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    16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus
    (2013-04-04) Shaye, Kivity; Katzav, Aviva; Arango, María-Teresa; Landau-Rabi, Moran; Zafrir, Yaron; Agmon-Levin, Nancy; Blank, Miri; Anaya, Juan-Manuel; Mozes, Edna; Chapman, Joab; Shoenfeld, Yehuda
    Background: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naive mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intracerebra-ventricularly (ICV) with the 16/6-Id antibody. Methods: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes. Results: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control. Conclusions: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.
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    1607. Una hipótesis sobre la formación de Estado en los Andes Colombianos
    (2006-10) Chaparro Amaya, Adolfo
    Actualmente es un lugar común de la filosofía política reconocer una violencia anterior, un exceso de fuerza que legitima y antecede toda fundación de Estado. En el caso colombiano, no está claro cómo y por qué el acontecimiento mismo de la fundación borra las huellas de esa violencia para hacer visible sólo el Estado-institución (Colonia), o para magnificar los ritos y los emblemas aglutinadores del Estado-nación (República). Nuestra pretensión es abordar el problema desde la investigación de la génesis del Estado en la Nueva Granada, con la intuición de que el diagrama básico de configuración estatal surgido en el siglo XVI es pertinente en un análisis actual del Estado-nación en Colombia.
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    20 años de la caída del Muro de Berlín
    (2010-01-01) Leiteritz, Ralf Juan
    Hace veinte años era un adolescente en último año de bachillerato en Leipzig, la segunda ciudad más grande de Alemania Oriental, a unos 150 kilómetros al sur de Berlín. Pasé mi niñez y cursé mi educación preuniversitaria en la República Democrática Alemana; en otras palabras, detrás de la llamada “Cortina de Hierro”. Mi educación estuvo dominada por la ideología socialista y fuertemente controlada por el Partido Comunista. El currículum presentaba una interpretación restringida de la historia a través del lente teórico del marxismo-leninismo. Materias como “Staatsbürgerkunde”, literalmente “currículum ciudadano”, tenían como fin implantar el dogma comunista en los cerebros de los estudiantes. Viéndolo desde el exterior, Alemania Oriental debió de haberse visto como la realización de la visión de George Orwell en 1984.
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    20 años de la caída del Muro de Berlín
    (2010-01-01) Leiteritz, Ralf Juan
    Hace veinte años era un adolescente en último año de bachillerato en Leipzig, la segunda ciudad más grande de Alemania Oriental, a unos 150 kilómetros al sur de Berlín. Pasé mi niñez y cursé mi educación preuniversitaria en la República Democrática Alemana; en otras palabras, detrás de la llamada “Cortina de Hierro”. Mi educación estuvo dominada por la ideología socialista y fuertemente controlada por el Partido Comunista. El currículum presentaba una interpretación restringida de la historia a través del lente teórico del marxismo-leninismo. Materias como “Staatsbürgerkunde”, literalmente “currículum ciudadano”, tenían como fin implantar el dogma comunista en los cerebros de los estudiantes. Viéndolo desde el exterior, Alemania Oriental debió de haberse visto como la realización de la visión de George Orwell en 1984.
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    20 Years of Securitization: Strengths, Limitations and A New Dual Framework
    (2019-10-03) Bassar, Baysal
    Copenhagen School scholars introduced Securitization Theory in 1998 in a comprehensive way. Since then, it has been used widely to examine diverse topics. The strength of the theory derives from its constructivist ontology and clear framework. However, the theory has various limitations including lack of the analysis of rival views. This study aims to outline the strengths and limitations of Securitization Theory and present a novel framework for securitization. The new framework provides a dual approach for examining non-violent oppositions and counter-securitizations. It also analyses the securitization process in three phases: decision/ definition, construction, and insecuritization-in-action.
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    20. Opinión pública y proceso de paz en Colombia en 2014
    (2016) Charry Joya, Carlos Andrés
    Este artículo presenta los principales eventos sobre el proceso de paz entre el gobierno colombiano y la guerrilla de las FARC durante 2014. Esta presentación se hizo dando una especial atención de las diferentes formas de difusión e interpretación del proceso expuesto por los medios de comunicación. En este trabajo se analizan los medios de comunicación como un actor esencial del proceso de construcción de la opinión pública; por esa razón, su punto de vista es una clave para entender los diálogos de paz, así como el desarrollo del conflicto armado en Colombia.
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    22q11.2 DS syndrome as a genetic subtype of schizophrenia
    (2015) Huertas-Rodríguez, Cindy Katherin; Payan-Gomez, Cesar; Forero-Castro, Ruth Maribel
    Introduction The 22q11.2 deletion syndrome (22q11.2 DS) is associated with the microdeletion of this chromosomal region, and represents the second most common genetic syndrome after Down's syndrome. In patients with schizophrenia, 22q11.2 DS has a prevalence of 2%, and in selected groups can be increased to between 32-53%. Objective To describe the generalities of 22q11.2 DS syndrome as a genetic subtype of schizophrenia, its clinical characteristics, molecular genetic aspects, and frequency in different populations. Methods A review was performed from 1967 to 2013 in scientific databases, compiling articles about 22q11.2 DS syndrome and its association with schizophrenia. Results The 22q11.2 DS syndrome has a variable phenotype associated with other genetic syndromes, birth defects in many tissues and organs, and a high rate of psychiatric disorders, particularly schizophrenia. Likewise, it has been identified in clinical populations with schizophrenia selected by the presence of common syndromic characteristics. FISH, qPCR and MLPA techniques, and recently, aCGH and NGS technologies, are being used to diagnose this microdeletion. Conclusions It is important in clinical practice to remember that people suffering the 22q11.2 DS have a high genetic risk for developing schizophrenia, and it is considered that the simultaneous presence of this disease and 22q11.2 DS represents a genetic subtype of schizophrenia. There are clear phenotypic criteria, molecular and cytogenetic methods to diagnose this group of patients, and to optimize a multidisciplinary approach in their monitoring. © 2014 Asociación Colombiana de Psiquiatría.
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    273 ANTIEPILEPTIC DRUGS IN PAIN CAUSED BY DIABETIC NEUROPATHY
    (2007-06) Gutierrez?Alvarez, A.M.; Beltran?Rodriguez, J.A.; Moreno, C.B.
