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Search Results: 1 - 10 of 604315 matches for " Mário Alberto C. Silva-Neto "
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A transient increase in total head phosphotyrosine levels is observed upon the emergence of Aedes aegypti from the pupal stage
Jablonka, Willy;Senna, Raquel;Nahu, Thaisa;Ventura, Guilherme;Menezes, Lidiane;Silva-Neto, Mário Alberto C;
Memórias do Instituto Oswaldo Cruz , 2011, DOI: 10.1590/S0074-02762011000500005
Abstract: phosphorylation and dephosphorylation of protein tyrosine residues constitutes a major biochemical regulatory mechanism for the cell. we report a transient increase in the total tyrosine phosphorylation of the aedes aegypti head during the first days after emergence from the pupal stage. this correlates with an initial reduction in total head protein tyrosine phosphatase (ptp) activity. similarly, phosphotyrosine (ptyr)-containing bands are seen in extracts prepared from both male and female heads and are spread among a variety of structures including the antennae, proboscis and the maxillary palps combined with the proboscis. also, mosquitoes treated with sodium orthovanadate, a classical ptp inhibitor, show reduced blood-feeding activity and higher head tyrosine phosphorylation levels. these results suggest that ptyr-mediated signalling pathways may play a role in the initial days following the emergence of the adult mosquito from the pupal stage.
Transcriptome Sequencing and Developmental Regulation of Gene Expression in Anopheles aquasalis
André L. Costa-da-Silva equal contributor,Osvaldo Marinotti equal contributor,José M. C. Ribeiro equal contributor,Maria C. P. Silva,Adriana R. Lopes,Michele S. Barros,Anderson Sá-Nunes,Bianca B. Kojin,Eneas Carvalho,Lincoln Suesdek,Mário Alberto C. Silva-Neto,Anthony A. James,Margareth L. Capurro
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0003005
Abstract: Background Anopheles aquasalis is a major malaria vector in coastal areas of South and Central America where it breeds preferentially in brackish water. This species is very susceptible to Plasmodium vivax and it has been already incriminated as responsible vector in malaria outbreaks. There has been no high-throughput investigation into the sequencing of An. aquasalis genes, transcripts and proteins despite its epidemiological relevance. Here we describe the sequencing, assembly and annotation of the An. aquasalis transcriptome. Methodology/Principal Findings A total of 419 thousand cDNA sequence reads, encompassing 164 million nucleotides, were assembled in 7544 contigs of ≥2 sequences, and 1999 singletons. The majority of the An. aquasalis transcripts encode proteins with their closest counterparts in another neotropical malaria vector, An. darlingi. Several analyses in different protein databases were used to annotate and predict the putative functions of the deduced An. aquasalis proteins. Larval and adult-specific transcripts were represented by 121 and 424 contig sequences, respectively. Fifty-one transcripts were only detected in blood-fed females. The data also reveal a list of transcripts up- or down-regulated in adult females after a blood meal. Transcripts associated with immunity, signaling networks and blood feeding and digestion are discussed. Conclusions/Significance This study represents the first large-scale effort to sequence the transcriptome of An. aquasalis. It provides valuable information that will facilitate studies on the biology of this species and may lead to novel strategies to reduce malaria transmission on the South American continent. The An. aquasalis transcriptome is accessible at http://exon.niaid.nih.gov/transcriptome/?An_aquasalis/Anaquexcel.xlsx.
