction induced nanoclusters. Using a rate-equation model developed to account the dynamics of both diffusing species on the Si(111)-(7 × 7) surface, we show that a stable nucleus of a 2D island appears when two mobile nanoclusters merge together while nucleation kinetics is limited by their attachment to island edges.

  3. Cortical phase changes in Alzheimer's disease at 7T MRI: a novel imaging marker.

    PubMed

    van Rooden, Sanneke; Versluis, Maarten J; Liem, Michael K; Milles, Julien; Maier, Andrea B; Oleksik, Ania M; Webb, Andrew G; van Buchem, Mark A; van der Grond, Jeroen

    2014-01-01

    Postmortem studies have indicated the potential of high-field magnetic resonance imaging (MRI) to visualize amyloid depositions in the cerebral cortex. The aim of this study is to test this hypothesis in patients with Alzheimer's disease (AD). T2*-weighted MRI was performed in 16 AD patients and 15 control subjects. All magnetic resonance images were scored qualitatively by visual assessment, and quantitatively by measuring phase shifts in the cortical gray matter and hippocampus. Statistical analysis was performed to assess differences between groups. Patients with AD demonstrated an increased phase shift in the cortex in the temporoparietal, frontal, and parietal regions (P < .005), and this was associated with individual Mini-Mental State Examination scores (r = -0.54, P < .05). Increased cortical phase shift in AD patients demonstrated on 7-tesla T2*-weighted MRI is a potential new biomarker for AD, which may reflect amyloid pathology in the early stages. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  4. Characterization of a Novel Rieske-Type Alkane Monooxygenase System in Pusillimonas sp. Strain T7-7

    PubMed Central

    Li, Ping; Wang, Lei

    2013-01-01

    The cold-tolerant bacterium Pusillimonas sp. strain T7-7 is able to utilize diesel oils (C5 to C30 alkanes) as a sole carbon and energy source. In the present study, bioinformatics, proteomics, and real-time reverse transcriptase PCR approaches were used to identify the alkane hydroxylation system present in this bacterium. This system is composed of a Rieske-type monooxygenase, a ferredoxin, and an NADH-dependent reductase. The function of the monooxygenase, which consists of one large (46.711 kDa) and one small (15.355 kDa) subunit, was further studied using in vitro biochemical analysis and in vivo heterologous functional complementation tests. The purified large subunit of the monooxygenase was able to oxidize alkanes ranging from pentane (C5) to tetracosane (C24) using NADH as a cofactor, with greatest activity on the C15 substrate. The large subunit also showed activity on several alkane derivatives, including nitromethane and methane sulfonic acid, but it did not act on any aromatic hydrocarbons. The optimal reaction condition of the large subunit is pH 7.5 at 30°C. Fe2+ can enhance the activity of the enzyme evidently. This is the first time that an alkane monooxygenase system belonging to the Rieske non-heme iron oxygenase family has been identified in a bacterium. PMID:23417490

  5. Small C7-T1 lordotic angle and muscle degeneration at C7 level were independent radiological characteristics of patients with cervical imbalance: a propensity score-matched analysis.

    PubMed

    Tamai, Koji; Romanu, Joshua; Grisdela, Phillip; Paholpak, Permsak; Zheng, Pengfei; Nakamura, Hiroaki; Buser, Zorica; Wang, Jeffrey C

    2018-01-31

    Cervical sagittal vertical axis (cSVA) of ≥40 mm is recognized as the key factor of poor health-related quality of life, poor surgical outcomes, and correction loss after surgery for cervical deformity. However, little is known about the radiological characteristics of patients with cSVA≥40 mm. The purpose of this study was to identify the radiological characteristics of patients with cervical imbalance. Retrospective analysis of weight-bearing cervical magnetic resonance (MR) images. Consecutive 1,500 MR images of symptomatic patients in weight-bearing position. Cervical sagittal vertical axis, cervical alignment, cervical balance parameters (T1 slope, Co-C2 angle, C2-C7 angle, C7-T1 angle, neck tilt, and thoracic inlet angle), disc degeneration (Pfirmann and Suzuki classification), end plate degeneration (Modic change), spondylolisthesis (antero- and retrolisthesis), anteroposterior (AP) diameter of dural sac, cross-sectional area (CSA), and fat infiltration ratio of the transversospinalis muscles at C4 and C7 levels. Patients were divided into two groups: cSVA≥40 mm and cSVA<40 mm. Gender, age, and cervical alignment were analyzed. Subsequently, matched imbalance (cSVA≥40 mm) and control (<40 mm) groups were created using the propensity score to adjust for age, gender, and cervical alignment. Cervicothoracic angular parameters, disc degeneration, Modic change, spondylolisthesis, and degeneration of the transversospinalis muscles at C4 and C7 were compared. Variables with p<.05 were included in the multinomial logistic regression model to identify factors that relate to the cervical balance grouping. The incidence of patients with cervical imbalance was 2.5% (37 patients). Those patients had a higher incidence of kyphosis, were older, and there were more male patients. In the matched imbalance group, the T1 slope was greater (p=.028), C7-T1 lordotic angle was smaller (p<.001), the number of anterolisthesis was greater (p=.012), and the fat

  6. CHRFAM7A: a human-specific α7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS

    PubMed Central

    Dang, Xitong; Eliceiri, Brian P.; Baird, Andrew; Costantini, Todd W.

    2015-01-01

    The human genome contains a unique, distinct, and human-specific α7-nicotinic acetylcholine receptor (α7nAChR) gene [CHRNA7 (gene-encoding α7-nicotinic acetylcholine receptor)] called CHRFAM7A (gene-encoding dup-α7-nicotinic acetylcholine receptor) on a locus of chromosome 15 associated with mental illness, including schizophrenia. Located 5′ upstream from the “wild-type” CHRNA7 gene that is found in other vertebrates, we demonstrate CHRFAM7A expression in a broad range of epithelial cells and sequenced the CHRFAM7A transcript found in normal human fetal small intestine epithelial (FHs) cells to prove its identity. We then compared its expression to CHRNA7 in 11 gut epithelial cell lines, showed that there is a differential response to LPS when compared to CHRNA7, and characterized the CHRFAM7A promoter. We report that both CHRFAM7A and CHRNA7 gene expression are widely distributed in human epithelial cell lines but that the levels of CHRFAM7A gene expression vary up to 5000-fold between different gut epithelial cells. A 3-hour treatment of epithelial cells with 100 ng/ml LPS increased CHRFAM7A gene expression by almost 1000-fold but had little effect on CHRNA7 gene expression. Mapping the regulatory elements responsible for CHRFAM7A gene expression identifies a 1 kb sequence in the UTR of the CHRFAM7A gene that is modulated by LPS. Taken together, these data establish the presence, identity, and differential regulation of the human-specific CHRFAM7A gene in human gut epithelial cells. In light of the fact that CHRFAM7A expression is reported to modulate ligand binding to, and alter the activity of, the wild-type α7nAChR ligand-gated pentameric ion channel, the findings point to the existence of a species-specific α7nAChR response that might regulate gut epithelial function in a human-specific fashion.—Dang, X., Eliceiri, B. P., Baird, A., Costantini, T. W. CHRFAM7A: a human-specific α7-nicotinic acetylcholine receptor gene shows differential

  7. Learning-based 3T brain MRI segmentation with guidance from 7T MRI labeling.

    PubMed

    Deng, Minghui; Yu, Renping; Wang, Li; Shi, Feng; Yap, Pew-Thian; Shen, Dinggang

    2016-12-01

    Segmentation of brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is crucial for brain structural measurement and disease diagnosis. Learning-based segmentation methods depend largely on the availability of good training ground truth. However, the commonly used 3T MR images are of insufficient image quality and often exhibit poor intensity contrast between WM, GM, and CSF. Therefore, they are not ideal for providing good ground truth label data for training learning-based methods. Recent advances in ultrahigh field 7T imaging make it possible to acquire images with excellent intensity contrast and signal-to-noise ratio. In this paper, the authors propose an algorithm based on random forest for segmenting 3T MR images by training a series of classifiers based on reliable labels obtained semiautomatically from 7T MR images. The proposed algorithm iteratively refines the probability maps of WM, GM, and CSF via a cascade of random forest classifiers for improved tissue segmentation. The proposed method was validated on two datasets, i.e., 10 subjects collected at their institution and 797 3T MR images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Specifically, for the mean Dice ratio of all 10 subjects, the proposed method achieved 94.52% ± 0.9%, 89.49% ± 1.83%, and 79.97% ± 4.32% for WM, GM, and CSF, respectively, which are significantly better than the state-of-the-art methods (p-values < 0.021). For the ADNI dataset, the group difference comparisons indicate that the proposed algorithm outperforms state-of-the-art segmentation methods. The authors have developed and validated a novel fully automated method for 3T brain MR image segmentation. © 2016 American Association of Physicists in Medicine.

  8. Learning-based 3T brain MRI segmentation with guidance from 7T MRI labeling.

    PubMed

    Deng, Minghui; Yu, Renping; Wang, Li; Shi, Feng; Yap, Pew-Thian; Shen, Dinggang

    2016-12-01

    Segmentation of brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is crucial for brain structural measurement and disease diagnosis. Learning-based segmentation methods depend largely on the availability of good training ground truth. However, the commonly used 3T MR images are of insufficient image quality and often exhibit poor intensity contrast between WM, GM, and CSF. Therefore, they are not ideal for providing good ground truth label data for training learning-based methods. Recent advances in ultrahigh field 7T imaging make it possible to acquire images with excellent intensity contrast and signal-to-noise ratio. In this paper, the authors propose an algorithm based on random forest for segmenting 3T MR images by training a series of classifiers based on reliable labels obtained semiautomatically from 7T MR images. The proposed algorithm iteratively refines the probability maps of WM, GM, and CSF via a cascade of random forest classifiers for improved tissue segmentation. The proposed method was validated on two datasets, i.e., 10 subjects collected at their institution and 797 3T MR images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Specifically, for the mean Dice ratio of all 10 subjects, the proposed method achieved 94.52% ± 0.9%, 89.49% ± 1.83%, and 79.97% ± 4.32% for WM, GM, and CSF, respectively, which are significantly better than the state-of-the-art methods (p-values < 0.021). For the ADNI dataset, the group difference comparisons indicate that the proposed algorithm outperforms state-of-the-art segmentation methods. The authors have developed and validated a novel fully automated method for 3T brain MR image segmentation.

  9. Creep Properties of the As-Cast Al-A319 Alloy: T4 and T7 Heat Treatment Effects

    NASA Astrophysics Data System (ADS)

    Erfanian-Naziftoosi, Hamid R.; Rincón, Ernesto J.; López, Hugo F.

    2016-08-01

    In this work, the creep behavior of a commercial Al-A319 alloy was investigated in the temperature range of 413 K to 533 K (140 °C to 260 °C). Tensile creep specimens in the as-cast condition and after heat treating by solid solution (T4) and by aging (T7) were tested in a stress range varying from 60 to 170 MPa. It was found that steady-state creep strain rate was significantly low in the T7 condition when compared with either the T4 or as-cast alloy conditions. As a result, the time to failure behavior considerably increased. The experimentally determined creep exponents measured from the stress-strain curves were 4 for the as-cast alloy, 7.5 in the solid solution, and 9.5 after aging. In particular, after solid solution a grain substructure was found to develop which indicated that creep in a constant subgrain structure was active, thus accounting for the n exponent of 7.5. In the aged condition, a stress threshold is considered to account for the power law creep exponent n of 9.5. Moreover, It was found that the creep activation energy values were rather similar for the alloys in the as-cast (134 kJ/mol) and T4 (146 kJ/mol) conditions. These values are close to the one corresponding to pure Al self-diffusion (143 kJ/mol). In the aged alloy, the apparent creep activation energy (202 kJ/mol) exceeded that corresponding to Al self-diffusion. This deviation in activation energy is attributed to the effect of temperature on the alloy elastic modulus. Microstructural observations using transmission electron microscopy provided further support for the various dislocation-microstructure interactions exhibited by the alloy under the investigated creep conditions and implemented heat treatments.

  10. Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology.

    PubMed

    Harrison, Daniel M; Oh, Jiwon; Roy, Snehashis; Wood, Emily T; Whetstone, Anna; Seigo, Michaela A; Jones, Craig K; Pham, Dzung; van Zijl, Peter; Reich, Daniel S; Calabresi, Peter A

    2015-08-01

    Pathology in both cortex and deep gray matter contribute to disability in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7-tesla (7T) MRI to visualize small lesions within the thalamus and to relate this to clinical information and cortical lesions. We obtained 7T MRI scans on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were related to demographic data, clinical disability measures, and lesions in cortical gray matter. Thalamic lesions were found in 24/34 of MS cases. Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse lesional areas lining the periventricular surface. The number of thalamic lesions was greater in progressive MS compared to relapsing-remitting (mean ±SD, 10.7 ±0.7 vs. 3.0 ±0.7, respectively, p < 0.001). Thalamic lesion burden (count and volume) correlated with EDSS score and measures of cortical lesion burden, but not with white matter lesion burden or white matter volume. Using 7T MRI allows identification of thalamic lesions in MS, which are associated with disability, progressive disease, and cortical lesions. Thalamic lesion analysis may be a simpler, more rapid estimate of overall gray matter lesion burden in MS. © The Author(s), 2015.

  11. Une complication exceptionnelle du tétanos généralisé: l’embolie pulmonaire

    PubMed Central

    Regaieg, Kais; Bahloul, Mabrouk; Gargouri, Rahma; Bouattour, Abir; Chelly, Hèdi; Bouaziz, Mounir

    2016-01-01

    Le tétanos est une maladie caractérisée par une paralysie spastique et des spasmes. C’est une pathologie grave. Elle nécessite une prise en charge en milieu de réanimation. La mortalité est essentiellement liée aux complications neurovégétatives et infectieuses. Les complications thromboemboliques sont exceptionnelles au cours de cette maladie. A notre connaissance, l’embolie pulmonaire n’a jamais été rapportée et confirmée au cours du tétanos généralisé. Nous présentons à travers cette observation un cas de tétanos généralisé compliqué d’une embolie pulmonaire fibrino cruorique. PMID:28292134

  12. miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4

    PubMed Central

    Okuda, Hiroshi; Xing, Fei; Pandey, Puspa R; Sharma, Sambad; Watabe, Misako; Pai, Sudha K.; Mo, Yin-Yuan; Iiizumi-Gairani, Megumi; Hirota, Shigeru; Liu, Yin; Wu, Kerui; Pochampally, Radhika; Watabe, Kounosuke

    2012-01-01

    Despite significant improvement in survival rates of breast cancer patients, prognosis of metastatic disease is still dismal. Cancer stem-like cells (CSCs) are considered to play a role in metastatic progression of breast cancer; however, the exact pathological role of CSCs is yet to be elucidated. In this report, we found that CSCs (CD24−/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ specific manner. The results of our microRNA profile analysis for these cells revealed that CSCs that are highly metastatic to bone and brain expressed significantly lower level of miR-7 and that this microRNA was capable of modulating one of the essential genes for induced pluripotent stem cell, KLF4. Interestingly, high expression of KLF4 was significantly and inversely correlated to brain- but not bone-metastasis free survival of breast cancer patients, and we indeed found that the expression of miR-7 significantly suppressed the ability of CSCs to metastasize to brain but not to bone in our animal model. We also examined the expression of miR-7 and KLF4 in brain-metastatic lesions and found that these genes were significantly down- or up-regulated, respectively, in the tumor cells in brain. Furthermore, the results of our in vitro experiments indicate that miR-7 attenuates the abilities of invasion and self-renewal of CSCs by modulating KLF4 expression. These results suggest that miR-7 and KLF4 may serve as biomarkers or therapeutic targets for brain metastasis of breast cancer. PMID:23384942

  13. Differential Protein Kinase C-dependent Modulation of Kv7.4 and Kv7.5 Subunits of Vascular Kv7 Channels*

    PubMed Central

    Brueggemann, Lioubov I.; Mackie, Alexander R.; Cribbs, Leanne L.; Freda, Jessica; Tripathi, Abhishek; Majetschak, Matthias; Byron, Kenneth L.

    2014-01-01

    The Kv7 family (Kv7.1–7.5) of voltage-activated potassium channels contributes to the maintenance of resting membrane potential in excitable cells. Previously, we provided pharmacological and electrophysiological evidence that Kv7.4 and Kv7.5 form predominantly heteromeric channels and that Kv7 activity is regulated by protein kinase C (PKC) in response to vasoconstrictors in vascular smooth muscle cells. Direct evidence for Kv7.4/7.5 heteromer formation, however, is lacking. Furthermore, it remains to be determined whether both subunits are regulated by PKC. Utilizing proximity ligation assays to visualize single molecule interactions, we now show that Kv7.4/Kv.7.5 heteromers are endogenously expressed in vascular smooth muscle cells. Introduction of dominant-negative Kv7.4 and Kv7.5 subunits in mesenteric artery myocytes reduced endogenous Kv7 currents by 84 and 76%, respectively. Expression of an inducible protein kinase Cα (PKCα) translocation system revealed that PKCα activation is sufficient to suppress endogenous Kv7 currents in A7r5 rat aortic and mesenteric artery smooth muscle cells. Arginine vasopressin (100 and 500 pm) and the PKC activator phorbol 12-myristate 13-acetate (1 nm) each inhibited human (h) Kv7.5 and hKv7.4/7.5, but not hKv7.4 channels expressed in A7r5 cells. A decrease in hKv7.5 and hKv7.4/7.5 current densities was associated with an increase in PKC-dependent phosphorylation of the channel proteins. These findings provide further evidence for a differential regulation of Kv7.4 and Kv7.5 channel subunits by PKC-dependent phosphorylation and new mechanistic insights into the role of heteromeric subunit assembly for regulation of vascular Kv7 channels. PMID:24297175

  14. Bioequivalence of clavulanate potassium and amoxicillin (1:7) dispersible tablets in healthy volunteers.

    PubMed

    Hu, Guoxin; Dai, Zongshun; Long, Lihong; Han, Ying; Hou, Shuxian; Wu, Li

    2002-01-01

    To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets, a randomized cross-over study was conducted in 18 healthy volunteers. A single oral dose of 1,000 mg Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high-performance liquid chromatography. The main parameters of T were: for Clavulanate Potassium and Amoxicillin, Cmax: 2.46 +/- 1.11 micrograms/ml and 18.81 +/- 7.26 micrograms/ml, Tmax: 1.12 +/- 0.23 h and 1.30 +/- 0.34 h, AUC(0-6 h): 5.18 +/- 2.24 micrograms.h/ml and 45.09 +/- 14.53 micrograms.h/ml, t1/2: 1.43 +/- 0.44 h and 1.09 +/- 0.22 h., respectively. The relative bioavailability of T to R were 96.5 +/- 19.2% and 98.4 +/- 26.1%, respectively. Statistical analysis showed that the two formulations were bioequivalent.

