Author
Pedro L. Oliveira
Other affiliations: Johns Hopkins University
Bio: Pedro L. Oliveira is an academic researcher from Federal University of Rio de Janeiro. The author has contributed to research in topics: Rhodnius prolixus & Heme. The author has an hindex of 44, co-authored 112 publications receiving 5565 citations. Previous affiliations of Pedro L. Oliveira include Johns Hopkins University.
Topics: Rhodnius prolixus, Heme, Hemolymph, Midgut, Hemozoin
Papers published on a yearly basis
Papers
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TL;DR: It is demonstrated that heme, but not its analogs/precursors, induced tumor necrosis factor-α (TNF-α) secretion by macrophages dependently on MyD88, TLR4, and CD14, and these findings support the concept that the broad ligand specificity ofTLR4 and the different activation profiles might in part reside in its ability to recognize different ligands in different binding sites.
492 citations
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Federal University of Rio de Janeiro1, Simon Fraser University2, National University of La Plata3, Oswaldo Cruz Foundation4, Washington University in St. Louis5, University of the Republic6, European Bioinformatics Institute7, National Institutes of Health8, Federal University of Uberlandia9, Universidade Federal de Minas Gerais10, Sao Paulo State University11, State University of Norte Fluminense12, Johns Hopkins University13, University of Notre Dame14, Universidade Federal Rural do Rio de Janeiro15, Pompeu Fabra University16, Centre national de la recherche scientifique17, University of Toronto18, Centers for Disease Control and Prevention19, Instituto Politécnico Nacional20, Florida International University21, Universidade Federal do Espírito Santo22, University of Illinois at Urbana–Champaign23, University of Santiago de Compostela24, Virginia Tech25, University of Cambridge26, University of Manitoba27
TL;DR: The first genome sequence of a nondipteran insect vector of an important human parasitic disease is described, which provides critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.
Abstract: Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.
293 citations
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TL;DR: In this paper, the authors review mechanisms by which heme can exert biological damage, together with a wide spectrum of adaptations developed by blood-feeding insects and ticks to counteract its deleterious effects.
293 citations
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TL;DR: A role for hemin as a proinflammatory agent able to induce polymorphonuclear neutrophil activation in situations of clinical relevance, such as hemolysis or hemoglobinemia is suggested.
263 citations
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TL;DR: It is proposed that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme, a pro-oxidant molecule released in large amounts upon hemoglobin degradation, which would represent a burden to the insect.
Abstract: The presence of bacteria in the midgut of mosquitoes antagonizes infectious agents, such as Dengue and Plasmodium, acting as a negative factor in the vectorial competence of the mosquito. Therefore, knowledge of the molecular mechanisms involved in the control of midgut microbiota could help in the development of new tools to reduce transmission. We hypothesized that toxic reactive oxygen species (ROS) generated by epithelial cells control bacterial growth in the midgut of Aedes aegypti, the vector of Yellow fever and Dengue viruses. We show that ROS are continuously present in the midgut of sugar-fed (SF) mosquitoes and a blood-meal immediately decreased ROS through a mechanism involving heme-mediated activation of PKC. This event occurred in parallel with an expansion of gut bacteria. Treatment of sugar-fed mosquitoes with increased concentrations of heme led to a dose dependent decrease in ROS levels and a consequent increase in midgut endogenous bacteria. In addition, gene silencing of dual oxidase (Duox) reduced ROS levels and also increased gut flora. Using a model of bacterial oral infection in the gut, we show that the absence of ROS resulted in decreased mosquito resistance to infection, increased midgut epithelial damage, transcriptional modulation of immune-related genes and mortality. As heme is a pro-oxidant molecule released in large amounts upon hemoglobin degradation, oxidative killing of bacteria in the gut would represent a burden to the insect, thereby creating an extra oxidative challenge to the mosquito. We propose that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme.
228 citations
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01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.
10,124 citations
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01 Jan 1979
5,044 citations
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TL;DR: A growing body of evidence supports the existence of a novel mechanism of human disease, namely, hemolysis-associated smooth muscle dystonia, vasculopathy, and endothelial dysfunction.
Abstract: ContextThe efficient sequestration of hemoglobin by the red blood cell membrane
and the presence of multiple hemoglobin clearance mechanisms suggest a critical
need to prevent the buildup of this molecule in the plasma. A growing list
of clinical manifestations attributed to hemoglobin release in a variety of
acquired and iatrogenic hemolytic disorders suggests that hemolysis and hemoglobinemia
should be considered as a novel mechanism of human disease.Evidence AcquisitionPertinent scientific literature databases and references were searched
through October 2004 using terms that encompassed various aspects of hemolysis,
hemoglobin preparations, clinical symptoms associated with plasma hemoglobin,
nitric oxide in hemolysis, anemia, pulmonary hypertension, paroxysmal nocturnal
hemoglobinuria, and sickle-cell disease.Evidence SynthesisHemoglobin is released into the plasma from the erythrocyte during intravascular
hemolysis in hereditary, acquired, and iatrogenic hemolytic conditions. When
the capacity of protective hemoglobin-scavenging mechanisms has been saturated,
levels of cell-free hemoglobin increase in the plasma, resulting in the consumption
of nitric oxide and clinical sequelae. Nitric oxide plays a major role in
vascular homeostasis and has been shown to be a critical regulator of basal
and stress-mediated smooth muscle relaxation and vasomotor tone, endothelial
adhesion molecule expression, and platelet activation and aggregation. Thus,
clinical consequences of excessive cell-free plasma hemoglobin levels during
intravascular hemolysis or the administration of hemoglobin preparations include
dystonias involving the gastrointestinal, cardiovascular, pulmonary, and urogenital
systems, as well as clotting disorders. Many of the clinical sequelae of intravascular
hemolysis in a prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria,
are readily explained by hemoglobin-mediated nitric oxide scavenging.ConclusionA growing body of evidence supports the existence of a novel mechanism
of human disease, namely, hemolysis-associated smooth muscle dystonia, vasculopathy,
and endothelial dysfunction.
1,370 citations
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TL;DR: In this paper, the authors show that the activation of HO-1 is an ubiquitous cellular response to oxidative stress, and that the reaction products of HO activity, biliverdin, and its subsequent metabolite bilirubin, have antioxidant properties.
781 citations
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TL;DR: Free heme acts as a pro-inflammatory molecule and heme-induced inflammation is involved in the pathology of diverse conditions; such as renal failure, arteriosclerosis, and complications after artificial blood transfusion, peritoneal endometriosis, and heart transplant failure.
746 citations