Adjuvant like effect of vaccinia virus 14K protein: a case study with malaria vaccine based on the circumsporozoite protein

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 13-06-201

A comparative study of insulin like growth factor binding protein-5 and transforming growth factor-beta 1 on epithelial-mesenchymal transition

Fibrosis is a disease which is characterised by scarring of tissues due to excessive production of extracellular matrix molecules. It has been described as unresolved wound healing. Previous studies have implicated IGFBP-5 and TGF-β1 as pivotal players in fibrosis. This study was undertaken to compare the effects of IGFBP-5 and TGF-β1 , with respect to one particular aspect of the response injury, epithelial mesenchymal transition (EMT). 1 developed Epithelial and Mesenchymal clones from NMuMg (epithelial) cells which were characterised by morphology and by expession of cell-surface markers. The ability of the Epithelial clone to undergo EMT with TGF-β1 and its increased sensitivity to TGF-β1 treatment compared with their mesenchymal counterparts made it an effective model to examine the effects of IGFBP-5. lGFBP-5 was not able to drive an EMT process since it failed to decrease E-cadherin expression (a marker of epithelial cells) and downregulated fibronectin expression (a mesenchymal marker) in mesenchymal clones.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Efecto adyuvante de la proteína A27 del virus vaccinia (14K) y sus aplicaciones en vacunas

[EN] The present invention relates to a vaccine strategy based on use of the Vaccinia virus 14K envelope protein, encoded by the A27L gene, fused to the CS protein of Plasmodium yoelii lacking the GPI domain, and which forms stable oligomers (denoted CS14K), thereby generating an immune response to malaria antigens that is greater than that described in connection with the use of other vaccine designs. This chimeric protein is tested in mice using heterologous immunization protocols and develops a potent humoral and cellular immune response to CS, which is evaluated by means of ELISA and flow-cytometry analysis.[ES] La presente invención se refiere a una estrategia vacunal basada en el uso de la proteina 14K de la envuelta del virus vaccinia, codificada por el gen A27L, sin los 28 primeros aminoácidos y fusionada con la proteina CS de Plasmodium yoelii que carece del dominio GPI y de la secuencia señal. Esta proteina, referida como CS14K, forma oligómeros estables, de manera que genera una respuesta inmune frente a antígenos de malaria superior a la descrita con el uso de otros diseños de vacuna. La proteina quimérica es ensayada en ratones usando protocolos de inmunización heterologos y desarrolla una potente respuesta inmune humoral y celular frente a CS evaluada mediante ELISA y análisis de citometría de flujo.Peer reviewedConsejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

Safeguarding women’s rights: india’s post-colonial legal journey towards gender justice

With an emphasis on post-colonial developments, this essay examines how legal reforms have advanced gender justice in India. By looking at significant legislative actions, constitutional clauses, and court rulings, the study seeks to understand how the Indian legal system has addressed calls for gender equality. The article’s methodology takes a doctrinal approach, examining secondary literature on gender justice in addition to primary sources including legislatons, case law, and constitutional articles. This includes historic legislation like the Protection of Women from Domestic Violence Act, 2005, and the Sexual Harassment of Women at  Workplace (Prevention, Prohibition, and Redressal) Act of 2013, along with major legislative reforms including the Hindu Marriage Act of 1955 and Hindu Succession Act of 1956 and their amendments. It is further amplified that, although the Indian society has progressed quite a lot in demolishing patriarchal structures, much is left due to deeprooted social and cultural mechanisms. The study derives the significance of judicial activism and affirmative action for gender justice in arguing for further legal reforms and their practical implementation for reaching the ultimate reality of gender equality.Haciendo hincapié en la evolución poscolonial, este ensayo examina cómo las reformas jurídicas han hecho avanzar la justicia de género en la India. A través del análisis de importantes medidas legislativas, cláusulas constitucionales y sentencias judiciales, el estudio trata de comprender cómo el sistema jurídico indio ha abordado los llamamientos en favor de la igualdad de género. La metodología del artículo adopta un enfoque doctrinal, examinando bibliografía secundaria sobre justicia de género, además de fuentes primarias, como leyes, jurisprudencia y artículos constitucionales. Esto incluye legislación histórica como la Ley de Protección de las Mujeres contra la Violencia Doméstica de 2005 y la Ley de Acoso Sexual de las Mujeres en el Lugar de Trabajo (Prevención, Prohibición y Reparación) de 2013, junto con importantes reformas legislativas como la Ley de Matrimonio Hindú de 1955 y la Ley de Sucesión Hindú de 1956 y sus enmiendas. Se amplía además que, aunque la sociedad india ha progresado bastante en la demolición de las estructuras patriarcales, queda mucho por hacer debido a mecanismos sociales y culturales profundamente arraigados. El estudio deduce la importancia del activismo judicial y de la acción afirmativa para la justicia de género a la hora de defender nuevas reformas legales y su aplicación práctica para alcanzar la realidad definitiva de la igualdad de género