    Pain is frequent in diabetic neuropathy and is hard tomanage. Antiepileptic drugs have been used in treatingpain for several decades now. Nevertheless, their e?ec-tiveness when used as analgesics in painful diabetic neu-ropathy still remains controversial. We conducted ameta-analysis for determining which antiepileptic drughad the best analgesic potential for managing pain inpatients su?ering from painful diabetic neuropathy. Thesearch covered the Cochrane, MEDLINE, EMBASEand LILAC S databases, between January 1966 and Sep-tember 2005.
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    3D Analysis of the TCR/pMHCII Complex Formation in Monkeys Vaccinated with the First Peptide Inducing Sterilizing Immunity against Human Malaria
    (2010) Patarroyo, Manuel A.; Bermudez, Adriana; López, Carolina; Yepes, Gloria; Patarroyo, Manuel E.
    T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2) and is known to bind to HLA-DR beta 1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of V beta 12 and V beta 6 TCR gene families in 67% of HLA-DR beta 1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DR beta 1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.
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    3D structure and immunogenicity of Plasmodium falciparum sporozoite induced associated protein peptides as components of fully-protective anti-malarial vaccine
    (2011) Alba M.P.; Almonacid H.; Calderón D.; Chacón E.A.; Poloche L.A.; Patarroyo M.A.; Patarroyo M.E.
    SIAP-1 and SIAP-2 are proteins which are implicated in early events involving Plasmodium falciparum infection of the Anopheles mosquito vector and the human host. High affinity HeLa and HepG2 cell binding conserved peptides have been previously identified in these proteins, i.e. SIAP-1 34893 ( 421KVQGLSYLLRRKNGTKHPVY 440) and SIAP-1 34899 ( 541YVLNSKLLNSRSFDKFKWIQ 560) and SIAP-2 36879 ( 181LLLYSTNSEDNLDISFGELQ 200). When amino acid sequences have been properly modified (replacements shown in bold) they have induced high antibody titres against sporozoites in Aotus monkeys (assessed by IFA) and in the corresponding recombinant proteins (determined by ELISA and Western blot). 1H NMR studies of these conserved native and modified high activity binding peptides (HABPs) revealed that all had ?-helical structures in different locations and lengths. Conserved and corresponding modified HABPs displayed different lengths between the residues fitting into MHCII molecule pockets 1-9 and different amino acid orientation based on their different HLA-DR?1 * binding motifs and binding registers, suggesting that such modifications were associated with making them immunogenic. The results suggested that these modified HAPBs could be potential targets for inclusion as components of a fully-effective, minimal sub-unit based, multi-epitope, and multistage anti-malarial vaccine. © 2011 Elsevier Inc..
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    3D structure determination of STARP peptides implicated in P. falciparum invasion of hepatic cells
    (2010) Bermudez, Adriana; Alba, Martha Patricia; Vanegas, Magnolia; Patarroyo, Manuel Elkin
    To block the different stages of Plasmodium falciparum invasion into human hepatocytes and red blood cells, we have focused on those proteins belonging to the pre-erythrocytic stage. One of these proteins is Sporozoite Threonine and Asparagine Rich Protein (STARP), which is a ligand used by P. falciparum parasites to bind Hepatic cells (HepG2). Previous studies on this protein identified two conserved peptides binding with high activity to HepG2 cells (namely 20546 and 20570) with corresponding critical hepatic-cell binding residues and determined an important role for these two peptides in the invasion process. This study shows the results of immunization trials in Aotus monkeys with native STARP peptides and analogues modified in critical hepatic-cell binding residues. The results show that native peptides are not immunogenic but can induce high-antibody titers when their critical residues are replaced by other with similar volume and mass but different polarity. Nuclear Magnetic Resonance (1H NMR) studies revealed that native peptides (non-immunogenic) displayed shorter ?-helical regions compared to their highly immunogenic modified analogues. Binding assays with HLA-DR?1* molecules showed that 20546 modified peptides inducing high-antibody titers (24972, 24320 and 24486) bound to HLA-DR?1*0301 molecules, while the 20570 modified analogue (24322) bound to HLA-DR?1*0101. The results support including these high-immunogenic STARP-derived modified peptides as pre-erythrocytic candidates to be included in the design of a synthetic antimalarial vaccine. © 2010 Elsevier Ltd.
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    433 Palynostratigraphy of the eocene esmeraldas formation, middle Magdalena Valley Basin, Colombia
    (2012) Rodriguez, Guillermo; Oboh-Ikuenobe, Francisca; Jaramillo, Carlos; Rueda, Milton; Cadena, Edwin Alberto
    The Eocene EsmeraldasFormation isa very importantoil reservoir intheMiddle Magdalena ValleyBasin, Colombia, which is a preduct of the fragmentatienof a Cenozoic forelandbasinby the uplift of the Northem Andes. Ihe lateralcentinuity of the formation,as well as its correlations with lithostratigraphic units inadjacent basins isnot clearly understood. The Los CorrosFossilHorizon,a molluscan horizonin the upper partof the Esmeraldas Formation,has been used to tracethe top of the formation, Thishorizonisnot laterallycontinuous over thebasinand its age is still debatable. Some of the key palynostratigraphic events inNorthernSouth America are net present inthepalynological record of the Esmeraldas, Palynologicaldata from 82 samples from an eutcrop section intheNuevo Mundo Synclinearea and from seven previouslystudied wells have been integratedwith a palynologicalzonation of nonhem South America inorder to datctheEsrneraldasForrnation.The age ranges from the lateEarly Eocene to the Late Eocene. The Esmeraldas Forrnationiscorrelative withthe upper Picacho ForTnation and the lowerpartof the ConcentracionForrnationin the EasternCoTdillera, and theupper Mirador Forrnationand thebaseof theCarboneraFormationintheLlanosFeothills. [[heLos Corros FossilHorizon is Late Eocene and is time-correlative with a marine transgression inthe central Llanos Foothills,A non-menic multidimensional scaling analysis suggests that florasfrom the Middle Magdalena Valleywere differentfromthe Llanos Foothillsarea during the Middle to Late Eocene. This is apparently due to taphonomic effects. The results efthis study conuibute to a betterunderstanding of theoverall evolution ef the Middle Magdalena ValleyBasin and the evolution of thenonhem Andes.
