1,978 research outputs found

    Reactive Glutamines and a Binding Site Region Contribute to FXIII Substrate Specificity for Fibrinogen αC

    Get PDF
    The reaction between transglutaminase factor XIII (FXIII) and fibrin is a key process in the final stages of blood coagulation. The αC region of fibrin contains three reactive glutamines (Q237, Q328, and Q366) which are crosslinked by FXIII, as well as a FXIII anchoring site (E396). Previous work has helped elucidate the FXIII-αC interaction, but much is still unknown about the key residues in the αC region. Four crosslinking assays were carried out to characterize the contribution of the αC anchoring site and reactive glutamines in crosslinking by FXIII. The effects of individual E396A, Q366N, and Q328P (Fibrinogen Seoul II mutant) mutations in Fbg αC were monitored through a GEE crosslinking/ MALDI-TOF MS strategy. These studies revealed that, at physiological conditions, the E396 anchoring site plays the largest role in crosslinking of the most reactive glutamine, Q237, while the other two glutamines had minimal impacts. In addition, the two less reactive glutamines, Q328 and Q366, appear to compete with each other as substrates for FXIII

    Restoring cholesterol homeostasis in familial hypercholesterolemia cell line model

    Get PDF
    Familial hypercholesterolemia (FH) is an autosomal dominant disorder that results in elevated levels of low-density lipoprotein cholesterol (LDL-C). This increase in serum cholesterol level has been shown to result in premature coronary artery disease (CAD) with devastating symptoms from a young age. Today, the prevalence of heterozygous FH (HeFH) and homozygous FH (HoFH) is estimated to be 1 in 320 and 1 in 160,000 people, respectively. FH is referred to as an underdiagnosed disease due to the large number of mutations that continues to grow. These mutations often exist in one of or a combination of three genes: low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB100), or proprotein convertase subtilin/kinase 9 (PCSK9). Mutations in the LDLR adapter protein 1 (LDLRAP1) were also identified as a less common cause of FH, the autosomal recessive variety, specifically. In treating the disease, patients are prescribed various treatment protocols aimed at reducing endogenous cholesterol synthesis, removal of excess cholesterol through extracorporeal machinery, and other medications aimed at upregulating the LDL receptors in the body. To this day, liver transplants remain as the only cure for FH. FH-induced pluripotent stem cells (FH-iPSC) derived from HoFH skin fibroblasts were permanently corrected using CRISPR technology to insert the three missing base pairs and restore transport of the LDL receptor from the endoplasmic reticulum (ER) to the Golgi body. Hepatocytes are the cells primarily responsible for LDL-C uptake from the plasma, so we differentiated non-corrected familial hypercholesterolemia (NC) and CRISPR-corrected (C) iPSC to hepatocyte-like cells (HLC) to analyze restoration of cholesterol homeostasis. iPSC and HLC were treated with Rosuvastatin, excess sterols, or tunicamycin and collected for mRNA analysis and protein analysis of LDLR and ER stress markers. HLC were also treated with Rosuvastatin and immunocytochemistry and the Thermofisher Amplex Red Cholesterol Assay kit were used to analyze localization of LDLR within the cell and internalization of cholesterol, respectively. Statin-treated NC-iPSC and HLC showed predominant expression of an immature LDLR protein that was not present in C-iPSC or HLC and this upregulation was not the result of regulation at the transcriptional level. The LDLR co-localized to ER resident-protein, Calnexin, in NC-HLC whereas the LDLR co-localized to the cell-membrane in the C-HLC. Upon correcting expression of the mature LDLR, cholesterol internalization increased overtime in C-HLC in contrast to a minimal amount internalized at the 24-hour mark in the NC-HLC. Lastly, statin-treated NC-iPS

