3D Analysis of the TCR/pMHCII Complex Formation in Monkeys Vaccinated with the First Peptide Inducing Sterilizing Immunity against Human Malaria

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.

Experiences, sensations and demands of citizen (in)security: recent complex configurations in Argentina

Over the last decades the issue of insecurity due to an increase in crime rates and its possible impact on the stability of Latin American democracies has sparked an ongoing debate. In this context, the present article studies, for the case of Argentina, how experiences and sensations of insecurity may be articulated to demands for greater punitive rigor. The analysis is based on two types of information. Initially, data from international surveys such as Latinoabarometer are considered. Then, these are compared to data from prolonged on-site observations in a poor neighborhood of a mid-sized Argentine city. The combination of these different types of data shows the complexity of the process. Contrary to what is often assumed, experiences and sensations of insecurity do not lineally lead to demands for greater punitive rigor. The way in which social actors elaborate their experiences of insecurity is highly situational and not systematic. We have found that there is not necessarily a consistent process of ‘meaning construction’ that articulates experiences and sensations of insecurity with political demands.

Leadership: A complex concept awaiting a new explanation?

Leaders have the task of developing future strategy while being consciously engaged in executing current strategy and mapping landmarks, pathways and obstacles which they meet asthey endeavor to traverse challenging, rapidly evolving terrain. In an era in which there is a global leadership credibility crisis, business as usual is no longer an option in the pursuit of the longer-term survival of any organization. The leadership approach to complexity outlined here is based on learning to achieve results through experimentation, learning, and reflection. A case study is presented that illustrates the application of this approach. In this paper, the reader is first introduced to a brief overview of some key definitions and debates, shifting leadership boundaries, and emerging accountabilities and opportunities. This is followed by a summary of some of the key topics and issues that face current and future leaders.

Convergencia de vías de señalización en un modelo de apoptosis

La sepsis es un evento inflamatorio generalizado del organismo inducido por un daño causado generalmente por un agente infeccioso. El patógeno más frecuentemente asociado con esta entidad es el Staphylococcus aureus, responsable de la inducción de apoptosis en células endoteliales debida a la producción de ceramida. Se ha descrito el efecto protector de la proteína C activada (PCA) en sepsis y su relación con la disminución de la apoptosis de las células endoteliales. En este trabajo se analizó la activación de las quinasas AKT, ASK1, SAPK/JNK y p38 en un modelo de apoptosis endotelial usando las técnicas de Western Blotting y ELISA. Las células endoteliales (EA.hy926), se trataron con C2-ceramida (130μM) en presencia de inhibidores químicos de cada una de estas quinasas y PCA. La supervivencia de las células en presencia de inhibidores químicos y PCA fue evaluada por medio de ensayos de activación de las caspasas 3, 7 y 9, que verificaban la muerte celular por apoptosis. Los resultados evidencian que la ceramida reduce la activación de AKT y aumenta la activación de las quinasas ASK, SAPK/JNK y p38, en tanto que PCA ejerce el efecto contrario. Adicionalmente se encontró que la tiorredoxina incrementa la activación/fosforilación de AKT, mientras que la quinasa p38 induce la defosforilación de AKT.

El món rural : un món complex i canviant. 'El mundo rural : un mundo complejo y cambiante'.

Resumen del autor en catalán

A systematic review of the complex organization of human cognitive domains and their heritability

Resumen tomado de la publicación