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    5-alpha-reductase inhibitors for lower urinary tract symptoms secondary to benign prostatic obstruction
    (2015) García?Perdomo, Herney A; Lopez, Hugo E; Tacklind, James
    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of 5-alpha-reductase inhibitors (5ARIs) for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). © 2015 The Cochrane Collaboration.
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    50 Jahre FARC: Geschichtsbild und Selbstverständnis der ältesten Guerilla Lateinamerikas
    (2015) Schuster, Sven Benjamín
    Im Mai 1964 erstürmte die kolumbianische Armee im Rahmen des sogenannten Plan LASO (Latin American Security Operation) die von Kommunisten gegründete Agrarkolonie Marquetalia im Süden Kolumbiens. Die sich über mehrere Monate erstreckende Militäroperation gegen die zwischen den Departements Huila und Tolima gelegene Enklave wurde von den USA logistisch unterstützt, wobei Tausende Soldaten, Hubschrauber sowie mit Brandbomben bestückte Kampfflugzeuge zum Einsatz kamen. Für die US-Regierung unter Präsident Lyndon B. Johnson war es im Kontext der bereits von Kennedy initiierten Alliance for Progress von größter Bedeutung, ein „zweites Kuba“ in Südamerika zu verhindern. Neben materiellen Hilfsleistungen und Kooperationen in den Bereichen der medizinischen Versorgung, dem Wohnungsbau und dem Bildungswesen war der Aspekt der counterinsurgency ein Kernstück des dezidiert antikommunistischen Programms.1 Trotz des massiven Aufgebots war der Militärschlag jedoch ein Misserfolg. So gelang den in Marquetalia ansässigen 48 kommunistischen Guerilleros sowie den in ihrem Einflussbereich lebenden Campesinos größtenteils die Flucht. Am Ende hatten die Guerilleros lediglich drei Tote zu beklagen, während sich die Zahl gefallener Soldaten auf über 300 belief.
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    52 Genetic Loci Influencing Myocardial Mass
    (2016) van der Harst, Pim; van Setten, Jessica; Verweij, Niek; Vogler, Georg; Franke, Lude; Maurano, Matthew T.; Wang, Xinchen; Leach, Irene Mateo; Eijgelsheim, Mark; Sotoodehnia, Nona; Hayward, Caroline; Sorice, Rossella; Meirelles, Osorio; Lyytikäinen, Leo-Pekka; Polašek, Ozren; Tanaka, Toshiko; Arking, Dan E.; Ulivi, Sheila; Trompet, Stella; Müller-Nurasyid, Martina; Smith, Albert V.; Dörr, Marcus; Kerr, Kathleen F.; Magnani, Jared W.; Del Greco M., Fabiola; Zhang, Weihua; Nolte, Ilja M.; Silva, Claudia T.; Padmanabhan, Sandosh; Tragante, Vinicius; Esko, Tõnu; Abecasis, Gonçalo R.; Adriaens, Michiel E.; Andersen, Karl; Barnett, Phil; Bis, Joshua C.; Bodmer, Rolf; Buckley, Brendan M.; Campbell, Harry; Cannon, Megan V.; Chakravarti, Aravinda; Chen, Lin Y.; Delitala, Alessandro; Devereux, Richard B.; Doevendans, Pieter A.; Dominiczak, Anna F.; Ferrucci, Luigi; Ford, Ian; Gieger, Christian; Harris, Tamara B.; Haugen, Eric; Heinig, Matthias; Hernandez, Dena G.; Hillege, Hans L.; Hirschhorn, Joel N.; Hofman, Albert; Hubner, Norbert; Hwang, Shih-Jen; Iorio, Annamaria; Kähönen, Mika; Kellis, Manolis; Kolcic, Ivana; Kooner, Ishminder K.; Kooner, Jaspal S.; Kors, Jan A.; Lakatta, Edward G.; Lage, Kasper; Launer, Lenore J.; Levy, Daniel; Lundby, Alicia; Macfarlane, Peter W.; May, Dalit; Meitinger, Thomas; Metspalu, Andres; Nappo, Stefania; Naitza, Silvia; Neph, Shane; Nord, Alex S.; Nutile, Teresa; Okin, Peter M.; Olsen, Jesper V.; Oostra, Ben A.; Penninger, Josef M.; Pennacchio, Len A.; Pers, Tune H.; Perz, Siegfried; Peters, Annette; Pinto, Yigal M.; Pfeufer, Arne; Pilia, Maria Grazia; Pramstaller, Peter P.; Prins, Bram P.; Raitakari, Olli T.; Raychaudhuri, Soumya; Rice, Ken M.; Rossin, Elizabeth J.; Rotter, Jerome I.; Schafer, Sebastian; Schlessinger, David; Schmidt, Carsten O.; Sehmi, Jobanpreet; Silljé, Herman H.W.; Sinagra, Gianfranco; Sinner, Moritz F.; Slowikowski, Kamil; Soliman, Elsayed Z.; Spector, Timothy D.; Spiering, Wilko; Stamatoyannopoulos, John A.; Stolk, Ronald P.; Strauch, Konstantin; Tan, Sian-Tsung; Tarasov, Kirill V.; Trinh, Bosco; Uitterlinden, Andre G.; van den Boogaard, Malou; van Duijn, Cornelia M.; van Gilst, Wiek H.; Viikari, Jorma S.; Visscher, Peter M.; Vitart, Veronique; Völker, Uwe; Waldenberger, Melanie; Weichenberger, Christian X.; Westra, Harm-Jan; Wijmenga, Cisca; Wolffenbuttel, Bruce H.; Yang, Jian; Bezzina, Connie R.; Munroe, Patricia B.; Snieder, Harold; Wright, Alan F.; Rudan, Igor; Boyer, Laurie A.; Asselbergs, Folkert W.; van Veldhuisen, Dirk J.; Stricker, Bruno H.; Psaty, Bruce M.; Ciullo, Marina; Sanna, Serena; Lehtimäki, Terho; Wilson, James F.; Bandinelli, Stefania; Alonso, Alvaro; Gasparini, Paolo; Jukema, J. Wouter; Kääb, Stefan; Gudnason, Vilmundur; Felix, Stephan B.; Heckbert, Susan R.; de Boer, Rudolf A.; Newton-Cheh, Christopher; Hicks, Andrew A.; Chambers, John C.; Jamshidi, Yalda; Visel, Axel; Christoffels, Vincent M.; Isaacs, Aaron; Samani, Nilesh J.; de Bakker, Paul I.W.
