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1.
Nat Immunol ; 15(4): 343-53, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24531343

RESUMO

The innate immune system responds to infection and tissue damage by activating cytosolic sensory complexes called 'inflammasomes'. Cytosolic DNA is sensed by AIM2-like receptors (ALRs) during bacterial and viral infections and in autoimmune diseases. Subsequently, recruitment of the inflammasome adaptor ASC links ALRs to the activation of caspase-1. A controlled immune response is crucial for maintaining homeostasis, but the regulation of ALR inflammasomes is poorly understood. Here we identified the PYRIN domain (PYD)-only protein POP3, which competes with ASC for recruitment to ALRs, as an inhibitor of DNA virus-induced activation of ALR inflammasomes in vivo. Data obtained with a mouse model with macrophage-specific POP3 expression emphasize the importance of the regulation of ALR inflammasomes in monocytes and macrophages.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Transporte/metabolismo , Infecções por Vírus de DNA/imunologia , Vírus de DNA/imunologia , Inflamassomos/metabolismo , Macrófagos/imunologia , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Sequência de Aminoácidos , Animais , Proteínas de Transporte/genética , Caspase 1/metabolismo , Proteínas de Ligação a DNA , Células HEK293 , Humanos , Imunidade/genética , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interferon gama/genética , Interferon gama/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Dados de Sequência Molecular , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Ligação Proteica/genética , Estrutura Terciária de Proteína/genética , Alinhamento de Sequência , Transgenes/genética , Proteínas Virais/genética , Homólogo LST8 da Proteína Associada a mTOR
2.
Immunity ; 43(2): 264-76, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26275995

RESUMO

In response to infections and tissue damage, ASC-containing inflammasome protein complexes are assembled that promote caspase-1 activation, IL-1ß and IL-18 processing and release, pyroptosis, and the release of ASC particles. However, excessive or persistent activation of the inflammasome causes inflammatory diseases. Therefore, a well-balanced inflammasome response is crucial for the maintenance of homeostasis. We show that the PYD-only protein POP1 inhibited ASC-dependent inflammasome assembly by preventing inflammasome nucleation, and consequently interfered with caspase-1 activation, IL-1ß and IL-18 release, pyroptosis, and the release of ASC particles. There is no mouse ortholog for POP1, but transgenic expression of human POP1 in monocytes, macrophages, and dendritic cells protected mice from systemic inflammation triggered by molecular PAMPs, inflammasome component NLRP3 mutation, and ASC danger particles. POP1 expression was regulated by TLR and IL-1R signaling, and we propose that POP1 provides a regulatory feedback loop that shuts down excessive inflammatory responses and thereby prevents systemic inflammation.


Assuntos
Síndromes Periódicas Associadas à Criopirina/imunologia , Células Dendríticas/imunologia , Inflamassomos/metabolismo , Macrófagos Peritoneais/imunologia , Monócitos/imunologia , Peritonite/imunologia , Ribonucleoproteínas/metabolismo , Animais , Apoptose/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Caspase 1/metabolismo , Linhagem Celular , Feminino , Regulação da Expressão Gênica/genética , Homeostase , Humanos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Peritonite/induzido quimicamente , Multimerização Proteica/genética , RNA Interferente Pequeno/genética , Ribonucleoproteínas/genética
3.
An Acad Bras Cienc ; 94(suppl 3): e20201846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36074425

RESUMO

Among the 26 Hybosorinae genera, seven are present exclusively in the Neotropical region. However, Hybosorinae from the New World have been less studied. One new genus and new species collected in Brazil is herein described to this subfamily. The genus is recognizable by the following combination of characters: labium with semicircular mentum; mandibles with lateral projection excavated, separated in the middle by longitudinal carina, inner side sheltering the labrum; antennae with nine antenomeres; scutellar shield with strong punctures at the proximal half; elytra with single rows formed by punctures; and protibia without well-defined denticles.


