251 research outputs found

    Proposals for the Future Development of Peace Education in Hiroshima City - Based on a Comparative Analysis of the Peace Education Curricula of Hiroshima and Dresden 【Article】

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    Every year students in schools in Hiroshima City study a unique Peace Education curriculum thatcame about as a direct result of the unique historical experience of the city. During the Second WorldWar, the city of Dresden in Germany suffered similar levels of destruction to Hiroshima. Due to the factthat the two cities endured similar historical experiences in this respect and also have other significantfactors in common, an investigation was carried out to compare and contrast their respective PeaceEducation curricula.Despite the fact that it was ascertained at an early stage that no directly comparable subject to thatexisting in Hiroshima was being taught in schools in Dresden, the investigation did identify severalareas of commonality between the cases, including a strong commitment at both the city governmentand popular level towards issues relating to peace and international understanding. Furthermore, it alsorevealed areas where aspects of the teaching of the subjects of History and Political Science in Dresdenschools could provide valuable suggestions for the future development of Peace Education in Hiroshimasince the Japanese city has been contending with a complex political controversy over the subject formore than two decades..

    Host skin immunity to arthropod vector bites: from mice to humans

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    Infections caused by vector-borne pathogens impose a significant burden of morbidity and mortality in a global scale. In their quest for blood, hematophagous arthropods penetrate the host skin and may transmit pathogens by the bite. These pathogens are deposited along with saliva and a complex mixture of vector derived factors. Hematophagous arthopod vectors have evolved a complex array of adaptations to modulate the host immune response at the bite site with the primary goal to improve blood feeding, which have been exploited throughout evolution by these pathogens to enhance infection establishment in the host. While this paradigm has been firmly established in mouse models, comparable data from human studies are scarce. Here we review how the host skin immune response to vector bites in animal models is hijacked by microbes to promote their pathogenesis. We mainly explored four distinct vector-pathogen pairs of global health importance: sand flies and Leishmania parasites, Ixodes scapularis ticks and Borrelia burgdorferi, Aedes aegypti mosquitoes and arboviruses, and Anopheles gambiae mosquitos and Plasmodium parasites. Finally, we outline how critical it is for the field of vector biology to shift from rodent models to clinical studies focused on the interface of vector-pathogen-host immune system to push further the frontiers of knowledge of the field

    Antibody-based inhibition of pathogenic new world hemorrhagic fever mammarenaviruses by steric occlusion of the human transferrin receptor 1 apical domain

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    Pathogenic clade B New World mammarenaviruses (NWM) can cause Argentine, Venezuelan, Brazilian, and Bolivian hemorrhagic fevers. Sequence variability among NWM glycoproteins (GP) poses a challenge to the development of broadly neutralizing therapeutics against the entire clade of viruses. However, blockade of their shared binding site on the apical domain of human transferrin receptor 1 (hTfR1/CD71) presents an opportunity for the development of effective and broadly neutralizing therapeutics. Here, we demonstrate that the murine monoclonal antibody OKT9, which targets the apical domain of hTfR1, can sterically block cellular entry by viral particles presenting clade B NWM glycoproteins (GP1-GP2). OKT9 blockade is also effective against viral particles pseudotyped with glycoproteins of a recently identified pathogenic Sabia-like virus. With nanomolar affinity for hTfR1, the OKT9 antigen binding fragment (OKT9-Fab) sterically blocks clade B NWM-GP1s and reduces infectivity of an attenuated strain of Junin virus. Binding of OKT9 to the hTfR1 ectodomain in its soluble, dimeric state produces stable assemblies that are observable by negative-stain electron microscopy. A model of the OKT9-sTfR1 complex, informed by the known crystallographic structure of sTfR1 and a newly determined structure of the OKT9 antigen binding fragment (Fab), suggests that OKT9 and the Machupo virus GP1 share a binding site on the hTfR1 apical domain. The structural basis for this interaction presents a framework for the design and development of high-affinity, broadly acting agents targeting clade B NWMs. IMPORTANCE Pathogenic clade B NWMs cause grave infectious diseases, the South American hemorrhagic fevers. Their etiological agents are Junin (JUNV), Guanarito (GTOV), Sabiá (SABV), Machupo (MACV), Chapare (CHAV), and a new Sabiá-like (SABV-L) virus recently identified in Brazil. These are priority A pathogens due to their high infectivity and mortality, their potential for person-to-person transmission, and the limited availability of effective therapeutics and vaccines to curb their effects. While low homology between surface glycoproteins of NWMs foils efforts to develop broadly neutralizing therapies targeting NWMs, this work provides structural evidence that OKT9, a monoclonal antibody targeting a single NWM glycoprotein binding site on hTfR1, can efficiently prevent their entry into cells.Fil: Ferrero, Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Flores, Maria D.. University of California at Los Angeles; Estados UnidosFil: Short, Connor. University of California at Los Angeles; Estados UnidosFil: Vázquez, Cecilia Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Clark, Lars E.. Harvard Medical School; Estados UnidosFil: Ziegenbein, James. University of California at Los Angeles; Estados UnidosFil: Zink, Samantha. University of California at Los Angeles; Estados UnidosFil: Fuentes, Daniel. University of California at Los Angeles; Estados UnidosFil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Batto, María V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Collazo, Michael. University of California at Los Angeles; Estados UnidosFil: García, Cybele C.. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Abraham, Jonathan. Harvard Medical School; Estados Unidos. Brigham and Women's Hospital; Estados UnidosFil: Cordo, Sandra Myriam. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rodriguez, Jose A.. University of California at Los Angeles; Estados UnidosFil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

    Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

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    BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution
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