    Background Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. Objectives This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. Methods We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. Results We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p  and lt; 1 × 10?8. These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. Conclusions Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets. © 2016 American College of Cardiology Foundation
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    5azadC treatment upregulates miR-375 level and represses HPV16 E6 expression
    (2017-05-02) Morel, Adrien; Baguet, Aurélie; Perrard, Jérôme; Demeret, Caroline; Jacquin, Elise; Guenat, David; Mougin, Christiane; Prétet, Jean-Luc
    High-risk human papillomaviruses are the etiological agents of cervical cancer and HPV16 is the most oncogenic genotype. Immortalization and transformation of infected cells requires the overexpression of the two viral oncoproteins E6 and E7 following HPV DNA integration into the host cell genome. Integration often leads to the loss of the E2 open reading frame and the corresponding protein can no longer act as a transcriptional repressor on p97 promoter. Recently, it has been proposed that long control region methylation also contributes to the regulation of E6/E7 expression. To determine which epigenetic mechanism is involved in HPV16 early gene regulation, 5-aza-2?-deoxycytidine was used to demethylate Ca Ski and SiHa cell DNA. Decreased expression of E6 mRNA and protein levels was observed in both cell lines in an E2-independent manner. E6 repression was accompanied by neither a modification of the main cellular transcription factor expression involved in long control region regulation, nor by a modification of the E6 mRNA splicing pattern. In contrast, a pronounced upregulation of miR-375, known to destabilize HPV16 early viral mRNA, was observed. Finally, the use of miR-375 inhibitor definitively proved the involvement of miR-375 in E6 repression. These results highlight that cellular DNA methylation modulates HPV16 early gene expression and support a role for epigenetic events in high-risk HPV associated-carcinogenesis.
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    El 9 de abril en Cali: cambio social, poder y liminalidad en el Valle del Cauca
    (2006) Charry Joya, Carlos Andrés
    A partir de los principios de la sociología procesual de Norbert Elias sobre las relaciones entre grupos sociales establecidos y marginados, y de los referentes analíticos expuestos por Victor Turner acerca de los estados liminales, se analizan en este artículo las implicaciones de los sucesos del 9 de Abril en Cali y el Valle del Cauca. En este sentido, se busca identificar las formas de configuración social de poder a nivel regional y el impacto que tuvo este acontecimiento histórico en tal proceso, donde se destaca una ampliación y mayor posicionamiento de los grupos sociales marginados en el campo social, a consecuencia de las transformaciones sociopolíticas acaecidas en la década de 1930 y, en especial, en la segunda mitad de la década de 1940, por la incidencia del gaitanismo y la denominada resistencia civil. Con el asesinato de Jorge Eliécer Gaitán se aprecia un cambio considerable en los equilibrios de poder entre sectores sociales, que contraviene la tendencia antes reseñada. Se considera que los elementos de constitución del campo simbólico son indispensables para la comprensión del proceso de cambio, así como de las formas sociales de estructuración del poder.
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    99 mTc-mebrofenin hepatobiliary scintigraphy in a patient with a bilio-pleural-bronchial fistula
    (2017) Arevalo-Leal, S.
    This is a 37 year old patient with a history of cryptogenic cirrhosis on liver transplant waiting list
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    A administração pública nas sociedades da informação e do conhecimento
    (2013-01) Valencia Tello, Diana Carolina; Diniz Lima, Edilson Vitorelli
    Na atualidade, a internet e as redes sociais estão mudando radicalmente as formas de interação entre os indivíduos nas sociedades da informação e do conhecimento, razão pela qual os estados e a administração pública em todos os níveis devem se preparar para enfrentar essa nova realidade, procurando responder às demandas da cidadania, que busca maior participação, transparência e efetividade do Estado. Nesse contexto, um dos elementos mais importantes para viabilizar a participação do cidadão nas decisões públicas que afetam a comunidade é o acesso à informação pública. Mas em burocracias de tipo weberiano, dominadas por interesses políticos e econômicos, a informação é protegida, entre outras razões, para evitar a crítica da sociedade. Para desenvolver melhor esse problema, analisaremos inicialmente a administração pública nas sociedades da informação e do conhecimento; no segundo item apresentaremos a burocracia em Weber e no terceiro item estudaremos as características da burocracia na América Latina. No quarto momento será tratado especificamente o caso brasileiro, com ênfase para o problema atual da divulgação dos gastos da Copa do Mundo de 2014. Finalmente, no quinto segmento se exporá o programa de governo eletrônico na Colômbia.
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    A B-lymphocyte binding peptide from BNRF1 induced antibodies inhibiting EBV-invasion of B-lymphocytes
    (2005-11) López, Ramsés; Urquiza, Mauricio; Patino, Helena; Suárez, Jorge; Reyes, Claudia; Patarroyo, Manuel A.; Patarroyo, Manuel E.
    Epstein–Barr virus (EBV) infects human target cells mainly through gp350/220-CD21 and gp42-MHCII interactions; however, it has been shown that these interactions are dispensable for EBV-invasion of susceptible cells, suggesting that other viral proteins are involved in this process. It is probable that tegument BNRF1/p140 protein is involved in EBV-invasion of target cells, since anti-p140 antibodies inhibit EBV-infection of B-lymphocytes and there is evidence that part of the protein is located on virus surface. Sixty-six peptides, covering the entire BNRF1/p140 sequence, were synthesised and tested in lymphoblastoid cell line binding assays. Peptides 11465 and 11521 bound with high affinity to Raji, Ramos and P3HR-1 cells but not to erythrocytes, showing cell-binding behaviour similar to EBV. These two peptides induced antibodies recognising live EBV-infected cells. Interestingly, peptide-11521 (YVLQNAHQIACHFHSNGTDA) or antibodies induced by this peptide inhibited EBV-binding to B-lymphocytes, suggesting that this p140-region could be involved in EBV and B-lymphocyte interaction.
