Spi6 in Dendritic Cell priming of CD8 T cell responses to virus

Spi6 is a serine protease inhibitor. Its main function is inhibition of granzyme B (GrB): it is therefore an anti-apoptotic protein in cytotoxic T cells (CTL), where leakage of GrB from cytotoxic granules into the cytosol can trigger apoptosis. CTLs use GrB release to kill infected cells but they can also induce apoptosis in antigenloaded mature dendritic cells (DC) during priming. Mature DCs upregulate Spi6 and in vitro have higher resistance to CTL-induced apoptosis compared to immature ones: when Spi6 is absent, this resistance is lost. However, whether Spi6 protects DCs from CTL-mediated apoptosis in vivo is still under debate. Using mice deficient in Spi6, the project focuses on the role of Spi6 in DC survival during the priming of naïve and memory anti-Lymphocytic Choriomeningitis virus (LCMV) CD8 T cell responses. CD8α+ DCs are professional antigen presenting cells responsible for cross-presentation of viral antigens in secondary lymphoid organs. Upon maturation, Spi6 is expressed by CD8α+ DC in vivo. In our model, Spi6 KO DC antigen-presentation ability was comparable to wild-type (WT) but their survival was impaired. This resulted in defective expansion of WT LCMV-specific CD8 T cells. A similar requirement for Spi6 was found for DC priming of memory CD8 T cell expansion. GrB KO CD8 T cells rescued the priming defect in Spi6 KO mice during both primary and secondary responses, demonstrating GrB is the physiological target of Spi6 in DCs. Thus, GrB is a major immunosuppressive agent controlling the DC priming of anti-viral T cell mediated immunity

Spi6 in dendritic cell priming of CD8 T cell responses to virus

Spi6 is a serine protease inhibitor. Its main function is inhibition of granzyme B (GrB): it is therefore an anti-apoptotic protein in cytotoxic T cells (CTL), where leakage of GrB from cytotoxic granules into the cytosol can trigger apoptosis. CTLs use GrB release to kill infected cells but they can also induce apoptosis in antigenloaded mature dendritic cells (DC) during priming. Mature DCs upregulate Spi6 and in vitro have higher resistance to CTL-induced apoptosis compared to immature ones: when Spi6 is absent, this resistance is lost. However, whether Spi6 protects DCs from CTL-mediated apoptosis in vivo is still under debate. Using mice deficient in Spi6, the project focuses on the role of Spi6 in DC survival during the priming of naïve and memory anti-Lymphocytic Choriomeningitis virus (LCMV) CD8 T cell responses. CD8α+ DCs are professional antigen presenting cells responsible for cross-presentation of viral antigens in secondary lymphoid organs. Upon maturation, Spi6 is expressed by CD8α+ DC in vivo. In our model, Spi6 KO DC antigen-presentation ability was comparable to wild-type (WT) but their survival was impaired. This resulted in defective expansion of WT LCMV-specific CD8 T cells. A similar requirement for Spi6 was found for DC priming of memory CD8 T cell expansion. GrB KO CD8 T cells rescued the priming defect in Spi6 KO mice during both primary and secondary responses, demonstrating GrB is the physiological target of Spi6 in DCs. Thus, GrB is a major immunosuppressive agent controlling the DC priming of anti-viral T cell mediated immunity.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Salivary glands abnormalities in oculo-auriculo-vertebral spectrum

BACKGROUND:Feeding and swallowing impairment are present in up to 80% of oculo-auriculo-vertebral spectrum (OAVS) patients. Salivary gland abnormalities have been reported in OAVS patients but their rate, features, and relationship with phenotype severity have yet to be defined. MATERIAL AND METHODS:Parotid and submandibular salivary gland hypo/aplasia was evaluated on head MRI of 25 OAVS patients (16 with severe phenotype, Goldenhar syndrome) and 11 controls. RESULTS:All controls disclosed normal salivary glands. Abnormal parotid glands were found exclusively ipsilateral to facial microsomia in 21/25 OAVS patients (84%, aplasia in six patients) and showed no association with phenotype severity (14/16 patients with Goldenhar phenotype vs 7/9 patients with milder phenotype, p = 0.6). Submandibular salivary gland hypoplasia was detected in six OAVS patients, all with concomitant ipsilateral severe involvement of the parotid gland (p 0.6). CONCLUSIONS:Salivary gland abnormalities are strikingly common in OAVS. Their detection might help the management of OAVS-associated swallowing and feeding impairment

IAPT chromosome data 31.

