Microarray detection of human parainfluenzavirus 4 infection associated with respiratory failure in an immunocompetent adult.

A pan-viral DNA microarray, the Virochip (University of California, San Francisco), was used to detect human parainfluenzavirus 4 (HPIV-4) infection in an immunocompetent adult presenting with a life-threatening acute respiratory illness. The virus was identified in an endotracheal aspirate specimen, and the microarray results were confirmed by specific polymerase chain reaction and serological analysis for HPIV-4. Conventional clinical laboratory testing using an extensive panel of microbiological tests failed to yield a diagnosis. This case suggests that the potential severity of disease caused by HPIV-4 in adults may be greater than previously appreciated and illustrates the clinical utility of a microarray for broad-based viral pathogen screening

Studies on morpholinosphingolipids: Potent inhibitors of glucosylceramide synthase

Synthetic 1-morpholino-1-deoxyceramides were designed to inhibit glucosylceramide synthase. The most potent inhibitor 2a possesses the unnatural R,R-configuration of D-threo-sphingosine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31632/1/0000566.pd

Conservation of Complex Nuclear Localization Signals Utilizing Classical and Non-Classical Nuclear Import Pathways in LANA Homologs of KSHV and RFHV

ORF73 latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is targeted to the nucleus of infected cells where it binds to chromatin and mediates viral episome persistence, interacts with cellular proteins and plays a role in latency and tumorigenesis. A structurally related LANA homolog has been identified in the retroperitoneal fibromatosis herpesvirus (RFHV), the macaque homolog of KSHV. Here, we report the evolutionary and functional conservation of a novel bi-functional nuclear localization signal (NLS) in KSHV and RFHV LANA. N-terminal peptides from both proteins were fused to EGFP or double EGFP fusions to examine their ability to induce nuclear transport of a heterologous protein. In addition, GST-pull down experiments were used to analyze the ability of LANA peptides to interact with members of the karyopherin family of nuclear transport receptors. Our studies revealed that both LANA proteins contain an N-terminal arginine/glycine (RG)-rich domain spanning a conserved chromatin-binding motif, which binds directly to importin β1 in a RanGTP-sensitive manner and serves as an NLS in the importin β1-mediated non-classical nuclear import pathway. Embedded within this domain is a conserved lysine/arginine-(KR)-rich bipartite motif that binds directly to multiple members of the importin α family of nuclear import adaptors in a RanGTP-insensitive manner and serves as an NLS in the classical importin α/β-mediated nuclear import pathway. The positioning of a classical bipartite kr-NLS embedded within a non-classical rg-NLS is a unique arrangement in these viral proteins, whose nuclear localization is critical to their functionality and to the virus life cycle. The ability to interact with multiple import receptors provides alternate pathways for nuclear localization of LANA. Since different import receptors can import cargo to distinct subnuclear compartments, a multifunctional NLS may provide LANA with an increased ability to interact with different nuclear components in its multifunctional role to maintain viral latency

A "democracia participativa y protagónica", o povo e o líder: a experência dos consejos comunales na parroquia 23 de Enero (Caracas/Venezuela)

Os Consejos Comunales/CCs são uma experiência de poder popular praticada nos últimos anos na Venezuela. Trata-se de micro-governos construídos no interior das comunidades, compostos e geridos pelos próprios moradores e que possuem poder deliberativo e executivo sobre a gestão das políticas locais voltadas, principalmente, para a melhoria das condições de vida das classes populares. Os CCs fazem parte de um projeto nacional de construção de um Estado Comunal articulado por federações e confederações de Consejos Comunales e/ou por Comunas. É um projeto ambicioso, orientado por uma proposta para o Socialismo del Siglo XXI, para a construção de uma “democracia participativa e protagônica” que prevê não apenas a participação política do povo, mas também que este seja o sujeito principal na resolução dos seus problemas, além de envolver o desenvolvimento de um projeto econômico endógeno e autossustentável para o país. Apesar de fortemente incentivado pelo presidente Hugo Chávez Frias, este projeto encontra suas raízes em experiências e demandas existentes nas bases da sociedade desde longa data. Deste modo, a eleição de Chávez, em 1998, a posterior abertura de uma assembleia constituinte com um chamado para repensar o Estado Venezuelano e a proposta de construção da Asambleas de Ciudadanos y Ciudadanas como instâncias de poder local são fruto de um longo processo de desgaste da institucionalidade liberal que ocorreu durante o regime puntofijista anterior ao governo atual, bem como da articulação da sociedade civil sob diferentes formas com vistas a construir alternativas àquele regime. O objetivo desta dissertação é analisar de que maneira se deu esse processo de construção de uma “democracia participativa e protagônica” na prática, observando as tensões e dilemas provocados pelas pressões dos poderes desde arriba e os dinamismos das bases desde abajo, utilizando como estudo de caso a Parroquia 23 de Enero, de Caracas, por se tratar de um território reconhecido por suas tradições de organização popular anteriores à eleição de Chávez e por ser considerado um dos principais bastiões de sustentação do governo atualmente254 f