  15. Évolution nycthémérale des composantes biochimiques du phytoplancton de la retenue du barrage Idriss premier (Fès, Maroc)

    NASA Astrophysics Data System (ADS)

    Bahhou, J.; Alaoui Mhamdi, M.

    1999-03-01

    The diel changes of the biochemical composition of the phytoplankton were studied in the Idriss first reservoir (located on the Inaouen river at thirty Km from the city of Fes, Morrocco) during September 1994. Several biomass and metabolic indicators (proteins, carbohydrates, lipids, chlorophyll a and primary production) were assessed every fourth hour over tow days (7, 8 and 9 September). Since the Protein/Carbohydrates ratio (P/C) is largely recognised as a good integrator of the metabolic functions of the cells, we examined its distribution pattern concomitantly with aforementioned parameters. The results demonstrated enhanced P/C ratios clearly indicating that nutrients were sufficiently available for growth. In addition, this index showed a diel significant variation with levels higher in the night than in the day. Moreover, these results suggest that phytoplankton species during the night used the day-synthesised carbohydrates to insure the cell metabolic functioning. The P/C presents relatively high values in proposition to the ones that have been recorded in temperate regions, and seems to be related to azotic inputs of the Inaouen river. Dans le but de parfaire nos connaissances sur le fonctionnement du sous écosystème phytoplancton, nous nous sommes intéressés à étudier son cycle nycthéméral et son métabolisme cellulaire dans la retenue du barrage Idriss premier. Cette dernière, construite sur l'Oued Inaouène, est située à une trentaine de Km de la ville de Fès. Au cours de ce cycle, les prélèvements ont été effectués selon une séquence temporelle de 4 heures pendant 48 heures, les 7, 8 et 9 septembre 1994. L'étude de l'évolution des composantes biochimiques des cellules phytoplanctoniques à savoir les protéines, les glucides et les lipides a permis de mettre en évidence des variations nycthémérales importantes. Ces variations sont d'autant plus importantes que les variations spatiales observées entre les profondeurs. De plus

  16. SL-7 Extreme Stress Data Collection and Reduction.

    DTIC Science & Technology

    1981-06-01

    w c- o b - C.I I’S ~ ~ ~ ~ I’ ’I, , W0 z II 4i4 00 I.cc ’Sc 4 Z Z IZ O * 3 I 3~ 1 t £ 3 I MS 9 4 V CONTENTS Page I. BACKGROUND 1 II. FUNCTIONAL...SL-7-5, (SSC-257) - S-7 Ins: rumen tati-on Th’ooran Background! and Fesearoh Plan by W. J. Siekierka, R. A. Johnson, and CDR C. S. Loosmore, USCG

  17. [125I]Iodo-ASEM, a specific in vivo radioligand for α7-nAChR

    PubMed Central

    Gao, Yongjun; Mease, Ronnie C.; Olson, Thao T.; Kellar, Kenneth J.; Dannals, Robert F.; Pomper, Martin G.; Horti, Andrew G.

    2014-01-01

    [125I]Iodo-ASEM, a new radioligand with high affinity and selectivity for α7-nAChRs (Ki = 0.5 nM; α7/α4β2 = 3,414), has been synthesized in radiochemical yield of 33 ± 6% from the corresponding di-butyltriazene derivative and at high specific radioactivity (1,600 Ci/mmol; 59.2 MBq/μmol). [125I]Iodo-ASEM readily entered the brains of normal CD-1 mice and specifically and selectively labeled cerebral α7-nAChRs. [125I]iodo-ASEM is a new useful tool for studying α7-nAChR. PMID:25687449

  18. Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential

    PubMed Central

    Yu, Yuan; Li, Jialu; Zhu, Xuejun; Tang, Xiaowen; Bao, Yangyi; Sun, Xiang; Huang, Yuhui; Tian, Fang; Liu, Xiaomei; Yang, Lin

    2017-01-01

    Background Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies]), are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells. To pursue the possibility of translating those immunotoxins into clinics, we humanized the nanobody sequences (designated as dhuVHH6) as well as further truncated the Pseudomonas exotoxin A (PE)-derived PE38 toxin to produce a more protease-resistant form, which is named as PE-LR, by deleting majority of PE domain II. Methods and results Three new types of immunotoxins, dhuVHH6-PE38, dVHH6-PE-LR, and dhuVHH6-PE-LR, were successfully constructed. These recombinant immunotoxins were expressed in Escherichia coli and showed that nanobody immunotoxins have the benefits of easy soluble expression in a prokaryotic expression system. Flow cytometry results revealed that all immunotoxins still maintained the ability to bind specifically to CD7-positive T lymphocyte strains without binding to CD7-negative control cells. Laser scanning confocal microscopy revealed that these proteins can be endocytosed into the cytoplasm after binding with CD7-positive cells and that this phenomenon was not observed in CD7-negative cells. WST-8 experiments showed that all immunotoxins retained the highly effective and specific growth inhibition activity in CD7-positive cell lines and primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Further in vivo animal model experiments showed that humanized dhuVHH6-PE38 immunotoxin can tolerate higher doses and extend the survival of NOD-Prkdcem26Il

  19. The late-glacial fluvial terrace t7 at Raunheim (lower River Main), Germany. Constraining the chronological placement by optical stimulated luminescence dating.

    NASA Astrophysics Data System (ADS)

    Thiemeyer, Heinrich; Kadereit, Annette; Zipf, Lars; Flettner, Stephan

    2017-04-01

    younger ages, around ca. 17 ka and ca. 14 ka, indicate that fluvial activity continued into late glacial times and that the deposits were last partly reworked. The colluvial deposits date from approximately 5000 BP until today reflecting the long lasting agricultural use of the old settled river terraces on the lower River Main. A peat layer indicates that the channel in the t7 was still active in Holocene times and finally filled only in the Middle Ages, according to palynological investigations. Murray, A.S. & Wintle, A.G. (2000): Luminescence dating of quartz using an improved single aliquot regenerative-dose protocol. - Radiation Measurements 32: 57-73. Semmel, A. (1969): Quartär. - Erl. Geologische Karte von Hessen 1:25000 Blatt 5916 Hochheim a. Main, 3. Aufl., 209 pp., Wiesbaden.

  20. Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation.

    PubMed

    Di Virgilio, Francesco; Giuliani, Anna L; Vultaggio-Poma, Valentina; Falzoni, Simonetta; Sarti, Alba C

    2018-01-01

    The P2X7 receptor (P2X7R) is a ligand-gated plasma membrane ion channel belonging to the P2X receptor subfamily activated by extracellular nucleotides. General consensus holds that the physiological (and maybe the only) agonist is ATP. However, scattered evidence generated over the last several years suggests that ATP might not be the only agonist, especially at inflammatory sites. Solid data show that NAD + covalently modifies the P2X7R of mouse T lymphocytes, thus lowering the ATP threshold for activation. Other structurally unrelated agents have been reported to activate the P2X7R via a poorly understood mechanism of action: (a) the antibiotic polymyxin B, possibly a positive allosteric P2X7R modulator, (b) the bactericidal peptide LL-37, (c) the amyloidogenic β peptide, and (d) serum amyloid A. Some agents, such as Alu-RNA, have been suggested to activate the P2X7R acting on the intracellular N- or C-terminal domains. Mode of P2X7R activation by these non-nucleotide ligands is as yet unknown; however, these observations raise the intriguing question of how these different non-nucleotide ligands may co-operate with ATP at inflammatory or tumor sites. New information obtained from the cloning and characterization of the P2X7R from exotic mammalian species (e.g., giant panda) and data from recent patch-clamp studies are strongly accelerating our understanding of P2X7R mode of operation, and may provide hints to the mechanism of activation of P2X7R by non-nucleotide ligands.

  1. The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma.

    PubMed

    Reeder, Kristen M; Dunaway, Chad W; Blackburn, Jonathan P; Yu, Zhihong; Matalon, Sadis; Hastie, Annette T; Ampleford, Elizabeth J; Meyers, Deborah A; Steele, Chad

    2018-06-15

    Asthmatics sensitized to fungi are reported to have more severe asthma, yet the immunopathogenic pathways contributing to this severity have not been identified. In a pilot assessment of human asthmatics, those subjects sensitized to fungi demonstrated elevated levels of the common γ-chain cytokine IL-7 in lung lavage fluid, which negatively correlated with the lung function measurement PC20. Subsequently, we show that IL-7 administration during experimental fungal asthma worsened lung function and increased the levels of type 2 cytokines (IL-4, IL-5, IL-13), proallergic chemokines (CCL17, CCL22) and proinflammatory cytokines (IL-1α, IL-1β). Intriguingly, IL-7 administration also increased IL-22, which we have previously reported to drive immunopathogenic responses in experimental fungal asthma. Employing IL22 Cre R26R eYFP reporter mice, we identified γδ T cells, iNKT cells, CD4 T cells and ILC3s as sources of IL-22 during fungal asthma; however, only iNKT cells were significantly increased after IL-7 administration. IL-7-induced immunopathogenesis required both type 2 and IL-22 responses. Blockade of IL-7Rα in vivo resulted in attenuated IL-22 production, lower CCL22 levels, decreased iNKT cell, CD4 T-cell and eosinophil recruitment, yet paradoxically increased dynamic lung resistance. Collectively, these results suggest a complex role for IL-7 signaling in allergic fungal asthma.

  2. Immune protection of microneme 7 (EmMIC7) against Eimeria maxima challenge in chickens.

    PubMed

    Huang, Jingwei; Zhang, Zhenchao; Li, Menghui; Song, Xiaokai; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

    2015-10-01

    In the present study, the immune protective effects of recombinant microneme protein 7 of Eimeria maxima (rEmMIC7) and a DNA vaccine encoding this antigen (pVAX1-EmMIC7) on experimental challenge were evaluated. Two-week-old chickens were randomly divided into five groups. Experimental groups of chickens were immunized with 100 μg DNA vaccine pVAX1-MIC7 or 200 μg rEmMIC7, while control groups of chickens were injected with pVAX1 plasmid or sterile phosphate buffered saline (PBS). The results showed that the anti-EmMIC7 antibody titres in chickens of both rEmMIC7 and pVAX1-MIC7 groups were significantly higher as compared to PBS and pVAX1 control (P < .05). The splenocytes from both vaccinated groups of chickens displayed significantly greater proliferation response compared with the controls (P < .05). Serum from chickens immunized with pVAX1-MIC7 and rEmMIC7 displayed significantly high levels of interleukin-2, interferon-γ, IL-10, IL-17, tumour growth factor-β and IL-4 (P < .05) compared to those of negative controls. The challenge experiment results showed that both the recombinant antigen and the DNA vaccine could obviously alleviate jejunum lesions, body weight loss and enhance oocyst decrease ratio. The anti-coccidial index (ACI) of the pVAX1-MIC7 group was 167.84, higher than that of the recombinant MIC7 protein group, 167.10. Our data suggested that immunization with EmMIC7 was effective in imparting partial protection against E. maxima challenge in chickens and it could be an effective antigen candidate for the development of new vaccines against E. maxima.

  3. Smad7 Protein Interacts with Receptor-regulated Smads (R-Smads) to Inhibit Transforming Growth Factor-β (TGF-β)/Smad Signaling.

    PubMed

    Yan, Xiaohua; Liao, Hongwei; Cheng, Minzhang; Shi, Xiaojing; Lin, Xia; Feng, Xin-Hua; Chen, Ye-Guang

    2016-01-01

    TGF-β is a pleiotropic cytokine that regulates a wide range of cellular actions and pathophysiological processes. TGF-β signaling is spatiotemporally fine-tuned. As a key negative regulator of TGF-β signaling, Smad7 exerts its inhibitory effects by blocking receptor activity, inducing receptor degradation or interfering with Smad-DNA binding. However, the functions and the molecular mechanisms underlying the actions of Smad7 in TGF-β signaling are still not fully understood. In this study we report a novel mechanism whereby Smad7 antagonizes TGF-β signaling at the Smad level. Smad7 oligomerized with R-Smad proteins upon TGF-β signaling and directly inhibited R-Smad activity, as assessed by Gal4-luciferase reporter assays. Mechanistically, Smad7 competes with Smad4 to associate with R-Smads and recruits the E3 ubiquitin ligase NEDD4L to activated R-Smads, leading to their polyubiquitination and proteasomal degradation. Similar to the R-Smad-Smad4 oligomerization, the interaction between R-Smads and Smad7 is mediated by their mad homology 2 (MH2) domains. A positive-charged basic region including the L3/β8 loop-strand module and adjacent amino acids in the MH2 domain of Smad7 is essential for the interaction. These results shed new light on the regulation of TGF-β signaling by Smad7. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Confinement in Wendelstein 7-X Limiter Plasmas

    DOE PAGES

    Hirsch, M.; Dinklage, A.; Alonso, A.; ...

    2017-06-14

    Observations on confinement in the first experimental campaign on the optimized Stellarator Wendelstein 7-X are summarized. In this phase W7-X was equipped with five inboard limiters only and thus the discharge length restricted to avoid local overheating. Stationary plasmas are limited to low densities <2–3 centerdot 10 19 m -3. With the available 4.3 MW ECR Heating core T e ~ 8 keV, T i ~ 1–2 keV are achieved routinely resulting in energy confinement time τ E between 80 ms to 150 ms. For these conditions the plasmas show characteristics of core electron root confinement with peaked T e-profilesmore » and positive E r up to about half of the minor radius. Lastly, profiles and plasma currents respond to on- and off-axis heating and co- and counter ECCD respectively.« less

  5. T7 RNA polymerase-driven inducible cell lysis for DNA transfer from Escherichia coli to Bacillus subtilis.

    PubMed

    Juhas, Mario; Ajioka, James W

    2017-11-01

    The majority of the good DNA editing techniques have been developed in Escherichia coli; however, Bacillus subtilis is better host for a plethora of synthetic biology and biotechnology applications. Reliable and efficient systems for the transfer of synthetic DNA between E. coli and B. subtilis are therefore of the highest importance. Using synthetic biology approaches, such as streamlined lambda Red recombineering and Gibson Isothermal Assembly, we integrated genetic circuits pT7L123, Repr-ts-1 and pLT7pol encoding the lysis genes of bacteriophages MS2, ΦX174 and lambda, the thermosensitive repressor and the T7 RNA polymerase into the E. coli chromosome. In this system, T7 RNA polymerase regulated by the thermosensitive repressor drives the expression of the phage lysis genes. We showed that T7 RNA polymerase significantly increases efficiency of cell lysis and transfer of the plasmid and bacterial artificial chromosome-encoded DNA from the lysed E. coli into B. subtilis. The T7 RNA polymerase-driven inducible cell lysis system is suitable for the efficient cell lysis and transfer of the DNA engineered in E. coli to other naturally competent hosts, such as B. subtilis. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  6. 26 CFR 1.482-7T - Methods to determine taxable income in connection with a cost sharing arrangement (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Methods to determine taxable income in connection with a cost sharing arrangement (temporary). 1.482-7T Section 1.482-7T Internal Revenue INTERNAL...) Adjustments § 1.482-7T Methods to determine taxable income in connection with a cost sharing arrangement...

  7. 26 CFR 1.482-7T - Methods to determine taxable income in connection with a cost sharing arrangement (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Methods to determine taxable income in connection with a cost sharing arrangement (temporary). 1.482-7T Section 1.482-7T Internal Revenue INTERNAL...) Adjustments § 1.482-7T Methods to determine taxable income in connection with a cost sharing arrangement...

  8. A probabilistic template of human mesopontine tegmental nuclei from in vivo 7T MRI.

    PubMed

    Bianciardi, Marta; Strong, Christian; Toschi, Nicola; Edlow, Brian L; Fischl, Bruce; Brown, Emery N; Rosen, Bruce R; Wald, Lawrence L

    2018-04-15

    Mesopontine tegmental nuclei such as the cuneiform, pedunculotegmental, oral pontine reticular, paramedian raphe and caudal linear raphe nuclei, are deep brain structures involved in arousal and motor function. Dysfunction of these nuclei is implicated in the pathogenesis of disorders of consciousness and sleep, as well as in neurodegenerative diseases. However, their localization in conventional neuroimages of living humans is difficult due to limited image sensitivity and contrast, and a stereotaxic probabilistic neuroimaging template of these nuclei in humans does not exist. We used semi-automatic segmentation of single-subject 1.1mm-isotropic 7T diffusion-fractional-anisotropy and T 2 -weighted images in healthy adults to generate an in vivo probabilistic neuroimaging structural template of these nuclei in standard stereotaxic (Montreal Neurological Institute, MNI) space. The template was validated through independent manual delineation, as well as leave-one-out validation and evaluation of nuclei volumes. This template can enable localization of five mesopontine tegmental nuclei in conventional images (e.g. 1.5T, 3T) in future studies of arousal and motor physiology (e.g. sleep, anesthesia, locomotion) and pathology (e.g. disorders of consciousness, sleep disorders, Parkinson's disease). The 7T magnetic resonance imaging procedure for single-subject delineation of these nuclei may also prove useful for future 7T studies of arousal and motor mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Molecular mechanism of serine/threonine protein phosphatase 1 (PP1cα-PP1r7) in spermatogenesis of Toxocara canis.