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    A Bayesian examination of the relationship of internal and external touchpoints in the customer experience process across various service environments
    (2020) Siqueira, Jose Ribamar; Horst, Enrique ter; Molina, German; Losada, Mauricio; Mateus, Marelby Amado
    Customer experience (CX) is an aggregate of consumer touch points that can be brand-owned (completely controlled by the firm), partner-owned (collectively controlled by the firm and one or more of its partners), customer-owned (where the firm or its partner cannot exert any control or influence) or represented by social/external touch points that account for the importance of the roles of others in the customer experience process. Although the concept of CX is widely used, not much has been examined about how external touch points impact customer perception of experience. Therefore, the main purpose of this study is to examine the role and impact of internal and external touchpoints as dimensions of customer experience and how CX can impact consumer word-of-mouth intention. Service outcome and peace of mind were used to represent internal experience touchpoints and peer to peer quality (PTP) was used to represent an external experience touchpoint. A total of 293 usable surveys were used for analysis using a Bayesian model developed for this study instead of the more traditional SEM approaches. Results showed that an external experience touchpoint has a similar impact to those of internal experience touchpoints in the experience process. CX was also found to have a strong effect on customer word of mouth intention. These findings make various contributions to the literature on CX, especially to research differentiating internal from external experience touchpoints. On the practical side, this study provides recommendations to retailers about how to manage an external touchpoint. © 2019 Elsevier Ltd
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    A behavioral investigation of supply chain contracts for a newsvendor problem in a developing economy
    (2019) Castañeda, Jaime Andrés; Brennan M.; Goentzel J.
    The business context in developing economies introduces challenges in scaling production that are often distinct from those faced in mature economies. This study focuses on the potential for risk-sharing mechanisms to overcome some of those challenges for agricultural supply chains in Uganda. The study follows a two-stage research approach conducted in collaboration with the United Nations World Food Programme (WFP), which supported adoption of hermetic crop storage products such as silos in the country since 2013. In the first stage, through interviews with six artisanal silo manufacturers we identified three constraints in scaling silo production that were accentuated by the newsvendor dynamics in this market. In the second stage, we considered the potential for risk-sharing contracts to help alleviate some of those constraints and explored behavioral explanations to account for differences. We ran a laboratory experiment using two contracts that our interviews suggest are feasible in this business context: a buyback mechanism that allows manufacturers to share the risks of procuring excess metal sheets and a salvage mechanism that allows them to share the risks of over-producing silos. The results reveal a consistent under-ordering across both contracts. They also show that while buyback participants respond to contract prices as existing theory would predict, salvage participants do not. Our study provides insights regarding the potential, and the limitations, of different risk-sharing mechanisms to increase the supply of products in developing economies. © 2019 Elsevier B.V.
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    A behavioural investigation of power and gender heterogeneity in operations management under uncertainty
    (2019) Villa S.; Castañeda, Jaime Andrés
    Purpose: The paper aims to explore how power and gender influence decision making in an operational and risky context. Design/methodology/approach: The authors run a laboratory experiment. The experimental factors are power and operational profitability. Power is manipulated using an episodic priming task, while profitability, by changing a newsvendor-type product’s procurement cost. Participants’ risk attitude is captured using a risk lottery. Findings: Participants deviate from the optimal order regardless of the power condition and their risk profile. Risk-seeking women order consistently more than risk-seeking men, which allow women to offer a higher service level. In the low-profit condition, men prefer to make more conservative decisions, which allow them to place orders that are closer to the economical benchmark, where both men’ induced power and the risk-seeking tendencies from both genders play a role. Behavioural models in the high-power condition explain the observed differences in ordering behaviours. Originality/value: This paper provides behavioural research to explore how differences in power and gender, and their links with risky decision making, influence decision making in an uncertain operations management context, representing thus an important departure from mainstream studies. © 2019, Emerald Publishing Limited.
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    A best–worst scaling in Colombian patients to rank the characteristics of HIV/AIDS treatment
    (2018) Hendriks A.; Wijnen B.; van Engelen R.; Conde R.; Evers S.M.; González Rodríguez, Javier Leonardo; Govers M.; Mühlbacher A.; Hiligsmann M.
    Aim: To elicit patients’ preferences for HIV/AIDS treatment characteristics in Colombia. Materials and methods: A best–worst scaling case was used to provide a ranking of 26 HIV/AIDS treatment characteristics that were similar to a previous study conducted in Germany. In each choice task, participants were asked to choose the most important and the least important treatment characteristics from a set of five from the master list. Using the Hierarchical Bayes method, relative importance scores were calculated. Sub-group analyses were conducted according to sex, education, source of infection, symptoms, and age. Results: A total of 195 patients fully completed the questionnaire. The three most important characteristics were “drug has very high efficacy” (relative importance score [RIS] = 10.1), “maximum prolongation of life expectancy” (RIS = 9.7), and “long duration of efficacy” (RIS = 7.4). Sub-group analysis showed only three significant (but minor) differences between older and younger people. Conclusion: This study suggests that treatment characteristics regarding efficacy and prolongation of life are particularly important for patients in Colombia. Further investigation on how patients make trade-offs between these important characteristics and incorporating this information in clinical and policy decision-making would be needed to improve adherence with HIV/AIDS medication. © 2018 Informa UK Limited, trading as Taylor and Francis Group.
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    A bibliometric outlook of the most cited documents in business, management and accounting in Ibero-America
    (2020) Cortés Sánchez, Julián David
    Research on business, management and accounting (BMA) in the past century has been overwhelming. Regardless of its significance, regions such as Ibero-America have been overlooked from exhaustive studies on bibliometrics in the subject of BMA. Here, a bibliometric outlook of the subject of BMA in Ibero-America using 19 variables was conducted by analyzing the ten most cited documents in BMA in each country from 1996 to 2017 using the citation database Scopus. The main findings showed a rapid increase in intellectual production led by Spain and Portugal, which also constitute most of the citations. The majority of the most cited studies are behind paywalls. Institutional status (i.e., private or public) has a significant effect on AACSB accreditation. A negative concern that arises for the whole region, mainly Latin-America, is the discriminated use of a journal with predatory features. © 2019 AEDEM
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    A Biomechanical Analysis of Free Squat Exercise Employing Self-Organizing Maps
    (2019) Blanco Diaz C.F.; Katerine Quitian González A.; Isaza S.J.; Orjuela Cañón, Alvaro David
    With the current employment of visualization tools, different techniques may be used to understand multivariable information. This document presents an alternative method for the analysis of biomechanical phenomena, presenting the knee joint execution of free squat exercise. For this, the MaxTRAQ software and the open-source and cross-platform software Mokka were employed. A system of cameras allowed to digitize the movements. Then, with the use of Self-Organizing Maps tasks of visualization and clustering were developed for multivariate data. Results showed that this tool allows finding nonlinear relations between the analyzed input variables and outputs, when the data treatment demands an extra-work because of its dimensionality. © 2019 IEEE.
