1,450 research outputs found

    Mkp3 is a negative feedback modulator of Fgf8 signaling in the mammalian isthmic organizer

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    The pivotal mechanisms that govern the correct patterning and regionalization of the distinct areas of the mammalian CNS are driven by key molecules that emanate from the so-called secondary organizers at neural plate and tube stages. FGF8 is the candidate morphogenetic molecule to pattern the mesencephalon and rhombencephalon in the isthmic organizer (IsO). Recognizable relevance has been given to the intracellular pathways by which Fgf8 is regulated and modulated. In chick limb bud development, a dual mitogen-activated protein kinase phosphatase-3 (Mkp3) plays a role as a negative feedback modulator of Fgf8 signaling. We have investigated the role of Mkp3 and its functional relationship with the Fgf8 signaling pathway in the mouse IsO using gene transfer microelectroporation assays and protein-soaked bead experiments. Here, we demonstrate that MKP3 has a negative feedback action on the MAPK/ERK-mediated FGF8 pathway in the mouse neuroepithelium. (C) 2004 Elsevier Inc. All rights reserved.info:eu-repo/semantics/publishedVersio

    On the use of organic semiconductors as handles for optical tweezers experiments: trapping and manipulating polyaniline (PANI) microparticles

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    Here we propose the use of the organic semiconductor polyaniline (PANI) for the preparation of spherical-shaped microparticles to serve as handles in optical tweezers (OT) experiments. The stable trapping and manipulation of PANI beads was demonstrated for the first time, using a Gaussian (TEM00TEM_{00}) beam optical tweezers. The trap stiffness was characterized for various different parameters such as the bead radius, the laser power and the distance between the bead and the coverslip of the sample chamber, attesting the viability of using such material for optical manipulation. Since the effective optical properties of PANI can be modulated by the synthesis process, new related applications are also proposed. The results of the present work therefore open the door for using semiconductor polymeric materials in OT applications.Comment: 10 pages and 5 figure

    Escala de Disposição à Nostalgia: Desenvolvimento e Evidências Psicométricas

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    This study aimed to develop the Disposition to Nostalgia Scale (DNS) and to investigate evidence for its factorial validity, convergent validity and internal consistency. The aim was to assemble 20 items that were in the literature or were designed with the purpose of describing nostalgic experiences. Participants were 208 undergraduate students (Mage=22.8 years, SD=6.13, ranging from 18 to 60), the majority male (50.7%), single (86.5%), and from the middle social class (54.1%). They answered the initial items of the DNS and two other measures that assess the same construct: The Nostalgia Inventory (NI) and the Southampton Nostalgia Scale (SNS), in addition to demographic questions. Factorial analysis (PAF) was performed, identifying a general factor that accounted for 42.3% of the total variance, presenting adequate reliability (α=.84). Corroborating evidence for its convergent validity, the DNS scores correlated positively with the two other nostalgia measures (NI and SNS). In conclusion, the DNS presents adequate psychometric properties and can be used to assess the disposition to nostalgia.O presente estudo teve como objetivo desenvolver a Escala de Disposição à Nostalgia (EDN), reunindo evidências de validades baseada na estrutura interna, concorrente e consistência interna. Procurou-se reunir 20 itens que constavam na literatura ou foram elaborados com o fim de descrever vivências nostálgicas. Os participantes do estudo foram 208 estudantes universitários (Midade=22,8; DP=6,13; variando de 18 a 60 anos), a maioria do sexo masculino (50,7%), solteira (86,5%) e de classe social média (54,1%). Estes responderam aos itens iniciais da EDN e duas outras medidas que avaliam o mesmo construto: Inventário de Nostalgia (IN) e Southampton Nostalgia Scale (SNS), além de perguntas demográficas. Uma análise fatorial (PAF) foi realizada, identificando um fator geral que explicou 42,3% da variância total, apresentando precisão adequada (α=0,84). Corroborando evidências de validade convergente, as pontuações da EDN se correlacionaram positivamente com as duas outras medidas de nostalgia (IE e SNS). Conclui-se que a EDN pode ser usada para avaliar a disposição à nostalgia, mostrando evidências psicométricas adequadas.Este estudio ha tenido como objetivo desarrollar la Escala de Disposición Nostálgica (EDN), concentrando evidencias de validez factorial, validez convergente y fiabilidad. Se reunieron 20 ítems, de los cuales, algunos fueron respaldados por la literatura, y otros fueron elaborados con la finalidad de describir vivencias nostálgicas. Participaron del estudio 208 estudiantes universitarios (MEdad=22.8, SD=6.13, variando de 18 a 60 años), la mayoría del sexo masculino (50.7%), soltero (86.5%) y de clase social media (54.1%). Estos contestaron a los ítems de la versión inicial de la EDN y otras dos medidas que evalúan el mismo constructo: Inventario de Nostalgia (IN) y Southampton Nostalgia Scale (SNS), además de cuestiones demográficas. Se realizó un análisis factorial (PAF), identificando un factor general que explicó un 42.3% de la varianza total, presentando fiabilidad adecuada (α=0.84). Corroborando evidencias de validez convergentes, los resultados de la EDN se correlacionaron positivamente con las otras dos medidas de nostalgia (IN y SNS). Se concluyó que la EDN puede ser utilizada para evaluar la disposición nostálgica, mostrando evidencias psicométricas adecuadas

    Subversion of early innate antiviral responses during antibody-dependent enhancement of Dengue virus infection induces severe disease in immunocompetent mice