Assuntos
Besouros , Himenópteros , Animais , Brasil
4.
Immunity ; 36(3): 464-76, 2012 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-22361007

RESUMO

Cytosolic pathogen- and damage-associated molecular patterns are sensed by pattern recognition receptors, including members of the nucleotide-binding domain and leucine-rich repeat-containing gene family (NLR), which cause inflammasome assembly and caspase-1 activation to promote maturation and release of the inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 and induction of pyroptosis. However, the contribution of most of the NLRs to innate immunity, host defense, and inflammasome activation and their specific agonists are still unknown. Here we describe identification and characterization of an NLRP7 inflammasome in human macrophages, which is induced in response to microbial acylated lipopeptides. Activation of NLRP7 promoted ASC-dependent caspase-1 activation, IL-1ß and IL-18 maturation, and restriction of intracellular bacterial replication, but not caspase-1-independent secretion of the proinflammatory cytokines IL-6 and tumor necrosis factor-α. Our study therefore increases our currently limited understanding of NLR activation, inflammasome assembly, and maturation of IL-1ß and IL-18 in human macrophages.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Inflamassomos/imunologia , Lipopeptídeos/imunologia , Macrófagos/imunologia , Infecções Bacterianas/imunologia , Proteínas Adaptadoras de Sinalização CARD , Proteínas de Transporte/imunologia , Caspase 1/metabolismo , Proteínas do Citoesqueleto/imunologia , Humanos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , Macrófagos/microbiologia , Complexos Multiproteicos/imunologia , Mycoplasma/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fator de Necrose Tumoral alfa/metabolismo
5.
J Chem Ecol ; 47(8-9): 777-787, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34287796

RESUMO

The "River Disease" (RD), a disorder impacting honeybee colonies located close to waterways with abundant riparian vegetation (including Sebastiania schottiana, Euphorbiaceae), kills newly hatched larvae. Forager bees from RD-affected colonies collect honeydew excretions from Epormenis cestri (Hemiptera: Flatidae), a planthopper feeding on trees of S. schottiana. First-instar honeybee larvae fed with this honeydew died. Thus, we postulated that the nectars of RD-affected colonies had a natural toxin coming from either E. cestri or S. schottiana. An untargeted metabolomics characterization of fresh nectars extracts from colonies with and without RD allowed to pinpoint xanthoxylin as one of the chemicals present in higher amounts in nectar from RD-affected colonies than in nectars from healthy colonies. Besides, xanthoxylin was also found in the aerial parts of S. schottiana and the honeydew excreted by E. cestri feeding on this tree. A larva feeding assay where xanthoxylin-enriched diets were offered to 1st instar larvae showed that larvae died in the same proportion as larvae did when offered enriched diets with nectars from RD-colonies. These findings demonstrate that a xenobiotic can mimic the RD syndrome in honeybee larvae and provide evidence of an interspecific flow of xanthoxylin among three trophic levels. Further, our results give information that can be considered when implementing measures to control this honeybee disease.


Assuntos
Acetofenonas/análise , Abelhas/fisiologia , Euphorbiaceae/química , Acetofenonas/farmacologia , Animais , Abelhas/crescimento & desenvolvimento , Dieta/veterinária , Análise Discriminante , Euphorbiaceae/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Larva/efeitos dos fármacos , Larva/fisiologia , Análise dos Mínimos Quadrados , Espectroscopia de Ressonância Magnética , Metabolômica/métodos , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Néctar de Plantas/química
6.
An Acad Bras Cienc ; 93(4): e20201452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34586321

RESUMO

The colorful genus Erotylina Curran was proposed to include a group of species originally described in Erotylus Fabricius but differing by the lack of three longitudinal carinae on the tibiae. The taxonomy of Erotylina is mostly based on coloration while information on mouthparts, thorax, male and female abdominal terminalia remain unknown. In addition, little is known about the factors underlying coloration in Erotylina and Erotylidae in general. Here we redescribe the type species of Erotylina, Erotylus leopardus Lacordaire providing the first descriptions of several morphological structures, and new data on its geographical distribution. Erotylus nicaraguae Crotch is proposed as new junior synonymy of E. leoparda. Lectotypes are designated for the following species: Erotylus leopardus Lacordaire, Erotylus nicaraguae Crotch and Erotylus confluens Crotch. Based on the geographical records, specimen labels, literature and online environmental databases, we show that E. leoparda includes two discrete morphs distributed across a latitudinal gradient, with intermediate and continuous variations distributed across altitudinal and temperature gradients. The present study sheds light on the taxonomy of Erotylina and provides the first clearest evidence of a relation between coloration, latitude, altitude, temperature variations and the distributional patterns of a taxon in Erotylidae.


