DOCSLIB.ORG

Rickettsia-Macrophage Tropism:Alink to Rickettsial Pathogenicity?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rickettsia-Macrophage Tropism:Alink to Rickettsial Pathogenicity? Pedro Tiago Cardoso Pedro Cardoso Tiago Curto ? ? ATHOGENICITY P ICKETTSIAL ICKETTSIAL R O T INK INK L A : Pedro Tiago Cardoso Curto ROPISM T RICKETTSIA-MACROPHAGE TROPISM: A LINK TO RICKETTSIAL PATHOGENICITY? ACROPHAGE ACROPHAGE -M ICKETTSIA R Tese no âmbito do Doutoramento em Biologia Experimental e Biomedicina, especialidade em Biotecnologia e Saúde orientada pela Doutora Isaura Isabel Gonçalves Simões e pelo Doutor Juan J. Martinez e apresentada ao Instituto de Investigação Interdisciplinar da Universidade de Coimbra. Julho de 2018 Instituto de Investigação Interdisciplinar da Universidade de Coimbra RICKETTSIA-MACROPHAGE TROPISM: A LINK TO RICKETTSIAL PATHOGENICITY? Pedro Tiago Cardoso Curto Tese no âmbito do programa doutoral em Biologia Experimental e Biomedicina, na área de Biotecnologia e Saúde orientada pela Doutora Isaura Isabel Gonçalves Simões e pelo Doutor Juan J. Martinez e apresentada ao Instituto de Investigação Interdisciplinar da Universidade de Coimbra. Julho de 2018 Este trabalho foi realizado no grupo biotecnologia molecular e microbiana do Centro de Neurociências e Biologia Celular (Universidade de Coimbra, Portugal) e no departamento de ciências patobiológicas da Universidade do Estado de Louisiana, orientado pela Doutora Isaura Simões e Doutor Juan J. Martinez. Pedro Tiago Cardoso Curto é um estudante do programa doutoral em biologia experimental e biomedicina do Centro de Neurociências e Biologia Celular da Universidade de Coimbra, Portugal. Este trabalho foi elaborado ao abrigo de uma bolsa de doutoramento financiada pela Fundação para a Ciência e Tecnologia (FCT, SFRH/BD/96769/2013) suportada por Fundos nacionais do Ministério da Ciência, Tecnologia e Ensino Superior e pelo Fundo Social Europeu através do POCH – Programa Operacional Capital Humano. Parte do trabalho foi financiado pelo projeto com a referência POCI-01- 0145-FEDER-029592, financiado pelo Programa Operacional Competitividade e Internacionalização na sua componente FEDER e pelo orçamento da Fundação para a Ciência e a Tecnologia na sua componente OE; por fundos FEDER através do Programa Operacional Factores de Competitividade – COMPETE 2020 e por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia no âmbito do projeto Estratégico com referência atribuída pelo COMPETE: POCI-01-0145-FEDER- 007440 (ref.; UID/NEU/04539/2013); pelo projeto PTDC/SAU-MII/107942/2008; e pelo “National Institute of Allergy and Infectious Diseases of the National Institutes of Health” através dos projetos R01AI072606 and 5R21AI111086-02. RICKETTSIA‐MACROPHAGE TROPISM: A LINK TO RICKETTSIAL PATHOGENICITY? III Agradecimentos / Acknowledgments Uma tese de doutoramento consiste em uma busca incessante pelo conhecimento. Para mim, desde que me lembro de conseguir pensar, que me fascina entender o que ainda não é compreendido. Contudo, descobrir algo novo é um processo longo, duro, com obstáculos e que requer muita persistência, apoio e suporte de várias pessoas. Desta forma, gostaria de deixar algumas palavras de profundo e sincero agradecimento a todos aqueles que, de alguma forma, deixaram o seu contributo durante este percurso. Em primeiro lugar, gostaria de deixar um agradecimento especial à minha orientadora Doutora Isaura Simões. No entanto, sinto que as palavras que escolherei serão sempre poucas. Muito obrigado por todos estes momentos de partilha e amizade. Irei, para sempre, apreciar ter tido a oportunidade de trabalhar consigo. A sua forma de ver e fazer ciência é algo que me fascina. Obrigado por todo o seu apoio, ajuda e amizade ao longo destes anos. O caminho nem sempre tem sido fácil mas, é quando assim é, que se vêm os verdadeiros laços. Muito obrigado por tudo. Faço votos