Lysophosphatidylcholine: A Novel Modulator of Trypanosoma cruzi Transmission
Mário A. C. Silva-Neto,Alan B. Carneiro,Livia Silva-Cardoso,Georgia C. Atella
Journal of Parasitology Research , 2012, DOI: 10.1155/2012/625838
Abstract: Lysophosphatidylcholine is a bioactive lipid that regulates a large number of cellular processes and is especially present during the deposition and infiltration of inflammatory cells and deposition of atheromatous plaque. Such molecule is also present in saliva and feces of the hematophagous organism Rhodnius prolixus, a triatominae bug vector of Chagas disease. We have recently demonstrated that LPC is a modulator of Trypanosoma cruzi transmission. It acts as a powerful chemoattractant for inflammatory cells at the site of the insect bite, which will provide a concentrated population of cells available for parasite infection. Also, LPC increases macrophage intracellular calcium concentrations that ultimately enhance parasite invasion. Finally, LPC inhibits NO production by macrophages stimulated by live T. cruzi, and thus interferes with the immune system of the vertebrate host. In the present paper, we discuss the main signaling mechanisms that are likely used by such molecule and their eventual use as targets to block parasite transmission and the pathogenesis of Chagas disease. 1. Immune Response to Trypanosoma cruzi Infection in the Vertebrate Host T. cruzi infects the vertebrate host through bite wounds produced in skin by a feeding bug or through the interaction of the parasite with conjunctival mucosa. Such interaction sometimes produces visible signs called Roma?a’s sign or chagoma inoculation. The histology of this initial site of infection is defined by an elevated number of mononuclear cells [1]. This first sign of infection suggests that T. cruzi can stimulate skin cells to produce mediators that trigger a local inflammatory response. Despite controversies about the mechanism of the pathogenesis of Chagas disease [2–5], until recently, some authors believed that the disease was limited to an acute phase, followed by a chronic phase that was considered an autoimmune disease, where the parasites would be physically linked to sites of inflammation in the heart and esophagus [6–8]. However, nowadays, the disease is considered multifactorial, with multiple and continuous interactions between pathogen and host [9]. After the incubation period of 2 to 3 weeks, infection with T. cruzi is manifested by the presence of a large number of parasites in the blood and tissues. Acute infection is accompanied by an excessive activation of the immune system that includes the production of high levels of cytokines, intense activation of T and B cells, lymphadenopathy, splenomegaly, and intense inflammation associated with tissue infection niches. The acute
Ethanol Intake during Lactation Alters Milk Nutrient Composition and Growth and Mineral Status of Rat Pups
Biological Research , 2008,
Abstract: Lactating Wistar rats were fed a liquid diet containing either ethanol [ethanol-fed group (EFG)] or an isocaloric amount of carbohydrate [pair-fed group (PFG)] from day 1 postpartum up to day 14 of lactation, to investigate micro/macronutrient milk composition and the mineral status of pups. EFG presented a reduction of daily milk production and milk composition was significantly higher in protein and lower in carbohydrate, while the lipid content was similar to that of PFG. When compared to PFG, the milk of EFG had a decreased proportion of C22:6 n-3 fatty acid and an increase in medium-chain fatty acids and of several minerals. Pups of EFG showed reduced growth and a lower concentration of Cu and Sr in plasma and lower concentrations of Ca, P and Cl, and higher concentrations of Cd in the brain. We conclude that maternal EtOH intake greatly impairs lactational performance and modifies the mineral status of pups.
Oogenesis and egg development in triatomines: a biochemical approach
Atella, Georgia C.;Gondim, Katia C.;Machado, Ednildo A.;Medeiros, Marcelo N.;Silva-Neto, Mário A.C.;Masuda, Hatisaburo;
Anais da Academia Brasileira de Ciências , 2005, DOI: 10.1590/S0001-37652005000300005
Abstract: in triatomines, as well as in other insects, accumulation of yolk is a process in which an extra-ovarian tissue, the fat body, produces yolk proteins that are packed in the egg. the main protein, synthesized by the fat body, which is accumulated inside the oocyte, is vitellogenin. this process is also known as vitellogenesis. there are growing evidences in triatomines that besides fat body the ovary also produces yolk proteins. the way these yolk proteins enter the oocyte will be discussed. yolk is a complex material composed of proteins, lipids, carbohydrates and other minor components which are packed inside the oocyte in an organized manner. fertilization triggers embryogenesis, a process where an embryo will develop. during embryogenesis the yolk will be used for the construction of a new individual, the first instar nymph. the challenge for the next decade is to understand how and where these egg proteins are used up together with their non-protein components, in pace with the genetic program of the embryo, which enables cell differentiation (early phase of embryogenesis) and embryo differentiation (late phase) inside the egg.