Assuntos
Besouros , Distribuição Animal , Animais , Feminino , Geografia , Masculino
7.
ScientificWorldJournal ; 2015: 526969, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26075293

RESUMO

The sterile insect technique (SIT) is widely utilized in the biological control of fruit flies of the family Tephritidae, particularly against the Mediterranean fruit fly. This study investigated the interaction between mating success and morphometric variation in the wings and the production of acoustic signals among three male groups of Ceratitis capitata (Wiedemann): (1) wild males, (2) irradiated with Co-60 (steriles), and (3) irradiated (steriles) and treated with ginger oil. The canonical variate analysis discriminated two groups (males irradiated and males wild), based on the morphological shape of the wings. Among males that emit buzz signals, wild males obtained copulation more frequently than males in Groups 2 and 3. The individuals of Group 3 achieved more matings than those in Group 2. Wild males displayed lower pulse duration, higher intervals between pulses, and higher dominant frequency. Regarding the reproductive success, the morphological differences in the wings' shape between accepted and nonaccepted males are higher in wild males than in the irradiated ones. The present results can be useful in programs using the sterile insect technique for biological control of C. capitata.


Assuntos
Acústica , Ceratitis capitata/anatomia & histologia , Ceratitis capitata/fisiologia , Asas de Animais/anatomia & histologia , Asas de Animais/fisiologia , Comunicação Animal , Animais , Controle de Insetos , Masculino , Reprodução , Comportamento Sexual Animal
8.
Cell Rep ; 42(3): 112265, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36930645

RESUMO

Inflammatory responses are crucial for controlling infections and initiating tissue repair. However, excessive and uncontrolled inflammation causes inflammatory disease. Processing and release of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 depend on caspase-1 activation within inflammasomes. Assembly of inflammasomes is initiated upon activation of cytosolic pattern recognition receptors (PRRs), followed by sequential polymerization of pyrin domain (PYD)-containing and caspase recruitment domain (CARD)-containing proteins mediated by homotypic PYD and CARD interactions. Small PYD- or CARD-only proteins (POPs and COPs, respectively) evolved in higher primates to target these crucial interactions to limit inflammation. Here, we show the ability of COPs to regulate inflammasome activation by modulating homotypic CARD-CARD interactions in vitro and in vivo. CARD16, CARD17, and CARD18 displace crucial CARD interactions between caspase-1 proteins through competitive binding and ameliorate uric acid crystal-mediated NLRP3 inflammasome activation and inflammatory disease. COPs therefore represent an important family of inflammasome regulators and ameliorate inflammatory disease.


Assuntos
Gota , Inflamassomos , Animais , Inflamassomos/metabolismo , Inflamação/metabolismo , Caspase 1/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-1beta/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo
9.
Acta Diabetol ; 59(10): 1361-1368, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35879479