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    Dengue is a mosquito-borne disease caused by one of four serotypes of Dengue virus (DENV-1–4). Epidemiologic and observational studies demonstrate that the majority of severe dengue cases, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), occurs predominantly in either individuals with cross-reactive immunity following a secondary heterologous infection or in infants with primary DENV infections born from dengue-immune mothers, suggesting that B-cell-mediated and antibody responses impact on disease evolution. We demonstrate here that B cells play a pivotal role in host responses against primary DENV infection in mice. After infection, μMT[superscript −/−] mice showed increased viral loads followed by severe disease manifestation characterized by intense thrombocytopenia, hemoconcentration, cytokine production and massive liver damage that culminated in death. In addition, we show that poly and monoclonal anti-DENV-specific antibodies can sufficiently increase viral replication through a suppression of early innate antiviral responses and enhance disease manifestation, so that a mostly non-lethal illness becomes a fatal disease resembling human DHF/DSS. Finally, treatment with intravenous immunoglobulin containing anti-DENV antibodies confirmed the potential enhancing capacity of subneutralizing antibodies to mediate virus infection and replication and induce severe disease manifestation of DENV-infected mice. Thus, our results show that humoral responses unleashed during DENV infections can exert protective or pathological outcomes and provide insight into the pathogenesis of this important human pathogen

    Biopolymer-based membranes associated with osteogenic growth peptide for guided bone regeneration

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    Barrier membranes for guided bone regeneration (GBR) mainly promote mechanical maintenance of bone defect space and induce osteopromotion. Additionally, biopolymer-based membranes may provide greater bioactivity and biocompatibility due to their similarity to extracellular matrix (ECM).In this study, biopolymers-based membranes from bacterial cellulose (BC) and collagen (COL) associated with osteogenic growth peptide (OGP(10–14)) were evaluated to determine in vitro osteoinductive potential in early osteogenesis; moreover, histological study was performed to evaluate the BC–COL OGP(10–14) membranes on bone healing after GBR in noncritical defects in rat femur. The results showed that the BC–COL and BC–COL OGP(10–14) membranes promoted cell proliferation and alkaline phosphatase activity in osteoblastic cell cultures. However, ECMmineralization was similar between cultures grown on BC OGP(10–14) and BC–COL OGP(10–14) membranes. In vivo results showed that all the membranes tested, including the peptide-free BC membrane, promoted better bone regeneration than control group. Furthermore, the BC–COL OGP(10–14) membranes induced higher radiographic density in the repaired bone than the other groups at 1, 4 and 16 weeks. Histomorpho-metric analyses revealed that the BC–COL OGP(10–14) induced higher percentage of bone tissue in the repaired area at 2 and 4 weeks than others membranes. In general, these biopolymer-based membranes might be potential candidates for bone regeneration applications

    Anopheles aquasalis transcriptome reveals autophagic responses to Plasmodium vivax midgut invasion

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    BACKGROUND: Elimination of malaria depends on mastering transmission and understanding the biological basis of Plasmodium infection in the vector. The first mosquito organ to interact with the parasite is the midgut and its transcriptomic characterization during infection can reveal effective antiplasmodial responses able to limit the survival of the parasite. The vector response to Plasmodium vivax is not fully characterized, and its specificities when compared with other malaria parasites can be of fundamental interest for specific control measures. METHODS: Experimental infections were performed using a membrane-feeding device. Three groups were used: P. vivax-blood-fed, blood-fed on inactivated gametocytes, and unfed mosquitoes. Twenty-four hours after feeding, the mosquitoes were dissected and the midgut collected for transcriptomic analysis using RNAseq. Nine cDNA libraries were generated and sequenced on an Illumina HiSeq2500. Readings were checked for quality control and analysed using the Trinity platform for de novo transcriptome assembly. Transcript quantification was performed and the transcriptome was functionally annotated. Differential expression gene analysis was carried out. The role of the identified mechanisms was further explored using functional approaches. RESULTS: Forty-nine genes were identified as being differentially expressed with P. vivax infection: 34 were upregulated and 15 were downregulated. Half of the P. vivax-related differentially expressed genes could be related to autophagy; therefore, the effect of the known inhibitor (wortmannin) and activator (spermidine) was tested on the infection outcome. Autophagic activation significantly reduced the intensity and prevalence of infection. This was associated with transcription alterations of the autophagy regulating genes Beclin, DRAM and Apg8. CONCLUSIONS: Our data indicate that P. vivax invasion of An. aquasalis midgut epithelium triggers an autophagic response and its activation reduces infection. This suggests a novel mechanism that mosquitoes can use to fight Plasmodium infection.publishersversionpublishe

    A Model of DENV-3 Infection That Recapitulates Severe Disease and Highlights the Importance of IFN-γ in Host Resistance to Infection

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    There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ−/− mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2−/− mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection

    Draft genome sequence of Wickerhamomyces anomalus LBCM1105, isolated from cachaça fermentation

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    Wickerhamomyces anomalus LBCM1105 is a yeast isolated from cachaça distillery fermentation vats, notable for exceptional glycerol consumption ability. We report its draft genome with 20.5x in-depth coverage and around 90% extension and completeness. It harbors the sequences of proteins involved in glycerol transport and metabolism.The authors gratefully acknowledge Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE) and the Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) for support with the sequencing of LBCM1105. This work was supported by CAPES/Brazil (PNPD 2755/2011; PCF-PVE 021/2012), by CNPq (Brazil), processes 304815/2012 (research grant) and 305135/2015-5, and by AUXPE-PVES 1801/2012 (Process 23038.015294/2016-18) from Brazilian Government and by UFOP. C.L. is supported by the strategic program UID/BIA/04050/2013 [POCI-01-0145-FEDER-007569] funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional de Competitividade e Internacionalizacao (POCI). DMRP is a fellow from the CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) - Brazil (310080/2018-5)

    Standalone vertex finding in the ATLAS muon spectrometer

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    A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

    Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

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    Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson
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