para o caminho que iremos percorrer seja carregado de sucesso. To Doctor Juan J. Martinez, who kindly welcomed me in his lab, I deeply appreciate the opportunity to perform science in a different country and environment. Working alongside you allowed me to immerse myself in diversity by operating with different people, different backgrounds, and different mentalities. Additionally, our collaboration gave me a chance to be in touch with different methods of doing science. Thank you for your friendship and you are always welcome in Portugal. Gostaria também de extender os meus sinceros agradecimentos a todos os membros que partecem, ou em algum momento perteceram, ao laboratório de Biotecnologia Molecular do CNC por terem dado o seu contributo no meu crescimento enquanto cientista e pessoa. Assim, deixo um agradecimento especial ao Doutor Pedro Castanheira, Doutor Rui Cruz, Doutor André Soares, Doutora Ana Sofia Lourenço, Carla Almeida, Liliana Antunes, Paulo Santo, Ana Rita Leal e a todos os outros, pelos bons momentos de amizade e boa disposição. RICKETTSIA‐MACROPHAGE TROPISM: A LINK TO RICKETTSIAL PATHOGENICITY? V I would also like to extend my acknowledgments to everyone who made my experience at LSU so meaningful. Thus, I would like to thank Doctor Sean Riley, Doctor Kevin Macaluso and his lab members, Doctor Abbie Fish, Doctor Emma Harris, Daniel Garza, Nam, Bee, Ryan Avery and all the others that made Baton Rouge a welcoming home. To Matt, I don’t have the words to describe how important you were during my time in the States. Thanks for all the moments of joy and sharing that I will forever carry with me. You made my life in Baton Rouge so much easier and enjoyable. Because of the moments we shared, returning home was nothing short of arduous. I will always miss those moments and I have high hopes that our friendship stays strong. Saudades Gostaria de agradecer aos restantes colegas e amigos do UC-Biotec pelas boas recordações e momentos vividos. Assim, agradeço a todos os membros do laboratório do Doutor Ricardo Pires e do Doutor Bruno Manadas. Não poderia passar sem deixar um agradecimento especial à Cátia Santa e a Doutora Sandra Anjo pela ajuda e apoio na interpretação dos resultados de espectrometria de massa. A todos os meus amigos, um enorme obrigado por estarem sempre presentes e por partilharem comigo muitos momentos especiais. Assim, gostaria de deixar um agradecimento especial à Isabel, Luís, Carla, Daniela Faria, Joana Novo e à sua princesa Benedita, Andreia Filipa |risinhos daqueles| e Daniela Filipa. Por fim, gostaria de agradecer a toda a minha família por me ensinarem a ser quem sou. Aos meus Pais, Avós, Irmão, Tia Rosa e primo Marcelo deixo um grande obrigado por toda esta força e momentos de partilha. As batalhas têm sido duras, mas os bons momentos serão, para sempre, parte de nós. A força e a persistência que nos caracteriza está também presente neste documento. RICKETTSIA‐MACROPHAGE TROPISM: A LINK TO RICKETTSIAL PATHOGENICITY? VI Resumo Os membros do género Rickettsia são bactérias intracelulares obrigatórias, cuja transmissão a humanos pode ocorrer através de vetores artrópodes. São responsáveis por infeções severas, das quais se destacam a febre maculosa das montanhas rochosas (Rickettsia rickettsii) e a febre escaro- nodular (Rickettsia conorii). Embora o papel das células endoteliais no desenvolvimento de doenças provocadas por Rickettsia esteja bem estudado, nenhuma função foi até agora atribuída a outros tipos celulares para o desenvolvimento da infeção. Contudo, evidências obtidas em modelos animais demonstraram a presença de bactérias intactas em vários tipos de células, tais como macrófagos, neutrófilos e hepatócitos, levantando diversas questões acerca da função desempenhada por estas células no desenvolvimento de rickettsioses. Curiosamente, evidências experimentais com mais de quarenta anos mostram que estirpes