    PubMed

    Ma, Guang Xu; Zhou, Rong Qiong; Song, Zhen Hui; Zhu, Hong Hong; Zhou, Zuo Yong; Zeng, Yuan Qin

    2015-09-01

    Toxocariasis is one of the most important, but neglected, zoonoses, which is mainly caused by Toxocara canis. To better understand the role of serine/threonine protein phosphatase 1 (PP1) in reproductive processes of male adult T. canis, differential expression analysis was used to reveal the profiles of PP1 catalytic subunit α (PP1cα) gene Tc-stp-1 and PP1 regulatory subunit 7 (PP1r7) gene TcM-1309. Indirect fluorescence immunocytochemistry was carried out to determine the subcellular distribution of PP1cα. Double-stranded RNA interference (RNAi) assays were employed to illustrate the function and mechanism of PP1cα in male adult reproduction. Real-time quantitative PCR (qPCR) showed transcriptional consistency of Tc-stp-1 and TcM-1309 in sperm-producing germline tissues and localization research showed cytoplasmic distribution of PP1cα in sf9 cells, which indicated relevant involvements of PP1cα and PP1r7 in spermatogenesis. Moreover, spatiotemporal transcriptional differences of Tc-stp-1 were determined by gene knockdown analysis, which revealed abnormal morphologies and blocked meiotic divisions of spermatocytes by phenotypic aberration scanning, thereby highlighting the crucial involvement of PP1cα in spermatogenesis. These results revealed a PP1cα-PP1r7 mechanism by which PP1 regulates kinetochore-microtubule interactions in spermatogenesis and provided important clues to identify novel drug or vaccine targets for toxocariasis control. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Full shut-off of Escherichia coli RNA-polymerase by T7 phage requires a small phage-encoded DNA-binding protein

    PubMed Central

    Tabib-Salazar, Aline; Liu, Bing; Shadrin, Andrey; Burchell, Lynn; Wang, Zhexin; Wang, Zhihao; Goren, Moran G.; Yosef, Ido; Qimron, Udi; Severinov, Konstantin

    2017-01-01

    Abstract Infection of Escherichia coli by the T7 phage leads to rapid and selective inhibition of the bacterial RNA polymerase (RNAP) by the 7 kDa T7 protein Gp2. We describe the identification and functional and structural characterisation of a novel 7 kDa T7 protein, Gp5.7, which adopts a winged helix-turn-helix-like structure and specifically represses transcription initiation from host RNAP-dependent promoters on the phage genome via a mechanism that involves interaction with DNA and the bacterial RNAP. Whereas Gp2 is indispensable for T7 growth in E. coli, we show that Gp5.7 is required for optimal infection outcome. Our findings provide novel insights into how phages fine-tune the activity of the host transcription machinery to ensure both successful and efficient phage progeny development. PMID:28486695

  11. Troubles de l'hémostase en réanimation chirurgicale de l'Hôpital Universitaire Joseph Ravoahangy Andrianavalona Antananarivo

    PubMed Central

    Rasoamampianina, Lalaina Elianah; Rafanomezantsoa, Toky Andriamahefa; Rakotondrainibe, Aurélia; Rajaonera, Andriambelo Tovohery; Randriamanantany, Zely Arivelo; Alson, Olivat Rakoto; Raveloson, Nasolotsiry Enintsoa

    2015-01-01

    Les troubles de l'hémostase sont fréquemment observés en réanimation. L'objectif de cette étude est d'en déterminer l'incidence, les étiologies et la prise en charge pour en diminuer le risque de morbi-mortalité. Etude rétrospective sur une période de huit mois en réanimation chirurgicale du CHUA HUJRA. Les dossiers étudiés étaient ceux contenant tous les premiers bilans d'hémostase lors de l'admission du patient en réanimation, avec un âge supérieur à 15 ans. Etaient exclus les dossiers des post opérés (malade ayant subi une intervention chirurgicale). Les dossiers retenus pour l'étude étaient ceux qui ont présenté une ou plusieurs anomalies au niveau du bilan d'hémostase. Cent cinquante-cinq dossiers ont été colligés dont 20,64% ont présenté un trouble de l'hémostase. Les patients de sexe féminin (53,12%) étaient les plus concernés, avec une population âgée en moyenne de 49±19 ans. Trois patients (9,37%) ont présenté une notion de diathèse hémorragique à l'interrogatoire. Les différents troubles de l'hémostase étaient: une diminution du taux de prothrombine (100%), un taux de céphaline activé allongé (78,12%), un international normalized ratio élevé (43,75%) et des thrombopénies (40,62%). Chez 3,12% de ces cas, des accidents hémorragiques ont survenu. La plupart de ces troubles de l'hémostase étaient présents au décours d'hémorragies digestives (46,87%) dont la prise en charge était constituée par l'administration de vitamine K1 (68,75%) et de transfusion de plasma frais congelé (65,62%). D'autres pathologies ont été également incriminées. Une incidence de 15,62% de mortalité a été retrouvée. L'existence des troubles de l'hémostase en réanimation constitue un facteur pronostique imposant un dépistage et une prise en charge précoces et adéquats pour pouvoir en réduire le taux de mortalité. PMID:26848361

  12. Investigation de l'anisotropie du gap supraconducteur dans les composes Ba(Fe(1-x)Co(x))2As2, Ba(1-x)K(x)Fe2As2, LiFeAs et Fe1-deltaTe(1-x)Se(x)

    NASA Astrophysics Data System (ADS)

    Reid, Jean-Philippe

    ommaire La structure du gap supraconducteur et sa modulation sont intimement liees au potentiel d'interaction responsable de l'appariement des electrons d'un supraconducteur. Ainsi, l'etude de la structure du gap-SC et de sa modulation permettent de faire la lumiere sur la nature du mecanisme d'appariement des electrons. A cet egard, les resultats experimentaux des supraconducteurs a base de fer ne cadrent pas dans un seul ensemble, ce qui est en opposition au gap-SC universel des cuprates. Dans ce qui suit, nous presenterons une etude systematique du gap-SC pour plusieurs pnictides. En effet, en utilisant la conductivite thermique, une sonde directionnelle du gap-SC, nous avons ete en mesure de reveler la structure du gap-SC pour les composes suivants : Ba1-xKxFe 2As2, Ba(Fe1-xCo x)2As2, LiFeAs et Fe1-deltaTe 1-xSex. L'etude de ces quatre composes, de trois differentes familles structurales, a pu etablir un tableau partiel mais tres exhaustif de la structure du gap-SC de pnictides. En effet, tel qu'illustre dans cette these, ces quatre composes ne possedent aucun noeud dans leur structure du gap-SC a dopage optimal. Toutefois, a une concentration differente de celle optimale pour les composes K-Ba122 et Co-Ba122, des noeuds apparaissent sur la surface de Fermi, aux extremites 'du dome supraconducteur. Ceci suggere fortement que, pour ces composes, la presence de noeuds sur la surface de Fermi est nuisible a la phase supraconductrice. Mots-cles: Supraconducteurs a base de fer, Pnictides, Structure du gap supraconducteur, Conductivite thermique

  13. The expression of miR-21 and miR-143 is deregulated by the HPV16 E7 oncoprotein and 17β-estradiol.

    PubMed

    Gómez-Gómez, Yazmín; Organista-Nava, Jorge; Ocadiz-Delgado, Rodolfo; García-Villa, Enrique; Leyva-Vazquez, Marco Antonio; Illades-Aguiar, Berenice; Lambert, Paul F; García-Carrancá, Alejandro; Gariglio, Patricio

    2016-08-01

    MicroRNAs (miRNAs) are a class of non-coding RNAs that negatively regulate their target mRNAs at a posttranscriptional level, thereby affecting crucial processes in cancer development. However, little is known about the molecular events that control expression of miRNAs in cervical cancer (CC). HPV16 E7 oncoprotein in conjunction with estrogen are sufficient to produce high grade cervical dysplasia and invasive cervical malignancies in a mouse model. In the present study, we determined the potential role that the E7 oncoprotein and 17β-estradiol (E2) play in the deregulation of miR-21 and miR-143 expression levels by these two risk factors. We found that, while the expression of miR-21 was upregulated and the expression of miR-143 was downregulated by the HPV16 E7 oncoprotein in vivo, and in vitro and that E2 treatment is also implicated in the deregulation of these important miRNAs in vivo. Sustained upregulation of miR-21 resulted in suppression of PTEN expression, and repression of miR-143 increased the mRNA and protein levels from Bcl-2. These results suggested that HPV type 16 E7 oncoprotein and E2 play an important role in regulating miR-21 and miR-143 expression. We have observed similar results in CC patients containing HPV16 sequences, suggesting that these miRNAs could serve as diagnostic biomarkers in CC. The present study highlights the roles of miRNAs in cervical tissue and implicates these important molecules in cervical carcinogenesis.

  14. Excrétion rénale des ions divalents après homotransplantation rénale

    PubMed Central

    Cartier, F.; Popovtzer, M. M.; Robinette, J.; Pinggera, W. F.; Halgrimson, C. G.; Starzl, T. E.

    2010-01-01

    RÉSUMÉ L’élimination rénale des ions divalents, celle du Na et du K, ont été étudiées de façon comparative dans les suites immédiates de l’homotransplantation rénale chez 6 patients. Durant la période initiale polyurique (> 3ml/mn), le taux d’excrétion du Ca filtré (Cca/Ccr), du Mg, du P, du Na et du K, est élevé et il existe une corrélation étroite et quasi constante entre l’élimination du Ca, du Mg et du Na ; la corrélation n’est pas constante entre l’élimination du Na et du K, du Mg et du K. Pendant les deux jours suivants, le taux d’excrétion diminue, sauf pour le P ; il existe encore une corrélation entre l’excrétion du Ca, du Mg et du Na, non entre celle du Na et du K, du Mg et du K. L’excrétion du Ca l’emporte sur celle du Na au cours de la première période, non au cours de la seconde. A la lumière de ces données, on envisage l’intervention possible de divers facteurs, tels l’inflation hydrosique et l’hyperazotémie préalables, l’ischémie rénale contemporaine de la transplantation, les effets de la dénervation rénale, du traitement cortisonique, de l’hyperparathyroïdie et ceux des modifications circulatoires rénales. PMID:4574592

  15. GABA and Glutamate in Children with Primary Complex Motor Stereotypies: A 1H MRS Study at 7T

    PubMed Central

    Harris, A. D.; Singer, H. S.; Horska, A.; Kline, T.; Ryan, M.; Edden, R. A. E.; Mahone, E. Mark

    2015-01-01

    Background and Purpose Complex motor stereotypies (CMS) are rhythmic, repetitive, fixed, purposeful but purposeless movements that stop with distraction. They can occur in otherwise normal healthy children (primary stereotypies), as well in those with autism spectrum disorders (secondary stereotypies). The underlying neurobiological basis for these movements is unknown, but thought to involve cortical-striatal-thalamo-cortical pathways. In order to further clarify potential neurochemical alterations, GABA, glutamate (Glu), glutamine (Gln), N-acetyl aspartate (NAA) and choline (Cho) levels were measured in four frontostriatal regions, using 1H MRS at 7T. Materials and Methods A total of 18 children with primary CMS and 24 typically developing controls, ages 5-10 years completed MRS at 7T. Single voxel STEAM acquisitions from the anterior cingulate cortex (ACC), premotor cortex (PMC), dorsolateral prefrontal cortex (DLPFC) and striatum were obtained and metabolites were quantified with respect to creatine using LCModel. Results The 7T scan was well tolerated by all participants. Compared to controls, children with CMS had lower levels of GABA ACC (GABA/Cr, p=0.049; GABA/Glu: p=0.051) and striatum (GABA/Cr: p= 0.028; GABA/Glu: p=0.0037), but not the DLPFC or PMC. Glu, Gln, NAA, and Cho levels did not differ between groups in any of the aforementioned regions. Within the CMS group, reduced GABA/Cr in the ACC was significantly associated with greater severity of motor stereotypies (r=-0.59, p= 0.021). Conclusions These results suggest possible GABAergic dysfunction within corticostriatal pathways in children with primary CMS. PMID:26542237

  16. Airframe/Propulsion Interference

    DTIC Science & Technology

    1975-03-01

    elancee, en incidence, est prcsenic figure 14. L’intrados se caracterise par une divergence des lignes dc courant, et par une reducti.in ’es nombres...ale de la zone dissipative en R et A/S une fonction du nombre de Hach au recollement Mq et d’un parametre de forme Hiq caracterisant le...extralte d’une Etude expE- rimentale prEsentEe rEf. [13]. Bile se caractErise par un elancement assez important et un rapport de tronoature ft^ /\\M.t

  17. Depletion of host CCR7(+) dendritic cells prevented donor T cell tissue tropism in anti-CD3-conditioned recipients.

    PubMed

    He, Wei; Racine, Jeremy J; Johnston, Heather F; Li, Xiaofan; Li, Nainong; Cassady, Kaniel; Liu, Can; Deng, Ruishu; Martin, Paul; Forman, Stephen; Zeng, Defu

    2014-07-01

    We reported previously that anti-CD3 mAb treatment before hematopoietic cell transplantation (HCT) prevented graft-versus-host disease (GVHD) and preserved graft-versus-leukemia (GVL) effects in mice. These effects were associated with downregulated donor T cell expression of tissue-specific homing and chemokine receptors, marked reduction of donor T cell migration into GVHD target tissues, and deletion of CD103(+) dendritic cells (DCs) in mesenteric lymph nodes (MLN). MLN CD103(+) DCs and peripheral lymph node (PLN) DCs include CCR7(+) and CCR7(-) subsets, but the role of these DC subsets in regulating donor T cell expression of homing and chemokine receptors remain unclear. Here, we show that recipient CCR7(+), but not CCR7(-), DCs in MLN induced donor T cell expression of gut-specific homing and chemokine receptors in a retinoid acid-dependent manner. CCR7 regulated activated DC migration from tissue to draining lymph node, but it was not required for the ability of DCs to induce donor T cell expression of tissue-specific homing and chemokine receptors. Finally, anti-CD3 treatment depleted CCR7(+) but not CCR7(-) DCs by inducing sequential expansion and apoptosis of CCR7(+) DCs in MLN and PLN. Apoptosis of CCR7(+) DCs was associated with DC upregulation of Fas expression and natural killer cell but not T, B, or dendritic cell upregulation of FasL expression in the lymph nodes. These results suggest that depletion of CCR7(+) host-type DCs, with subsequent inhibition of donor T cell migration into GVHD target tissues, can be an effective approach in prevention of acute GVHD and preservation of GVL effects. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Profiling lethal factor interacting proteins from human stomach using T7 phage display screening.

    PubMed

    Cardona-Correa, Albin; Rios-Velazquez, Carlos

    2016-05-01

    The anthrax lethal factor (LF) is a zinc dependent metalloproteinase that cleaves the majority of mitogen-activated protein kinase kinases and a member of NOD-like receptor proteins, inducing cell apoptosis. Despite efforts to fully understand the Bacillus anthracis toxin components, the gastrointestinal (GI) anthrax mechanisms have not been fully elucidated. Previous studies demonstrated gastric ulceration, and a substantial bacterial growth rate in Peyer's patches. However, the complete molecular pathways of the disease that results in tissue damage by LF proteolytic activity remains unclear. In the present study, to identify the profile of the proteins potentially involved in GI anthrax, protein‑protein interactions were investigated using human stomach T7 phage display (T7PD) cDNA libraries. T7PD is a high throughput technique that allows the expression of cloned DNA sequences as peptides on the phage surface, enabling the selection and identification of protein ligands. A wild type and mutant LF (E687A) were used to differentiate interaction sites. A total of 124 clones were identified from 194 interacting‑phages, at both the DNA and protein level, by in silico analysis. Databases revealed that the selected candidates were proteins from different families including lipase, peptidase‑A1 and cation transport families, among others. Furthermore, individual T7PD candidates were tested against LF in order to detect their specificity to the target molecule, resulting in 10 LF‑interacting peptides. With a minimum concentration of LF for interaction at 1 µg/ml, the T7PD isolated pepsin A3 pre‑protein (PAP) demonstrated affinity to both types of LF. In addition, PAP was isolated in various lengths for the same protein, exhibiting common regions following PRALINE alignment. These findings will help elucidate and improve the understanding of the molecular pathogenesis of GI anthrax, and aid in the development of potential therapeutic agents.

  19. Tissue-specific alternative splicing of TCF7L2

    PubMed Central

    Prokunina-Olsson, Ludmila; Welch, Cullan; Hansson, Ola; Adhikari, Neeta; Scott, Laura J.; Usher, Nicolle; Tong, Maurine; Sprau, Andrew; Swift, Amy; Bonnycastle, Lori L.; Erdos, Michael R.; He, Zhi; Saxena, Richa; Harmon, Brennan; Kotova, Olga; Hoffman, Eric P.; Altshuler, David; Groop, Leif; Boehnke, Michael; Collins, Francis S.; Hall, Jennifer L.

    2009-01-01

    Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle, subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue-specific pattern of alternative splicing. We tested whether the expression of TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D. Expression of two splicing forms was lower in pancreatic islets with increasing counts of T2D-associated alleles of the SNPs: a ubiquitous splicing form (P = 0.018 for rs7903146 and P = 0.020 for rs12255372) and a splicing form found in pancreatic islets, pancreas and colon but not in other tissues tested here (P = 0.009 for rs12255372 and P = 0.053 for rs7903146). Expression of this form in glucose-stimulated pancreatic islets correlated with expression of proinsulin (r2 = 0.84–0.90, P < 0.00063). In summary, we identified a tissue-specific pattern of alternative splicing of TCF7L2. After adjustment for multiple tests, no association between expression of TCF7L2 in eight types of human tissue samples and T2D-associated genetic variants remained significant. Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164–FJ010174. PMID:19602480

  20. Relaxivity of Ferumoxytol at 1.5 T and 3.0 T.

    PubMed

    Knobloch, Gesine; Colgan, Timothy; Wiens, Curtis N; Wang, Xiaoke; Schubert, Tilman; Hernando, Diego; Sharma, Samir D; Reeder, Scott B

    2018-05-01

    The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Ferumoxytol was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 smM; r1plasma = 19.0 ± 1.7 smM; r2saline = 60.8 ± 3.8 smM; r2plasma = 64.9 ± 1.8 smM; r2*saline = 60.4 ± 4.7 smM; r2*plasma = 64.4 ± 2.5 smM; 3.0 T: r1saline = 10.0 ± 0.3 smM; r1plasma = 9.5 ± 0.2 smM; r2saline = 62.3 ± 3.7 smM; r2plasma = 65.2 ± 1.8 smM; r2*saline = 57.0 ± 4.7 smM; r2*plasma = 55.7 ± 4.4 smM). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

  1. Crystal structure and absolute configuration of (3aS,4S,5R,7aR)-2,2,7-trimethyl-3a,4,5,7a-tetra-hydro-1,3-benzodioxole-4,5-diol.