POACEAE Paspalum almum Chase, 2n = 12; Argentina, Corrientes, H & D 1703 (MNES), H & D 1704 (MNES).Paspalum conspersum Schrad., 2n = 60; Argentina, Misiones, H & D 1119 (MNES), H & D 1143 (MNES).Paspalum equitans Mez, 2n = 20; Argentina, Misiones, H & D 1447 (MNES).Paspalum fasciculatum Wild. ex Flüggé, 2n = 20; Argentina, Formosa, R 307 (BAA).Paspalum glaucescens Hack., 2n = 40; Argentina, Misiones, H & D 109 (MNES).Paspalum ionanthum Chase, n = 20; Paraguay, Cordillera, H & D 1177 (MNES).Paspalum maculosum Trin., 2n = 20, 40; Argentina, Misiones, H & D 1445 (MNES).Paspalum malacophyllum Trin., 2n = 40; Argentina, Salta, H & D 1448 (MNES).Paspalum notatum var. saurae Parodi, 2n = 20; Argentina, Santa Fe, H & D 1453 (MNES).Paspalum notatum Flüggé var. notatum, 2n = 40; Argentina, Misiones, H 220 (CTES, MNES); Argentina, Santa Fe, H & D 1304 (MNES); Argentina, Misiones, H & D 1603 (MNES).Paspalum pauciciliatum (Parodi) Herter, 2n = 40; Argentina, Misiones, H & D 465 (CTES, MNES).Paspalum paucifolium Swallen, 2n = 40; Paraguay, Paraguarí, H & D 1294 (MNES).Paspalum quarinii Morrone & Zuloaga, 2n = 20; Argentina, Misiones, H & D 1190 (CTES, MNES, SI).Paspalum regnellii Mez, 2n = 40; Argentina, Misiones, H & D 1118 (MNES).Fil: Marhold, Karol. Academia de Ciencias; EslovaquiaFil: Kurĕera, Jaromír. Academia de Ciencias; EslovaquiaFil: Aguiar-Melo, Camila. Universidade Federal do Rio Grande do Sul; BrasilFil: Almeida, Erton Mendonça de. Universidade Estadual da Paraiba; BrasilFil: Alves, Lânia Isis Ferreira. Universidade Estadual da Paraiba; BrasilFil: An'kova, Tatyana V.. Jardin botánico de Siberia Central; RusiaFil: Bered, Fernanda. Universidade Federal do Rio Grande do Sul; BrasilFil: Bonifácio, Kallyne. Universidade Estadual da Paraiba; BrasilFil: Carvalho, Luana. Universidade Federal do Rio Grande do Sul; BrasilFil: Chiarini, Franco Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Cordeiro, Joel M. P.. Universidade Estadual da Paraiba; BrasilFil: Costea, Mihai. Wilfrid Laurier School Of Business; CanadáFil: Daviña, Julio Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Ebel, Aleksandr L.. Tomsk State University; RusiaFil: Souto, Allan Falconi. Universidad Federal do Abc; BrasilFil: Felix, Cattleya M. P.. Universidade Estadual da Paraiba; BrasilFil: Felix, Leonardo P.. Universidade Estadual da Paraiba; BrasilFil: Fernandez, Aveliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: García, Miguel Ángel. University of Toronto; Canadá. Royal Botanic Gardens; Reino UnidoFil: García Ruiz, Ignacio. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Física; MéxicoFil: Gil, André dos Santos Bragança. Museu Paraense Emilio Goeldi; BrasilFil: Guerra, Marcelo. Universidade Federal de Pernambuco; BrasilFil: Hirsch, Luiza Domingues. Universidade Federal do Rio Grande do Sul; BrasilFil: Honfi, Ana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentina. Universidad Nacional de Misiones; ArgentinaFil: Kaltchuk Santos, Eliane. Universidade Federal do Rio Grande do Sul; BrasilFil: Knapp, Sandra. Natural History Museum; Reino UnidoFil: Kumar, Rohit. Punjabi University; IndiaFil: Kumari, Vandna. Punjabi University; IndiaFil: Lovo, Juliana. Instituto Tecnológico Vale. Departamento de Bioinformatica y Genomica Ambiental.; BrasilFil: Lucena, Reinaldo F. P.. Universidade Estadual da Paraiba; BrasilFil: Medeiros Neto, Enoque. Universidade Estadual da Paraiba; BrasilFil: Moraes, Ana Paula. Universidad Federal do Abc; BrasilFil: Nascimento, Rodrigo Garcia Silva. Universidade Estadual da Paraiba; BrasilFil: Neves, José Achilles Lima. Universidade Estadual da Paraiba; BrasilFil: Nollet, Felipe. Universidad Federal Rural Pernambuco; BrasilFil: Oliveira, Regina Célia de. Universidade do Brasília; BrasilFil: Orejuela, Andrés. Royal Botanic Gardens; Reino UnidoFil: Pozzobon, Marisa Toniolo. Ministerio da Agricultura Pecuaria e Abastecimento de Brasil. Empresa Brasileira de Pesquisa Agropecuaria; BrasilFil: Reutemann, Anna Verena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Oliveira Ribeiro, André Rodolfo de. Universidade do Brasília; Brasil. Universidade Estadual do Ceará; BrasilFil: Rua, Gabriel Hugo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Santos, Angeline M. S.. Universidade Estadual da Paraiba; BrasilFil: Silva, Anádria Stéphanie da. Universidade do Brasília; BrasilFil: Silva, Rosemere. Universidade Estadual da Paraiba; BrasilFil: Silva, Ronimeire Torres da. Universidade Estadual da Paraiba; BrasilFil: Singhal, Vijay Kumar. Punjabi University; IndiaFil: Souza Chies, Tatiana T.. Universidade Federal do Rio Grande do Sul; BrasilFil: Stefanović, Saša. University of Toronto; CanadáFil: Valls, José Francisco Montenegro. Ministerio da Agricultura Pecuaria e Abastecimento de Brasil. Empresa Brasileira de Pesquisa Agropecuaria; Brasil. Universidade do Brasília; BrasilFil: Welker, Cassiano A. D.. Universidade Federal de Uberlandia; BrasilFil: Zykova, Elena. Jardin botánico de Siberia Central; Rusi

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients