The Extracellular Domain of La Crosse Virus G1 Forms Oligomers and Undergoes pH-Dependent Conformational Changes

AbstractThe La Crosse virus G1 glycoprotein plays a critical role in virus binding to susceptible cells and in the subsequent fusion of viral and cellular membranes. A soluble form of the G1 glycoprotein (sG1) prepared in a recombinant baculovirus system mimics the cell-binding pattern of La Crosse virus and inhibits La Crosse virus infection (A. Pekoszet al., Virology214, 339–348, 1995), presumably by competing for a cellular receptor, a finding that implies that sG1 can perform some functions absent G2, the smaller of the two bunyavirus glycoproteins. We have performed experiments to determine whether sG1 is present as an oligomer and whether it undergoes the conformational changes associated with fusion (F. Gonzalez-Scarano,Virology140, 209–216, 1985). Our results indicate that both sG1 and native G1 undergo similar changes in conformation after exposure to an acidic environment, as detected by reactivity with monoclonal antibodies. Furthermore, using chemical cross-linking, both proteins were detected as oligomers (most likely dimers). Sucrose density gradient analysis of sG1 verified that it was present in monomeric and oligomeric forms. These results demonstrate that the isolated G1 glycoprotein can undergo a pH-dependent change in conformation in the absence of its transmembrane and cytoplasmic tail domains and that the extracellular portion of the glycoprotein can oligomerize

The neuropathogenesis of AIDS

HIV-associated dementia (HAD) is an important complication of the central nervous system in patients who are infected with HIV-1. Although the incidence of HAD has markedly decreased since it has become possible to effectively control viral replication in the blood by administering highly active antiretroviral therapy, a less severe form of HAD, comprising a milder cognitive and motor disorder, is now potentially a serious problem. Brain macrophages and microglia are the key cell types that are infected by HIV-1 in the central nervous system, and they are likely to mediate the neurodegeneration seen in patients with HAD; however, the precise pathogenesis of this neurodegeneration is still unclear. Here, we discuss the studies that are being carried out to determine the respective contributions of infection, and monocyte and macrophage activation, to disease progression

Analysis of the Intracellular Transport Properties of Recombinant La Crosse Virus Glycoproteins

AbstractThe G1 and G2 glycoproteins of La Crosse virus, a member of theBunyavirusgenus of the Bunyaviridae, are encoded as a single open reading frame (ORF) in the viral middle-sized RNA segment. The primary product from this ORF is processed, either cotranslationally or shortly after translation, into the two glycoproteins and a nonstructural protein, NSm, of unknown function. We have expressed La Crosse glycoproteins using vaccinia vectors and studied their processing and localization. When expressed in the native G2-NSm-G1 configuration, both G1 and G2 targeted to the Golgi apparatus as shown by their colocalization with wheat germ agglutinin and acquired resistance to endoglycosidase H. When expressed independently, G2 was targeted to the Golgi apparatus but G1 was retained in the endoplasmic reticulum, indicating that a G1–G2 association is required for Golgi targeting of G1. In contrast to results with other members of the Bunyaviridae, we found that expression of G1 and G2 from separate vectors did not lead to the transport of the G1–G2 complex to the Golgi. However, disruption of the NSm region with a foreign sequence did not interfere with transport of the complex. When a portion of the β-galactosidase gene was inserted in frame into NSm, the glycoproteins derived from this construct were processed and targeted properly and were capable of mediating cell-to-cell fusion

Planning Future Strategies for Domestic and International NeuroAIDS Research, July 24–25, 2008

The National Institute of Mental Health in cooperation with the National Institute on Drug Abuse and the National Institute of Neurological Disorders and Stroke organized a meeting on July 24–25, 2008 to develop novel research directions for neuroAIDS research. The deliberations of this meeting are outlined in this brief report. Several critical research areas in neuroAIDS were identified as areas of emphasis. Opportunities for collaborations between large NIH-funded projects were also discussed