    PubMed

    Macías, Mario A; Suescun, Leopoldo; Pandolfi, Enrique; Schapiro, Valeria; Tibhe, Gaurao D; Mombrú, Álvaro W

    2015-09-01

    The absolute configuration of the title compound, C10H16O4, determined as 3aS,4S,5R,7aR on the basis of the synthetic pathway, was confirmed by X-ray diffraction. The mol-ecule contains a five- and a six-membered ring that adopt twisted and envelope conformations, respectively. The dihedral angle between the mean planes of the rings is 76.80 (11)° as a result of their cis-fusion. In the crystal, mol-ecules are linked by two pairs of O-H⋯O hydrogen bonds, forming chains along [010]. These chains are further connected by weaker C-H⋯O inter-actions along [100], creating (001) sheets that inter-act only by weak van der Waals forces.

  2. Homozygous MYH7 R1820W mutation results in recessive myosin storage myopathy: scapuloperoneal and respiratory weakness with dilated cardiomyopathy.

    PubMed

    Yüceyar, Nur; Ayhan, Özgecan; Karasoy, Hatice; Tolun, Aslıhan

    2015-04-01

    Myosin storage myopathy (MSM) is a protein aggregate myopathy caused by the accumulation of myosin in muscle fibres and results from MYH7 mutation. Although MYH7 mutation is also an established cause of variable cardiomyopathy with or without skeletal myopathy, cardiomyopathy with MSM is a rare combination. Here, we update the clinical findings in the two brothers that we previously reported as having recessively inherited MSM characterized by scapuloperoneal distribution of weakness and typical hyaline-like bodies in type 1 muscle fibres. One of the patients, weak from childhood but not severely symptomatic until 28 years of age, had an unusual combination of MSM, severe dilated cardiomyopathy, and respiratory impairment at the age of 44 years. We identified homozygous missense mutation c.5458C>T (p.R1820W) in exon 37 in these patients as the second recessive MYH7 mutation reported to date. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

    PubMed

    Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Rosin, Diane L; Guyenet, Patrice G; Okusa, Mark D

    2016-05-02

    The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.

  4. Crystal-field, exchange interactions and magnetism in pyrochlore ferromagnet R2V2O7 (R3+=Y, Lu)

    NASA Astrophysics Data System (ADS)

    Ali Biswas, A.; Jana, Y. M.

    2013-03-01

    The temperature dependence of the observed bulk magnetic susceptibility, magnetization, paramagnetic Curie temperature θCW, magnetic specific heat of ferromagnetic semi-conducting pyrochlore-based vanadate compounds Y2V2O7 and Lu2V2O7, which are the simplest of R2M2O7 pyrochlore series of oxides, are simulated and analyzed, simultaneously and consistently, within the frame work of the appropriate crystal-field (CF) theory and a mean-field approximation by introducing effective anisotropic molecular-field tensors and also taking account of appreciable spin-orbit coupling. The electronic and magnetic properties are correlated to the structural parameters. Ten-fold degenerate 2D term of 3d1 V4+-ions is split into five Kramers doublets with overall CF splitting Δ1≈2 eV and the total splitting of the 2T2g state Δ0≈0.4 eV under combined actions of octahedral CF, trigonal (D3d) distortion at V-site and spin-orbit coupling. The ground doublet is a well-isolated effectively spin s=1/2 state, characterized by the anisotropic g-tensors and directional magnetic moments. The degeneracy of the ground state is lifted by the spin-spin correlations among V4-tetrahedra at T∼170 K, which causes the formation of ferromagnetic clusters in these pyrochlores. The temperature dependence of the calculated directional site-susceptibilities shows that the V4+ ions have a substantial easy-axis single-ion anisotropy along local <111> axis of a given V4-tetrahedron in the magnetic phase where ferromagnetic clusters coexist with paramagnetic phase.

  5. Rheumatoid arthritis synovial fibroblasts produce a soluble form of the interleukin-7 receptor in response to pro-inflammatory cytokines

    PubMed Central

    Badot, V; Durez, P; Van den Eynde, BJ; Nzeusseu-Toukap, A; Houssiau, FA; Lauwerys, BR

    2011-01-01

    Abstract We previously demonstrated that baseline synovial overexpression of the interleukin-7 receptor α-chain (IL-7R) is associated with poor response to tumour necrosis factor (TNF) blockade in rheumatoid arthritis (RA). We found that IL-7R gene expression is induced in fibroblast-like synovial cells (FLS) by the addition of TNF-α, IL-1β and combinations of TNF-α+ IL-1β or TNF-α+ IL-17, thereby suggesting that these cytokines play a role in the resistance to TNF blockade in RA. Because FLS and CD4 T cells also produce a soluble form of IL-7R (sIL-7R), resulting from an alternative splicing of the full-length transcript, we wondered whether expression of sIL-7R is similarly regulated by pro-inflammatory cytokines. We also investigated whether sIL-7R is detectable in the serum of RA patients and associated with response to TNF blockade. RA FLS were cultured in the presence of pro-inflammatory cytokines and sIL-7R concentrations were measured in culture supernatants. Similarly, sIL-7R titres were measured in sera obtained from healthy individuals, early untreated RA patients with active disease and disease-modifying anti-rheumatic drug (DMARD)-resistant RA patients prior to initiation of TNF-blockade. Baseline serum sIL-7R titres were correlated with validated clinical measurements of disease activity. We found that exposure of RA FLS to pro-inflammatory cytokines (TNF-α, IL-1β and combinations of TNF-α and IL-1β or TNF-α and IL-17) induces sIL-7R secretion. Activated CD4 T cells also produce sIL-7R. sIL-7R serum levels are higher in RA patients as compared to controls. In DMARD-resistant patients, high sIL-7R serum concentrations are strongly associated with poor response to TNF-blockade. In conclusion, sIL-7R is induced by pro-inflammatory cytokines in RA FLS. sIL-7R could qualify as a new biomarker of response to therapy in RA. PMID:21129157

  6. Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1.

    PubMed

    Li, Yuan; Shan, Fei; Chen, Jinglong

    2017-03-21

    The mechanisms of lipid raft regulation by microRNAs in breast cancer are not fully understood. This work focused on the evaluation and identification of miR-3908, which may be a potential biomarker related to the migration of breast cancer cells, and elucidates lipid-raft-regulating cell migration in breast cancer. To confirm the prediction that miR-3908 is matched with AdipoR1, we used 3'-UTR luciferase activity of AdipoR1 to assess this. Then, human breast cancer cell line MCF-7 was cultured in the absence or presence of the mimics or inhibitors of miR-3908, after which the biological functions of MCF-7 cells were analyzed. The protein expression of AdipoR1, AMPK, and SIRT-1 were examined. The interaction between AdipoR1 and Flotillin-1, or its effects on lipid rafts on regulating cell migration of MCF-7, was also investigated. AdipoR1 is a direct target of miR-3908. miR-3908 suppresses the expression of AdipoR1 and its downstream pathway genes, including AMPK, p-AMPK, and SIRT-1. miR-3908 enhances the process of breast cancer cell clonogenicity. miR-3908 exerts its effects on the proliferation and migration of MCF-7 cells, which are mediated by lipid rafts regulating AdipoR1's ability to bind Flotillin-1. miR-3908 is a crucial mediator of the migration process in breast cancer cells. Lipid rafts regulate the interactions between AdipoR1 and Flotillin-1 and then the migration process associated with miR-3908 in MCF-7 cells. Our findings suggest that targeting miR-3908 and the lipid raft, may be a promising strategy for the treatment and prevention of breast cancer.

  7. Circulating levels of miR-7, miR-152 and miR-192 respond to vitamin D supplementation in adults with prediabetes and correlate with improvements in glycemic control.

    PubMed

    Nunez Lopez, Yury O; Pittas, Anastassios G; Pratley, Richard E; Seyhan, Attila A

    2017-11-01

    Vitamin D may play an important role in modifying the risk of type 2 diabetes. Supplementation with cholecalciferol has been shown to improve β cell function and to attenuate the rise in glycated hemoglobin in people at high risk of diabetes. We examined whether circulating microRNAs (miRNAs) reflect disease progression and/or respond to vitamin D supplementation. We measured plasma levels of select miRNAs implicated in diabetes in people with prediabetes treated either with placebo (n=21) or 2000 U of cholecalciferol daily (n=21) for 4 months in the Calcium and Vitamin D for Diabetes Mellitus trial and compared the baseline-adjusted changes after correcting for age, body mass index, race, time of study entry (season) and baseline disposition index. Circulating levels of miR-7 (sixfold reduction, P=.01), miR-152 (1.5-fold increase, P=.03), and miR-192 (1.7-fold reduction, P=.026) displayed significant treatment-by-time interactions between the placebo- and the vitamin-D-treated groups. Plasma levels of miR-7 were reduced in the vitamin D and increased in the placebo group. The change in miR-152 positively correlated with the change in levels of the circulating metabolite 25-hydroxyvitamin D (r=0.33, P=.046) and negatively correlated with the change in glycated hemoglobin (r=-0.37, P=.024). The change in miR-192 positively correlated with the change in fasting glucose (r=0.41, P<.011). In conclusion, reduction of circulating miR-7 and miR-192, accompanied by elevation of miR-152, reflects a beneficial metabolic response to vitamin D treatment in people with prediabetes. These miRNAs may be useful biomarkers in diabetes prevention trials and other studies of vitamin D. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

    PubMed

    Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

    2016-03-01

    Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron

  9. Gold-rich R 3Au 7Sn 3: Establishing the interdependence between electronic features and physical properties

    DOE PAGES

    Provino, Alessia; Steinberg, Simon; Smetana, Volodymyr; ...

    2015-05-18

    Two new polar intermetallic compounds Y 3Au 7Sn 3 (I) and Gd 3Au 7Sn 3 (II) have been synthesized and their structures have been determined by single crystal X-ray diffraction (P6 3/m; Z = 2, a = 8.148(1)/8.185(3), and c = 9.394(2)/9.415(3) for I/II, respectively). They can formally be assigned to the Cu 10Sn 3 type and consist of parallel slabs of Sn centered, edge-sharing trigonal Au 6 antiprisms connected through R 3 (R = Y, Gd) triangles. Additional Au atoms reside in the centres of trigonal Au 6 prisms forming Au@Au 6 clusters with Au–Au distances of 2.906–2.960 Å,more » while the R–R contacts in the R 3 groups are considerably larger than the sums of their metallic radii. These exclusive structural arrangements provide alluring systems to study the synergism between strongly correlated systems, particularly, those in the structure of (II), and extensive polar intermetallic contacts, which has been inspected by measurements of the magnetic properties, heat capacities and electrical conductivities of both compounds. Gd 3Au 7Sn 3 shows an antiferromagnetic ordering at 13 K, while Y 3Au 7Sn 3 is a Pauli paramagnet and a downward curvature in its electrical resistivity at about 1.9 K points to a superconducting transition. DFT-based band structure calculations on R 3Au 7Sn 3 (R = Y, Gd) account for the results of the conductivity measurements and different spin ordering models of (II) provide conclusive hints about its magnetic structure. As a result, chemical bonding analyses of both compounds indicate that the vast majority of bonding originates from the heteroatomic Au–Gd and Au–Sn interactions, while homoatomic Au–Au bonding is evident within the Au@Au 6 clusters.« less

  10. Full shut-off of Escherichia coli RNA-polymerase by T7 phage requires a small phage-encoded DNA-binding protein.

    PubMed

    Tabib-Salazar, Aline; Liu, Bing; Shadrin, Andrey; Burchell, Lynn; Wang, Zhexin; Wang, Zhihao; Goren, Moran G; Yosef, Ido; Qimron, Udi; Severinov, Konstantin; Matthews, Steve J; Wigneshweraraj, Sivaramesh

    2017-07-27

    Infection of Escherichia coli by the T7 phage leads to rapid and selective inhibition of the bacterial RNA polymerase (RNAP) by the 7 kDa T7 protein Gp2. We describe the identification and functional and structural characterisation of a novel 7 kDa T7 protein, Gp5.7, which adopts a winged helix-turn-helix-like structure and specifically represses transcription initiation from host RNAP-dependent promoters on the phage genome via a mechanism that involves interaction with DNA and the bacterial RNAP. Whereas Gp2 is indispensable for T7 growth in E. coli, we show that Gp5.7 is required for optimal infection outcome. Our findings provide novel insights into how phages fine-tune the activity of the host transcription machinery to ensure both successful and efficient phage progeny development. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Assessment of magnetic field interactions and radiofrequency‐radiation‐induced heating of metallic spinal implants in 7 T field

    PubMed Central

    Tsukimura, Itsuko; Sasaki, Makoto; Endo, Hirooki; Yamabe, Daisuke; Oikawa, Ryosuke; Doita, Minoru

    2017-01-01

    ABSTRACT The safety of metallic spinal implants in magnetic resonance imaging (MRI) performed using ultrahigh fields has not been established. Hence, we examined whether the displacement forces caused by a static magnetic field and the heating induced by radiofrequency radiation are substantial for spinal implants in a 7 T field. We investigated spinal rods of various lengths and materials, a screw, and a cross‐linking bridge in accordance with the American Society for Testing and Materials guidelines. The displacement forces of the metallic implants in static 7 T and 3 T static magnetic fields were measured and compared. The temperature changes of the implants during 15‐min‐long fast spin‐echo and balanced gradient‐echo image acquisition sequences were measured in the 7 T field. The deflection angles of the metallic spinal materials in the 7 T field were 5.0–21.0° [median: 6.7°], significantly larger than those in the 3 T field (1.0–6.3° [2.2°]). Among the metallic rods, the cobalt–chrome rods had significantly larger deflection angles (17.8–21.0° [19.8°]) than the pure titanium and titanium alloy rods (5.0–7.7° [6.2°]). The temperature changes of the implants, including the cross‐linked rods, were 0.7–1.0°C [0.8°C] and 0.6–1.0°C [0.7°C] during the fast spin‐echo and balanced gradient‐echo sequences, respectively; these changes were slightly larger than those of the controls (0.4–1.1°C [0.5°C] and 0.3–0.9°C [0.6°C], respectively). All of the metallic spinal implants exhibited small displacement forces and minimal heating, indicating that MRI examinations using 7 T fields may be performed safely on patients with these implants. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1831–1837, 2017. PMID:27769107

  12. Assessment of magnetic field interactions and radiofrequency-radiation-induced heating of metallic spinal implants in 7 T field.

    PubMed

    Tsukimura, Itsuko; Murakami, Hideki; Sasaki, Makoto; Endo, Hirooki; Yamabe, Daisuke; Oikawa, Ryosuke; Doita, Minoru

    2017-08-01

    The safety of metallic spinal implants in magnetic resonance imaging (MRI) performed using ultrahigh fields has not been established. Hence, we examined whether the displacement forces caused by a static magnetic field and the heating induced by radiofrequency radiation are substantial for spinal implants in a 7 T field. We investigated spinal rods of various lengths and materials, a screw, and a cross-linking bridge in accordance with the American Society for Testing and Materials guidelines. The displacement forces of the metallic implants in static 7 T and 3 T static magnetic fields were measured and compared. The temperature changes of the implants during 15-min-long fast spin-echo and balanced gradient-echo image acquisition sequences were measured in the 7 T field. The deflection angles of the metallic spinal materials in the 7 T field were 5.0-21.0° [median: 6.7°], significantly larger than those in the 3 T field (1.0-6.3° [2.2°]). Among the metallic rods, the cobalt-chrome rods had significantly larger deflection angles (17.8-21.0° [19.8°]) than the pure titanium and titanium alloy rods (5.0-7.7° [6.2°]). The temperature changes of the implants, including the cross-linked rods, were 0.7-1.0°C [0.8°C] and 0.6-1.0°C [0.7°C] during the fast spin-echo and balanced gradient-echo sequences, respectively; these changes were slightly larger than those of the controls (0.4-1.1°C [0.5°C] and 0.3-0.9°C [0.6°C], respectively). All of the metallic spinal implants exhibited small displacement forces and minimal heating, indicating that MRI examinations using 7 T fields may be performed safely on patients with these implants. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1831-1837, 2017. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.

  13. Ultrashort Echo Time and Zero Echo Time MRI at 7T

    PubMed Central

    Larson, Peder E. Z.; Han, Misung; Krug, Roland; Jakary, Angela; Nelson, Sarah J.; Vigneron, Daniel B.; Henry, Roland G.; McKinnon, Graeme; Kelley, Douglas A. C.

    2016-01-01

    Object Zero echo time (ZTE) and ultrashort echo time (UTE) pulse sequences for MRI offer unique advantages of being able to detect signal from rapidly decaying short-T2 tissue components. In this paper, we applied 3D zero echo time (ZTE) and ultrashort echo time (UTE) pulse sequences at 7T to assess differences between these methods. Materials and Methods We matched the ZTE and UTE pulse sequences closely in terms of readout trajectories and image contrast. Our ZTE used the Water- and fat-suppressed solid-state proton projection imaging (WASPI) method to fill the center of k-space. Images from healthy volunteers obtained at 7T were compared qualitatively as well as with SNR and CNR measurements for various ultrashort, short, and long-T2 tissues. Results We measured nearly identical contrast-to-noise and signal-to-noise ratios (CNR/SNR) in similar scan times between the two approaches for ultrashort, short, and long-T2 components in the brain, knee and ankle. In our protocol, we observed gradient fidelity artifacts in UTE, and our chosen flip angle and readout also resulted as well as shading artifacts in ZTE due to inadvertent spatial selectivity. These can be corrected by advanced reconstruction methods or with different chosen protocol parameters. Conclusion The applied ZTE and UTE pulse sequences achieved similar contrast and SNR efficiency for volumetric imaging of ultrashort-T2 components. Several key differences are that ZTE is limited to volumetric imaging but has substantially reduced acoustic noise levels during the scan. Meanwhile, UTE has higher acoustic noise levels and greater sensitivity to gradient fidelity, but offers more flexibility in image contrast and volume selection. PMID:26702940

  14. Cancer-associated fibroblasts promote cancer cell growth through a miR-7-RASSF2-PAR-4 axis in the tumor microenvironment

    PubMed Central

    Yan, Ming; Li, Rongrong; Chen, Gang; Zhang, Jianjun; Chen, Wantao

    2017-01-01

    Cancer-associated fibroblasts (CAFs), a major component of cancer stroma, play an important role in cancer progression but little is known about how CAFs affect tumorigenesis and development. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate target mRNA expression at post-transcriptional levels. In head and neck cancer (HNC), our analysis of miRNA arrays showed that miR-7, miR-196 and miR-335 were significantly up-regulated in CAFs when compared with their paired normal fibroblasts (NFs). FAP, α-SMA and FSP, specific markers of CAFs, were significantly expressed in CAFs. Functionally, exogenous expression of miR-7 in NFs induced a functional conversion of NFs into CAFs. In contrast, inhibition of miR-7 expression in CAFs could induce a functional conversion of CAFs into NFs. Our study demonstrated that overexpression of miR-7 in NFs significantly increased the migration activity and growth rates of cancer cells in co-culture experiments. Mechanistically, we confirmed that the RASSF2-PAR-4 axis was mainly responsible for miR-7 functions in CAFs using bioinformatics methods. Overexpression of miR-7 in CAFs led to down-regulation of RASSF2, which dramatically decreased the secretion of PAR-4 from CAFs and then enhanced the proliferation and migration of the co-cultured cancer cells. Thus, these results reveal that the inactivation of the RASSF2-PAR-4 axis controlled by miR-7 may be a novel strategy for gene therapy in HNCs. PMID:27901488

  15. Direct role for the RNA polymerase domain of T7 primase in primer delivery

    PubMed Central

    Zhu, Bin; Lee, Seung-Joo; Richardson, Charles C.