RESUMO

AIMS: To access the impact of increasing use of metformin on cesarean section and large for gestational age rates, when compared to insulin. METHODS: A retrospective observational study was developed using data from the Portuguese National Registry, between 2011 and 2019, of 5038 Portuguese women with single pregnancies and gestational diabetes treated with metformin and/or insulin. Three groups were defined according to the therapeutic regimen adopted: g1-insulin in monotherapy (n = 3027[60.1%]); g2-metformin in monotherapy (n = 1366[27.1%]); g3-metformin and insulin (n = 645[12.8%]). Multivariate analysis was adjusted for statistically significant covariates. RESULTS: The cesarean section rate in g1 was similar to g2 (g1:36.9% vs. g2:37%, p = 0.982), although g3 was associated with cesarean delivery (g3:43.6% vs. g1:36.9%, p = 0.005; g3:43.6% vs. g1:37.0%, p = 0.002), with no differences reported in the multivariate analysis adjusted for year of delivery and pregestational body mass index. A delivery of a large for gestational age newborn was less frequently observed in g2 than in g1 (g2:4.1% vs. g1:5.4%, p = 0.044) and in g3 (g2:4.1% vs. g3:9.1%, p < 0.001), and in g1, when compared to g3 (g1:5.4% vs. g3:9.1%, p < 0.001). In the multivariate analysis, g2 showed lower odds of delivering a large for gestational age newborn, compared to g1 (ß = -0.511, OR = 0.596, CI95% = 0.428-0.832, p < 0.001). CONCLUSIONS: The use of metformin was not associated with higher cesarean section rates, compared to insulin. Instead, it was suggested a protective role of metformin on large gestational age rates. The concomitant use of dual therapy suggests more complex pregnancies, requiring closer surveillance that mitigate serious perinatal and obstetrical outcomes.


Assuntos
Diabetes Gestacional , Metformina , Peso ao Nascer , Cesárea , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Recém-Nascido , Insulina/uso terapêutico , Metformina/uso terapêutico , Portugal/epidemiologia , Gravidez
10.
Endocrinol Diabetes Nutr ; 69(7): 476-482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35128336

RESUMO

Introduction: In a person with type 1 diabetes, any change concerning daily routine may lead to changes in glycaemic control. This study aimed to evaluate the impact of work and lockdown on glycaemic control in adults with type 1 diabetes. Material and methods: A retrospective cohort was stratified into three activity groups (g1-students/telework/laid-off; g2-unemployed/retired; g3-work without lockdown). Continuous and categorical variations (reductions ≥ 0.4%) in glycated haemoglobin were obtained in 2020 (t3:December/2019-March/2020; t4:April/2020-July/2020) and in homologous periods of 2019. Intragroup comparisons between years and intergroups in the same year were made. Regression models were developed to predict the variation of glycated haemoglobin in 2020. Results: 241 participants were included, with a significant reduction between t4 and t3 (vs. t2 and t1) in g1 (p < 0.001) and g2 (p = 0.025) and in 2020 in g1 (vs. g2, p < 0.001; vs. g3, p < 0.001). Only g1 presented superiority in the reduction ≥0.4% in glycated haemoglobin in 2020 (vs. 2019, p < 0.001; vs. g2, p < 0.001; vs. g3, p < 0.001). The insulin regimens were comparable and the development of hypoglycaemia was found to be superimposed between t3 and t4, except for g1, which was higher at t3 (p = 0.029). G1 correlated with continuous reductions (vs. g2, p = 0.001; vs. g3, p < 0.001) and ≥0.4% in glycated haemoglobin in 2020 (vs. g2, OR 3.6, p < 0.001; vs. g3, OR 12.7, p < 0.001), regardless of the age and duration of type 1 diabetes. Conclusions: A more stable and better glycaemic control was observed in participants who transitioned from face-to-face work to total lockdown.