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    A brain-age model for preterm infants based on functional connectivity
    (2018-04-26) Caicedo Dorado, Alexander; Jansen, K; Dereymaeker, A; Naulaers, G; Van Huffel, S; Lavanga, M; De Wel, O
    In this study, the development of EEG functional connectivity during early development has been investigated in order to provide a predictive age model for premature infants. Approach: The functional connectivity has been assessed via the coherency function (its imaginary part (ImCoh) and its mean squared magnitude (MSC)), the phase locking value () and the Hilbert–Schimdt dependence (HSD) in a dataset of 30 patients, partially described and employed in previous studies (Koolen et al 2016 Neuroscience 322 298–307; Lavanga et al 2017 Complexity 2017 1–13). Infants' post-menstrual age (PMA) ranges from 27 to 42 weeks. The topology of the EEG couplings has been investigated via graph-theory indices. Main results: Results show a sharp decrease in ImCoh indices in ?, (4–8) Hz and ?, (8–16) Hz bands and MSC in ?, (16–32) Hz band with maturation, while a more modest positive correlation with PMA is found for HSD, and MSC in , ?, ? bands. The best performances for the PMA prediction were mean absolute error equal to 1.51 weeks and adjusted coefficient of determination equal to 0.8. Significance: The reported findings suggest a segregation of the cortex connectivity, which favours a diffused tasks architecture on the brain scalp. In summary, the results indicate that the neonates' brain development can be described via lagged-interaction network features.
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    A C-terminal cationic fragment derived from an arginine-rich peptide exhibits in vitro antibacterial and anti-plasmodial activities governed by its secondary structure properties
    (2009) Lesmes, Liliana Patricia; Bohorquez, Magda Yenith; Carreño, Luisa Fernanda; Patarroyo, Manuel Elkin; Lozano, José Manuel
    The differential in vitro antimicrobial activity of a 12-residue-long arginine-rich peptide derived from protamine was examined against bacterial and parasite microbes. A design of discrete peptide fragments based on the thermolysin-digestion map allowed us to propose three peptide fragments to be further assessed regarding their biological and secondary structural properties. Peptide structure allowed designing three arginine-rich fragments. All peptide fragments were assessed regarding their antimicrobial activity against Gram-positive and Gram-negative bacteria and a human malaria strain. Qualitative and quantitative assays carried out for determining all peptides' antibacterial activity at different concentration levels included radial diffusion and a time-controlled technique. Tests demonstrated that all assessed molecules inhibited invasion of Plasmodium falciparum parasites to human red blood cells. Cytolytic activity of the parent protamine peptide was completely abolished by strategically fragmenting its aminoacid sequence. Remarkably, the cationic C-fragment exhibited stronger biological activity than its parent peptide. Interestingly, the peptide fragment denoted as 2077 displays a typical ?-helix profile according to its CD spectrum. The results support proposing the protamine C-terminal fragment as a potential new antimicrobial peptide. © 2009 Elsevier Inc. All rights reserved.
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    A case of rapidly destructive osteoarthritis of the hip with onset of less than six weeks
    (2017) Huerfano, Elina; Bautista, Maria; Bonilla, Guillermo; Palau-Lazaro, Mauricio; Llinás, Adolfo; Monsalvo, Daniel
    Introduction Rapidly destructive osteoarthritis is characterized by a severe destruction of the hip joint developing over short periods of time. However, to date, there is no agreement on the biological process that triggers this condition. The aim of this report is to present a case of rapidly destructive osteoarthritis. Case report We report a case of a 76 year-old female who presented with hip pain of sudden onset and normal X-rays. Six weeks later she presented with increased pain intensity, functional limitation and evidence of a collapse of the femoral head in the X-rays. Discussion Rapidly destructive osteoarthritis of the hip is a complex entity that might be more frequent than previously described and which clinical course could vary between few weeks and several months. In order to make an accurate diagnosis, other causes of massive destruction of the joint should be excluded. © 2017
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    A Case of Sinus of Valsalva Aneurysm Rupture in a Patient with Bicuspid Aortic Valve
    (2019-12) Arcos, Laura C; Medina, Hector M; Sandoval, Nestor; Gelves, Julian; Salazar, Gabriel
    Aproximadamente 1 de cada 100 adultos nacen con cardiopatía congénita, que puede caracterizarse, según su complejidad, como simple, moderada o grave en función de la morbilidad y mortalidad asociadas con cada lesión.1El aneurisma del seno de Valsalva (SOV-A), aunque inusual, generalmente se manifiesta cuando hay una complicación como ruptura o endocarditis, y el pronóstico general es bueno con una corrección quirúrgica oportuna. Presentamos un caso de ruptura de SOV-A en un paciente joven con válvula aórtica bicúspide en el que la ecocardiografía tridimensional fue útil para el diagnóstico y la planificación quirúrgica.
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    A case report of esophageal tuberculosis
    (2014) Manrique M. C.A.; Salinas G. D.C.; Martínez J.D.; Garzón O. M.A.; Hernández C. G.; Hormaza A. N.; Lizarazo R. J.I.; Marulanda J.C.; Molano V. J.C.; Rey T. M.H.
    We report the case of an immune-competent man with symptoms of upper gastrointestinal bleeding secondary to esophageal ulcers of tubercular origin. Gastrointestinal involvement from Mycobacterium tuberculosis is rare even in patients with numerous occurrences of pulmonary and extrapulmonary diseases. The most frequently affected sites are the terminal ileum and the peritoneum. Esophageal tuberculosis is exotic and is usually secondary to extension from neighboring infected organs such as the mediastinal nodes and/or the bronchi. Clinical, endoscopic and radiological pictures of the esophageal disease often mimic malignancy. Tuberculosis treatment is the mainstay of treatment, and surgery is rarely required. © 2014 Asociaciones Colombianas de Gastroenterología, Endoscopia digestiva, Coloproctología y Hepatología.
