733 research outputs found
Oxidized LDL induces alternative macrophage phenotype through activation of CD36 and PAFR
OxLDL is recognized by macrophage scavenger receptors, including CD36; we have recently found that Platelet-Activating Factor Receptor (PAFR) is also involved. Since PAFR in macrophages is associated with suppressor function, we examined the effect of oxLDL on macrophage phenotype. It was found that the presence of oxLDL during macrophage differentiation induced high mRNA levels to IL-10, mannose receptor, PPARÎł and arginase-1 and low levels of IL-12 and iNOS. When human THP-1 macrophages were pre-treated with oxLDL then stimulated with LPS, the production of IL-10 and TGF-ÎČ significantly increased, whereas that of IL-6 and IL-8 decreased. In murine TG-elicited macrophages, this protocol significantly reduced NO, iNOS and COX2 expression. Thus, oxLDL induced macrophage differentiation and activation towards the alternatively activated M2-phenotype. In murine macrophages, oxLDL induced TGF-ÎČ, arginase-1 and IL-10 mRNA expression, which were significantly reduced by pre-treatment with PAFR antagonists (WEB and CV) or with antibodies to CD36. The mRNA expression of IL-12, RANTES and CXCL2 were not affected. We showed that this profile of macrophage activation is dependent on the engagement of both CD36 and PAFR. We conclude that oxLDL induces alternative macrophage activation by mechanisms involving CD36 and PAFR
Boosting Adaptive Immunity: A New Role for PAFR Antagonists.
We have previously shown that the Platelet-Activating Factor Receptor (PAFR) engagement in murine macrophages and dendritic cells (DCs) promotes a tolerogenic phenotype reversed by PAFR-antagonists treatment in vitro. Here, we investigated whether a PAFR antagonist would modulate the immune response in vivo. Mice were subcutaneously injected with OVA or OVA with PAFR-antagonist WEB2170 on days 0 and 7. On day 14, OVA-specific IgG2a and IgG1 were measured in the serum. The presence of WEB2170 during immunization significantly increased IgG2a without affecting IgG1 levels. When WEB2170 was added to OVA in complete Freund's adjuvant, enhanced IgG2a but not IgG1 production was also observed, and CD4+ FoxP3+ T cell frequency in the spleen was reduced compared to mice immunized without the antagonist. Similar results were observed in PAFR-deficient mice, along with increased Tbet mRNA expression in the spleen. Additionally, bone marrow-derived DCs loaded with OVA were transferred into naĂŻve mice and their splenocytes were co-cultured with fresh OVA-loaded DCs. CD4(+) T cell proliferation was higher in the group transferred with DCs treated with the PAFR-antagonist. We propose that the activation of PAFR by ligands present in the site of immunization is able to fine-tune the adaptive immune response
Surprises in the Orbital Magnetic Moment and g-Factor of the Dynamic Jahn-Teller Ion C_{60}^-
We calculate the magnetic susceptibility and g-factor of the isolated
C_{60}^- ion at zero temperature, with a proper treatment of the dynamical
Jahn-Teller effect, and of the associated orbital angular momentum, Ham-reduced
gyromagnetic ratio, and molecular spin-orbit coupling. A number of surprises
emerge. First, the predicted molecular spin-orbit splitting is two orders of
magnitude smaller than in the bare carbon atom, due to the large radius of
curvature of the molecule. Second, this reduced spin-orbit splitting is
comparable to Zeeman energies, for instance, in X-band EPR at 3.39KGauss, and a
field dependence of the g-factor is predicted. Third, the orbital gyromagnetic
factor is strongly reduced by vibron coupling, and so therefore are the
effective weak-field g-factors of all low-lying states. In particular, the
ground-state doublet of C_{60}^- is predicted to show a negative g-factor of
\sim -0.1.Comment: 19 pages RevTex, 2 postscript figures include
ATIVIDADE LEISHMANICIDA in vitro DE FRAĂĂES DO EXTRATO HIDROALCOĂLICO DAS FOLHAS DE Chenopodium ambrosioides L.
