Systemic Lupus Erythematosus 2014

Systemic lupus erythematosus (SLE, lupus) is the prototype of systemic autoimmune disease (AD). Immune system activation in SLE is characterized by exaggerated B-cell and T-cell responses and loss of immune tolerance against selfantigens. Production and defective elimination of antibodies, circulation and tissue deposition of immune complexes, and complement and cytokine activation contribute to clinical manifestations that range from fatigue and joint pain to severe, life-threatening organ damage

Immunosenescence, Aging, and Systemic Lupus Erythematous

Senescence is a normal biological process that occurs in all organisms and involves a decline in cell functions. This process is caused by molecular regulatory machinery alterations, and it is closely related to telomere erosion in chromosomes. In the context of the immune system, this phenomenon is known as immunosenescence and refers to the immune function deregulation. Therefore, functions of several cells involved in the innate and adaptive immune responses are severely compromised with age progression (e.g., changes in lymphocyte subsets, decreased proliferative responses, chronic inflammatory states, etc.). These alterations make elderly individuals prone to not only infectious diseases but also to malignancy and autoimmunity. This review will explore the molecular aspects of processes related to cell aging, their importance in the context of the immune system, and their participation in elderly SLE patients

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.

MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus

We previously reported that the G allele of rs3853839 at 3′untranslated region (UTR) of Toll-like receptor 7 (TLR7) was associated with elevated transcript expression and increased risk for systemic lupus erythematosus (SLE) in 9,274 Eastern Asians [P = 6.5×10−10, odds ratio (OR) (95%CI) = 1.27 (1.17–1.36)]. Here, we conducted trans-ancestral fine-mapping in 13,339 subjects including European Americans, African Americans, and Amerindian/Hispanics and confirmed rs3853839 as the only variant within the TLR7-TLR8 region exhibiting consistent and independent association with SLE (Pmeta = 7.5×10−11, OR = 1.24 [1.18–1.34]). The risk G allele was associated with significantly increased levels of TLR7 mRNA and protein in peripheral blood mononuclear cells (PBMCs) and elevated luciferase activity of reporter gene in transfected cells. TLR7 3′UTR sequence bearing the non-risk C allele of rs3853839 matches a predicted binding site of microRNA-3148 (miR-3148), suggesting that this microRNA may regulate TLR7 expression. Indeed, miR-3148 levels were inversely correlated with TLR7 transcript levels in PBMCs from SLE patients and controls (R2 = 0.255, P = 0.001). Overexpression of miR-3148 in HEK-293 cells led to significant dose-dependent decrease in luciferase activity for construct driven by TLR7 3′UTR segment bearing the C allele (P = 0.0003). Compared with the G-allele construct, the C-allele construct showed greater than two-fold reduction of luciferase activity in the presence of miR-3148. Reduced modulation by miR-3148 conferred slower degradation of the risk G-allele containing TLR7 transcripts, resulting in elevated levels of gene products. These data establish rs3853839 of TLR7 as a shared risk variant of SLE in 22,613 subjects of Asian, EA, AA, and Amerindian/Hispanic ancestries (Pmeta = 2.0×10−19, OR = 1.25 [1.20–1.32]), which confers allelic effect on transcript turnover via differential binding to the epigenetic factor miR-3148.

A sociological view of family law in Colombia. Radicalism-1945

This paper affirms that the economic and political failure of the Radical Period provided opportunities for those who proposed Regeneration as a means of defending authority. Family law became an important tool in that process. During the period studied by this article, the equality clause remained in Colombian constitutions without any practical affect for the majority of the people. Discrimination was imposed through family law over those who had born outside of a Catholic marriage and/or had not previously legitimized their union through a Catholic ceremony. By the middle of the 20th century, the dramatic situation of the nation’s children led to efforts to change the social prejudices through legislation, that is, in the same way the prejudices had been imposed.

Some elements for the construction of a definition of human rights

This article seeks to demystify the foundations of rights. It looks at the search for some systemic differentiation. It emphasizes effectiveness, legitimacy, the importance of convention and of political participation as common elements of the different theoretical approaches to human rights. By analysing these elements it is possible to build the term “human rights” as a concept capable of being measured accurately by studying the effectiveness of legal rules as applied to human rights in specific contexts.

Impulsivity: A view from the behavioral neuroscience and developmental psychology

Impulsivity has been linked to three main factors: performing without direct involvement of the frontal lobe functions, an increase in the speed of response, and the acquisition of immediate gratification. This behavioral inhibition deficit involves a variety of behaviors including aspects of hyperexcitability, behavioral disinhibition and higher order decision making. Although by tradition, the definition of this executive function has been conceptualized from a psychopathological view, currently, the wide variety of neuropsychological, developmental and animal models assessment techniques encourage us to establish dialogues that integrate the knowledge of these theoretical perspectives for the interpretation and understanding of impulsivity.