    Los "informales" y su rol en la disputa capital-trabajo

    Get PDF
    En el año 2011 se crea la Confederación de Trabajadores de la Economía Popular (CTEP) con el objetivo inicial de nuclear y organizar los reclamos y demandas de los trabajadores de las cooperativas del Programa de Ingreso Social con Trabajo, Argentina Trabaja, ampliando luego su representación al conjunto de la denominada “economía popular". Desde su conformación, dicho espacio organizativo tomo como eje de sus reivindicaciones la demanda de reconocimiento por parte del Ministerio de Trabajo, Empleo y Seguridad Social de la Nación como una instancia gremial legítima. Una instancia gremial de los “informales". En este artículo propongo, a través de una breve descripción del proceso de conformación de la Confederación de Trabajadores de la Economía Popular, analizar cuáles han sido las transformaciones que hoy le permiten a un sector, cuyas demandas han sido tradicionalmente absorbidas por el ámbito asistencial del estado, poner en discusión su rol como parte del mundo del trabajo. Dicho recorrido, a su vez, habilita interrogantes en torno a la viabilidad de la organización actual del mismo, la visibilización de nuevos sujetos en el ámbito de la disputa capital-trabajo y el rol de la economía popular, entre otros.Fil: Hindi, Guadalupe. Universidad de Buenos Aire

    Urban forms at intersection of Imperialism and Colonialism

    Get PDF
    Towards the end of the 19th century and the WWI geopolitical aftermath, Beirut presents a case along the Eastern Mediterranean at the intersection of two major colonial powers, the Ottoman Imperialism and French Colonialism. Dissociated from the province of Damascus in 1888, Beirut was elevated to the rank of provincial capital of Wilâya, the geographical borders of which spanned the equivalent of four actual countries. Following this administrative upgrade Beirut benefited from the Tanzimat reforms and the Sultan Abdul Hamid II jubilee in 1901. This paper will highlight the implementations of these political moments on urban forms and the urban landmarks for the ruler’s glory. Under the French mandate, Beirut role shifted from being provincial capital of a Wilâya part of the Ottoman Empire, to being capital of a Republic country with newly defined borders. Preceding the French Colonialism, Sultan Abdul Hamid II envisioned Westernizing some of the Ottoman Empire cities to the image of the European urban model. Alternately, the French were very enthusiastic to modernize Beirut, their prime image in the Levant. At this moment, Beirut’s urban fate was at the intersection of two visions of Westernization, the late Ottoman Imperialism and the early French Colonialism. An attempt to better understand the urban implications of this turn of century intersection, will be achieved by highlighting urban forms continuities and ruptures as a methodology observed in the broader geopolitical context. It is a chance to reflect on the modes of borrowing Western urban forms and examining the blurred boundaries of their planning, juxtaposition or imposition on an existing urban order. It will as well unfold in a parallel mode how each colonial power approached and applied different urban practices on their occupied territories

    Recurrent Warscape in Beirut public spaces: forty years later (1975-2015)

    Get PDF
    In the context of a tormented Middle East geopolitics and the ongoing Arabo-Israeli conflict, a civil war erupted in Lebanon in 1975 and went uninterrupted for fifteen long years. As early as the first two-years-round of civil war in 1975-77, violent armed conflict manifested itself in an urban nature and contextualized in the capital Beirut. Back then, the civil war targeted systematically the public spaces and achieved purposefully the dual objective of mutating social practice and mutilating their urban form into a geography of fear. Intriguingly, during the unreconciled civil war aftermath, the display of instability and conflict kept on marking sporadically the same public spaces at different incidents. Three decades following the eruption of urban violence in 1975, intermittent events of social and political nature took place between 2005 and 2015, triggered by the assassination of the prime minister. This paper will tackle the two case studies of public spaces which are the pivots of the recurrent warscape: Place des Martyrs and the seaside hotels’ area, both symbols of social and geographic contestations at simultaneous times of peace and war. Based on an interdisciplinary literature, the socio political manifestations will be highlighted by unfolding them across time and space. Signs of discontentment and instability are manifested under different facets and patterns varying from passive intangible representations to active outbursts. The perpetuation of events hitherto occurring in the same urban spaces will be studied from the perspective of the social and political realities. In the absence of a mono-causal factor for warscape recurrence, mapping conflict in the urban space is a suggested tool to approach the perpetuation issue from a context-specific perspective. It is as well an opportunity to raise the question on the relation between the socio-political claims and their reverberation in the same urban spaces
    • …
    corecore