Introducción: En una persona con diabetes tipo 1, cualquier cambio en la rutina diaria puede provocar cambios en el control glucémico. Este estudio tuvo como objetivo evaluar el impacto del trabajo y el confinamiento en el control glucémico en adultos con diabetes tipo 1. Material y métodos: Se estratificó una cohorte retrospectiva en tres grupos de actividad (g1-estudiantes/teletrabajo/despido; g2-desempleados/jubilados; g3-trabajo sin encierro). Se obtuvieron variaciones continuas y categóricas (reducciones ≥ 0,4%) en la hemoglobina glucosilada en 2020 (t3: diciembre/2019-marzo/2020; t4: abril/2020-julio/2020) y en períodos homólogos de 2019. Se desarrollaron modelos de regresión para predecir la variación de la hemoglobina glucosilada en 2020. Resultados: Se incluyeron 241 participantes, con una reducción significativa entre t4 y t3 (vs. t2 y t1) en g1 (p < 0,001) y g2 (p = 0,025) y en 2020 en g1 (vs. g2, p < 0,001; vs. g3, p < 0,001). Solo g1 demostró superioridad en la reducción ≥ 0,4% de la hemoglobina glucosilada en 2020 (vs. 2019, p < 0,001; vs. g2, p < 0,001; vs. g3, p < 0,001). Los regímenes de terapia con insulina fueron comparables y el desarrollo de hipoglucemia fue superponible entre t3 y t4, excepto para g1, que fue mayor en t3 (p = 0,029). G1 se correlacionó con reducciones continuas (vs. g2, p = 0,001; vs. g3, p < 0,001) y ≥ 0,4% en la hemoglobina glucosilada en 2020 (vs. g2, odds ratio [OR] 3,6, p < 0,001; vs. g3, OR 12,7, p < 0,001), independientemente de la edad y la duración de la diabetes tipo 1. Conclusiones: Se observó un control glucémico más optimizado a los participantes que pasaron del trabajo presencial al confinamiento total.

11.
Front Immunol ; 13: 912069, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225929

RESUMO

Canonical inflammasomes are innate immune protein scaffolds that enable the activation of inflammatory caspase-1, and subsequently the processing and release of interleukin (IL)-1ß, IL-18, and danger signals, as well as the induction of pyroptotic cell death. Inflammasome assembly and activation occurs in response to sensing of infectious, sterile and self-derived molecular patterns by cytosolic pattern recognition receptors, including the Nod-like receptor NLRP3. While these responses are essential for host defense, excessive and uncontrolled NLRP3 inflammasome responses cause and contribute to a wide spectrum of inflammatory diseases, including gout. A key step in NLRP3 inflammasome assembly is the sequentially nucleated polymerization of Pyrin domain (PYD)- and caspase recruitment domain (CARD)-containing inflammasome components. NLRP3 triggers polymerization of the adaptor protein ASC through PYD-PYD interactions, but ASC polymerization then proceeds in a self-perpetuating manner and represents a point of no return, which culminates in the activation of caspase-1 by induced proximity. In humans, small PYD-only proteins (POPs) lacking an effector domain regulate this key process through competitive binding, but limited information exists on their physiological role during health and disease. Here we demonstrate that POP1 expression in macrophages is sufficient to dampen MSU crystal-mediated inflammatory responses in animal models of gout. Whether MSU crystals are administered into a subcutaneous airpouch or into the ankle joint, the presence of POP1 significantly reduces neutrophil infiltration. Also, airpouch exudates have much reduced IL-1ß and ASC, which are typical pro-inflammatory indicators that can also be detected in synovial fluids of gout patients. Exogenous expression of POP1 in mouse and human macrophages also blocks MSU crystal-induced NLRP3 inflammasome assembly, resulting in reduced IL-1ß and IL-18 secretion. Conversely, reduced POP1 expression in human macrophages enhances IL-1ß secretion. We further determined that the mechanism for the POP1-mediated inhibition of NLRP3 inflammasome activation is through its interference with the crucial NLRP3 and ASC interaction within the inflammasome complex. Strikingly, administration of an engineered cell permeable version of POP1 was able to ameliorate MSU crystal-mediated inflammation in vivo, as measured by neutrophil infiltration. Overall, we demonstrate that POP1 may play a crucial role in regulating inflammatory responses in gout.