Characterization of resistance in vitro to different antimicrobial in strains of Staphylococcus spp. in a hospital of the city of Valledupar between January and July 2009

The Staphylococcus spp. they can cause a wide range of infections systemic and located in community and hospital patients. Its high pathogenicity and growing resistance to multiple antimicrobials including methicillin, causes high morbiditymortality rates, causing a high epidemiological impact. Objective: to determine the phenotypic profile of resistance to different antimicrobials in strains of the genus Staphylococcus spp. Materials and methods: collected 75 strains and determined them susceptibility to different antibiotics by the Kirby-Bauer method. The production of betalactamasecheck using the nitrocefin test. (Resistance to Methicillin in S. aureus was conductedusing Mueller Hinton with 4% NaCl and oxacillin 6 μg/mL). Inducible clindamycin resistance tamizo by D-Test test. Results: they were isolated by 38% of staphylococcus coagulase negative (SNA) and 62% of S. aureus. 53% were penicillin resistant staphylococci: S. aureus with 58% and 42% SNA. 47% of the strains showed resistance to methicillin: S. aureus with 61% and SNA with 39%. A strain of S. aureus showed inducible resistance to clindamycin (1.33%). Coagulase negative staphylococci were isolated mostly from blood samples (31%), blood (29%), tip of catheter (5%) and came mostly from neonatal ICU (25%), medical (21%) and surgery (16%).Conclusions: S. aureus and SNA were isolated with greater frequency in blood and wounds from surgery and neonatal ICU. The predominant resistance phenotypes were penicillin and oxacillin.

Point of inflexion between the companies and the universities as opposed to the relation University, Company and State in Colombia

The Relation University, Company and State UEE defined through the eight committees created in Colombia to position the investigation like central axis of the triad one, impliesthe revision of the paper that in ahead must assume the companies and the universities for the success of the nexus. The scene raises the debt that both estates show as opposed to the definition of the subjects that in particular force them to work jointly within the triad one. The systemic methodology, drawn up under the epilogue of the order of the organizations, stipulates that these can work in unison or in key when they are understood like structure, and recognize what they do to each other. However, slope has left all a leaf of conciliations, understandings and repairs that they will have to be reviewed to the light of spirit UEE.

Exporting Culture: a Requirement for Competitive Internationalization*

his paper proposes a concept of “culture for internationalization” and “exporting culture” –a highly relevant concept for developing countries’ firms that are likely to follow a gradualinternationalization process– based on the strong relationship binding the concept proposed to strategy and systemic competitiveness. These three items are paramount to Understand the conditions underlying internationalizationas it is characterized by particular traits that make it a key alternative for a firm’s growth and successful perdurability based on competitiveness. “Culture for internationalization” and its variation, “exporting culture”, overflow the conceptsof organizational or corporate culture and involve some major interaction among the micro, meso and macro levels of a national economy in order to operationalize strategies thatpromote such culture and assure successful firm and economy internationalization. Discussion remains open as to the concept and its applicability with the hope that it contributesto the understanding and creation of appropriate conditions for firms to be able to access international markets with greater advantage and generate as much benefit as possible totheir nations, particularly in developing countries. 

Desarrollo territorial y eficiencia sistémica El caso de la cuenca lechera caprina de Santiago del Estero (Argentina)

Este trabajo nos da un pantallazo general sobre dos aspectos muy estudiados en la actualidad: el desarrollo territorial rural y la eficiencia (como elemento clave para la competitividad) y se propone dar visibilidad a la relación existente entre ambos, destacando el papel de la eficiencia a la hora de fortalecer estos procesos de desarrollo. Para abordar estas temáticas, en primera instancia el artículo realiza una breve descripción de la conformación de la cuenca lechera, proceso histórico donde las diversas actividades y micro procesos no surgen de mecánicas preestablecidas y conexas entre los actores locales, sino más bien admiten la idea de que en el territorio se produce la coordinación/descoordinación de las acciones de todos los agentes locales. Como conclusión de este punto se muestra que para el caso estudiado se han sentado las precondiciones tendientes a consolidar el proceso de desarrollo territorial. Entre ellas se pueden citar una identidad tambera caprina, un mercado dinámico que falta profundizar en su conocimiento pero que existe, alianzas que aunque fueron muy limitadas en su accionar, como también en el tiempo, fueron generando una actitud y una acumulación de capital social tendiente a la valoración de las especificidades del propio territorio. A continuación este documento se introduce en el segundo concepto analizado, la eficiencia, mediante estudios prácticos y ejemplos concretos para cada uno de los principales eslabones de la cadena productiva: el ordeñe, la industrialización y la comercialización. A modo de conclusión se plantea que para el diseño de estrategias tendientes a fortalecer el desarrollo territorial como primera medida los actores involucrados deben contar con toda la información y conocimiento posible sobre el proceso productivo. Esto facilitaría el acompañamiento a los distintos eslabones en el proceso de solución de sus ineficiencias, las que habitualmente son trasladadas al resto del complejo productivo. Finalmente, se deja abierto el interrogante de quién se hace cargo de las ineficiencias presentes en el sector y cómo se asume ese costo. 