O Estado plurinacional e comunitário na Bolívia: as lutas populares e o bem viver a partir de El Alto

A eleição do primeiro presidente indígena da América Latina e a assinatura de uma nova Constituição que tornou a Bolívia um Estado Plurinacional e Comunitário trouxeram a tona um novo arsenal ideológico e epistêmico. Na interseção entre a modernidade ocidental e as culturas milenares originárias de nosso continente, encontra-se um fértil caminho para se vislumbrar alternativas antissistêmicas tendo como ponto de partida o protagonismo indígena. A proposta desta pesquisa é analisar a cultura política que desencadeou esse processo de transformação do Estado a partir de um duplo movimento: desde arriba, isto é, compreender quais as condições que propiciaram a eleição de Evo Morales e de que maneira o governo se apropria e faz uso das tradições originárias, especialmente no que tange à temática do Bem Viver como uma proposta de transformação radical da realidade (também definida como ―Proceso de Cambio‖ ou ―Revolución Democrática y Cultural‖); e desde abajo, do ponto de vista das bases sociais, isto é, como o povo, e em especial as classes populares e indígenas, comporta-se em seu cotidiano diante das contradições e conflitos que permeiam o princípio normativo anunciado pelo governo e a sua prática social. Em relação ao último aspecto, utilizaremos como estudo de caso, a experiência da cidade de El Alto. Localizada a cerca de 10km de La Paz, também considerada uma cidade insurgente, possui um histórico de lutas que remonta à resistência ao Império Espanhol. Nos dias atuais, teve um papel protagônico na Guerra do Gás de 2003 e foi determinante na derrubada de dois presidentes antes de contribuir na eleição de Evo Morales em 2005. Sob o atual governo, é objeto de grandes disputas, pois é uma cidade-chave para a manutenção da estabilidade política no país. As juntas vecinales consistem em umas das principais formas de organização coletiva e popular e combinam elementos modernos (pois se assemelham às associações de moradores) e tradicionais (pois trazem aspectos constitutivos do poder da comunidade indígena oriunda dos ayllus). Acredito que a análise mais aprofundada sobre a experiência de El Alto, tendo como base a perspectiva de algumas de suas lideranças locais, permitirá também uma reflexão mais substancial sobre os dilemas e possibilidades que surgem com a apresentação do Bem Viver (Buen Vivir, Vivir Bien, Suma Kamaña, Suma Kawsay, TeKo Kevi, Ñandareko etc) enquanto alternativa pós-capitalista, bem como os desdobramentos referentes à reflexão da possível articulação entre Estado, Democracia e Comunidade.Conselho Nacional de Desenvolvimento Científico e TecnológicoThe election of the first indigenous president of Latin America and the signing of a new constitution that made Bolivia a Plurinational and Community State brought to the fore a new ideological and epistemic arsenal. At the intersection between Western modernity and the millennial cultures that originated in our continent, there is a fertile way to glimpse antisystemic alternatives having as its starting point the indigenous protagonism. The proposal of this research is to analyze the political culture that triggered this process of transformation of the State from a double movement: from above, that is, to understand the conditions that propitiated the election of Evo Morales and how the government appropriates and makes use of the original traditions, especially with regard to the theme of Well-Living as a proposal for radical transformation of reality (also defined as "Process of Change" or "Cultural and Democratic Revolution"); and from below, from the point of view of social bases, that is, how the people, and especially the indigenous and popular classes, behave in their everyday life in the face of the contradictions and conflicts that permeate the normative principle announced by the government and its social practice. Regarding the last aspect, we will use as a case study the experience of the city of El Alto. Located about 10km from La Paz, also considered an insurgent city, it has a history of fighting that goes back to resistance to the Spanish Empire. Nowadays, he played a leading role in the 2003 Gas War and was instrumental in overthrowing two presidents before contributing to Evo Morales' 2005 election. Under the current administration he is the subject of major disputes as he is a key city to maintain political stability in the country. The neighborhood councils consist of one of the main forms of collective and popular organization and combine modern elements (because they resemble residents' associations) and traditional elements (because they bring constitutive aspects of the power of the indigenous community originated by the ayllus). I believe that a more in-depth analysis of El Alto's experience, based on the perspective of some of its local leaders, will also allow a more substantial reflection on the dilemmas and possibilities that arise with the presentation of Bem Viver (Buen Vivir, Vivir Bien , Suma Kamaña, Suma Kawsay, TeKo Kevi, Ñandareko etc.) as a post-capitalist alternative, as well as the developments regarding the reflection of the possible articulation between State, Democracy and Community.223 p