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    A case report of malignant gastrointestinal melanoma of unknown primary origin
    (2019) Sandra Patricia Cifuentes A.; Sandra Lorena Santacruz R.
    One of the unusual characteristics of cutaneous melanoma is its ability to metastasize in the small intestine. It is often diagnosed during autopsies of cutaneous melanoma patients. Metastatic deposits have been found in 50% to 60% of these autopsies, but less than 2% to 4% of patients diagnosed with melanoma have gastrointestinal metastasis during the course of the disease. Between 4% and 9% of gastrointestinal melanoma cases have unknown primary tumors. Rapid identification and resection of melanoma in the digestive tract could improve the patient survival rate and prevent complications such as intestinal obstructions from occurring. We present a rare clinical case of gastrointestinal melanoma of unknown primary origin. The patient had a clinical picture of nausea, hyporexia, epigastralgia, fatigue, paresthesias in the right dorsal region and had lost nine kilograms in three weeks. An abdominal CT scan showed three predominantly isodense liver lesions in the parenchyma, with some areas of lower density located in segments 2,5,7 and 8 of the liver. These were biopsied. Upper digestive tract endoscopy took biopsy samples of two hyperpigmented lesions in the second portion of the duodenum. Histopathological examination showed malignant melanoma. All typical locations of primary melanoma were excluded during the diagnostic procedure. © 2019 Asociaciones Colombianas de Gastroenterología, Endoscopia digestiva, Coloproctología y Hepatología.
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    A changing role in global climate governance: São Paulo mixing its climate and international policies
    (2019) Mauad, Ana; Betsill, Michele
    Cities have been playing an important role in global climate governance for the last two decades, providing climate responses such as mitigation and adaptation policies. The city of São Paulo has positioned itself as one of the “new leaders” combining climate responses with an active international strategy. We analyze the role of São Paulo in global climate governance by crossing its climate and its international agendas from 2005 to 2018. The results demonstrate that São Paulo performed a leadership role during the phase of designing and adopting climate responses, but failed to sustain this position during the implementation phase. © 2019, INSTBRASILEIRORELACOESINT. All rights reserved.
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    A clinical study of adhd symptoms with relation to symptoms of learning disorders in schoolchildren in Bogota, Colombia
    (2012) Talero Gutiérrez, Claudia; Vélez van Meerbeke, Alberto Francisco; Reyes, Rodrigo González
    Objective: To investigate possible relationships between symptoms of ADHD and of learning disorder (LD) in a population geographically, culturally, and linguistically distinct from previous studies. Method: The authors evaluated a cross section of 834 Colombian schoolchildren for childhood neurological pathologies on the basis of a medical examination and performance with reference to the Diagnostic and Statistical Manual (4th ed.) attention checklist, the General and Differential Aptitudes Battery, and the Visual-Motor Integration (VMI) test. Results: Of the total sample, 382 were classified as 'ADHD only,' 54 as 'LD only,' and 75 as 'ADHD + LD.' A total of 459 had low VMI scores. ADHD, LD, and low VMI were significantly interrelated. Among the children with ADHD, the attention deficit subtype tended to have more learning problems than the hyperactive subtype, who showed no major deficiencies in their learning ability. Conclusions: This study provides additional evidence demonstrating a relationship between LD and ADHD, particularly with respect to verbal reasoning, visual-auditory memory, and VMI. © 2012 SAGE Publications.
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    A Coffee with Sugar Please. La Fundación Rockefeller y la Salud Pública en Centroamérica, hacia una mirada comparativa
    (2001-01-01) Quevedo Vélez, Emilio
    El fenómeno de organización institucional sanitaria estatal en los países centroamerícanos no se dio tanto en torno a la sanidad maritima y portuaria como ocurrió en la mayoria de los paises latinoamerícanos, sino alrededor de la económia de exportación del cultivo del café, del banano y un poco de azúcar. A qui se presenta un análisis preliminar comparativo del caso centroaméricano, tomando como punto de referencía el papel desempeñado por la fundación Rockefeller en ese proceso. Esta fundación fue creada para la investigación y el control de la salud pública, que a partir de un nuevo concepto transformó los servicios de salud en dichos paises.
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    A cohort study of two intravenous treatments for iron deficiency in patients with heart failure
    (2019) Arias-Barrera C.; Palacios-Ariza M.A.; Pradilla I.; Alvarez-Moreno C.
    Background: Iron deficiency (ID) in patients with heart failure (HF) leads to greater morbidity and mortality and its treatment has been associated with significant improvements in quality of life. Since no head-to-head studies are available, there is uncertainty as to which intravenous iron supplement should be used. This study aimed to compare the effect of ferric carboxymaltose (FCM) and iron saccharate (IS) on clinical and biochemical outcomes in patients with HF and ID. Methods: We reviewed electronic health records from a referral centre in Bogotá, Colombia for patients with HF. We selected records with a follow-up of at least 2 years. Primary outcomes were clinically significant changes in EuroQol-5D (EQ-5D), 6-minute-walk test (6MWT), resolution of ID, and direct costs. Results: We obtained data on 119 patients with a median age of 69 years and a median left ventricular ejection fraction (LVEF) of 35%. All patients met criteria for ID, and 58% were treated with FCM. A significant difference in GFR of 11 mL/min/1.72 m2 was found at baseline between groups. Neither bivariate, nor multivariate analyses could identify significant differences between patients receiving FCM and IS for any of the primary outcomes. Direct cost analysis showed that FCM use generates 2.8 times the cost associated with saccharate use. Conclusions: This retrospective cohort study did not identify any significant differences in clinical or biochemical outcomes between HF patients with ID receiving FCM or IS. Direct cost analysis favoured use of IS in this group of patients. © 2019, © 2019 Belgian Society of Cardiology.
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    A colorimetric bioassay for quantitation of both basal and insulin-induced glucose consumption in 3T3-L1 adipose cells
    (2020) Diaz, Paola A. Rivera; Camargo, Doris E. Gómez; Ondo Méndez, Alejandro Oyono; Gómez-Alegría, Claudio J.