de Rickettsia do grupo tifo, com diferentes graus de patogenicidade em humanos, apresentam padrões de crescimento distintos em culturas celulares de macrófagos. No entanto, estes resultados permaneceram por explorar e os mecanismos moleculares que definem e distinguem patogenicidade entre espécies do género Rickettsia continuam por esclarecer. Este trabalho mostra que duas espécies de Rickettsia do grupo das febres exantemáticas, com diferentes graus de patogenicidade em humanos, também apresentam fenótipos intracelulares distintos em células THP-1 diferenciadas em macrófagos. Especificamente, a bactéria patogénica (R. conorii) sobrevive e prolifera dentro destas células fagocitárias, enquanto que a bactéria não patogénica (R. montanensis) é rapidamente eliminada. Estes resultados reforçam uma possível correlação entre patogenicidade no géneroRickettsia e a capacidade de sobreviver e proliferar em macrófagos, e sugerem o reposicionamento dos macrófagos comoementos el centrais no desenvolvimento da infeção. Assim, o estudo detalhado dos mecanismos moleculares que regulam a interação de bactérias do géneroRickettsia com macrófagos é fundamental para uma melhor compreensão da doença. Usando R. conorii e R. montanensis como modelos de estudo, demonstrámos também que estas duas espécies de Rickettsia apresentam requisitos distintos no que respeita aos fatores de sinalização do hospedeiro recrutados durante o processo de invasão de células do tipo macrófago. O RICKETTSIA‐MACROPHAGE TROPISM: A LINK TO RICKETTSIAL PATHOGENICITY? VII processo de entrada da bactéria patogénica R. conorii revela uma maior dependência da atividade da cinase PAK1 e de trocadores de N+/H+ (NHE), características de mecanismos de endocitose do tipo macropinocitose. Os nossos resultados sugerem assim que a bactéria R. conorii usa um mecanismo alternativo de entrada do tipo macropinocitose, envolvendo o eixo de sinalização PAK-NHE-TK. A utilização
Load more

Recommended publications
  • Reconstructability Analysis As a Tool for Identifying Gene-Gene Interactions in Studies of Human Diseases
    Portland State University PDXScholar Systems Science Faculty Publications and Presentations Systems Science 3-2010 Reconstructability Analysis As A Tool For Identifying Gene-Gene Interactions In Studies Of Human Diseases Stephen Shervais Eastern Washington University Patricia L. Kramer Oregon Health & Science University Shawn K. Westaway Oregon Health & Science University Nancy J. Cox University of Chicago Martin Zwick Portland State University, [email protected] Follow this and additional works at: https://pdxscholar.library.pdx.edu/sysc_fac Part of the Bioinformatics Commons, Diseases Commons, and the Genomics Commons Let us know how access to this document benefits ou.y Citation Details Shervais, S., Kramer, P. L., Westaway, S. K., Cox, N. J., & Zwick, M. (2010). Reconstructability Analysis as a Tool for Identifying Gene-Gene Interactions in Studies of Human Diseases. Statistical Applications In Genetics & Molecular Biology, 9(1), 1-25. This Article is brought to you for free and open access. It has been accepted for inclusion in Systems Science Faculty Publications and Presentations by an authorized administrator of PDXScholar. Please contact us if we can make this document more accessible: [email protected]. Statistical Applications in Genetics and Molecular Biology Volume 9, Issue 1 2010 Article 18 Reconstructability Analysis as a Tool for Identifying Gene-Gene Interactions in Studies of Human Diseases Stephen Shervais∗ Patricia L. Kramery Shawn K. Westawayz Nancy J. Cox∗∗ Martin Zwickyy ∗Eastern Washington University, [email protected] yOregon Health & Science University, [email protected] zOregon Health & Science University, [email protected] ∗∗University of Chicago, [email protected] yyPortland State University, [email protected] Copyright c 2010 The Berkeley Electronic Press.