    2010-01-01

    Gene 4 protein (gp4) encoded by bacteriophage T7 contains a C-terminal helicase and an N-terminal primase domain. After synthesis of tetraribonucleotides, gp4 must transfer them to the polymerase for use as primers to initiate DNA synthesis. In vivo gp4 exists in two molecular weight forms, a 56-kDa form and the full-length 63-kDa form. The 56-kDa gp4 lacks the N-terminal Cys4 zinc-binding motif important in the recognition of primase sites in DNA. The 56-kDa gp4 is defective in primer synthesis but delivers a wider range of primers to initiate DNA synthesis compared to the 63-kDa gp4. Suppressors exist that enable the 56-kDa gp4 to support the growth of T7 phage lacking gene 4 (T7Δ4). We have identified 56-kDa DNA primases defective in primer delivery by screening for their ability to support growth of T7Δ4 phage in the presence of this suppressor. Trp69 is critical for primer delivery. Replacement of Trp69 with lysine in either the 56- or 63-kDa gp4 results in defective primer delivery with other functions unaffected. DNA primase harboring lysine at position 69 fails to stabilize the primer on DNA. Thus, a primase subdomain not directly involved in primer synthesis is involved in primer delivery. The stabilization of the primer by DNA primase is necessary for DNA polymerase to initiate synthesis. PMID:20439755

  16. Hazard Studies for Solid Propellant Rocket Motors (Etude des Risque pour les Moteurs-Fusees a Propergols Solides)

    DTIC Science & Technology

    1990-09-01

    RESEARCH AND DEVELOPMENT (ORGANISATION DU TRAITE DE LATIANTIOUF NORD) AGARDograph No.3 16 Hazard Studies for Solid Propellant Rocket Motors (Etudes de...member nations to use their research and development capabilities for the common benefit of the NATO community; - Providing scientific and technical...advice and assistance to the Military Committee in the field of aerospace research and development (with particular regard to its military application

  17. Effect of dilution in the cobalt subsystem on phase transitions in rare-earth cobaltites RBaCo4- x M x O7 (R = Dy-Er, Yb, Y; M = Al, Zn)

    NASA Astrophysics Data System (ADS)

    Kazei, Z. A.; Snegirev, V. V.; Kozeeva, L. P.; Kameneva, M. Yu.

    2016-01-01

    We have experimentally studied the structural and elastic characteristics of rare-earth cobaltites RBaCo4- x M x O7 (R = Dy-Er, Yb, Y), in which cobalt ions are partly substituted by diamagnetic Al or Zn ions. It was found that small substitution of Co3+ ions by Al3+ ions in the YbRBaCo4- x M x O7 system ( x = 0.1, 0.2, 0.5) leads to a rapid decrease and smearing of Δ E( T) /E 0 anomalies of the Young's modulus in the region of the structural phase transition, which is accompanied by increasing hysteresis. Pure rare-earth cobaltites RBaCo4O7 (R = Dy-Er, Y) exhibit a correlation between the room-temperature structure distortion and hysteresis on the Δ E( T)/ E 0 curve in a temperature interval of 80-280 K. In Zn-substituted cobaltites RBaCoZn3O7, both the hysteresis and Δ E( T)/ E 0 anomalies disappear, as do low-temperature sound absorption maxima. This behavior is evidence of the suppression of structural and magnetic phase transitions and the retention of only short-range correlations of the order parameter in Zn-substituted samples.

  18. Constitutional t(5;7)(q11;p15) rearranged to acquire monosomy 7q and trisomy 1q in a patient with myelodysplastic syndrome transforming to acute myelocytic leukemia.

    PubMed

    Ganly, Peter; McDonald, Margaret; Spearing, Ruth; Morris, Christine M

    2004-03-01

    We report the case of a 61-year-old woman who presented with a myelodysplastic syndrome (MDS) and a t(5;7)(q11.2;p15) in her bone marrow cells. Subsequent analysis of phytohemagglutinin-stimulated peripheral blood lymphocytes and cultured skin fibroblasts showed that the translocation was constitutional. Disruption of chromosome bands 5q11.2 and 7p15 has been described recurrently in MDS and acute myelocytic leukemia (AML) and, although the age of onset was not earlier than usual, it is nonetheless possible that genes interrupted by this translocation may been a predisposing factor for her condition. With progression to AML, a further rearrangement of the constitutional der(7)t(5;7) occurred, involving chromosome arm 1q. Fluorescence in situ hybridization (FISH) with whole-chromosome paints showed that the result of the second rearrangement, a t(1;7)(q32.1;q32), was observed, leading to trisomy of the segment 1q32.1 approximately qter and monosomy of the segment 7q32.1 approximately qter. The acquired imbalances, particularly loss of 7q, are commonly associated with MDS/AML and a poor prognosis; however, this patient remained in remission after treatment for more than two years before AML relapse, perhaps because the affected regions fall outside of the critical regions of imbalance.

  19. A Numerical Study of Flare Stabilized Projectiles at Mach 7.0.

    DTIC Science & Technology

    1988-01-01

    vlue of expansion over the nose shoulder, decreases the grid spacing at the wall was 0.5 x 10 . gradual ly along the cylinder body, and jumps quickly at...34Aerodynamic H1ea t ing to t he It ype r.,o t ic l en gthIts f or ’oI 1 cofi i rit ions h,’ h-on R e soar ch1 A ir c r aft X -2 4 C,’’ A IA A P.-iper 7...III~r zj Wr TI)~w 1117T 1)111 RVIS w Ron _ o ’Ij.’. wa ,, F)J HOW1 ll~ k l’\\ I (C 1, l jja r i 1, . *-XE I’ X II)FII, I ,!’.1 11 ’A ot’’rI II)’L’’𔃺 S

  20. [Construction and immunogenicity of recombinant bacteriophage T7 vaccine expressing M2e peptides of avian influenza virus].

    PubMed

    Xu, Hai; Wang, Yi-Wei; Tang, Ying-Hua; Zheng, Qi-Sheng; Hou, Ji-Bo

    2013-06-01

    To construct a recombinant T7 phage expressing matrix protein 2 ectodomain (M2e) peptides of avian influenza A virus and test immunological and protective efficacy in the immunized SPF chickens. M2e gene sequence was obtained from Genbank and two copies of M2e gene were artificially synthesised, the M2e gene was then cloned into the T7 select 415-1b phage in the multiple cloning sites to construct the recombinant phage T7-M2e. The positive recombinant phage was identified by PCR and sequencing, and the expression of surface fusion protein was confirmed by SDS-PAGE and Western-blot. SPF chickens were subcutaneously injected with 1 X 10(10) pfu phage T7-M2e, sera samples were collected pre- and post-vaccination, and were tested for anti-M2e antibody by ELISA. The binding capacity of serum to virus was also examined by indirect immunofluorescence assay in virus- infected CEF. The immunized chickens were challenged with 200 EID50 of H9 type avian influenza virus and viral isolation rate was calculated to evaluate the immune protective efficacy. A recombinant T7 phage was obtained displaying M2e peptides of avian influenza A virus, and the fusion protein had favorable immunoreactivity. All chickens developed a certain amount of anti-M2e antibody which could specially bind to the viral particles. In addition, the protection efficacy of phage T7-M2e vaccine against H9 type avian influenza viruses was 4/5 (80%). These results indicate that the recombinant T7 phage displaying M2e peptides of avian influenza A virus has a great potential to be developed into a novel vaccine for the prevention of avian influenza infection.

  1. B7-H1 limits the entry of effector CD8(+) T cells to the memory pool by upregulating Bim.

    PubMed

    Gibbons, Rachel M; Liu, Xin; Pulko, Vesna; Harrington, Susan M; Krco, Christopher J; Kwon, Eugene D; Dong, Haidong

    2012-10-01

    Protective T‑cell immunity against cancer and infections is dependent on the generation of a durable effector and memory T‑cell pool. Studies from cancer and chronic infections reveal that B7-H1 (PD-L1) engagement with its receptor PD-1 promotes apoptosis of effector T cells. It is not clear how B7-H1 regulates T‑cell apoptosis and the subsequent impact of B7-H1 on the generation of memory T cells. In immunized B7-H1-deficient mice, we detected an increased expansion of effector CD8(+) T cells and a delayed T‑cell contraction followed by the emergence of a protective CD8(+) T‑cell memory capable of completely rejecting tumor metastases in the lung. Intracellular staining revealed that antigen-primed CD8(+) T cells in B7-H1-deficient mice express lower levels of the pro-apoptotic molecule Bim. The engagement of activated CD8(+) T cells by a plate-bound B7-H1 fusion protein led to the upregulation of Bim and increased cell death. Assays based on blocking antibodies determined that both PD-1 and CD80 are involved in the B7-H1-mediated regulation of Bim in activated CD8(+) T cells. Our results suggest that B7-H1 may negatively regulate CD8(+) T‑cell memory by enhancing the depletion of effector CD8(+) T cells through the upregulation of Bim. Our findings may provide a new strategy for targeting B7-H1 signaling in effector CD8(+) T cells to achieve protective antitumor memory responses.

  2. Prolonged evolution of virus-specific memory T cell immunity post severe avian influenza A (H7N9) virus infection.

    PubMed

    Zhao, Min; Chen, Junbo; Tan, Shuguang; Dong, Tao; Jiang, Hui; Zheng, Jiandong; Quan, Chuansong; Liao, Qiaohong; Zhang, Hangjie; Wang, Xiling; Wang, Qianli; Bi, Yuhai; Liu, Fengfeng; Feng, Luzhao; Horby, Peter W; Klenerman, Paul; Gao, George F; Liu, William J; Yu, Hongjie

    2018-06-20

    Since 2013, influenza A/H7N9 has emerged as the commonest avian influenza subtype causing human infection, and is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of forty-five H7N9 survivors followed for up to 15 months after infection. Humoral and cellular immune responses were analyzed in sequential samples obtained at 1.5-4 months, 6-8 months and 12-15 months post-infection. H7N9-specific antibody concentrations declined over time, and protective antibodies persisted longer in severely ill patients admitted to ICU and patients presenting with ARDS than that in patients with mild disease. Frequencies of virus-specific IFN-γ secreting T cells were lower in critically ill patients requiring ventilation than those in patients without ventilation within four months after infection. The percentages of H7N9-specific IFN-γ secreting T cells tended to increase over time in patients ≥60 years or critically ill patients requiring ventilation. Elevated levels of antigen-specific CD8 + T cells expressing lung-homing marker CD49a were observed at 6-8 months after H7N9 infection compared to samples obtained at 1.5-4 months. Our findings indicate the prolonged reconstruction and evolution of virus-specific T cell immunity in older or critically ill patients, and provide implications for T-cell directed immunization strategies. IMPORTANCE Avian influenza A H7N9 remains a major threat to public health. However, no previous studies have determined the characteristics and dynamics of virus specific T cell immune memory in patients who have recovered from H7N9 infection. Our findings showed that establishment of H7N9-specific T cell memory after H7N9 infection was prolonged in older and severely affected patients. Severely ill patients mounted lower T cell responses in the first 4 months after infection, while T cell responses tended to increase

  3. Prise en charge des traumatismes graves du rein

    PubMed Central

    Lakmichi, Mohamed Amine; Jarir, Redouane; Sadiki, Bader; Zehraoui; Bentani; Wakrim, Bader; Dahami, Zakaria; Moudouni; Sarf, Ismail

    2015-01-01

    Les traumatismes graves du rein de grade III, IV et V selon la classification de l'Amercan Society for Surgery For Trauma (ASST) sont plus rares et se retrouvent dans 5% des cas en moyenne. Leur prise en charge est souvent délicate, nécessitant alors des centres expérimentés dotés de moyen adéquats d'imagerie (scanner spiralé). Cependant, durant ces dernières années, la prise en charge de ces traumatismes a évolué vers une attitude de moins en moins chirurgicale grâce à l’évolution des techniques de la radiologie interventionnelle, de l'endourologie et des moyens de surveillance aux urgences et de réanimation. L'objectif de cette étude est d’évaluer notre expérience dans la prise en charge des traumatismes rénaux de haut grade. Notre étude rétrospective porte sur 25 cas de traumatismes grave du rein de grade III, IV et V selon la classification de l'ASST, colligés entre Janvier 2002 et Juin 2009 au service d'urologie du centre Hospitalier Universitaire Mohammed VI, Université Cadi Ayyad de Marrakech, Maroc. Nous avons étudié les données épidémiologiques, les signes cliniques et biologiques à l'admission (état de choc hémorragique, taux d'hémoglobine), les données radiologiques (échographie et scanner), les lésions associées, la prise en charge thérapeutique et les complications. L’âge moyen de nos patients était de 24,9 ans 15 et 58 ans, avec une prédominance masculine (sex-ratio = 7, 3). Le rein droit était intéressé dans 15 cas (60%). Le traumatisme rénal était fermé dans 15 cas, et ouvert par arme blanche dans 10 cas. Huit patients se sont présentés en état de choc hémorragique (32%). Une anémie inférieur à 10g /100ml a été observée dans 10 cas (40%). L'uroscanner fait systématiquement à l'admission a retrouvé un grade III (10 cas), grade IV (13 cas) et grade V (2 cas). La prise en charge a consisté en une exploration chirurgicale avec néphrectomie chez 2 cas de Grade IV pour une instabilité h

  4. Effects of solar ultraviolet radiations on Bacillus subtilis spores and T-7 bacteriophage

    NASA Technical Reports Server (NTRS)

    Spizizen, J.; Isherwood, J. E.; Taylor, G. R.

    1975-01-01

    Spores of Bacillus subtilis HA 101 and the DNA polymerase I-defective mutant HA 101 (59)F were exposed to selected wavelengths of solar ultraviolet light and space vacuum during the return of Apollo 16. In addition, coliphage T-7 suspensions were exposed to solar ultraviolet radiation as part of the Microbial Response to Space Environment Experiment. Optical filters were employed to provide different energy levels at wavelengths 254 nm and 280 nm. Dose-response curves for lethal and mutagenic effects were compared with ground-based data. A close parallel was observed between the results of solar radiation and ground tests with spores of the two strains. However, significantly greater inactivation of T-7 bacteriophage was observed after exposure to solar ultraviolet radiation.

  5. Novel approaches to study the involvement of α7-nAChR in human diseases.

    PubMed

    Palma, Eleonora; Conti, Luca; Roseti, Cristina; Limatola, Cristina

    2012-05-01

    The alpha7 nicotinic acetylcholine receptor (α7 nAChR) is widely distributed in the human brain and has been implicated in a number of human central nervous system (CNS) diseases, including Alzheimer's and Parkinson's disease, schizophrenia and autism. Recently, new roles for α7 nAChRs in lung cancer and heart disease have been elucidated. Despite the importance of this receptor in human pathology, many technical difficulties are still encountered when investigating the role of α7 nAChRs. Electrophysiological analysis of the receptor upon heterologous expression or in human tissues was limited by the fast desensitization of α7-mediated nicotinic currents and by tissue availability. In addition, animal models for the human diseases related to α7 nAChRs have long been unavailable. The recent development of new imaging and analysis approaches such as PET and receptor microtransplantation have rendered the study of α7 nAChRs increasingly feasible, paving new roads to the design of therapeutic drugs. This review summarizes the current knowledge and recent findings obtained by these novel approaches.

  6. 7T MRI-Histologic Correlation Study of Low Specific Absorption Rate T2-Weighted GRASE Sequences in the Detection of White Matter Involvement in Multiple Sclerosis.

    PubMed

    Bagnato, Francesca; Hametner, Simon; Pennell, David; Dortch, Richard; Dula, Adrienne N; Pawate, Siddharama; Smith, Seth A; Lassmann, Hans; Gore, John C; Welch, Edward B

    2015-01-01

    The high value of the specific absorption rate (SAR) of radio-frequency (RF) energy arising from the series of RF refocusing pulses in T2-weighted (T2-w) turbo spin echo (TSE) MRI hampers its clinical application at 7.0 Tesla (7T). T2-w gradient and spin echo (GRASE) uses the speed from gradient refocusing in combination with the chemical-shift/static magnetic field (B0) inhomogeneity insensitivity from spin-echo refocusing to acquire T2-w images with a limited number of refocusing RF pulses, thus reducing SAR. To investigate whether low SAR T2-w GRASE could replace T2-w TSE in detecting white matter (WM) disease in MS patients imaged at 7T. The .7 mm3 isotropic T2-w TSE and T2-w GRASE images with variable echo times (TEs) and echo planar imaging (EPI) factors were obtained on a 7T scanner from postmortem samples of MS brains. These samples were derived from brains of 3 female MS patients. WM lesions (WM-Ls) and normal-appearing WM (NAWM) signal intensity, WM-Ls/NAWM contrast-to-noise ratio (CNR) and MRI/myelin staining sections comparisons were obtained. GRASE sequences with EPI factor/TE = 3/50 and 3/75 ms were comparable to the SE technique for measures of CNR in WM-Ls and NAWM and for detection of WM-Ls. In all sequences, however, identification of areas with remyelination, Wallerian degeneration, and gray matter demyelination, as depicted by myelin staining, was not possible. T2-w GRASE images may replace T2-w TSE for clinical use. However, even at 7T, both sequences fail in detecting and characterizing MS disease beyond visible WM-Ls. Copyright © 2015 by the American Society of Neuroimaging.

