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Garulli B.,Parasitic and Immune mediated Diseases | Garulli B.,University of Rome La Sapienza | Di Mario G.,Parasitic and Immune mediated Diseases | Stillitano M.G.,Parasitic and Immune mediated Diseases | And 4 more authors.
Vaccine | Year: 2014

HIV-1 vaccines based on recombinant vectors have been developed to elicit immune responses; however, the failure of the STEP HIV-1 vaccine trial has caused concern regarding the impact on vaccine efficacy of pre-existing vector seropositivity in humans. By using a mouse model of infection, we evaluated the immune responses elicited by intranasal and vaginal immunization with the recombinant influenza virus WSN/CKG carrying the PCLUS3-P18 peptide and a Gag epitope in its hemagglutinin, and the impact of pre-existing vector immunity on protection against recombinant vaccinia virus challenge. We found that despite the protective immunity induced in naïve mice by the WSN/CKG virus via either route, the vaginal immunization of mice with pre-existing influenza immunity restricted vPE16 replication more significantly in the ovaries than intranasal immunization. Thus, successful vaccination strategies under limiting conditions, such as pre-existing vector immunity, require the local induction of mucosal immunity at the site of virus infection. © 2014 Elsevier Ltd.

News Article
Site: www.nanotech-now.com

Abstract: Healthcare practitioners may one day be able to physically screen for breast cancer using pressure-sensitive rubber gloves to detect tumors, owing to a transparent, bendable and sensitive pressure sensor newly developed by Japanese and American teams. Conventional pressure sensors are flexible enough to fit to soft surfaces such as human skin, but they cannot measure pressure changes accurately once they are twisted or wrinkled, making them unsuitable for use on complex and moving surfaces. Additionally, it is difficult to reduce them below 100 micrometers thickness because of limitations in current production methods. To address these issues, an international team of researchers led by Dr. Sungwon Lee and Professor Takao Someya of the University of Tokyo's Graduate School of Engineering has developed a nanofiber-type pressure sensor that can measure pressure distribution of rounded surfaces such as an inflated balloon and maintain its sensing accuracy even when bent over a radius of 80 micrometers, equivalent to just twice the width of a human hair. The sensor is roughly 8 micrometers thick and can measure the pressure in 144 locations at once. The device demonstrated in this study consists of organic transistors, electronic switches made from carbon and oxygen based organic materials, and a pressure sensitive nanofiber structure. Carbon nanotubes and graphene were added to an elastic polymer to create nanofibers with a diameter of 300 to 700 nanometers, which were then entangled with each other to form a transparent, thin and light porous structure. "We've also tested the performance of our pressure sensor with an artificial blood vessel and found that it could detect small pressure changes and speed of pressure propagation," says Lee. He continues, "Flexible electronics have great potential for implantable and wearable devices. I realized that many groups are developing flexible sensors that can measure pressure but none of them are suitable for measuring real objects since they are sensitive to distortion. That was my main motivation and I think we have proposed an effective solution to this problem." ### This work was conducted in collaboration with the research group of Professor Zhigang Suo at Harvard University, USA. Collaborating institutions Osaka University Harvard University, USA Funding Japan Science and Technology Agency (JST) Exploratory Research for Advanced Technology (ERATO) Someya Bio-Harmonized Electronics Project About University of Tokyo The University of Tokyo is Japan's leading university and one of the world's top research universities. The vast research output of some 6,000 researchers is published in the world's top journals across the arts and sciences. Our vibrant student body of around 15,000 undergraduate and 15,000 graduate students includes over 2,000 international students. Find out more at www.u-tokyo.ac.jp/en/ or follow us on Twitter at @UTokyo_News_en. For more information, please click Contacts: Research contact Professor Takao Someya Department of Electrical Engineering and Information Systems Graduate School of Engineering The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656, Japan Tel: +81-3-5841-0411/6756 Fax: +81-3-5841-6709 Press officer contact Graduate School of Engineering Public Relations Office The University of Tokyo The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656, Japan Tel: 03-5841-1790 Fax: 03-5841-0529 If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Li C.,University of Wisconsin - Madison | Hatta M.,University of Wisconsin - Madison | Nidom C.A.,Airlangga University | Muramoto Y.,University of Tokyo | And 6 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