Assuntos
Gota , Inflamassomos , Ribonucleoproteínas/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 1/metabolismo , Gota/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
12.
Endocrinol Diabetes Nutr (Engl Ed) ; 69(7): 476-482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36084987

RESUMO

INTRODUCTION: In a person with type 1 diabetes, any change concerning daily routine may lead to changes in glycaemic control. This study aimed to evaluate the impact of work and lockdown on glycaemic control in adults with type 1 diabetes. MATERIAL AND METHODS: A retrospective cohort was stratified into three activity groups (g1-students/telework/laid-off; g2-unemployed/retired; g3-work without lockdown). Continuous and categorical variations (reductions≥0.4%) in glycated haemoglobin were obtained in 2020 (t3:December/2019-March/2020; t4:April/2020-July/2020) and in homologous periods of 2019. Intragroup comparisons between years and intergroups in the same year were made. Regression models were developed to predict the variation of glycated haemoglobin in 2020. RESULTS: 241 participants were included, with a significant reduction between t4 and t3 (vs. t2 and t1) in g1 (p<0.001) and g2 (p=0.025) and in 2020 in g1 (vs. g2, p<0.001; vs. g3, p<0.001). Only g1 presented superiority in the reduction ≥0.4% in glycated haemoglobin in 2020 (vs. 2019, p<0.001; vs. g2, p<0.001; vs. g3, p<0.001). The insulin regimens were comparable and the development of hypoglycaemia was found to be superimposed between t3 and t4, except for g1, which was higher at t3 (p=0.029). G1 correlated with continuous reductions (vs. g2, p=0.001; vs. g3, p<0.001) and ≥0.4% in glycated haemoglobin in 2020 (vs. g2, OR 3.6, p<0.001; vs. g3, OR 12.7, p<0.001), regardless of the age and duration of type 1 diabetes. CONCLUSIONS: A more stable and better glycaemic control was observed in participants who transitioned from face-to-face work to total lockdown.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Adulto , Controle de Doenças Transmissíveis , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas , Controle Glicêmico , Humanos , Pandemias , Estudos Retrospectivos
13.
J Neuroinflammation ; 8: 79, 2011 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-21733175

RESUMO

BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical to elucidate intracellular signaling pathways that are significant contributors to cytokine overproduction in microglia exposed to specific stressors, especially pathways amenable to drug interventions. The serine/threonine protein kinase p38α MAPK is a key enzyme in the parallel and convergent intracellular signaling pathways involved in stressor-induced production of IL-1ß and TNFα in peripheral tissues, and is a drug development target for peripheral inflammatory diseases. However, much less is known about the quantitative importance of microglial p38α MAPK in stressor-induced cytokine overproduction, or the potential of microglial p38α MAPK to be a druggable target for CNS disorders. Therefore, we examined the contribution of microglial p38αMAPK to cytokine up-regulation, with a focus on the potential to suppress the cytokine increase by inhibition of the kinase with pharmacological or genetic approaches. METHODS: The microglial cytokine response to TLR ligands 2/3/4/7/8/9 or to Aß1-42 was tested in the presence of a CNS-penetrant p38α MAPK inhibitor, MW01-2-069A-SRM. Primary microglia from mice genetically deficient in p38α MAPK were used to further establish a linkage between microglia p38α MAPK and cytokine overproduction. The in vivo significance was determined by p38α MAPK inhibitor treatment in a LPS-induced model of acute neuroinflammation. RESULTS: Increased IL-1ß and TNFα production by the BV-2 microglial cell line and by primary microglia cultures was inhibited in a concentration-dependent manner by the p38α MAPK-targeted inhibitor. Cellular target engagement was demonstrated by the accompanying decrease in the phosphorylation state of two p38α MAPK protein substrates, MK2 and MSK1. Consistent with the pharmacological findings, microglia from p38α-deficient mice showed a diminished cytokine response to LPS. Further, oral administration of the inhibitor blocked the increase of IL-1ß in the cerebral cortex of mice stressed by intraperitoneal injection of LPS. CONCLUSION: The p38α MAPK pathway is an important contributor to the increased microglial production of proinflammatory cytokines induced by diverse stressors. The results also indicate the feasibility of targeting p38α MAPK to modulate CNS proinflammatory cytokine overproduction.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Citocinas/metabolismo , Microglia/efeitos dos fármacos , Microglia/enzimologia , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptores Toll-Like/agonistas , Regulação para Cima/efeitos dos fármacos , Animais , Linhagem Celular , Feminino , Interleucina-1beta/metabolismo , Ligantes , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/citologia , Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 14 Ativada por Mitógeno/genética , Piridazinas/metabolismo , Pirimidinas/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
J Insect Sci ; 11: 151, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22236152