A Conversation with David Usher

David Anthony Usher was born in Harrow in the UK on November 1st, 1936, and emigrated with his family to Wellington, New Zealand in 1948. After a year at Wellesley College in Days Bay he became a boarder in Grey House at Wanganui Collegiate School. He attended Victoria University of Wellington where he received a BSc (1958) and MSc with First Class Honours (1960). He then moved to Cambridge, England, where he received a PhD in Chemistry, working with D. M. Brown. After two year’s postdoctoral at Harvard University with Frank Westheimer, he joined the faculty at Cornell University in the Department of Chemistry where he has remained ever since. His early work was on the mechanism of the enzyme ribonuclease, where he identified two possible geometries for the reaction, in-line or adjacent. In subsequent work he showed that the mechanism was in-line for both steps. This work led to a prediction that if RNA were 2’,5’-linked, instead of 3’,5’-linked as it is in nature, it would hydrolyze more rapidly when it was part of a double helix. By contrast, he predicted that 3’,5’-linked RNA would be stabilized by becoming part of a double helix. Later work in the Usher laboratory showed that this prediction was correct. In addition, this work suggested a possible mechanism for the formation of RNA under prebiotic conditions. Usher was one of the first to see the potential for what has become known as antisense technology, and developed a novel amide-linked oligonucleotide analog. In more recent years, Dr Usher has turned his attention to possible mechanisms for the prebiotic formation of the peptide bond using novel oligonucleotide templates, as a model for the origin of protein synthesis. His interest in the Origin of Life is broad, and includes collaborative research with Jonathan Lunine of Cornell’s Department of Space Sciences, investigating possible chemical evolution on Saturn’s moon Titan. In addition to his research activities in chemistry, Usher has appeared as the tenor lead in thirteen Gilbert and Sullivan shows that were mounted by the Cornell Savoyards. He has a national ranking in the top 20 in tennis doubles in his age group. With his partner Dale Wise, he won the gold medal for tennis doubles in his age group at the 2013 National Senior Games in Cleveland.1_omoivbpl1_h37icd0

A Conversation with Jerrold Meinwald

Jerrold Meinwald, the Goldwin Smith Professor Emeritus of the Chemistry and Chemical Biology Department, shares insights into the factors that drew him into the world of Chemistry and later into Chemical Ecology, a field he co-founded with the late professor Tom Eisner of CALS; he also reflects upon some highlights of his own career, how he was mentored, and shares perspectives on the evolution of Chemical Biology. The interview was conducted by a colleague of many years, Professor Bruce Ganem. Running time: 99 minutes.1_hbjbw55

A Conversation with Dave Collum

David B. Collum, the Betty R. Miller Professor of Chemistry in the Department of Chemistry and Chemical Biology, describes his unusual entry into chemistry while an undergraduate at Cornell University, a exciting experience in graduate school at Columbia University, and his movement from organic synthesis to physical organometallic chemistry in his early days as an assistant professor at Cornell. The interviewer and former mentor, Professor Bruce Ganem, wander through life at Cornell, the temperament of the department, life as department chairman, and emerging interests in political economics.1_jr7635h