    [Show full text]
  • Evaluation of the Genetic Susceptibility to the Metabolic Syndrome by the CAPN10 SNP19 Gene in the Population of South Benin
    International Journal of Molecular Biology: Open Access Research Article Open Access Evaluation of the genetic susceptibility to the metabolic syndrome by the CAPN10 SNP19 gene in the population of South Benin Abstract Volume 4 Issue 6 - 2019 Metabolic syndrome is a multifactorial disorder whose etiology is resulting from the Nicodème Worou Chabi,1,2 Basile G interaction between genetic and environmental factors. Calpain 10 (CAPN10) is the first Sognigbé,1 Esther Duéguénon,1 Véronique BT gene associated with type 2 diabetes that has been identified by positional cloning with 1 1 sequencing method. This gene codes for cysteine ​​protease; ubiquitously expressed in all Tinéponanti, Arnaud N Kohonou, Victorien 2 1 tissues, it is involved in the fundamental physiopathological aspects of insulin resistance T Dougnon, Lamine Baba Moussa and insulin secretion of type 2 diabetes. The goal of this study was to evaluate the genetic 1Department of Biochemistry and Cell Biology, University of susceptibility to the metabolic syndrome by the CAPN10 gene in the population of southern Abomey-Calavi, Benin 2 Benin. This study involved apparently healthy individuals’ aged 18 to 80 in four ethnic Laboratory of Research in Applied Biology, Polytechnic School of Abomey-Calavi, University of Abomey-Calavi, Benin groups in southern Benin. It included 74 subjects with metabolic syndrome and 323 non- metabolic syndrome patients who served as controls, with 222 women versus 175 men Correspondence: Nicodème Worou Chabi, Laboratory with an average age of 40.58 ± 14.03 years old. All subjects were genotyped for the SNP of Biochemistry and Molecular Biology, Department of 19 polymorphism of the CAPN10 gene with the PCR method in order to find associations Biochemistry and Cell Biology, Faculty of Science and between this polymorphism and the metabolic syndrome.
    [Show full text]
  • Calpain-10 Regulates Actin Dynamics by Proteolysis of Microtubule-Associated Protein 1B
    www.nature.com/scientificreports OPEN Calpain-10 regulates actin dynamics by proteolysis of microtubule-associated protein 1B Received: 15 September 2015 Tomohisa Hatta1, Shun-ichiro Iemura1,6, Tomokazu Ohishi2, Hiroshi Nakayama3, Accepted: 1 November 2018 Hiroyuki Seimiya 2, Takao Yasuda4, Katsumi Iizuka5, Mitsunori Fukuda4, Jun Takeda5, Published: xx xx xxxx Tohru Natsume1 & Yukio Horikawa5 Calpain-10 (CAPN10) is the calpain family protease identifed as the frst candidate susceptibility gene for type 2 diabetes mellitus (T2DM). However, the detailed molecular mechanism has not yet been elucidated. Here we report that CAPN10 processes microtubule associated protein 1 (MAP1) family proteins into heavy and light chains and regulates their binding activities to microtubules and actin flaments. Immunofuorescent analysis of Capn10−/− mouse embryonic fbroblasts shows that MAP1B, a member of the MAP1 family of proteins, is localized at actin flaments rather than at microtubules. Furthermore, fuorescence recovery after photo-bleaching analysis shows that calpain-10 regulates actin dynamics via MAP1B cleavage. Moreover, in pancreatic islets from CAPN10 knockout mice, insulin secretion was signifcantly increased both at the high and low glucose levels. These fndings indicate that defciency of calpain-10 expression may afect insulin secretion by abnormal actin reorganization, coordination and dynamics through MAP1 family processing. Calpains are a family of intracellular non-lysosomal calcium-activated neutral cysteine proteases known to cleave various substrate proteins and modulate their activities. Tere are 16 calpains, some of which are ubiquitously expressed and others displaying tissue-specifc distribution. Some calpains contain a penta-EF-hand domain (typical or classical calpains), and others do not (atypical calpains). Several calpain family members are impli- cated in the development of various diseases including Alzheimer’s disease, cataracts, ischemic stroke, traumatic brain injury, limb-girdle muscular dystrophy 2A and type 2 diabetes mellitus (T2DM)1.