The Brazilian Tunable Filter Imager for the SOAR telescope

This paper presents a new Tunable Filter Instrument for the SOAR telescope. The Brazilian Tunable Filter Imager (BTFI) is a versatile, new technology, tunable optical imager to be used in seeing-limited mode and at higher spatial fidelity using the SAM Ground-Layer Adaptive Optics facility at the SOAR telescope. The instrument opens important new science capabilities for the SOAR community, from studies of the centers of nearby galaxies and the insterstellar medium to statistical cosmological investigations. The BTFI takes advantage of three new technologies. The imaging Bragg Tunable Filter concept utilizes Volume Phase Holographic Gratings in a double-pass configuration, as a tunable filter, while a new Fabry-Perot (FP) concept involves technologies which allow a single FP etalon to act over a large range of interference orders and spectral resolutions. Both technologies will be in the same instrument. Spectral resolutions spanning the range between 25 and 30,000 can be achieved through the use of iBTF at low resolution and scanning FPs beyond R ~2,000. The third new technologies in BTFI is the use of EMCCDs for rapid and cyclically wavelength scanning thus mitigating the damaging effect of atmospheric variability through data acquisition. An additional important feature of the instrument is that it has two optical channels which allow for the simultaneous recording of the narrow-band, filtered image with the remaining (complementary) broad-band light. This avoids the uncertainties inherent in tunable filter imaging using a single detector. The system was designed to supply tunable filter imaging with a field-of-view of 3 arcmin on a side, sampled at 0.12" for direct Nasmyth seeing-limited area spectroscopy and for SAM's visitor instrument port for GLAO-fed area spectroscopy. The instrument has seen first light, as a SOAR visitor instrument. It is now in comissioning phase.Comment: accepted in PAS

Delineation of phenotypes and genotypes related to cohesin structural protein RAD21

RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype–phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in NIPBL or SMC1A for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the RAD21 variant is uncertain. Variants were frequently familial, and genotype–phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a RAD21 variation.Spanish Ministry of Science, Innovation and Universities/State Research Agency RTC-2017-6494-1 and RTI2018-094434-B-I00 (MCIU/AEI/FEDER, UE) as well as funds from the European JPIAMR-VRI network “CONNECT” to PG-

CARAVANA "LUAR DO SERTÃO": UNINDO POLOS DO MNPEF PARA O ENSINO DE FISICA E ASTRONOMIA NO NORDESTE

In this work, we present the formation of a group composed by MNPEF/Northeast hubs dedicated to the Teaching and Dissemination of Physics and Astronomy, joining local efforts for a collaborative regional action of at least two years. Thus, celebrating the 50th anniversary of the Apollo missions and the current Artemis Project, in which the first woman and the first black person will walk on the moon, we will present scientific dissemination actions proposed in public spaces to promote critical thinking and inclusion. Starting from telescopic observations of our satellite and parallel activities, we will present refutations to conspiracy theories that deny that the humanity's were on the Moon and the spherical shape of the Earth. In partnership with the MNPEF hubs, a module on “Astronomy and Space Exploration”, according the BNCC and the New High School Teaching it will be offered, turning our students, multipliers. With this capillarity and logistics together with the Regional Education Departments, we will prepare teachers for nighttime observations and training activities, with their students and the population. Materials and strategies are already defined, and will impact 30 northeastern cities, sharing a dialogic and pleasant experience between local and scientific knowledge. Approved in first place at CNPq 36/2022 call for proposals, the project should leave as a legacy the inter-institutional and community connection; materials that favor scientific literacy for training multipliers and; resources that push the extension, teaching and research activities of our network, which we intend to expand on a national scale.Apresentamos neste trabalho a formação de um grupo de polos do MNPEF/Nordeste dedicado ao Ensino e Divulgação da Física e Astronomia, somando esforços locais para uma ação regional colaborativa de pelo menos dois anos. Assim, celebrando os 50 anos das missões Apollo e o atual Projeto Artemis, em que a primeira mulher e a primeira pessoa negra pisarão na Lua, apresentaremos as ações de divulgação científica propostas em espaços públicos para promover os sensos crítico e de inclusão. Partindo de observações telescópicas itinerantes de nosso satélite e atividades paralelas, apresentaremos refutações às teorias de conspiração que negam a ida da humanidade à Lua e o formato esférico da Terra. Em parceria com os polos do MNPEF, um módulo sobre “Astronomia e Exploração Espacial”, à luz da BNCC e do Novo Ensino Médio será ofertado aos nossos discentes, tornando-os polos multiplicadores. Com esta capilaridade e logística em parcerias feitas com as Secretarias de Educação, prepararemos os professores para as observações noturnas e atividades formativas, com a participação de seus estudantes e da população. Materiais e estratégias da ação já estão definidos, e impactarão as comunidades de 30 municípios nordestinos, compartilhando uma experiência dialógica e lúdica entre saberes locais e científicos. Aprovado em primeira colocação na chamada 36/2022 do CNPq, o projeto deverá deixar como legado as conexões interinstitucionais e comunitárias; materiais que favoreçam o letramento científico e a formação de multiplicadores e; recursos que alavanquem as atividades de extensão, ensino e pesquisa de nossa rede, que pretendemos ampliar a uma escala nacional

大加勒比地区的中国印象: 昨天与今日

Con autorización de la editorial para este libro. Coordinación del libro a cargo de Mu-Kien Adriana Sang Ben.La versión en español de este libro puede encontrarse en el siguiente enlace: http://hdl.handle.net/10261/263728Connected Worlds: The Caribbean, Origin of Modern World. European Union´s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement Nº 823846.Peer reviewe