El sistema de transporte de carga en la Ciudad de México Factores a considerar en el análisis del transporte de carga y la movilidad de mercancías

El artículo presenta un análisis del sistema de transporte de carga en la Ciudad de México desde el punto de vista sistémico, considerando las variables económicas, políticas, técnicas, sociales que permitan comprender la problemática que actualmente enfrenta esta ciudad en la movilidad de mercancías. Es una reflexión de carácter multidisciplinario basada en el método cualitativo para explicar y comprender la situación actual del transporte de carga en México dentro del contexto de la globalización económica, para identificar así la naturaleza profunda de la estructura dinámica del transporte de carga en la Ciudad y la nueva forma de conceptualizar al transporte de mercancías. Se estudia el comportamiento de los flujos e infraestructura de las redes viales, las características urbanas, los instrumentos jurídicos en las políticas del transporte, la problemática del transporte de carga, así como la movilidad y los diferentes problemas que enfrenta el sector en relación con la ciudad. El objetivo principal de presente artículo es enunciar las razones por las que no existe un sistema de transporte articulado y se privilegia el uso del autotransporte de carga. Finalmente, de acuerdo a las diversas variables analizadas, se establece en las conclusiones que el análisis y la planificación de los transportes debe ser multi e interdisciplinario por naturaleza, con una visión integral para establecer un equilibrio entre los modos de transporte. 

La imperiosa necesidad de ser diferente en la globalización: el mercadeo territorial. La experiencia de las regiones chilenas

The paper focuses on an emergent Tepic: the new role of territorios in the worldwide competente pushed by globalization. Each and everyone territory seeks the same result: attract capital, innovations, turism and, at the same time, sell its goods and services worldwide. As an old African proverb states: “in the African plain no matter what you are, lion or antelope, you better start running from the eve to avoid dying, either from starving or in the gullet of a depredator”. In Latin America the importance granted to territorial marketing is scarce bur growing. It is necessary to apply to territories the prescriptions that Aristóteles wrote on rethorics, the art of delivering a discourse. These rules are based on ethos (the essential characteristics of who speaks), on pathos (the emocional appeal contained in the speech) and on logos (the reason or rationality). Text is structured in four sections: a) Introduction, a description of the problem to be discussed including a revision of the concept of globalization making clear its systemic nature and its most likely result: a unique commercial space and multiple production spaces; b) Competence and territorial marketing, discussing the main theoretical issues involved; c) Chilean experience on territorial marketing; d) Final comments.

Development, resistance and change. A point of view from Río Negro’s steppe

In this paper we search the concept of nonviolent resistance inquiring a rural experience from Rio Negro´s steppe. The initiative highlights the need to recognize  the context of the resistance exercise and the consideration of three aspects: the evaluation and interpretation of space, the dispute to public policy and the  restructuring of the family order. These three elements, which overlap material  and symbolic aspects, are discussed from an organization of trade domestic craft production. The notion of “development” is discovered on the basis of the  frameworks of values from which the reproduction of subordination is associated  with this idea, and even the challenge of change is the basis of the proposal which reviews that development idea, and illuminates from this complexity the notion  of “nonviolent resistance”.

Colombia - Oposición, competencia electoral y reformas para la paz en Colombia

Los problemas que enfrenta la oposición parlamentaria en Colombia requieren un enfoque sistémico en su solución que supere la perspectiva tradicional limitada a la discusión de un estatuto. Para una propuesta de reforma política es necesario evaluar los elementos que componen el sistema político, entendiendo que esos elementos están interactuando permanentemente entre ellos, demarcando el escenario de la competencia partidista, y que sus efectos estimulan u obstaculizan el funcionamiento de la oposición. Un contexto político que facilite la oposición parlamentaria y el esquema gobierno–oposición es más apropiado para el funcionamiento de partidos minoritarios y para el tránsito de organizaciones armadas que quieran pasar a la vida civil. Ninguna organización insurgente, a menos que militarmente esté derrotada, querrá desmovilizarse para tener una efímera participación en política.-----The problems faced by parliamentary opposition in Colombia need a systemic approach to go beyond the old outlook whereby all disputes are short-sightedly restricted to one statute. In order to consider a plausible political reform, it is first necessary to properly assess the elements that make up the current political system, under the assumption that they permanently interact with each other and mark out the arena where political parties compete; the effects of such competition either encourage or hinder the opposition’s action. A political context where parliamentary opposition and the government-opposition scheme are fostered is much more appropriate for minority parties and for the transition of armed groups into civil society. No insurgent group (unless militarily defeated) will ever demobilize only to play an ephemeral political role.