    [Show full text]
  • Calpain-10 and Adiponectin Gene Polymorphisms in Korean Type 2 Diabetes Patients
    Original Endocrinol Metab 2018;33:364-371 https://doi.org/10.3803/EnM.2018.33.3.364 Article pISSN 2093-596X · eISSN 2093-5978 Calpain-10 and Adiponectin Gene Polymorphisms in Korean Type 2 Diabetes Patients Ji Sun Nam1,2, Jung Woo Han1, Sang Bae Lee1, Ji Hong You1, Min Jin Kim1, Shinae Kang1,2, Jong Suk Park1,2, Chul Woo Ahn1,2 1Department of Internal Medicine, 2Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea Background: Genetic variations in calpain-10 and adiponectin gene are known to influence insulin secretion and resistance in type 2 diabetes mellitus. Recently, several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene have been report- ed to be associated with type 2 diabetes and various metabolic derangements. We investigated the associations between specific cal- pain-10 and adiponectin gene polymorphisms and Korean type 2 diabetes patients. Methods: Overall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The clinical char- acteristics and measure of glucose metabolism were compared within these genotypes. Results: Among calpain-10 polymorphisms, SNP-63 T/T were more frequent in diabetes patients, and single SNP-63 increases the susceptibility to type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in adiponectin gene were not signifi- cantly associated with diabetes, insulin resistance, nor insulin secretion. Conclusion: Variations in calpain-10, SNP-63 seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43 and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism.
    [Show full text]
  • Supplementary Information.Pdf
    Supplementary Information Whole transcriptome profiling reveals major cell types in the cellular immune response against acute and chronic active Epstein‐Barr virus infection Huaqing Zhong1, Xinran Hu2, Andrew B. Janowski2, Gregory A. Storch2, Liyun Su1, Lingfeng Cao1, Jinsheng Yu3, and Jin Xu1 Department of Clinical Laboratory1, Children's Hospital of Fudan University, Minhang District, Shanghai 201102, China; Departments of Pediatrics2 and Genetics3, Washington University School of Medicine, Saint Louis, Missouri 63110, United States. Supplementary information includes the following: 1. Supplementary Figure S1: Fold‐change and correlation data for hyperactive and hypoactive genes. 2. Supplementary Table S1: Clinical data and EBV lab results for 110 study subjects. 3. Supplementary Table S2: Differentially expressed genes between AIM vs. Healthy controls. 4. Supplementary Table S3: Differentially expressed genes between CAEBV vs. Healthy controls. 5. Supplementary Table S4: Fold‐change data for 303 immune mediators. 6. Supplementary Table S5: Primers used in qPCR assays. Supplementary Figure S1. Fold‐change (a) and Pearson correlation data (b) for 10 cell markers and 61 hypoactive and hyperactive genes identified in subjects with acute EBV infection (AIM) in the primary cohort. Note: 23 up‐regulated hyperactive genes were highly correlated positively with cytotoxic T cell (Tc) marker CD8A and NK cell marker CD94 (KLRD1), and 38 down‐regulated hypoactive genes were highly correlated positively with B cell, conventional dendritic cell
    [Show full text]
  • ADCY5, CAPN10 and JAZF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes
    life Article ADCY5, CAPN10 and JAZF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes Przemysław Ustianowski 1 , Damian Malinowski 2 , Patrycja Kopytko 3, Michał Czerewaty 3, Maciej Tarnowski 3 , Violetta Dziedziejko 4 , Krzysztof Safranow 4 and Andrzej Pawlik 3,* 1 Department of Obstetrics and Gynecology, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] 2 Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] 3 Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] (P.K.); [email protected] (M.C.); [email protected] (M.T.) 4 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] (V.D.); [email protected] (K.S.) * Correspondence: [email protected] Abstract: Gestational diabetes mellitus (GDM) is carbohydrate intolerance that occurs during preg- nancy. This disease may lead to various maternal and neonatal complications; therefore, early diagnosis is very important. Because of the similarity in pathogenesis of type 2 diabetes and GDM, Citation: Ustianowski, P.; the genetic variants associated with type 2 diabetes are commonly investigated in GDM. The aim Malinowski, D.; Kopytko, P.; of the present study was to examine the associations between the polymorphisms in the ADCY5 Czerewaty, M.; Tarnowski, M.; (rs11708067, rs2877716), CAPN10 (rs2975760, rs3792267), and JAZF1 (rs864745) genes and GDM as Dziedziejko, V.; Safranow, K.; Pawlik, well as to determine the expression of these genes in the placenta. This study included 272 pregnant A. ADCY5, CAPN10 and JAZF1 Gene women with GDM and 348 pregnant women with normal glucose tolerance.