An Insight into the Transcriptome of the Digestive Tract of the Bloodsucking Bug, Rhodnius prolixus
José M. C. Ribeiro ,Fernando A. Genta,Marcos H. F. Sorgine,Raquel Logullo,Rafael D. Mesquita,Gabriela O. Paiva-Silva,David Majerowicz,Marcelo Medeiros,Leonardo Koerich,Walter R. Terra,Clélia Ferreira,André C. Pimentel,Paulo M. Bisch,Daniel C. Leite,Michelle M. P. Diniz,Jo?o Lídio da S. G. V. Junior,Manuela L. Da Silva,Ricardo N. Araujo,Ana Caroline P. Gandara,Sébastien Brosson,Didier Salmon,Sabrina Bousbata,Natalia González-Caballero,Ariel Mariano Silber,Michele Alves-Bezerra,Katia C. Gondim,Mário Alberto C. Silva-Neto,Georgia C. Atella,Helena Araujo,Felipe A. Dias,Carla Polycarpo,Raquel J. Vionette-Amaral,Patrícia Fampa,Ana Claudia A. Melo,Aparecida S. Tanaka,Carsten Balczun,José Henrique M. Oliveira,Renata L. S. Gon?alves,Cristiano Lazoski,Rolando Rivera-Pomar,Luis Diambra,Günter A. Schaub,Elói S. Garcia,Patrícia Azambuja,Glória R. C. Braz ,Pedro L. Oliveira
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002594
Abstract: The bloodsucking hemipteran Rhodnius prolixus is a vector of Chagas' disease, which affects 7–8 million people today in Latin America. In contrast to other hematophagous insects, the triatomine gut is compartmentalized into three segments that perform different functions during blood digestion. Here we report analysis of transcriptomes for each of the segments using pyrosequencing technology. Comparison of transcript frequency in digestive libraries with a whole-body library was used to evaluate expression levels. All classes of digestive enzymes were highly expressed, with a predominance of cysteine and aspartic proteinases, the latter showing a significant expansion through gene duplication. Although no protein digestion is known to occur in the anterior midgut (AM), protease transcripts were found, suggesting secretion as pro-enzymes, being possibly activated in the posterior midgut (PM). As expected, genes related to cytoskeleton, protein synthesis apparatus, protein traffic, and secretion were abundantly transcribed. Despite the absence of a chitinous peritrophic membrane in hemipterans - which have instead a lipidic perimicrovillar membrane lining over midgut epithelia - several gut-specific peritrophin transcripts were found, suggesting that these proteins perform functions other than being a structural component of the peritrophic membrane. Among immunity-related transcripts, while lysozymes and lectins were the most highly expressed, several genes belonging to the Toll pathway - found at low levels in the gut of most insects - were identified, contrasting with a low abundance of transcripts from IMD and STAT pathways. Analysis of transcripts related to lipid metabolism indicates that lipids play multiple roles, being a major energy source, a substrate for perimicrovillar membrane formation, and a source for hydrocarbons possibly to produce the wax layer of the hindgut. Transcripts related to amino acid metabolism showed an unanticipated priority for degradation of tyrosine, phenylalanine, and tryptophan. Analysis of transcripts related to signaling pathways suggested a role for MAP kinases, GTPases, and LKBP1/AMP kinases related to control of cell shape and polarity, possibly in connection with regulation of cell survival, response of pathogens and nutrients. Together, our findings present a new view of the triatomine digestive apparatus and will help us understand trypanosome interaction and allow insights into hemipteran metabolic adaptations to a blood-based diet.
CK2 Phosphorylation of Schistosoma mansoni HMGB1 Protein Regulates Its Cellular Traffic and Secretion but Not Its DNA Transactions
Isabel Caetano de Abreu da Silva, Vitor Coutinho Carneiro, Renata de Moraes Maciel, Rodrigo Furtado Madeiro da Costa, Daniel Rodrigues Furtado, Francisco Meirelles Bastos de Oliveira, Mário Alberto Cardoso da Silva-Neto, Franklin David Rumjanek, Marcelo Rosado Fantappié
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023572
Abstract: Background The helminth Schistosoma mansoni parasite resides in mesenteric veins where fecundated female worms lay hundred of eggs daily. Some of the egg antigens are trapped in the liver and induce a vigorous granulomatous response. High Mobility Group Box 1 (HMGB1), a nuclear factor, can also be secreted and act as a cytokine. Schistosome HMGB1 (SmHMGB1) is secreted by the eggs and stimulate the production of key cytokines involved in the pathology of schistosomiasis. Thus, understanding the mechanism of SmHMGB1 release becomes mandatory. Here, we addressed the question of how the nuclear SmHMGB1 can reach the extracellular space. Principal Findings We showed in vitro and in vivo that CK2 phosphorylation was involved in the nucleocytoplasmic shuttling of SmHMGB1. By site-directed mutagenesis we mapped the two serine residues of SmHMGB1 that were phosphorylated by CK2. By DNA bending and supercoiling assays we showed that CK2 phosphorylation of SmHMGB1 had no effect in the DNA binding activities of the protein. We showed by electron microscopy, as well as by cell transfection and fluorescence microscopy that SmHMGB1 was present in the nucleus and cytoplasm of adult schistosomes and mammalian cells. In addition, we showed that treatments of the cells with either a phosphatase or a CK2 inhibitor were able to enhance or block, respectively, the cellular traffic of SmHMGB1. Importantly, we showed by confocal microscopy and biochemically that SmHMGB1 is significantly secreted by S. mansoni eggs of infected animals and that SmHMGB1 that were localized in the periovular schistosomotic granuloma were phosphorylated. Conclusions We showed that secretion of SmHMGB1 is regulated by phosphorylation. Moreover, our results suggest that egg-secreted SmHMGB1 may represent a new egg antigen. Therefore, the identification of drugs that specifically target phosphorylation of SmHMGB1 might block its secretion and interfere with the pathogenesis of schistosomiasis.
