Resultados Semilleros de Investigación 2009-2010

La publicación recoge los doce informes finales de investigación presentados por los estudiantes de ocho Semilleros 1 y cuatro Semilleros 2, correspondientes a la convocatoria 2009–2010 y se constituye en el Número 25 de la Serie de Investigaciones en Construcción, si bien este es el primer Número publicado en formato digital que UNIJUS se permite poner a disposición no sólo de la comunidad universitaria, sino también de la sociedad colombiana e internacional, interesada en los temas estudiados por los jóvenes investigadores de la Facultad de Derecho, Ciencias Políticas y Sociales de la Universidad Nacional de Colombia

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Pasear con el paseante: Walter Benjamín, la pregunta por el flâneur y el sujeto del capitalismo

En su libro de los pasajes, Walter Benjamín aporta una serie de reflexiones sobre la figura del Flâneur, palabra francesa con la que se designa a ese personaje que deambula, va a la deriva por las calles, que se pierde en la muchedumbre, figura urbana que observa la ciudad, sus transformaciones. Un sujeto que no se deja seducir por las vitrinas, que hace del acto de caminar; un placer en sí mismo. El funcionamiento capitalista del siglo XXI ha alterado la relación de los sujetos con la ciudad, los escenarios citadinos parecen estar hechos para el consumo, para la compra y venta de productos, es así, como el acto de caminar termina atravesado por las lógicas del uso y la utilidad, hoy se camina con afanes, sin contemplar, sin implicarse con el entorno urbano, la tecnología, la velocidad y el consumismo generan efectos sobre el modo en el que los sujetos se relacionan en las urbes. En el presente artículo, se explora la noción de flâneur en la obra del filósofo Walter Benjamín, su articulación a la obra del poeta Charles Baudelaire, así como la crítica al capitalismo que se encarna en las prácticas de este personaje surgido en los albores de París del siglo XIX, a partir de esta exploración se presentan algunas reflexiones sobre las nuevas formas de relacionarse con espacio vital de la ciudad y las configuraciones de la subjetividad actual. Todo este recorrido finaliza con algunas consideraciones sobre la pregunta: ¿se puede ser flâneur en esta época

Identification of Key Proteins from the Alternative Lengthening of Telomeres-Associated Promyelocytic Leukemia Nuclear Bodies Pathway

Alternative lengthening of telomeres-associated promyelocytic leukemia nuclear bodies (APBs) are a hallmark of telomere maintenance. In the last few years, APBs have been described as the main place where telomeric extension occurs in ALT-positive cancer cell lines. A different set of proteins have been associated with APBs function, however, the molecular mechanisms behind their assembly, colocalization, and clustering of telomeres, among others, remain unclear. To improve the understanding of APBs in the ALT pathway, we integrated multiomics analyses to evaluate genomic, transcriptomic and proteomic alterations, and functional interactions of 71 APBs-related genes/proteins in 32 Pan-Cancer Atlas studies from The Cancer Genome Atlas Consortium (TCGA). As a result, we identified 13 key proteins which showed distinctive mutations, interactions, and functional enrichment patterns across all the cancer types and proposed this set of proteins as candidates for future ex vivo and in vivo analyses that will validate these proteins to improve the understanding of the ALT pathway, fill the current research gap about APBs function and their role in ALT, and be considered as potential therapeutic targets for the diagnosis and treatment of ALT-positive cancers in the future

Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome

The association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and β2-glycoprotein I (β2GPI), the main antigen for antiphospholipid antibodies. Here, we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies. Anti-A2 antibodies (titer > 3 SDs) were significantly more prevalent in patients with APS (22.6%; venous, 17.5%; arterial, 34.3%; and mixed thrombosis, 40.4%) than in healthy individuals (2.1%, P < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001). Anti–A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold ± 0.13-fold SE), blocked A2-supported plasmin generation in a tPAdependent generation assay (19%-71%) independently of β2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%. We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome

ENGIU: Encuentro Nacional de Grupos de Investigación de UNIMINUTO.

El desarrollo del prototipo para el sistema de detección de Mina Antipersona (MAP), inicia desde el semillero ADSSOF perteneciente al programa de Administración en Seguridad y Salud en el trabajo de la UNIMINUTO, se realiza a partir de un detector de metales que emite una señal audible, que el usuario puede interpretar como aviso de presencia de un objeto metálico, en este caso una MAP. La señal audible se interpreta como un dato, como ese dato no es perceptible a 5 metros de distancia, se implementa el transmisor de Frecuencia Modulada FM por la facilidad de modulación y la escogencia de frecuencia de transmisión de acuerdo con las normas y resolución del Ministerio de Comunicaciones; de manera que esta sea la plataforma base para enviar los datos obtenidos a una frecuencia establecida. La idea es que el ser humano no explore zonas peligrosas y buscar la forma de crear un sistema que permita eliminar ese riesgo, por otro lado, buscar la facilidad de uso de elementos ya disponibles en el mercado

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