The spread of avian H5N1 influenza viruses around the globe has become a worldwide public health concern. To evaluate the pathogenic potential of reassortant viruses between currently cocirculating avian H5N1 and human H3N2 influenza viruses, we generated all the 254 combinations of reassortant viruses between A/chicken/South Kalimantan/UT6028/06 (SK06, H5N1) and A/Tokyo/Ut-Sk-1/07 (Tok07, H3N2) influenza viruses by reverse genetics. We found that the presence of Tok07 PB2 protein in the ribonucleoprotein (RNP) complex allowed efficient viral RNA transcription in a minigenome assay and that RNP activity played an essential role in the viabilityandreplicative ability of the reassortant viruses. When the pathogenicity of 75 reassortant H5 viruses was tested in mice, 22 were more pathogenic than the parental SK06 virus, and three were extremely virulent. Strikingly, all 22 of these viruses obtained their PB2 segment from Tok07 virus. Further analysis showed that Tok07 PB1 alone lacked the ability to enhance the pathogenicity of the reassortant viruses but could do so by cooperating with Tok07 PB2. Our data demonstrate that reassortment between an avian H5N1 virus with low pathogenicity in mice and a human virus could result in highly pathogenic viruses and that the human virus PB2 segment functions in the background of an avian H5N1 virus, enhancing its virulence. Our findings highlight the importance of surveillance programs to monitor the emergence of human H5 reassortant viruses, especially those containing a PB2 segment of human origin.

Bornholdt Z.A.,Scripps Research Institute | Noda T.,Tokyo Medical University | Abelson D.M.,Scripps Research Institute | Halfmann P.,University of Wisconsin - Madison | And 6 more authors.
Cell | Year: 2013

Proteins, particularly viral proteins, can be multifunctional, but the mechanisms behind multifunctionality are not fully understood. Here, we illustrate through multiple crystal structures, biochemistry, and cellular microscopy that VP40 rearranges into different structures, each with a distinct function required for the ebolavirus life cycle. A butterfly-shaped VP40 dimer traffics to the cellular membrane. Once there, electrostatic interactions trigger rearrangement of the polypeptide into a linear hexamer. These hexamers construct a multilayered, filamentous matrix structure that is critical for budding and resembles tomograms of authentic virions. A third structure of VP40, formed by a different rearrangement, is not involved in virus assembly but instead uniquely binds RNA to regulate viral transcription inside infected cells. These results provide a functional model for ebolavirus matrix assembly and the other roles of VP40 in the virus life cycle and demonstrate how a single wild-type, unmodified polypeptide can assemble into different structures for different functions. PaperFlick © 2013 Elsevier Inc.

Fan S.,University of Wisconsin - Madison | Hatta M.,University of Wisconsin - Madison | Kim J.H.,University of Wisconsin - Madison | Kim J.H.,University of Michigan | And 10 more authors.
Nature Communications | Year: 2014

Highly pathogenic avian H5N1 influenza viruses have sporadically transmitted to humans causing high mortality. The mechanistic basis for adaptation is still poorly understood, although several residues in viral protein PB2 are known to be important for this event. Here, we demonstrate that three residues, 147T, 339T and 588T, in PB2 play critical roles in the virulence of avian H5N1 influenza viruses in a mammalian host in vitro and in vivo and, together, result in a phenotype comparable to that conferred by the previously known PB2-627K mutation with respect to virus polymerase activity. A virus with the three residues and 627K in PB2, as has been isolated from a lethal human case, is more pathogenic than viruses with only the three residues or 627K in PB2. Importantly, H5N1 viruses bearing the former three PB2 residues have circulated widely in recent years in avian species in nature. & © 2014 Macmillan Publishers Limited. All rights reserved.

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