    [Show full text]
  • Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis
    Getting “Under the Skin”: Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis by Kristen Monét Brown A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiological Science) in the University of Michigan 2017 Doctoral Committee: Professor Ana V. Diez-Roux, Co-Chair, Drexel University Professor Sharon R. Kardia, Co-Chair Professor Bhramar Mukherjee Assistant Professor Belinda Needham Assistant Professor Jennifer A. Smith © Kristen Monét Brown, 2017 [email protected] ORCID iD: 0000-0002-9955-0568 Dedication I dedicate this dissertation to my grandmother, Gertrude Delores Hampton. Nanny, no one wanted to see me become “Dr. Brown” more than you. I know that you are standing over the bannister of heaven smiling and beaming with pride. I love you more than my words could ever fully express. ii Acknowledgements First, I give honor to God, who is the head of my life. Truly, without Him, none of this would be possible. Countless times throughout this doctoral journey I have relied my favorite scripture, “And we know that all things work together for good, to them that love God, to them who are called according to His purpose (Romans 8:28).” Secondly, I acknowledge my parents, James and Marilyn Brown. From an early age, you two instilled in me the value of education and have been my biggest cheerleaders throughout my entire life. I thank you for your unconditional love, encouragement, sacrifices, and support. I would not be here today without you. I truly thank God that out of the all of the people in the world that He could have chosen to be my parents, that He chose the two of you.
    [Show full text]
  • WO 2012/054896 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number ι (43) International Publication Date ¾ ί t 2 6 April 2012 (26.04.2012) WO 2012/054896 Al (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, C12N 5/00 (2006.01) C12N 15/00 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, C12N 5/02 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (21) International Application Number: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, PCT/US201 1/057387 ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (22) International Filing Date: NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, 2 1 October 201 1 (21 .10.201 1) RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (25) Filing Language: English ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/406,064 22 October 2010 (22.10.2010) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 61/415,244 18 November 2010 (18.1 1.2010) US UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, (71) Applicant (for all designated States except US): BIO- DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, TIME INC.
    [Show full text]
  • Elevated Levels of Calpain 14 in Nasal Tissue in Chronic Rhinosinusitis
    ORIGINAL RESEARCH LETTER Elevated levels of calpain 14 in nasal tissue in chronic rhinosinusitis To the Editor: Recently, calpain (CAPN) 14 was identified by a genome-wide genetic association study to play a role in eosinophilic oesophagitis [1]. CAPN14 expression is also linked with asthma and allergy sensitivity [2]. The overexpression of CAPN14 impairs epithelial barrier function and CAPN14 expression is triggered by Th2-associated signalling, such as interleukin (IL)-13 and IL-4 [3]. CAPNs are intracellular regulatory proteases, and there are 16 members of the human CAPN family. CAPNs perform a number of functions, including cytoskeletal and membrane proteins restructuring, signal transduction and inactivating enzymes involved in cell cycle progression, gene expression and apoptosis [4]. Therefore, our group performed a small pilot study to investigate CAPN gene expression profiles in tissue from another disease associated with eosinophilia and epithelial barrier function, chronic rhinosinusitis (CRS) [5]. Sinusitis is a condition associated with inflammation in the paranasal sinuses and contiguous nasal mucosa and ∼30 million adults report sinusitis symptoms annually in the United States [6]. Sinusitis is deemed chronic if symptoms persist more than 3 months, with most episodes of sinusitis associated with viral upper respiratory tract infections, asthma, allergic rhinitis and exposure to environmental factors, such as cigarette smoke [7]. Steroids are effective in treating sinusitis, thereby underlining the importance of inflammation in disease pathophysiology, with inflammatory cells such as eosinophils linked to nasal polyps formation that contribute to nasal obstruction [8]. Here, we investigated nasal tissue samples collected from patients with documented CRS, who met diagnostic criteria set forth by the Adult Sinusitis Clinical Practice Guideline [9].