  7. L’évaluation du syndrome du Burnout chez les médecins en formation au CHU Ibn Rochd de Casablanca

    PubMed Central

    El Kettani, Assiya; Serhier, Zineb; Othmani, Mohammed Bennani; Agoub, Mohamed; Battas, Omar

    2017-01-01

    Introduction Le Burnout est très répandu en milieu hospitalier et sa gravité est encore plus accrue chez les jeunes médecins. L'objectif est de déterminer la prévalence du burnout parmi les médecins en formation (internes et résidents) au CHU Ibn Rochd de Casablanca et chercher les facteurs associés. Méthodes Étude transversale descriptive menée en 2013- 2014 auprès d'un échantillon de 300 médecins à l'aide d'un questionnaire auto-administré; le burnout était évalué par la version française du Maslash Burnout Inventory (MBI). Résultats Un total de191 médecins a participé à l'étude (taux de réponse à 63,7%) avec une prédominance féminine à 79,1% et une moyenne d'âge de 26,7ans (ET = 3). Les scores moyens des sous-dimensions du MBI: l'épuisement émotionnel, la dépersonnalisation et l'accomplissement personnel étaient respectivement de (33,7 ± 10,7), (12,2 ± 6,5) et (30,6 ± 8,3). Le burnout sévère touchait 31,8% des participants. Il était associé aux problèmes de communication au sein de l'équipe soignante (p < 0,01), l'accompagnement insuffisant (p < 0,05), l'insatisfaction des séniors (p = 0,01), la crainte de faire des erreurs médicales (p < 0,05), le recours à un psychothérapeute (p < 0,001), la consommation de psychotropes (p = 0,001), les troubles anxieux (p < 0,01), la dépression (p < 0,01) et les idées suicidaires (p < 0,05). Les facteurs protecteurs étaient représentés par: le sentiment d'équité au sein de l'équipe soignante (p < 0,01) et la pratique de loisirs (p < 0,05). Le changement d'orientation de carrière était associé au burnout sévère (p < 0,05). Conclusion Ces résultats rejoignent ceux des études précédentes et justifient l'intérêt d'un programme de prévention à différents niveaux. Introduction Burnout is very widespread in the hospital setting and it becomes much more severe in young physicians. The objective of this study aims to evaluate the prevalence of burnout among doctors

  8. Aldosterone Upregulates Transient Receptor Potential Melastatin 7 (TRPM7)*

    PubMed Central

    Valinsky, William C.; Jolly, Anna; Miquel, Perrine

    2016-01-01

    Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed Mg2+-permeable ion channel fused to a C-terminal α-kinase domain. Recently, aldosterone was shown to increase intracellular Mg2+ levels and alter inflammatory signaling in TRPM7-expressing HEK293 cells. This study was undertaken to assess whether these effects were related to an aldosterone-mediated increase of TRPM7 current and/or plasma membrane localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h application of aldosterone significantly increased TRPM7 current and TRPM7 plasma membrane protein expression by 48% and 34%, respectively. The aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases the plasma membrane expression of TRPM7, which is associated with an increase of TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade involving SGK1 and a functioning TRPM7 α-kinase domain. We suggest that this mechanism may be of general relevance when interpreting the effects of aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and SGK1 are ubiquitously expressed. PMID:27466368

  9. Aldosterone Upregulates Transient Receptor Potential Melastatin 7 (TRPM7).

    PubMed

    Valinsky, William C; Jolly, Anna; Miquel, Perrine; Touyz, Rhian M; Shrier, Alvin

    2016-09-16

    Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed Mg(2+)-permeable ion channel fused to a C-terminal α-kinase domain. Recently, aldosterone was shown to increase intracellular Mg(2+) levels and alter inflammatory signaling in TRPM7-expressing HEK293 cells. This study was undertaken to assess whether these effects were related to an aldosterone-mediated increase of TRPM7 current and/or plasma membrane localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h application of aldosterone significantly increased TRPM7 current and TRPM7 plasma membrane protein expression by 48% and 34%, respectively. The aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases the plasma membrane expression of TRPM7, which is associated with an increase of TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade involving SGK1 and a functioning TRPM7 α-kinase domain. We suggest that this mechanism may be of general relevance when interpreting the effects of aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and SGK1 are ubiquitously expressed. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Breast MRI at 7 Tesla with a bilateral coil and T1-weighted acquisition with robust fat suppression: image evaluation and comparison with 3 Tesla.

    PubMed

    Brown, Ryan; Storey, Pippa; Geppert, Christian; McGorty, KellyAnne; Leite, Ana Paula Klautau; Babb, James; Sodickson, Daniel K; Wiggins, Graham C; Moy, Linda

    2013-11-01

    To evaluate the image quality of T1-weighted fat-suppressed breast MRI at 7 T and to compare 7-T and 3-T images. Seventeen subjects were imaged using a 7-T bilateral transmit-receive coil and 3D gradient echo sequence with adiabatic inversion-based fat suppression (FS). Images were graded on a five-point scale and quantitatively assessed through signal-to-noise ratio (SNR), fibroglandular/fat contrast and signal uniformity measurements. Image scores at 7 and 3 T were similar on standard-resolution images (1.1 × 1.1 × 1.1-1.6 mm(3)), indicating that high-quality breast imaging with clinical parameters can be performed at 7 T. The 7-T SNR advantage was underscored on 0.6-mm isotropic images, where image quality was significantly greater than at 3 T (4.2 versus 3.1, P ≤ 0.0001). Fibroglandular/fat contrast was more than two times higher at 7 T than at 3 T, owing to effective adiabatic inversion-based FS and the inherent 7-T signal advantage. Signal uniformity was comparable at 7 and 3 T (P < 0.05). Similar 7-T image quality was observed in all subjects, indicating robustness against anatomical variation. The 7-T bilateral transmit-receive coil and adiabatic inversion-based FS technique produce image quality that is as good as or better than at 3 T. • High image quality bilateral breast MRI is achievable with clinical parameters at 7 T. • 7-T high-resolution imaging improves delineation of subtle soft tissue structures. • Adiabatic-based fat suppression provides excellent fibroglandular/fat contrast at 7 T. • 7- and 3-T 3D T1-weighted gradient-echo images have similar signal uniformity. • The 7-T dual solenoid coil enables bilateral imaging without compromising uniformity.

  11. Prediction du profil de durete de l'acier AISI 4340 traite thermiquement au laser

    NASA Astrophysics Data System (ADS)

    Maamri, Ilyes

    Les traitements thermiques de surfaces sont des procedes qui visent a conferer au coeur et a la surface des pieces mecaniques des proprietes differentes. Ils permettent d'ameliorer la resistance a l'usure et a la fatigue en durcissant les zones critiques superficielles par des apports thermiques courts et localises. Parmi les procedes qui se distinguent par leur capacite en terme de puissance surfacique, le traitement thermique de surface au laser offre des cycles thermiques rapides, localises et precis tout en limitant les risques de deformations indesirables. Les proprietes mecaniques de la zone durcie obtenue par ce procede dependent des proprietes physicochimiques du materiau a traiter et de plusieurs parametres du procede. Pour etre en mesure d'exploiter adequatement les ressources qu'offre ce procede, il est necessaire de developper des strategies permettant de controler et regler les parametres de maniere a produire avec precision les caracteristiques desirees pour la surface durcie sans recourir au classique long et couteux processus essai-erreur. L'objectif du projet consiste donc a developper des modeles pour predire le profil de durete dans le cas de traitement thermique de pieces en acier AISI 4340. Pour comprendre le comportement du procede et evaluer les effets des differents parametres sur la qualite du traitement, une etude de sensibilite a ete menee en se basant sur une planification experimentale structuree combinee a des techniques d'analyse statistiques eprouvees. Les resultats de cette etude ont permis l'identification des variables les plus pertinentes a exploiter pour la modelisation. Suite a cette analyse et dans le but d'elaborer un premier modele, deux techniques de modelisation ont ete considerees, soient la regression multiple et les reseaux de neurones. Les deux techniques ont conduit a des modeles de qualite acceptable avec une precision d'environ 90%. Pour ameliorer les performances des modeles a base de reseaux de neurones, deux

  12. SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

    PubMed Central

    Zheng, Xiaowei; Wang, Changwei; Xing, Yuanming; Chen, Siying; Meng, Ti; You, Haisheng; Ojima, Iwao; Dong, Yalin

    2017-01-01

    Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. The aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms. The results of MTT assay showed that SB-T-121205 has much higher potency to human breast cancer cells (MCF-7/S, MCF-7/PTX and MDA-MB-453 cells) than paclitaxel, while that the non-tumorigenic human bronchial epithelial cells (BEAS-2B) were slightly less sensitive to SB-T-121205 than paclitaxel. Flow cytometry and western blot methods revealed that SB-T-121205 induced cell cycle arrest at the G2/M phase and apoptosis in MCF-7/PTX cells through accelerating mitochondrial apoptotic pathway, resulting in reduction of Bcl-2/Bax ratio, as well as elevation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) levels. Moreover, SB-T-121205 changed epithelial-mesenchymal transition (EMT) property, and suppressed migration and invasion abilities of MCF-7/PTX cells. Additionally, SB-T-121205 exerted antitumor activity by inhibiting the transgelin 2 and PI3K/Akt pathway. These findings indicate that SB-T-121205 is a potent antitumor agent that promotes apoptosis and also recedes migration/invasion abilities of MCF-7/PTX cells by restraining the activity of transgelin 2 and PI3K/Akt, as well as mitochondrial apoptotic pathway. Such results suggest a potential clinical value of SB-T-121205 in breast cancer treatment. PMID:28197640

  13. Etude de la flore bactérienne contaminant les téléphones mobiles avant et après la désinfection: comparaison entre les professionnels soignants de l'hôpital militaire d'instruction Mohammed V de Rabat et les témoins

    PubMed Central

    Uwingabiye, Jean; Moustanfii, Wafaa; Chadli, Meryem; Sekhsokh, Yassine

    2015-01-01

    Introduction L'objectif de notre travail était évaluer la contamination microbienne des téléphones mobiles utilisés par les personnels soignants des différents services de l'hôpital militaire d'instructions Mohammed V de Rabat et la comparer à celui d'une population témoin et aussi démontrer l'efficacité des solutions hydroalcoolique dans la désinfection de ces téléphones mobiles. Méthodes Il s'agit d'une étude descriptive transversale réalisée sur une période de 9 mois entre septembre 2010 et juin 2011, dans le service de bactériologie de l'hôpital militaire d'Instruction Mohammed V. Résultats L’étude bactériologique a été faite sur 240 téléphones mobiles dont 50% provenaient de personnels de sante. Le taux de contamination bactérienne de tous les téléphones mobiles était de 100%. Les cultures des bactéries isolées au niveau des téléphones mobiles du personnel médical étaient plus polymorphes que celles de la population témoin (p=0,028). Parmi 437 bactéries isolées: 223(51%) provenaient de téléphones de personnels de santé et 214(49%) de téléphones de la population témoin avec une différence qui n’était pas statistiquement significative(p>0,05) sauf pour les isolats de Staphylocoque à coagulase négative et Staphylococcus aureus. Les bactéries isolées étaient représentées par: Staphylocoque à coagulase (57,7%), Staphylococcus aureus (18,1%), Corynebacterium sp (18,8%), Bacillus sp (2,3%) et autres (2,2%). La différence entre la prévalence des bactéries isolées selon les services et les fonctions des personnels de santé n’était pas statistiquement significative (p>0,05). La désinfection des téléphones portables par la solution hydroalcoolique a réduit à 99,5% le nombre des colonies. Conclusion Ce travail montre que les téléphones portables pourraient jouer un rôle dans la transmission des infections nosocomiales et communautaires. Dans le cadre de prévention de ces risques, il faut

  14. In vivo 1D and 2D correlation MR spectroscopy of the soleus muscle at 7T

    PubMed Central

    Ramadan, Saadallah; Ratai, Eva-Maria; Wald, Lawrence L.; Mountford, Carolyn E.

    2013-01-01

    Aim This study aims to (1) undertake and analyse 1D and 2D MR correlation spectroscopy from human soleus muscle in vivo at 7T, and (2) determine T1 and T2 relaxation time constants at 7T field strength due to their importance in sequence design and spectral quantitation. Method Six healthy, male volunteers were consented and scanned on a 7T whole-body scanner (Siemens AG, Erlangen, Germany). Experiments were undertaken using a 28 cm diameter detunable birdcage coil for signal excitation and an 8.5 cm diameter surface coil for signal reception. The relaxation time constants, T1 and T2 were recorded using a STEAM sequence, using the ‘progressive saturation’ method for the T1 and multiple echo times for T2. The 2D L-Correlated SpectroscopY (L-COSY) method was employed with 64 increments (0.4 ms increment size) and eight averages per scan, with a total time of 17 min. Results T1 and T2 values for the metabolites of interest were determined. The L-COSY spectra obtained from the soleus muscle provided information on lipid content and chemical structure not available, in vivo, at lower field strengths. All molecular fragments within multiple lipid compartments were chemically shifted by 0.20–0.26 ppm at this field strength. 1D and 2D L-COSY spectra were assigned and proton connectivities were confirmed with the 2D method. Conclusion In vivo 1D and 2D spectroscopic examination of muscle can be successfully recorded at 7T and is now available to assess lipid alterations as well as other metabolites present with disease. T1 and T2 values were also determined in soleus muscle of male healthy volunteers. PMID:20206561

  15. Acceptabilité du test VIH proposé aux nourrissons dans les services pédiatriques, en Côte d'Ivoire, Significations pour la couverture du diagnostic pédiatrique

    PubMed Central

    Oga, Maxime; Brou, Hermann; Dago-Akribi, Hortense; Coffie, Patrick; Amani-Bossé, Clarisse; Ékouévi, Didier; Yapo, Vincent; Menan, Hervé; Ndondoki, Camille; Timité-Konan, M.; Leroy, Valériane

    2014-01-01

    Résumé Problème: Le dépistage VIH chez les enfants a rarement été au centre des préoccupations des chercheurs. Quand le dépistage pédiatrique a retenu l'attention, cela a été pour éclairer seulement sur les performances diagnostiques en ignorant même que le test pédiatrique comme bien d'autres peut s'accepter ou se refuser. Cet article met au cœur de son analyse les raisons qui peuvent expliquer qu'on accepte ou qu'on refuse de faire dépister son enfant. Objectif: Etudier chez les parents, les mères, les facteurs explicatifs de l'acceptabilité du test VIH des nourrissons de moins de six mois. Méthodes: Entretien semi-directif à passages répétés avec les parents de nourrissons de moins de six mois dans les formations sanitaires pour la pesée/vaccination et les consultations pédiatriques avec proposition systématique d'un test VIH pour leur nourrisson. Résultats: Nous retenons que la réalisation effective du test pédiatrique du VIH chez le nourrisson repose sur trois éléments. Primo, le personnel de santé par son discours (qui dénote de ses connaissances et perceptions même sur l'infection) orienté vers les mères influence leur acceptation ou non du test. Secundo, la mère qui par ses connaissances et perceptions même sur le VIH, dont le statut particulier, l'impression de bien-être chez elle et son enfant influence toute réalisation du test pédiatrique VIH. Tertio, l'environnement conjugal de la mère, particulièrement caractérisé par les rapports au sein du couple, sur la facilité de parler du test VIH et sa réalisation chez les deux parents ou chez la mère seulement sont autant de facteurs qui influencent la réalisation effective du dépistage du VIH chez l'enfant. Le principe préventif du VIH, et le désir de faire tester l'enfant ne suffisent pas à eux seuls pour aboutir à sa réalisation effective, selon certaines mères confrontées au refus du conjoint. A l'opposé, les autres mères refusant la r

  16. A mutation in the extracellular domain of the α7 nAChR reduces calcium permeability.

    PubMed

    Colón-Sáez, José O; Yakel, Jerrel L

    2014-08-01

    The α7 neuronal nicotinic acetylcholine receptor (nAChR) displays the highest calcium permeability among the different subtypes of nAChRs expressed in the mammalian brain and can impact cellular events including neurotransmitter release, second messenger cascades, cell survival, and apoptosis. The selectivity for cations in nAChRs is thought to be achieved in part by anionic residues which are located on either side of the channel mouth and increase relative cationic concentration. Mutagenesis studies have improved our understanding of the role of the second transmembrane domain and the intracellular loop of the channel in ion selectivity. However, little is known about the influence that the extracellular domain (ECD) plays in ion permeation. In the α7 nAChR, it has been found that the ECD contains a ring of ten aspartates (two per subunit) that is believed to face the lumen of the pore and could attract cations for permeation. Using mutagenesis and a combination of electrophysiology and imaging techniques, we tested the possible involvement of these aspartate residues in the calcium permeability of the rat α7 nAChR. We found that one of these residues (the aspartate at position 44) appears to be essential since mutating it to alanine resulted in a decrease in amplitude for both whole cell and single-channel responses and in the complete disappearance of detectable calcium changes in most cells, which indicates that the ECD of the α7 nAChR plays a key role in calcium permeation.

  17. A mutation in the extracellular domain of the α7 nAChR reduces calcium permeability

    PubMed Central

    Colón-Sáez, José O.