Compartmentalized Antimicrobial Defenses in Response to Flagellin

Motility is often a pathogenicity determinant of bacteria targeting mucosal tissues. Flagella constitute the machinery that propels bacteria into appropriate niches. Besides motility, the structural component, flagellin, which forms the flagella, targets Toll-like receptor 5 (TLR5) to activate innate immunity. The compartmentalization of flagellin-mediated immunity and the contribution of epithelial cells and dendritic cells in detecting flagellin within luminal and basal sides are highlighted here, respectively. While a direct stimulation of the epithelium mainly results in recruitment of immune cells and production of antimicrobial molecules, TLR5 engagement on parenchymal dendritic cells can contribute to the stimulation of innate lymphocytes such as type 3 innate lymphoid cells, as well as T helper cells. This review, therefore, illustrates how the innate and adaptive immunity to flagellin are differentially regulated by the epithelium and the dendritic cells in response to pathogens that either colonize or invade mucosa.Fil: Vijayan, Aneesh. Centre National de la Recherche Scientifique; FranciaFil: Rumbo, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Carnoy, Christophe. Centre National de la Recherche Scientifique; FranciaFil: Sirard, Jean-Claude. Centre National de la Recherche Scientifique; Franci

Crimes Against Humanity: Evolution, Prosecution, and Challenges for the International Criminal Court

In international law, the term crimes against humanity refers to crimes, including murder, torture, enforced disappearance, etc., committed in a large-scale manner against civilians irrespective of their nationality. The crimes against humanity, together with crimes such as genocide, war crimes, and crimes against aggression, form part of core crimes in international criminal law. The idea of crimes against humanity traces its development to the early 1900s, and subsequently, it received serious attention during the Second World War. The Agreement for the Prosecution and Punishment of the Major War Criminals of the European Axis, adopted in 1945, has defined the term crimes against humanity for the first time in its history. Subsequently, several developments occurred, including the Nuremberg Trials, the Tokyo Trial, the International Criminal Tribunal for Former Yugoslavia and the International Criminal Tribunal for Rwanda, etc. All these have significantly influenced the moulding of crimes against humanity. Finally, adopting the Statute of the International Criminal Court has given a final shape to the concept of crimes against humanity and the methods to deal with its prosecution, punishment, etc. Being one of the core international criminal law crimes, this paper examines the historical evolution, the concept of crimes against humanity and the various criticisms and challenges in prosecuting crimes against humanity under international criminal law

The GM-CSF released by airway epithelial cells orchestrates the mucosal adjuvant activity of flagellin

International audienceThe TLR5 agonist flagellin is a potent adjuvant and is currently being developed for use in vaccines. The mechanisms that drive flagellin's activity are influenced by its administration route. Previous studies showed that lung structural cells (especially epithelial cells lining the conducting airways) are pivotal for the efficacy of intranasally administered flagellin-containing vaccines. In this study, we looked at how the airway epithelial cells (AECs) regulate the flagellin-dependent stimulation of Ag-specific CD4+ T cells and the Ab response in mice. Our results demonstrate that after sensing flagellin, AECs trigger the release of GM-CSF in a TLR5-dependent fashion and the doubling of the number of activated type 2 conventional dendritic cells (cDC2s) in draining lymph nodes. Furthermore, the neutralization of GM-CSF reduced cDC2s activation. This resulted in lower of Ag-specific CD4+ T cell count and Ab titers in mice. Our data indicate that during pulmonary immunization, the GM-CSF released by AECs orchestrates the cross-talk between cDC2s and CD4+ T cells and thus drives flagellin's adjuvant effect