    [Show full text]
  • Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Kellie A
    University of Kentucky UKnowledge Spinal Cord and Brain Injury Research Center Spinal Cord and Brain Injury Research Faculty Publications 5-2016 Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses Kellie A. Schaefer University of Iowa Marcus A. Toral University of Iowa Gabriel Velez University of Iowa Allison J. Cox University of Iowa Sheila A. Baker University of Iowa See next page for additional authors Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/scobirc_facpub Part of the Neurology Commons Repository Citation Schaefer, Kellie A.; Toral, Marcus A.; Velez, Gabriel; Cox, Allison J.; Baker, Sheila A.; Borcherding, Nicholas C.; Colgan, Diana F.; Bondada, Vimala; Mashburn, Charles B.; Yu, Chen Guang; Geddes, James W.; Tsang, Stephen H.; Bassuk, Alexander G.; and Mahajan, Vinit B., "Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses" (2016). Spinal Cord and Brain Injury Research Center Faculty Publications. 12. https://uknowledge.uky.edu/scobirc_facpub/12 This Article is brought to you for free and open access by the Spinal Cord and Brain Injury Research at UKnowledge. It has been accepted for inclusion in Spinal Cord and Brain Injury Research Center Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Authors Kellie A. Schaefer, Marcus A. Toral, Gabriel Velez, Allison J. Cox, Sheila A. Baker, Nicholas C. Borcherding, Diana F. Colgan, Vimala Bondada, Charles B. Mashburn, Chen Guang Yu, James W. Geddes, Stephen H. Tsang, Alexander G.
    [Show full text]
  • A Genome-Wide Scan for Loci Linked to Plasma Levels of Glucose and Hba1c in a Community-Based Sample of Caucasian Pedigrees the Framingham Offspring Study James B
    A Genome-Wide Scan for Loci Linked to Plasma Levels of Glucose and HbA1c in a Community-Based Sample of Caucasian Pedigrees The Framingham Offspring Study James B. Meigs,1 Carolien I. M. Panhuysen,2 Richard H. Myers,3 Peter W.F. Wilson,4,5 and L. Adrienne Cupples2 Elevated blood glucose levels are the hallmark of type 2 populations, pointing to this large chromosomal region diabetes as well as a powerful risk factor for develop- as worthy of more detailed scrutiny in the search for ment of the disease. We conducted a genome-wide type 2 diabetes susceptibility genes. Diabetes 51: search for diabetes-related genes, using measures of 833–840, 2002 glycemia as quantitative traits in 330 pedigrees from the Framingham Heart Study. Of 3,799 attendees at the 5th Offspring Study exam cycle (1991–1995), 1,461, ype 2 diabetes is a common metabolic disorder 1,251, and 771 men (49%) and women provided infor- defined by the presence of markedly elevated mation on levels of 20-year mean fasting glucose, cur- levels of plasma glucose (1). Subtle elevations in rent fasting glucose, and HbA1c, respectively, and 1,308 contributed genotype data (using 401 microsatellite Tglucose levels commonly precede the develop- markers with an average spacing of 10 cM). Levels of ment of type 2 diabetes and are a powerful predictor of glycemic traits were adjusted for age, cigarette smok- future disease (2). Levels of glucose and HbA1c (a time- ing, alcohol and estrogen use, physical activity, and integrated measure of antecedent glycemic status) (3,4) BMI.
    [Show full text]
  • A Genomic Analysis of Rat Proteases and Protease Inhibitors
    A genomic analysis of rat proteases and protease inhibitors Xose S. Puente and Carlos López-Otín Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain Send correspondence to: Carlos López-Otín Departamento de Bioquímica y Biología Molecular Facultad de Medicina, Universidad de Oviedo 33006 Oviedo-SPAIN Tel. 34-985-104201; Fax: 34-985-103564 E-mail: [email protected] Proteases perform fundamental roles in multiple biological processes and are associated with a growing number of pathological conditions that involve abnormal or deficient functions of these enzymes. The availability of the rat genome sequence has opened the possibility to perform a global analysis of the complete protease repertoire or degradome of this model organism. The rat degradome consists of at least 626 proteases and homologs, which are distributed into five catalytic classes: 24 aspartic, 160 cysteine, 192 metallo, 221 serine, and 29 threonine proteases. Overall, this distribution is similar to that of the mouse degradome, but significatively more complex than that corresponding to the human degradome composed of 561 proteases and homologs. This increased complexity of the rat protease complement mainly derives from the expansion of several gene families including placental cathepsins, testases, kallikreins and hematopoietic serine proteases, involved in reproductive or immunological functions. These protease families have also evolved differently in the rat and mouse genomes and may contribute to explain some functional differences between these two closely related species. Likewise, genomic analysis of rat protease inhibitors has shown some differences with the mouse protease inhibitor complement and the marked expansion of families of cysteine and serine protease inhibitors in rat and mouse with respect to human.
    [Show full text]