    2013-01-01

    The α7 neuronal nicotinic acetylcholine receptor (nAChR) displays the highest calcium permeability among the different subtypes of nAChRs expressed in the mammalian brain and can impact cellular events including neurotransmitter release, second messenger cascades, cell survival, and apoptosis. The selectivity for cations in nAChRs is thought to be achieved in part by anionic residues which are located on either side of the channel mouth and increase relative cationic concentration. Mutagenesis studies have improved our understanding of the role of the second transmembrane domain and the intracellular loop of the channel in ion selectivity. However, little is known about the influence that the extracellular domain (ECD) plays in ion permeation. In the α7 nAChR, it has been found that the ECD contains a ring of ten aspartates (two per subunit) that is believed to face the lumen of the pore and could attract cations for permeation. Using mutagenesis and a combination of electrophysiology and imaging techniques, we tested the possible involvement of these aspartate residues in the calcium permeability of the rat α7 nAChR. We found that one of these residues (the aspartate at position 44) appears to be essential since mutating it to alanine resulted in a decrease in amplitude for both whole cell and single-channel responses and in the complete disappearance of detectable calcium changes in most cells, which indicates that the ECD of the α7 nAChR plays a key role in calcium permeation. PMID:24177919

  18. La violence sur les réseaux canadiens de télévision

    PubMed Central

    Paquette, Guy

    2003-01-01

    La question des effets de la violence à la télévision occupe une place très importante dans l’opinion publique depuis les vingt dernières années, et des centaines d’études y ont été consacrées. Plusieurs chercheurs concluent à une influence négative de cette violence sur le comportement. Le public, les diffuseurs et les autorités politiques ont tous endossé l’idée de réduire la quantité totale de violence présentée au petit écran – en particulier dans les émissions accessibles aux enfants. Nous avons analysé un millier d’émissions de fiction présentées entre 1993 et 2001 sur les principaux réseaux généralistes de télévision au Canada : TVA et TQS ainsi que CTV et Global pour les réseaux privés français et anglais, ainsi que Radio-Canada français et anglais pour les réseaux publics. La méthodologie utilisée est l’analyse de contenu classique, où l’acte de violence constitue l’unité d’analyse. Les données recueillies démontrent que la quantité de violence a augmenté régulièrement depuis 1993, malgré la volonté affirmée des télédiffuseurs de présenter une programmation moins violente. C’est le cas du nombre brut d’actes et du nombre d’actes à l’heure, qui est lui aussi en forte croissance. Les réseaux privés véhiculent trois fois plus de violence que les réseaux publics. On constate également qu’une très forte proportion d’actes de violence figure dans des émissions qui commencent avant 21 h, et que de nombreux enfants y sont probablement exposés. Nous signalons finalement la place de plus en plus importante occupée par la violence psychologique. PMID:20020031

  19. Multiplex detection of microRNAs by combining molecular beacon probes with T7 exonuclease-assisted cyclic amplification reaction.

    PubMed

    Liu, Yacui; Zhang, Jiangyan; Tian, Jingxiao; Fan, Xiaofei; Geng, Hao; Cheng, Yongqiang

    2017-01-01

    A simple, highly sensitive, and specific assay was developed for the homogeneous and multiplex detection of microRNAs (miRNAs) by combining molecular beacon (MB) probes and T7 exonuclease-assisted cyclic amplification. An MB probe with five base pairs in the stem region without special modification can effectively prevent the digestion by T7 exonuclease. Only in the presence of target miRNA is the MB probe hybridized with the target miRNA, and then digested by T7 exonuclease in the 5' to 3' direction. At the same time, the target miRNA is released and subsequently initiates the nuclease-assisted cyclic digestion process, generating enhanced fluorescence signal significantly. The results show that the combination of T7 exonuclease-assisted cyclic amplification reaction and MB probe possesses higher sensitivity for miRNA detection. Moreover, multiplex detection of miRNAs was successfully achieved by designing two MB probes labeled with FAM and Cy3, respectively. As a result, the method opens a new pathway for the sensitive and multiplex detection of miRNAs as well as clinical diagnosis. Graphical Abstract A simple, highly sensitive, and specific assay was developed for the detection of microRNAs by combining molecular beacon probes with T7 exonuclease-assisted cyclic amplification reaction.

  20. La prise en charge du pneumothorax spontané: à propos de 138 cas

    PubMed Central

    Habibi, Bouchra; Achachi, Leila; Hayoun, Sohaib; Raoufi, Mohammed; Herrak, Laila; Ftouh, Mustapha El

    2017-01-01

    Le pneumothorax est définit par la présence d’air dans la cavité pleurale. L’objectif de notre étude rétrospective du pneumothorax spontanés au servie de pneumologie à l’hôpital Ibn Sina rabat (2009-2011) est de déterminer le profil épidémiologique, clinique, radiologique, thérapeutique et évolutif. Il s’agit de 138 patients: 128 hommes et 10 femmes (17 à 83 ans), un âge moyen de 44,5 +/- 17,4 ans; sexe ratio 12/8. Le tabagisme est noté chez 81,2%. La symptomatologie clinique est la douleur thoracique (92%), la dyspnée (60%). Et sur la radiographie thoracique: on trouve un PNO (pneumothorax) unilatéral total (110 cas); partiel (10 cas); localisé (6 cas); bilatéral (4 cas); à droite dans 51,4% et à gauche dans 45,7%. On a recensé 70% de pneumothorax spontanés primitifs et 30% de PNO secondaire à (BPCO 44%, et tuberculose pulmonaire 39%). La prise en charge initiale est l’hospitalisation de tous les patients : le drainage thoracique (95%), l’exsufflation à l’aiguille (1%). Le repos et l’O2 (4%). Le retour du poumon à la paroi a été obtenu avant 10 jours chez 63%. L’évolution est favorable chez 89%. Et les complications immédiates: l’emphysème sous cutané (5 cas); une infection (6 cas) et 3 décès (arrêt cardio-respiratoire); les complications à distance sont les récidives dans 11,6%; une 1ère récidive chez 13 cas (drainage thoracique chez 11 cas et oxygénothérapie chez 2 cas) et une 2ème récidive chez 3 cas (recours à la chirurgie). Ce travail montre l’intérêt du drainage thoracique et la surveillance dans la prise en charge du pneumothorax pour éviter les complications et surtout pour éviter les récidives avec un éventuel recours à la chirurgie. PMID:28533875

  1. Initiation and Reinitiation of DNA Synthesis during Replication of Bacteriophage T7*

    PubMed Central

    Dressler, David; Wolfson, John; Magazin, Marilyn

    1972-01-01

    In its first round of replication, the T7 chromosome follows a simple pattern, as viewed in the electron microscope. The iniation of DNA synthesis occurs about 17% from the genetic left end of the viral DNA rod. Bidirectional DNA synthesis from this origin then generates a replicating intermediate that we call an “eye form.” In the eye form, when synthesis in the leftward direction reaches the left end of the viral chromosome, the molecule is converted into a Y-shaped replicating rod. The remaining growing point continues synthesis rightward, until presumably it runs off the right end of the DNA rod, thus terminating replication. Numerous T7 chromosomes were found in which a second round of replication had begun before the first round had finished. Analysis of these reinitiated DNA molecules showed that the second round of replication, like the first, began 17% from the end of the chromosome and involved bidirectional DNA synthesis. Images PMID:4554539

  2. Accouchements sur utérus cicatriciel en République Démocratique du Congo: épreuve utérine et facteurs déterminants de l’issue

    PubMed Central

    Momat, Félix Kitenge wa; Zalagile, Pierre Akilimali; Mukalenge, Faustin Chenge; Luboya, Oscar Numbi; Kalala, Cléophas Tshibangu; Mashinda, Désiré; Grangé, Gilles; Mukuku, Olivier; Kaj, Fanny Malonga; Lubamba, Chamy Cham; Bwama, Joseph Bagambe; Mukoko, Célestin Kayembe; Kakoma, Jean Baptiste; Kalungwe, Justin Kizonde

    2017-01-01

    Introduction L'objectif était d'identifier les principaux facteurs de risque associés à un échec d'épreuve utérine et définir un score prédictif d'accouchement sur utérus cicatriciel en République Démocratique du Congo. Méthodes Étude multicentrique, transversale et analytique des patientes porteuses d'un utérus cicatriciel sur la période du 1er janvier au 31 décembre 2013 dans quatre maternités de la République Démocratique du Congo (RDC). Un modèle de régression logistique a été construit pour identifier les facteurs associés à l'échec de l'épreuve utérine. De ce modèle, un score prédictif a été construit pour prédire l'échec de l'épreuve utérine dans les maternités de la RDC. La courbe ROC a été utilisée pour évaluer la capacité du score construit à identifier les patientes à risque de connaitre un échec de l'épreuve utérine. Le cut off point du score prédictif a été déterminé en fonction de la sensibilité et spécificité optimale via l'index de Youden. Tous les tests ont été réalisés au seuil de signification α=0,05. Résultats Deux types de facteurs explicatifs de l'échec de l'épreuve utérine ont été retenus. Il s'agit d'un facteur sociodémographique (âge maternel) et de trois facteurs obstétricaux (hauteur utérine, présentation du fœtus et rupture prématurée des membranes). Le score de prédiction a été défini pour prédire l'échec de l'épreuve utérine. La construction de ce score s'est basée sur quatre éléments : l'âge maternel, l'état de la poche des eaux à l'admission, la hauteur utérine et la présentation fœtale. Le score minimal est de 4 et le score maximal est de 16. Le seuil est de 7. Un Score total supérieur ou égal à 7 traduit un risque d'échec de l'épreuve utérine. Conclusion L'utilisation de ce score prédictif chez les patientes pourra améliorer la qualité dans les indications de la voie haute, l'augmentation des taux de césariennes prophylactiques

  3. Exploring the energy landscape of resistive switching in antiferromagnetic S r3I r2O7

    NASA Astrophysics Data System (ADS)

    Williamson, Morgan; Shen, Shida; Cao, Gang; Zhou, Jianshi; Goodenough, John B.; Tsoi, Maxim

    2018-04-01

    We study the resistive switching triggered by an applied electrical bias in the antiferromagnetic Mott insulator S r3I r2O7 . The switching was previously associated with an electric-field-driven structural transition. Here we use time-resolved measurements to probe the thermal activation behavior of the switching process and acquire information about the energy barrier associated with the transition. We quantify the changes in the energy-barrier height with respect to the applied bias and find a linear decrease of the barrier with increasing bias. Our observations support the potential of antiferromagnetic transition-metal oxides for spintronic applications.

  4. Induction of protective anti-CTL epitope responses against HER-2-positive breast cancer based on multivalent T7 phage nanoparticles.

    PubMed

    Pouyanfard, Somayeh; Bamdad, Taravat; Hashemi, Hamidreza; Bandehpour, Mojgan; Kazemi, Bahram

    2012-01-01

    We report here the development of multivalent T7 bacteriophage nanoparticles displaying an immunodominant H-2k(d)-restricted CTL epitope derived from the rat HER2/neu oncoprotein. The immunotherapeutic potential of the chimeric T7 nanoparticles as anti-cancer vaccine was investigated in BALB/c mice in an implantable breast tumor model. The results showed that T7 phage nanoparticles confer a high immunogenicity to the HER-2-derived minimal CTL epitope, as shown by inducing robust CTL responses. Furthermore, the chimeric nanoparticles protected mice against HER-2-positive tumor challenge in both prophylactic and therapeutic setting. In conclusion, these results suggest that CTL epitope-carrying T7 phage nanoparticles might be a promising approach for development of T cell epitope-based cancer vaccines.

  5. Induction of Protective Anti-CTL Epitope Responses against HER-2-Positive Breast Cancer Based on Multivalent T7 Phage Nanoparticles

    PubMed Central

    Pouyanfard, Somayeh; Bamdad, Taravat; Hashemi, Hamidreza; Bandehpour, Mojgan; Kazemi, Bahram

    2012-01-01

    We report here the development of multivalent T7 bacteriophage nanoparticles displaying an immunodominant H-2kd-restricted CTL epitope derived from the rat HER2/neu oncoprotein. The immunotherapeutic potential of the chimeric T7 nanoparticles as anti-cancer vaccine was investigated in BALB/c mice in an implantable breast tumor model. The results showed that T7 phage nanoparticles confer a high immunogenicity to the HER-2-derived minimal CTL epitope, as shown by inducing robust CTL responses. Furthermore, the chimeric nanoparticles protected mice against HER-2-positive tumor challenge in both prophylactic and therapeutic setting. In conclusion, these results suggest that CTL epitope-carrying T7 phage nanoparticles might be a promising approach for development of T cell epitope-based cancer vaccines. PMID:23166703

  6. Interleukin-7 (IL-7) enhances class switching to IgE and IgG4 in the presence of T cells via IL-9 and sCD23.

    PubMed

    Jeannin, P; Delneste, Y; Lecoanet-Henchoz, S; Gretener, D; Bonnefoy, J Y

    1998-02-15

    Interleukin-7 (IL-7) is a B-cell growth factor produced by both bone marrow stroma cells and follicular dendritic cells (FDCs) located in primary lymphoid follicles and germinal centers. In this study, we have evaluated the role of IL-7 on human Ig class switching. IL-7 was added to peripheral blood mononuclear cells (PBMCs) or tonsillar B cells in the absence or presence of IL-4 and/or anti-CD40 monoclonal antibody (MoAb). Alone, IL-7 did not affect Ig production by PBMCs or by anti-CD40 MoAb-stimulated B cells. Rather, IL-7 potentiated IL-4-induced IgE and IgG4 production by PBMCs. In parallel, IgG3 production was also enhanced but to a lesser extent, whereas the production of the other isotypes was unaltered. The activity of IL-2, IL-9, or IL-15, which share usage of the common gamma chain for signaling, was also assessed. IL-9, like IL-7, potentiated mainly IgE and IgG4 production by IL-4-stimulated PBMCs. IL-15, in contrast, was ineffective, whereas IL-2 enhanced the production of all isotypes. More precisely, IL-7 potentiation of IgE and IgG4 production required the presence of T cells and was accompanied by an increase of the expression of two soluble molecules favoring preferentially IgE and IgG4 synthesis: CD23 (sCD23) and IL-9. Moreover, neutralizing anti-CD23 and anti-IL-9 antibodies partly inhibited the increase of IgE synthesis induced by IL-7. Thus, IL-7 produced locally in the germinal centers by FDCs may interact with T cells and potentiate human IgE and IgG4 switching by favoring IL-9 and sCD23 production.

  7. Association with the Plasma Membrane Is Sufficient for Potentiating Catalytic Activity of Regulators of G Protein Signaling (RGS) Proteins of the R7 Subfamily.

    PubMed

    Muntean, Brian S; Martemyanov, Kirill A

    2016-03-25

    Regulators of G protein Signaling (RGS) promote deactivation of heterotrimeric G proteins thus controlling the magnitude and kinetics of responses mediated by G protein-coupled receptors (GPCR). In the nervous system, RGS7 and RGS9-2 play essential role in vision, reward processing, and movement control. Both RGS7 and RGS9-2 belong to the R7 subfamily of RGS proteins that form macromolecular complexes with R7-binding protein (R7BP). R7BP targets RGS proteins to the plasma membrane and augments their GTPase-accelerating protein (GAP) activity, ultimately accelerating deactivation of G protein signaling. However, it remains unclear if R7BP serves exclusively as a membrane anchoring subunit or further modulates RGS proteins to increase their GAP activity. To directly answer this question, we utilized a rapidly reversible chemically induced protein dimerization system that enabled us to control RGS localization independent from R7BP in living cells. To monitor kinetics of Gα deactivation, we coupled this strategy with measuring changes in the GAP activity by bioluminescence resonance energy transfer-based assay in a cellular system containing μ-opioid receptor. This approach was used to correlate changes in RGS localization and activity in the presence or absence of R7BP. Strikingly, we observed that RGS activity is augmented by membrane recruitment, in an orientation independent manner with no additional contributions provided by R7BP. These findings argue that the association of R7 RGS proteins with the membrane environment provides a major direct contribution to modulation of their GAP activity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. A pathway of costimulation that prevents anergy in CD28- T cells: B7- independent costimulation of CD1-restricted T cells

    PubMed Central

    1995-01-01

    A class of molecules that is expressed on antigen presenting cells, exemplified by CD80 (B7), has been found to provide a necessary costimulatory signal for T cell activation and proliferation. CD28 and CTLA4 are the B7 counterreceptors and are expressed on the majority of human CD4+ T cells and many CD8+ T cells. The signal these molecules mediate is distinguished from other costimulatory signals by the finding that T cell recognition of antigen results in a prolonged state of T cell unresponsiveness or anergy, unless these costimulatory molecules are engaged. However, nearly half of the CD8+ and CD4-CD8- T cells lack CD28, and the costimulatory signals required for the activation of such cells are unknown. To understand the pathways of activation used by CD28- T cells, we have examined the costimulatory requirements of antigen-specific CD4-CD8- TCR(+)-alpha/beta circulating T cells that lack the expression of CD28. We have characterized two T cell lines, DN1 and DN6, that recognize a mycobacterial antigen, and are restricted not by major histocompatibility complex class I or II, but by CD1b or CD1c, two members of a family of major histocompatibility complex-related molecules that have been recently implicated in a distinct pathway for antigen presentation. Comparison of antigen-specific cytolytic responses of the DN1 and DN6 T cell lines against antigen-pulsed CD1+ monocytes or CD1+ B lymphoblastoid cell lines (B-LCL) demonstrated that these T cells recognized antigen presented by both types of cells. However, T cell proliferation occurred only when antigen was presented by CD1+ monocytes, indicating that the CD1+ monocytes expressed a costimulatory molecule that the B- LCL transfectants lacked. This hypothesis was confirmed by demonstrating that the T cells became anergic when incubated with the CD1(+)-transfected B-LCL in the presence of antigen, but not in the absence of antigen. The required costimulatory signal occurred by a CD28-independent mechanism since

  9. Etude par Imagerie à faible Niveau dans le proche Infrarouge d'une Emission de la haute Atmosphère

    NASA Astrophysics Data System (ADS)

    Pautet, Pierre-Dominique

    2000-12-01

    Le travail effectué a eu pour but la mise en place d'un protocole d'observation et de traitement des images, ainsi que les outils appropriés, visant à l'étude d'une émission de la haute atmosphère terrestre dans le proche infrarouge. Il existe actuellement des télescopes comme le VLT (Very Large Telescope), installé au Chili, qui permettent d'observer des astres et des galaxies distants de plusieurs millions de parsecs. A cause de l'expansion de l'Univers, des objets situés aussi loin s'éloignent très rapidement de nous. Le spectre de leur émission qui nous parvient alors est décalé vers le rouge ou l'infrarouge, du fait de l'effet Doppler. Il faut donc observer ces objets dans des longueurs d'onde appropriées. Malheureusement, l'atmosphère terrestre qui nous sépare d'eux est aussi le siège de nombreuses émissions qui peuvent venir perturber les mesures. De toutes ces émissions, la principale est due au radical OH dont les raies de rotation-vibration couvrent tout le spectre entre 0,7 et 2,5 microns. Cette émission a lieu au niveau d'une couche assez fine de la haute atmosphère appelée mésopause et située à environ 85 kilomètres d'altitude. Le travail effectué a eu pour but de mettre en évidence les principales caractéristiques de cette émission qui n'est pas uniforme et constante dans le temps. Un programme d'observations dans le proche infrarouge a été élaboré. Plusieurs algorithmes de traitement d'image ont été développés. Un programme d'inversion de perspective a été mis au point pour une utilisation en temps réel sur le terrain. Les caractéristiques des images peuvent être ensuite analysées. La première partie du mémoire comporte une description des différentes émissions lumineuses que l'on peut observer la nuit lorsque l'on regarde la voûte céleste. Ces émissions peuvent avoir deux origines: astronomique ou atmosphérique. Le problème de l'absorption atmosphérique et plus précisément les conditions

  10. Capture and detection of T7 bacteriophages on a nanostructured interface.

    PubMed

    Han, Jin-Hee; Wang, Min S; Das, Jayanti; Sudheendra, L; Vonasek, Erica; Nitin, Nitin; Kennedy, Ian M

    2014-04-09

    A highly ordered array of T7 bacteriophages was created by the electrophoretic capture of phages onto a nanostructured array with wells that accommodated the phages. Electrophoresis of bacteriophages was achieved by applying a positive potential on an indium tin oxide electrode at the bottom of the nanowells. Nanoscale arrays of phages with different surface densities were obtained by changing the electric field applied to the bottom of the nanowells. The applied voltage was shown to be the critical factor in generating a well-ordered phage array. The number of wells occupied by a phage, and hence the concentration of phages in a sample solution, could be quantified by using a DNA intercalating dye that rapidly stains the T7 phage. The fluorescence signal was enhanced by the intrinsic photonic effect made available by the geometry of the platform. It was shown that the quantification of phages on the array was 6 orders of magnitude better than could be obtained with a fluorescent plate reader. The device opens up the possibility that phages can be detected directly without enrichment or culturing, and by detecting phages that specifically infect bacteria of interest, rapid pathogen detection becomes possible.

