Red alert: labile heme is an alarmin

This publication hasn't any creative commons license associated.This deposit is composed by the main article, and it hasn't any supplementary materials associated. There is no public supplementary material available.The deposited article is a pre-print version.Alarmins are a heterogeneous group of endogenous molecules that signal cellular damage when sensed extracellularly. Heme is an endogenous molecule that acts as a prosthetic group of hemoproteins, such as hemoglobin and myoglobin. When released from damaged red blood cells or muscle cells, oxidized hemoglobin and myoglobin release their prosthetic heme groups, respectively. This generates labile heme, which is sensed by pattern recognition receptors (PRR) expressed by innate immune cells and possibly regulatory T cells (TREG). The ensuing adaptive response, which alerts for the occurrence of red blood cell or muscle cell damage, regulates the pathologic outcome of hemolysis or rhabdomyolysis, respectively. In conclusion, we propose that labile heme is an alarmin.Fundação para a Ciência e Tecnologia grants: (PTDC/SAU TOX/116627/2010, HMSP-ICT/0022/2010, RECI/IMI-IMU/0038/2012); Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro; Conselho Nacional de Pesquisa, INCTDengue, Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior.info:eu-repo/semantics/publishedVersio

Fungal Surface and Innate Immune Recognition of Filamentous Fungi

The innate immune system performs specific detection of molecules from infectious agents through pattern recognition receptors. This recognition triggers inflammatory responses and activation of microbicidal mechanisms by leukocytes. Infections caused by filamentous fungi have increased in incidence and represent an important cause of mortality and morbidity especially in individuals with immunosuppression. This review will discuss the innate immune recognition of filamentous fungi molecules and its importance to infection control and disease

Particle motion and gravitational lensing in the metric of a dilaton black hole in a de Sitter universe

We consider the metric exterior to a charged dilaton black hole in a de Sitter universe. We study the motion of a test particle in this metric. Conserved quantities are identified and the Hamilton-Jacobi method is employed for the solutions of the equations of motion. At large distances from the black hole the Hubble expansion of the universe modifies the effective potential such that bound orbits could exist up to an upper limit of the angular momentum per mass for the orbiting test particle. We then study the phenomenon of strong field gravitational lensing by these black holes by extending the standard formalism of strong lensing to the non-asymptotically flat dilaton-de Sitter metric. Expressions for the various lensing quantities are obtained in terms of the metric coefficients.Comment: 8 pages, RevTex, 1 eps figures; discussion improved; typos corrected; references adde

The role of corticosteroids in severe community-acquired pneumonia: a systematic review

Submitted by Sandra Infurna ([email protected]) on 2019-04-04T12:26:57Z No. of bitstreams: 1 JorgeIF_Salluh_etal_IOC_2008.pdf: 215501 bytes, checksum: fb18fede448c1eb9f08f5dc05c97d47c (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-04-04T12:37:41Z (GMT) No. of bitstreams: 1 JorgeIF_Salluh_etal_IOC_2008.pdf: 215501 bytes, checksum: fb18fede448c1eb9f08f5dc05c97d47c (MD5)Made available in DSpace on 2019-04-04T12:37:41Z (GMT). No. of bitstreams: 1 JorgeIF_Salluh_etal_IOC_2008.pdf: 215501 bytes, checksum: fb18fede448c1eb9f08f5dc05c97d47c (MD5) Previous issue date: 2008Instituto Nacional de Câncer. Unidade de Cuidados Intensivos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Hospital de São Francisco Xavier. Centro Hospitalar de Lisboa Ocidental. Unidade de Terapia Intensiva Médica. Lisboa, Portugal.Instituto Nacional de Câncer. Unidade de Cuidados Intensivos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Introduction: The purpose of this review was to evaluate the impact of corticosteroids on the outcomes of patients with severe community-acquired pneumonia (CAP). Methods: We performed a systematic MEDLINE, Cochrane database, and CINAHL search (1966 to November 2007) to identify full-text publications that evaluated the use of corticosteroids in CAP. Results: An initial literature search yielded 109 articles, and 105 studies were excluded after the first analysis. We found four studies eligible for analysis. On the basis of their results, the use of corticosteroids as adjunctive therapy in severe CAP should be categorized as a weak recommendation (two studies) and a strong recommendation (two studies) with either low- or moderate-quality evidence. However, no evidence of adverse outcomes or harm is present in the evaluated studies. Conclusion: According to the GRADE system, available studies do not support the recommendation of corticosteroids as a standard of care for patients with severe CAP. Further randomized controlled trials with this aim should enroll a larger number of severely ill patients. However, in patients needing corticosteroids, it may be reasonable to conclude that corticosteroid administration is safe in patients with severe infections receiving antimicrobial therapy

Estimating the parameters of the Sgr A* black hole

The measurement of relativistic effects around the galactic center may allow in the near future to strongly constrain the parameters of the supermassive black hole likely present at the galactic center (Sgr A*). As a by-product of these measurements it would be possible to severely constrain, in addition, also the parameters of the mass-density distributions of both the innermost star cluster and the dark matter clump around the galactic center.Comment: Accepted for publication on General Relativity and Gravitation, 2010. 11 Pages, 1 Figur

Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity

<p>Abstract</p> <p>Background</p> <p>Dengue virus pathogenesis is not yet fully understood and the identification of patients at high risk for developing severe disease forms is still a great challenge in dengue patient care. During the present study, we evaluated prospectively the potential of cytokines present in plasma from patients with dengue in stratifying disease severity.</p> <p>Methods</p> <p>Seventeen-cytokine multiplex fluorescent microbead immunoassay was used for the simultaneous detection in 59 dengue patients. GLM models using bimodal or Gaussian family were determined in order to associate cytokines with clinical manifestations and laboratory diagnosis.</p> <p>Results</p> <p>IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue). In contrast, increased MIP-1β levels were observed in patients with mild dengue. MIP-1β was also associated with CD56+NK cell circulating rates. IL-1β, IL-8, TNF-α and MCP-1 were associated with marked thrombocytopenia. Increased MCP-1 and GM-CSF levels correlated with hypotension. Moreover, MIP-1β and IFN-γ were independently associated with both dengue severity and disease outcome.</p> <p>Conclusion</p> <p>Our data demonstrated that the use of a multiple cytokine assay platform was suitable for identifying distinct cytokine profiles associated with the dengue clinical manifestations and severity. MIP-β is indicated for the first time as a good prognostic marker in contrast to IFN-γ that was associated with disease severity.</p

Gravitational Lensing by Black Holes

We review the theoretical aspects of gravitational lensing by black holes, and discuss the perspectives for realistic observations. We will first treat lensing by spherically symmetric black holes, in which the formation of infinite sequences of higher order images emerges in the clearest way. We will then consider the effects of the spin of the black hole, with the formation of giant higher order caustics and multiple images. Finally, we will consider the perspectives for observations of black hole lensing, from the detection of secondary images of stellar sources and spots on the accretion disk to the interpretation of iron K-lines and direct imaging of the shadow of the black hole.Comment: Invited article for the GRG special issue on lensing (P. Jetzer, Y. Mellier and V. Perlick Eds.). 31 pages, 12 figure

Shadows of a maximal acceleration

A quantum mechanical upper limit on the value of particle accelerations, or maximal acceleration (MA), is applied to compact stars. A few MA fermions are at most present in canonical white dwarfs and neutron stars. They drastically alter a star's stability conditions.Comment: 11 page

Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.Peer reviewe