A leishmaniose Ă© uma doença infecciosa causada por protozoĂĄrios do gĂȘnero Leishmania e representa sĂ©rio problema de saĂșde pĂșblica em paises da Ăfrica, Ăsia e AmĂ©rica Latina. Chenopodium ambrosioides L., popularmente conhecido como mastruz, tem sido utilizado no MaranhĂŁo para o tratamento tĂłpico de Ășlceras leishmaniĂłticas. O trabalho avaliou a eficĂĄcia das fraçÔes do extrato hidroalcoĂłlico das folhas de C. ambrosioides contra formas promastigotas da espĂ©cie Leishmania amazonensis. O fracionamento foi realizado pela partição sequencial do extrato hidroalcoĂłlico de folhas de C. ambrosioides com solventes de polaridade crescente (hexano, clorofĂłrmio e acetato de etila). As formas promastigotas foram cultivadas em meio RPMI 1640 com e sem as fraçÔes. ApĂłs 24h de incubação a 26ÂșC, o nĂșmero de promastigotas viĂĄveis foi contado pelo mĂ©todo direto em cĂąmara de Neubauer. As concentraçÔes que inibem o crescimento de 50% (CI50 ) das promastigotas de L. amazonensis foram calculadas a partir da avaliação da mortalidade das promastigotas in vitro. De acordo com escores padrĂ”es nas fraçÔes de acetato de etila e hidroalcoĂłlica remanescente nĂŁo foi observada atividade leishmanicida significativa, mas as fraçÔes hexĂąnica e clorofĂłrmica apresentaram-se ativas. Os resultados obtidos demonstram uma ação leishmanicida promissora das fraçÔes. Estudos futuros sĂŁo necessĂĄrios para investigar a eficĂĄcia destas fraçÔes no tratamento da leishmaniose em modelos experimentais in vivo.Descritores: Chenopodium ambrosioides L.; Mastruz; Leishmaniose; in vitro. Abstract: In vitro leishmanicidal activity of fractions obtained from hydroalcoholic extracts of Chenopodium ambrosioidesâ leaves. Leishmaniasis is an infectious disease caused by protozoa of the genus Leishmania and represents serious public health problem in Africa, Asia and Latin America. Chenopodium ambrosioides, popularly known as âmastruzâ, has been used in MaranhĂŁo for the topical treatment of leishmanial ulcers. The study evaluated the effectiveness of the fractions from hydroalcoholic extract of C. ambrosioidesâ leaves against the promastigotes of Leishmania amazonensis. Fractionation as accomplished by partition sequential extract of leaves of C. ambrosioides with solvents of increasing polarity (hexane, chloroform and ethyl acetate). The promastigotes forms were cultured in supplemented RPMI 1640 with or without fractions. After 24h incubation at 26°C, the number of viable promastigotes was counted by the direct method in a Neubauer chamber. The concentrations that inhibit growth of 50% (IC50 ) of L. amazonensisâ promastigotes were calculated from the assessment of the mortality of promastigotes in vitro. According to standard scores, in the ethyl acetate and hydroalcoholic remaining fractions there was no leishmanicidal activity, while the hexane and chloroform fractions were actives. The results showed a promissor leishmanicidal activity of fraction. Future studies are necessary to investigate the effectiveness of these fractions in the treatment of these fractions in experimental models in vivo.Descriptors: Chenopodium ambrosioides L.; Mastruz; Leishmaniasis; in vitro
Impact of a Tutored Theoretical-Practical Training to Develop Undergraduate Studentsâ Skills for the Detection of Caries Lesions: Study Protocol for a Multicenter Controlled Randomized Study
Background: Tutored laboratorial activities could be a manner of improving the competency development of students. However, its impact over conventional theoretical classes has not yet been tested. Additionally, different university contexts could influence this issue and should be explored.
Objective: To assess the impact of a tutored theoretical-practical training for teaching undergraduate students to detect caries lesions as compared with theoretical teaching activities. The impact of these teaching/learning activities will be assessed in terms of efficacy, cost/benefit, retention of knowledge/acquired competences, and student acceptability.
Methods: Sixteen centers (7 centers from Brazil and 9 centers from other countries throughout the world) are involved in the inclusion of subjects for this protocol. A randomized controlled study with parallel groups will be conducted. One group (control) will be exposed to a 60- to 90-minute conventional theoretical class and the other group (test) will be exposed to the same theoretical class and also a 90-minute laboratory class, including exercises and discussions based on the evaluation of a pool of images and extracted teeth. The mentioned outcomes will be evaluated immediately after the teaching activities and also in medium- and long-term analyses. To compare the long-term outcomes, students who enrolled in the university before the participating students will be interviewed for data collection and these data will be used as a control and compared with the trained group. This stage will be a nonrandomized phase of this study, nested in the main study. Appropriate statistical analysis will be performed according to the aims of this study. Variables related to the centers will also be analyzed and used to model adjustment as possible sources of variability among results.
Results: This ongoing study is funded by a Brazilian national funding agency (CNPq- 400736/2014-4). We expect that the tutored theoretical-practical training will improve the undergraduate studentsâ performance in the detection of caries lesions and subsequent treatment decisions, mainly in terms of long-term retention of knowledge. Our hypothesis is that tutored theoretical-practical training is a more cost-effective option for teaching undergraduate students to detect caries lesions.
Conclusions: If our hypothesis is confirmed, the use of laboratory training in conjunction with theoretical classes could be used as an educational strategy in Cariology to improve the development of undergraduate studentsâ skills in the detection of caries lesions and clinical decision-making
Age- and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts
Measurement of the branching fraction
The branching fraction is measured in a data sample
corresponding to 0.41 of integrated luminosity collected with the LHCb
detector at the LHC. This channel is sensitive to the penguin contributions
affecting the sin2 measurement from The
time-integrated branching fraction is measured to be . This is the most precise measurement to
date
Model-independent search for CP violation in D0âKâK+ÏâÏ+ and D0âÏâÏ+Ï+Ïâ decays
A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states KâK+ÏâÏ+ and ÏâÏ+Ï+Ïâ is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fbâ1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the KâK+ÏâÏ+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the ÏâÏ+Ï+Ïâ final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity
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