Lysophosphatidylcholine Triggers TLR2- and TLR4-Mediated Signaling Pathways but Counteracts LPS-Induced NO Synthesis in Peritoneal Macrophages by Inhibiting NF-κB Translocation and MAPK/ERK Phosphorylation
Alan Brito Carneiro, Bruna Maria Ferreira Iaciura, Lilian Lie Nohara, Carla Duque Lopes, Esteban Mauricio Cordero Veas, Vania Sammartino Mariano, Patricia Torres Bozza, Ulisses Gazos Lopes, Georgia Correa Atella, Igor Correia Almeida, Mário Alberto Cardoso Silva-Neto
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076233
Abstract: Background Lysophosphatidylcholine (LPC) is the main phospholipid component of oxidized low-density lipoprotein (oxLDL) and is usually noted as a marker of several human diseases, such as atherosclerosis, cancer and diabetes. Some studies suggest that oxLDL modulates Toll-like receptor (TLR) signaling. However, effector molecules that are present in oxLDL particles and can trigger TLR signaling are not yet clear. LPC was previously described as an attenuator of sepsis and as an immune suppressor. In the present study, we have evaluated the role of LPC as a dual modulator of the TLR-mediated signaling pathway. Methodology/Principal Findings HEK 293A cells were transfected with TLR expression constructs and stimulated with LPC molecules with different fatty acid chain lengths and saturation levels. All LPC molecules activated both TLR4 and TLR2-1 signaling, as evaluated by NF-?B activation and IL-8 production. These data were confirmed by Western blot analysis of NF-?B translocation in isolated nuclei of peritoneal murine macrophages. However, LPC counteracted the TLR4 signaling induced by LPS. In this case, NF-?B translocation, nitric oxide (NO) synthesis and the expression of inducible nitric oxide synthase (iNOS) were blocked. Moreover, LPC activated the MAP Kinases p38 and JNK, but not ERK, in murine macrophages. Interestingly, LPC blocked LPS-induced ERK activation in peritoneal macrophages but not in TLR-transfected cells. Conclusions/Significance The above results indicate that LPC is a dual-activity ligand molecule. It is able to trigger a classical proinflammatory phenotype by activating TLR4- and TLR2-1-mediated signaling. However, in the presence of classical TLR ligands, LPC counteracts some of the TLR-mediated intracellular responses, ultimately inducing an anti-inflammatory phenotype; LPC may thus play a role in the regulation of cell immune responses and disease progression.
Ethanol Intake during Lactation Alters Milk Nutrient Composition and Growth and Mineral Status of Rat Pups
Biological Research , 2008, DOI: 10.4067/S0716-97602008000300008
Abstract: lactating wistar rats were fed a liquid diet containing either ethanol [ethanol-fed group (efg)] or an isocaloric amount of carbohydrate [pair-fed group (pfg)] from day 1 postpartum up to day 14 of lactation, to investigate micro/macronutrient milk composition and the mineral status of pups. efg presented a reduction of daily milk production and milk composition was significantly higher in protein and lower in carbohydrate, while the lipid content was similar to that of pfg. when compared to pfg, the milk of efg had a decreased proportion of c22:6 n-3 fatty acid and an increase in medium-chain fatty acids and of several minerals. pups of efg showed reduced growth and a lower concentration of cu and sr in plasma and lower concentrations of ca, p and cl, and higher concentrations of cd in the brain. we conclude that maternal etoh intake greatly impairs lactational performance and modifies the mineral status of pups.
Blood Meal-Derived Heme Decreases ROS Levels in the Midgut of Aedes aegypti and Allows Proliferation of Intestinal Microbiota
Jose Henrique M. Oliveira,Renata L. S. Gon?alves,Flavio A. Lara,Felipe A. Dias,Ana Caroline P. Gandara,Rubem F. S. Menna-Barreto,Meredith C. Edwards,Francisco R. M. Laurindo,Mário A. C. Silva-Neto,Marcos H. F. Sorgine,Pedro L. Oliveira
PLOS Pathogens , 2011, DOI: 10.1371/journal.ppat.1001320
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.
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