Oligomerization, Secretion, and Biological Function of an Anchor-Free Parainfluenza Virus Type 2 (PI2) Fusion Protein

AbstractA number of studies indicate that the transmembrane domain, the cytoplasmic domain, or both regions of viral surface glycoproteins are involved in quaternary structure formation. In this report, the transmembrane domain and cytoplasmic tail coding sequence of the fusion (F) glycoprotein gene from parainfluenza type 2 virus was truncated by PCR and the resulting gene (PI2F′) was expressed in HeLa-T4 cells by using the vaccinia virus-T7 transient expression system. Pulse–chase experiments indicated that the anchor-free PI2F′ was expressed and processed into F1 and F2 subunits. Both the processed and the unprocessed anchor-free PI2F′ proteins were found to be efficiently secreted into the culture medium. Examination of the oligomeric form of the anchor-free PI2F′ by chemical cross-linking demonstrated that it assembles posttranslationally into dimers and trimers with a pattern similar to that of the wild-type PI2F protein. In an effort to better understand the biological properties of the truncated form of PI2F′, we anchored PI2F′ by a glycosyl-phosphatidylinositol (GPI) linkage. The GPI-anchored PI2F′ protein, when coexpressed with PI2HN, did not induce cell fusion seen as syncytium formation, but was found to initiate lipid mixing (hemifusion) as observed by transfer of R-18 rhodamine from red blood cells to the GPI-PI2F′/PI2HN cotransfected cells. The results therefore indicate that the extracellular domain of the PI2 fusion protein contains not only the structural information sufficient to direct assembly into higher oligomers, but also is competent to initiate membrane fusion, suggesting that the anchor-free PI2F′ may be useful for further structural studies

O paradigma das global cities nas estratégias de desenvolvimento local

Este artigo trata das novas estratégias de desenvolvimento econômico para as cidades no contexto da reestruturação produtiva. Ele enfoca o papel atribuído às cidades como centros de gestão dos fluxos de capitais, o qual permite uma articulação entre o local e o global sem a intermediação das esferas regional e nacional. Primeiramente, apresenta as contribuições teóricas no Terceiro Mundo que mais têm influenciado o debate urbano sobre a emergência de uma economia de fluxos, cuja organização em rede impõe as cidades como nós de conexão. Em seguida, analisa a construção paradigmática das global cities, com base na generalização de alguns pressupostos teóricos e de tendências empiricamente observadas. Finalmente, examina as estratégias que estão sendo difundidas por consultores internacionais e relacionadas à vocação inexorável das cidades para o terciário avançado.

Metropolitan ungovernability

Although most of the population already live in metropolitan areas, in the Brazilian legal framework, there is still no appropriate legal ruling for managing these territories. The federal pact resulting from the Federal Constitution of 1988 established that it was at the prerogative of the states to create metropolitan regions, urban agglomerations and micro-regions, but did not attribute sufficient powers to them so they could conduct public functions of common interest (FPICs, in Portuguese), given the municipal autonomy likewise granted by the Constitution. In no other aspect does this legal conflict appear more evident than in territorial organization, since virtually all the instruments for the control of land use are of exclusively municipal competence. The purpose of this article is to discuss the possibilities of smoothing the way to an understanding on the limits of local autonomy in conurbations, thereby subordinating the “local” interest to the common interest, with regard to the regulating urban occupation. Therefore, we start with a brief analysis of the 1973 Law which set up the first metropolitan areas in Brazil, and thereby seek to identify advances and retrograde steps that the Constitution represented in relation to the division of powers between federal entities with respect to land management. Then, we investigate the role that post-1988 federal law reserves to metropolitan bodies in organizing, planning and carrying out FPICs in order to catch sight of windows of opportunity to bring them into force with regard to regulating the use of land. Finally, we discuss if the Statute of the Metropolis, which has recently been approved, provides the legal framework needed to overcome the antagonisms that criss-cross metropolitan governance.

Transitions to Second Birth and Birth Intervals in France and Spain: Time Squeeze or Social Norms?