  11. Capture and Detection of T7 Bacteriophages on a Nanostructured Interface

    PubMed Central

    2015-01-01

    A highly ordered array of T7 bacteriophages was created by the electrophoretic capture of phages onto a nanostructured array with wells that accommodated the phages. Electrophoresis of bacteriophages was achieved by applying a positive potential on an indium tin oxide electrode at the bottom of the nanowells. Nanoscale arrays of phages with different surface densities were obtained by changing the electric field applied to the bottom of the nanowells. The applied voltage was shown to be the critical factor in generating a well-ordered phage array. The number of wells occupied by a phage, and hence the concentration of phages in a sample solution, could be quantified by using a DNA intercalating dye that rapidly stains the T7 phage. The fluorescence signal was enhanced by the intrinsic photonic effect made available by the geometry of the platform. It was shown that the quantification of phages on the array was 6 orders of magnitude better than could be obtained with a fluorescent plate reader. The device opens up the possibility that phages can be detected directly without enrichment or culturing, and by detecting phages that specifically infect bacteria of interest, rapid pathogen detection becomes possible. PMID:24650205

  12. [Effect of Evn-50 on cell growth and apoptosis in tamoxifen-resistance human breast cancer cell line MCF-7/TAM-R].

    PubMed

    Hu, Hui-yong; Zhou, Jun; Wan, Fang; Dong, Li-feng; Zhang, Feng; Wang, Yi-ke; Chen, Fang-fang; Chen, Yi-ding

    2012-09-01

    To investigate the effect of Evn-50 extracted from Vitex negundo on human breast cancer cell line MCF-7 and MCF-7/TAM-R cells in vitro. MCF-7 and tamoxifen-resistant MCF-7/TAM-R cells were treated with Evn-50,tamoxifen or combination of Evn-50 and tamoxifen. Cell proliferation inhibition rates were determined by MTT assay. The apoptosis rate and the change of cell cycle were detected by PI staining flow cytometry. Protein expression of phospho-MAPK 44/42 (Thr202/Tyr204),MAPK P44/42, phospho-AKT (Ser473) and AKT were detected with Western blotting. The viability of MCF-7 cells was decreased in combination group [(28.65 ±11.43)%] and Evn-50 group [(53.02 ±15.14)%] compared with TAM group (P<0.01). The cell viability of MCF-7/TAM-R in combination group [(42.11 ±14.30)%] was significantly lower than that in TAM group [(92.18 ±13.16)%] (P<0.01). The cell apoptosis rate was dependent on the time of treatment in all groups,the effects on apoptosis and G2/M phase cells were most prominent at 72 h (P<0.01). Western blotting revealed that protein levels of phosphorylated AKT and p-MAPK44/42 decreased,while the expression of total AKT and MAPK44/42 was stable. In MCF-7/TAM-R cells,the expression of phosphorylation of AKT and MAPK44/42 protein was not changed in Evn-50 or TAM alone group,but significantly inhibited in the combination group at 72 h. Evn-50 can inhibit cell growth and induce apoptosis in MCF-7 and MCF-7/TAM-R cells,it can reverse tamoxifen-resistance of MCF-7/TAM-R cells.The mechanisms may be related to the down-regulation of phosphorylated ERK1/2 in MAPK signal pathway and phosphorylated AKT in AKT signal pathway.

  13. Quantitative Susceptibility Mapping of Amyloid-β Aggregates in Alzheimer's Disease with 7T MR.

    PubMed

    Tiepolt, Solveig; Schäfer, Andreas; Rullmann, Michael; Roggenhofer, Elisabeth; Gertz, Hermann-Josef; Schroeter, Matthias L; Patt, Marianne; Bazin, Pierre-Louis; Jochimsen, Thies H; Turner, Robert; Sabri, Osama; Barthel, Henryk

    2018-05-28

    PET imaging is an established technique to detect cerebral amyloid-β (Aβ) plaques in vivo. Some preclinical and postmortem data report an accumulation of redox-active iron near Aβ plaques. Quantitative susceptibility mapping (QSM) at high-field MRI enables iron deposits to be depicted with high spatial resolution. Aim of this study was to examine whether iron and Aβ plaque accumulation is related and thus, whether 7T MRI might be an additive diagnostic tool to Aβ PET imaging. Postmortem human Alzheimer's disease (AD) and healthy control (HC) frontal gray matter (GM) was imaged with 7T MRI which resulted in T1 maps and QSM. Aβ plaque load was determined by histopathology. In vivo, 10 Aβ PET-positive AD patients (74.1±6.0a) and 10 Aβ PET-negative HCs (67.1±4.4a) underwent 7T MR examination and QSM maps were analyzed. Severity of cognitive deficits was determined by MMSE. Postmortem, the susceptibility of Aβ plaque-containing GM were higher than those of Aβ plaque-free GM (0.011±0.002 versus - 0.008±0.003 ppm, p <  0.001). In vivo, only the bilateral globus pallidus showed significantly higher susceptibility in AD patients compared to HCs (right: 0.277±0.018 versus - 0.009±0.009 ppm; left: 0.293±0.014 versus - 0.007±0.012 ppm, p <  0.0001). The pallidal QSM values were negatively correlated with those of the MMSE (r = - 0.69, p = 0.001). The postmortem study revealed significant susceptibility differences between the Aβ plaque-containing and Aβ plaque-free GM, whereas in vivo only the QSM values of the globus pallidus differed significantly between AD and HC group. The pallidal QSM values correlated with the severity of cognitive deficits. These findings encourage efforts to optimize the 7T-QSM methodology.

  14. Thermal and urea-induced unfolding in T7 RNA polymerase: Calorimetry, circular dichroism and fluorescence study

    PubMed Central

    Griko, Yuri; Sreerama, Narasimha; Osumi-Davis, Patricia; Woody, Robert W.; Woody, A-Young Moon

    2001-01-01

    Structural changes in T7 RNA polymerase (T7RNAP) induced by temperature and urea have been studied over a wide range of conditions to obtain information about the structural organization and the stability of the enzyme. T7RNAP is a large monomeric enzyme (99 kD). Calorimetric studies of the thermal transitions in T7RNAP show that the enzyme consists of three cooperative units that may be regarded as structural domains. Interactions between these structural domains and their stability strongly depend on solvent conditions. The unfolding of T7RNAP under different solvent conditions induces a highly stable intermediate state that lacks specific tertiary interactions, contains a significant amount of residual secondary structure, and undergoes further cooperative unfolding at high urea concentrations. Circular dichroism (CD) studies show that thermal unfolding leads to an intermediate state that has increased β-sheet and reduced α-helix content relative to the native state. Urea-induced unfolding at 25°C reveals a two-step process. The first transition centered near 3 M urea leads to a plateau from 3.5 to 5.0 M urea, followed by a second transition centered near 6.5 M urea. The CD spectrum of the enzyme in the plateau region, which is similar to that of the enzyme thermally unfolded in the absence of urea, shows little temperature dependence from 15° to 60°C. The second transition leads to a mixture of poly(Pro)II and unordered conformations. As the temperature increases, the ellipticity at 222 nm becomes more negative because of conversion of poly(Pro)II to the unordered conformation. Near-ultraviolet CD spectra at 25°C at varying concentrations of urea are consistent with this picture. Both thermal and urea denaturation are irreversible, presumably because of processes that follow unfolding. PMID:11274475

  15. New trends in the cyber and street market of recreational drugs? The case of 2C-T-7 ('Blue Mystic').

    PubMed

    Schifano, Fabrizio; Deluca, Paolo; Agosti, Lisa; Martinotti, Giovanni; Corkery, John M; Alex, Baldacchino; Caterina, Bonan; Heikki, Bothas; Raffaella, Brigada; Anna, Comacchio; Lucia, Di Furia; Dorte, Duarte Rui Eastwood; Magi, Farré; Susana, Ferreira; Irene, Flores; Claude, Guionnet; Lisbet, Harder; Lene, Stokholm Jensen; Mauro, Leoni; Christopher, Littlejohn; Aino, Majava; Teuvo, Peltoniemi; Milena, Pizza; Salman, Rawaf; Damien, Robert; Angela, Rossi Maria; Francesco, Rovetto; Norbert, Scherbaum; Holger, Siemann; Josep, Tarrago; Marta, Torrens; Francesco, Zambello

    2005-11-01

    2C-T-7 ('Blue Mystic'), an illicit compound which shows similarities with MDMA and other designer drugs, has been only occasionally identified in the EU, but discussion on the Internet between experimenters has recently grown significantly. We aimed at collecting together in a review the available information on 2C-T-7, both at the cyber and at the street market level. 2C-T-7 was first synthesized in 1986; its desired effects include both a sense of empathy and of well-being. Hallucinations, nausea, anxiety, panic attacks and paranoid ideation are anecdotally reported. According to the different European sources here approached, the availability of 2C-T-7 at street level seems to be currently very low, although one death related to a mono-intoxication with 2C-T-7 has been documented in the USA. With respect to information on 2C-T-7 available online, due to both redundancy and relevance issues the initial identified sample of 360 was reduced to 118 websites. In 14 (11.9%) websites, the detailed description of the 2C-T-7 synthesis was given. Harm Reduction websites appeared significantly earlier in the search engines results' list than Anti drugs (p 0.006) websites. Five (4.2%) websites apparently offered 2C-T-7 for sale. The large body of knowledge available online seems to contrast with small numbers of seizures at street level; an exhaustive web mapping of drug-related issues may be of interest for the clinician. Projects aimed at designing more 'attractive' prevention websites should be planned and future studies should better assess the characteristics of those consumers who take advantage of the online information of hallucinogenic compounds.

  16. Lineage determination of CD7+ CD5- CD2- and CD7+ CD5+ CD2- lymphoblasts: studies on phenotype, genotype, and gene expression of myeloperoxidase, CD3 epsilon, and CD3 delta.

    PubMed

    Yoneda, N; Tatsumi, E; Teshigawara, K; Nagata, S; Nagano, T; Kishimoto, Y; Kimura, T; Yasunaga, K; Yamaguchi, N

    1994-04-01

    The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+ CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T-lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO-negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T-lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+ CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5- CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases with entire germ-line genes and without mRNA of the three molecules (MPO, CD3 epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior to their commitment to either T- or myeloid-lineage. The co-expression of the genes of MPO

  17. Identification of trimannoside-recognizing peptide sequences from a T7 phage display screen using a QCM device.

    PubMed

    Nishiyama, Kazusa; Takakusagi, Yoichi; Kusayanagi, Tomoe; Matsumoto, Yuki; Habu, Shiori; Kuramochi, Kouji; Sugawara, Fumio; Sakaguchi, Kengo; Takahashi, Hideyo; Natsugari, Hideaki; Kobayashi, Susumu

    2009-01-01

    Here, we report on the identification of trimannoside-recognizing peptide sequences from a T7 phage display screen using a quartz-crystal microbalance (QCM) device. A trimannoside derivative that can form a self-assembled monolayer (SAM) was synthesized and used for immobilization on the gold electrode surface of a QCM sensor chip. After six sets of one-cycle affinity selection, T7 phage particles displaying PSVGLFTH (8-mer) and SVGLGLGFSTVNCF (14-mer) were found to be enriched at a rate of 17/44, 9/44, respectively, suggesting that these peptides specifically recognize trimannoside. Binding checks using the respective single T7 phage and synthetic peptide also confirmed the specific binding of these sequences to the trimannoside-SAM. Subsequent analysis revealed that these sequences correspond to part of the primary amino acid sequence found in many mannose- or hexose-related proteins. Taken together, these results demonstrate the effectiveness of our T7 phage display environment for affinity selection of binding peptides. We anticipate this screening result will also be extremely useful in the development of inhibitors or drug delivery systems targeting polysaccharides as well as further investigations into the function of carbohydrates in vivo.

  18. Le rôle du soutien parental dans la relation entre la victimisation homophobe, l’homophobie intériorisée et la détresse psychologique chez les jeunes de minorités sexuelles (JMS) : une approche de médiation modérée

    PubMed Central

    Bergeron, Félix-Antoine; Blais, Martin; Hébert, Martine

    2016-01-01

    Résumé Cet article explore le rôle modérateur du soutien parental dans les relations entre la victimisation homophobe, l’homophobie intériorisée et la détresse psychologique chez des jeunes de minorités sexuelles (JMS), que l’on dit aussi lesbiennes, gais, bisexuels ou en questionnement. Il vise à 1) documenter la prévalence des différentes formes de victimisation homophobe vécue par les JMS, et ce, selon le genre et l’âge et 2) à explorer l’effet modérateur du soutien parental dans la relation entre la victimisation homophobe, l’homophobie intériorisée et la détresse psychologique. Un échantillon de 228 JMS âgés de 14 à 22 ans, non exclusivement hétérosexuels, recrutés en milieu communautaire dans le cadre de l’enquête sur le Parcours Amoureux des Jeunes (PAJ) du Québec a été analysé. L’impact de la victimisation homophobe, du soutien parental, de l’homophobie intériorisée sur la détresse psychologique est exploré par un modèle de régression linéaire avec effets de médiation modérée. Le rôle modérateur du soutien parental est confirmé dans la relation entre la victimisation homophobe et la détresse psychologique. Ces variables peuvent constituer des leviers pour prévenir les effets négatifs des préjudices homophobes sur la santé mentale des JMS. PMID:26966851

  19. α4+β7hiCD4+ Memory T cells Harbor Most Th-17 cells and are Preferentially Infected During Acute SIV Infection

    PubMed Central

    Kader, Muhamuda; Wang, Xiaolei; Piatak, Michael; Lifson, Jeffrey; Roederer, Mario; Veazey, Ronald; Mattapallil, Joseph J.

    2009-01-01

    HIV/SIV are thought to infect minimally activated CD4+ T cells after viral entry. Not much is known about why SIV selectively targets these cells. Here we show that CD4+ T cells that express high levels of the α4β7 heterodimer are preferentially infected very early during the course of SIV infection. At day 2–4 post infection, α4+β7hiCD4+ T cells had ∼ 5x more SIV-gag DNA than β7−CD4+ T cells. α4+β7hiCD4+ T cells displayed a predominantly central memory (CD45RA−CD28+CCR7+) and resting (CD25−CD69−HLA-DR−Ki-67−) phenotype. Though the expression of detectable CCR5 was variable on α4+β7hi and β7−CD4+ T cells, both CCR5+ and CCR5− subsets of α4+β7hi and β7−CD4+ T cells were found to express sufficient levels of CCR5 mRNA suggesting that both these subsets could be efficiently infected by SIV. In line with this, we found similar levels of SIV infection in β7−CD4+CCR5+ and β7−CD4+CCR5− T cells. α4β7hiCD4+ T cells were found to harbor most Th-17 cells that were significantly depleted during acute SIV infection. Taken together, our results show that resting memory α4+β7hiCD4+ T cells in blood are preferentially depleted during acute SIV infection, and the loss of these cells alters the balance between Th-17 and Th-1 responses thereby contributing to disease pathogenesis. PMID:19571800

  20. IL-7Rα and E47: independent pathways required for development of multipotent lymphoid progenitors

    PubMed Central

    Kee, Barbara L.; Bain, Gretchen; Murre, Cornelis

    2002-01-01

    Mice that lack the transcription factors encoded by the E2A gene or the receptor for interleukin 7 (IL-7R) have severe overlapping defects in lymphocyte development. Here, we show that E2A proteins are required for the survival of early T-lineage cells; however, they function through a pathway that is distinct from the survival pathway initiated by IL-7R signaling. While E2A proteins are required to suppress caspase 3 activation, ectopic expression of the anti-apoptotic protein Bcl-2 is not sufficient to overcome the lymphopoietic defects observed in the absence of E2A. Remarkably, mice that lack both IL-7Rα and E47 display a synergistic decrease in the number of T-cell, NK-cell and multipotent progenitors in the thymus, indicating that these distinct survival pathways converge to promote the development of multipotent lymphoid progenitors. PMID:11782430