    Introduction: The quantitation of glucose consumption in animal cell cultures is mainly based on the use of radiolabeled or fluorescent analogues, resulting in expensive and tedious procedures, requiring special equipment and, sometimes, with potential health and environmental risks. Objectives: The objective of this work was to evaluate the application of a blood plasma colorimetric assay to quantify glucose consumption in in vitro cultures of adipose cells. Methods: We worked with 3T3-L1 adipose cells differentiated by 7–8 days, which were exposed to different initial glucose concentrations (5.5, 2.8 and 1.4 mM) for variable times, either in the absence or the presence of 100 nM insulin. Using a commercial colorimetric glucose assay, extracellular glucose was determined, and glucose uptake was calculated as the difference between the initial and final glucose concentration. Results: The colorimetric assay allowed us to quantify glucose uptake in our cell model, observing a linear response over time (r2?0.9303) to the different glucose concentrations, both in the basal and insulin-induced condition. The insulin-stimulated glucose consumption was higher than basal consumption at all glucose concentrations evaluated, but significant differences were observed at 120-, 360- and 480-min in glucose 5.5 mM (p ? 0.01, n = 5), and 240 min in glucose 1.4 mM (p ? 0.01, n = 5). A Vmax of 4.1 and 5.9 nmol/ml/min (basal and insulin-induced, respectively) and a Km of 1.1 mM (same in basal vs insulin-stimulated) were calculated. The bioassay was also useful in a pharmacological context: in glucose 1.4 mM, glucose consumption showed an effect that depended on insulin concentration, with a calculated EC50 of 18.4 ± 1.1 nM. Conclusions: A simple and low-cost bioassay is proposed to quantify glucose consumption in 3T3-L1 adipose cells. Biological Sciences; Cell biology; Cell Culture; Cell Differentiation; Metabolism; Biological Assay; bioassay; In Vitro Techniques; Adipocytes; 3T3-L1 Cells; Glucose consumption; Glucose uptake; Insulin; Insulin action; Insulin response. © 2020 The Authors
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    A column generation approach for solving a green bi-objective inventory routing problem
    (2016) Franco Franco, Carlos Alberto; López-Santana E.R.; Méndez-Giraldo G.
    The aim of this paper is present a multi-objective algorithm embedded with column generation to solve a green bi-objective inventory routing problem. In contrast with the classic Inventory Routing Problem where the main objective is to minimize the total cost overall supply chain network, in the green logistics besides this objective a minimization of the CO2emisions is included. For solving the bi-objective problem, we proposed the use of NISE (Noninferior Set Estimation) algorithm combined with column generation for reduce the amount of variables in the problem. © Springer International Publishing AG 2016.
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    A combined linkage and exome sequencing analysis for electrocardiogram parameters in the erasmus rucphen family study
    (2016) Tamar Silva, Claudia; Zorkoltseva, Irina V.; Amin, Najaf; Demirkan, Ayse; van Leeuwen, Elisabeth M.; Kors, Jan A.; van den Berg, Marten; Stricker, Bruno H.; Uitterlinden, André; Kirichenko, Anatoly V.; Witteman, Jacqueline C. M.; Willemsen, Rob; Oostra, Ben A.; Axenovich, Tatiana I.; van Duijn, Cornelia M.; Isaacs, Aaron
    Electrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF). Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2 gene associated with QT (rs74608430; P = 2.8 × 10-4, minor allele frequency = 0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the trait's genetic variability in ERF (P = 0.02). Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3) and AMPK stimulated fatty acid oxidation in muscle (P = 4.1 × 10-3). Look-ups in bioinformatics resources showed that expression of FCRL2 is associated with ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam study. Combining the bioinformatics information with the association and linkage analyses, FCRL2 emerges as a strong candidate gene for QT interval. © 2016 Silva, Zorkoltseva, Amin, Demirkan, van Leeuwen, Kors, van den Berg, Stricker, Uitterlinden, Kirichenko, Witteman, Willemsen, Oostra, Axenovich, van Duijn and Isaacs.
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    A combined linkage, microarray and exome analysis suggests MAP3K11 as a candidate gene for left ventricular hypertrophy
    (2018) Tamar Silva, Claudia; Zorkoltseva, Irina V.; Niemeijer, Maartje N.; van den Berg, Marten E.; Amin, Najaf; Demirkan, Ayşe; Leeuwen, Elisa van; Iglesias, Adriana I.; Piñeros-Hernández, Laura B.; Restrepo Fernández, Carlos Martín; Kors, Jan A.; Kirichenko, Anatoly V.; Willemsen, Rob; Oostra, Ben A.; Stricker, Bruno H.; Uitterlinden, André G.; Axenovich, Tatiana I.; Duijn, Cornelia M. van; Isaacs, Aaron; Center for Research in Genetics and Genomics (CIGGUR); Institute of Translational Medicine (IMT); GENIUROS Research group
    Background: Electrocardiographic measures of left ventricular hypertrophy (LVH) are used as predictors of cardiovascular risk. We combined linkage and association analyses to discover novel rare genetic variants involved in three such measures and two principal components derived from them. Methods: The study was conducted among participants from the Erasmus Rucphen Family Study (ERF), a Dutch family-based sample from the southwestern Netherlands. Variance components linkage analyses were performed using Merlin. Regions of interest (LOD > 1.9) were fine-mapped using microarray and exome sequence data. Results: We observed one significant LOD score for the second principal component on chromosome 15 (LOD score = 3.01) and 12 suggestive LOD scores. Several loci contained variants identified in GWAS for these traits; however, these did not explain the linkage peaks, nor did other common variants. Exome sequence data identified two associated variants after multiple testing corrections were applied. Conclusions: We did not find common SNPs explaining these linkage signals. Exome sequencing uncovered a relatively rare variant in MAPK3K11 on chromosome 11 (MAF = 0.01) that helped account for the suggestive linkage peak observed for the first principal component. Conditional analysis revealed a drop in LOD from 2.01 to 0.88 for MAP3K11, suggesting that this variant may partially explain the linkage signal at this chromosomal location. MAP3K11 is related to the JNK pathway and is a pro-apoptotic kinase that plays an important role in the induction of cardiomyocyte apoptosis in various pathologies, including LVH. © 2018 The Author(s).