As first births are increasingly postponed across Europe, a strong two-child family norm persists. Past research has examined educational differentials in progressions to second birth, testing various hypotheses but overlooking normative aspects. Comparing fertility surveys from France and Spain, we explore whether late first-time mothers, who have fewer reproductive biological years left to conceive, accelerate the transition to a subsequent child (time squeeze effect). We also consider a normative dimension, i.e., whether women have their first child earlier or later than others in their educational and cohort groups. In both countries, among first-time mothers between 25 and 34 years of age, highly-educated women transitioned to second birth more frequently than less-educated women did. Within the same age group, highly-educated women in Spain had a second child more quickly after the firstborn than their less educated counterparts did, while there is no such difference in France. These results hold after controlling for cohort effects, but are only partly explained by a time squeeze effect. Different normative ages at first birth by education and birth cohort explain the educational gap in the likelihood of transitioning to second birth, but not the birth intervals in Spain. In sum, our analysis demonstrates a persistent educational gap in second births in this country that cannot be reduced to biological or normative effects. This suggests that a broad range of economic constraints play a role, such as unfavourable individual economic conditions and lower levels of institutional support for parenthood

A cidade contra a favela: a nova ameaça ambiental

Este artigo trata da apropriação do discurso da preservação ambiental para a retomada da discussão sobre remoções de favelas no Rio de Janeiro que haviam sido rechaçadas no processo de redemocratização do país. Depois da favela como foco de epidemias e antro de marginais, a mais nova representação social que vem sendo construída apresenta-a como fator de degradação ambiental. Auxiliada pelo saber técnico-científico que demonstra empiricamente os danos ao meio ambiente causados pelas ocupações irregulares, observa-se a constituição de um movimento conservador que busca pressionar os poderes públicos a reprimi-las, sobretudo nas áreas mais valorizadas da cidade. O presente trabalho se propõe a evidenciar a estratégia discursiva dos principais protagonistas deste movimento, a partir da análise de uma campanha promovida, no ano de 2005, por um importante jornal local, intitulada “Ilegal. E daí?”, e que teve como conseqüência uma ação movida pelo Ministério Público Estadual solicitando à Prefeitura a remoção de 13 áreas favelizadas.

Sin nombre virus glycoprotein trafficking

AbstractSin Nombre virus (SNV) is a major representative of the New World hantaviruses and the most common cause of hantavirus pulmonary syndrome (HPS) with high mortality in North America. Unlike other members of the family Bunyaviridae which mature in the Golgi complex, New World hantaviruses have been previously reported to mature at the cell surface. For family Bunyaviridae viruses, retention of the viral glycoproteins at the Golgi complex is thought to be responsible for their Golgi maturation. In our studies, the majority of SNV glycoproteins, G1 and G2, was localized in the Golgi complex when expressed from a full-length GPC clone or in SNV-infected cells, in agreement with data for other members of the family Bunyaviridae, including the Old World hantaviruses. However, the SNV glycoproteins could also be detected at the cell surface at advanced posttransfection or postinfection time points. G1 expressed in the absence of G2 did not accumulate in the Golgi, but remained predominantly associated with the endoplasmic reticulum (ER). Overexpressed amounts of apparently misfolded G1 were aggregated in a subcellular compartment likely to represent the aggresome. Unexpectedly, an additional major pool of G1 was detected intracellularly in SNV-infected and GPC-expressing transfected cells, by using a SNV G1-specific Fab antibody. This pool of G1 is predominantly localized in late endosomes–lysosomes

Recueil de pièces sur la Floride, inédit.

A collection by various authors of 16th century documents relating to Florida, most previously unpublished.https://stars.library.ucf.edu/floridaheritage/1133/thumbnail.jp

Virus-Like Particle Vaccine Protects against 2009 H1N1 Pandemic Influenza Virus in Mice

Background: The 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines. Methodology/Principal Findings: We generated influenza virus-like particles (VLPs) containing proteins derived from the A/ California/04/2009 virus, and tested their efficacy as a vaccine in mice. A single intramuscular vaccination with VLPs provided complete protection against lethal challenge with the A/California/04/2009 virus and partial protection against A/ PR/8/1934 virus, an antigenically distant human isolate. VLP vaccination induced predominant IgG2a antibody responses, high hemagglutination inhibition (HAI) titers, and recall IgG and IgA antibody responses. HAI titers after VLP vaccination were equivalent to those observed after live virus infection. VLP immune sera also showed HAI responses against diverse geographic pandemic isolates. Notably, a low dose of VLPs could provide protection against lethal infection. Conclusion/Significance: This study demonstrates that VLP vaccination provides highly effective protection against the 2009 pandemic influenza virus. The results indicate that VLPs can be developed into an effective vaccine, which can b