RESUMO

The state of Rio Grande do Norte is an important fruit-producing and exporting area in northeastern Brazil. The success of this industry depends on fruit fly population control, especially in fly-free exporting zones. However, many fruits are not exported because of quarantine restrictions imposed by importing countries. A survey in the state has detected a considerable increase of the fruit fly, Anastrepha zenildae Zucchi (Diptera: Tephritidae), probably a result of the introduction of irrigated guava orchards that make fruit available all year. Knowledge of the sexual behavior of Tephritidae has great importance to pest control programs, particularly those that employ the Sterile Insect Technique. In order to characterize the reproductive behavior of A. zenildae, 32 individuals (16 males; 16 females) in each of six generations were submitted to an artificial 12:12 L:D cycle (750: < 1 lux, lights on 07:00-19:00) and observed over their lifetimes. The courtship and copulation occurred in leks and the episodes varied with the time of day, courtship being most frequent between Zeitgeber time (ZT) 3 and ZT 7, peaking at ZT 5-6. Copulations occurred between ZT 2 and ZT 8, with a higher frequency between ZT 5-7 and a peak at ZT 6. Mean duration was 0.28 ± 0.03 min/male (range: 5-163 min). Males in the leks attempted to copulate mainly between ZT 3 and ZT 7 with a peak at ZT 6, and males outside leks peaked at ZT 7. The different timing of sexual behaviors among related sympatric species, including A. zenildae, may contribute to species isolation.


Assuntos
Comportamento Sexual Animal , Tephritidae , Animais , Feminino , Masculino , Fatores de Tempo
15.
Zootaxa ; 4949(1): zootaxa.4949.1.13, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33757004

RESUMO

Coccinellidae (Coleoptera), commonly known as ladybirds or ladybugs, are a highly diversified family comprising nearly 6000 described species (Vandenberg 2002) distributed in 2 subfamilies and 24 tribes (Seago et al. 2011). The genus Nephus Mulsant, 1846, present worldwide, is currently placed in the vast Coccidulini tribe (Seago et al. 2011). There are different classifications for Nephus: Gordon (1976, 1985) considered five Nephus subgenera (Depressoscymnus Gordon, Nephus Mulsant, Scymnobius Casey, Sidis Mulsant, and Turboscymnus Gordon), while Fürsch (1987) considered nine Nephus subgenera, and later (Fürsch 1996) excluded Diomus Mulsant, 1850 as subgenus, leaving Bipunctatus Fürsch, 1987, Depressoscymnus Gordon, 1976, Geminosipho Fürsch, 1987, Nephus Mulsant, 1846, Parascymnus Chapin, 1965, Scymnobius Casey, 1899, Sidis Mulsant, 1850 and Turboscymnus Gordon, 1976. Gordon and González (2002) elevated Scymnobius to genus.


Assuntos
Besouros , Animais
16.
Zootaxa ; 4938(1): zootaxa.4938.1.1, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33756982

RESUMO

A taxonomic revision of the Liogenys Guérin-Méneville, 1831 (Coleoptera: Scarabaeidae: Melolonthinae: Diplotaxini) from the Chacoan Biogeographical Province is presented. Liogenys now includes 92 species, including four new species described here: L. neoforcipata Cherman, new species; L. foveata Cherman, new species; L. isotarsis Cherman, new species; and L. truncata Cherman, new species; and the female of L. tarsalis Moser is described for the first time. Six new synonymies are proposed: L. denticulata Moser, 1918 is a new synonym of L. denticeps Blanchard, 1851; L. ophtalmica Frey, 1973 is a new synonym of L. bidenticeps Moser, 1919; L. mendozana incisa Frey, 1969 is a new synonym of L. mendozana Moser, 1918; L. flavicollis Blanchard, 1851 and L. fulvescens Blanchard, 1851 are new synonyms of L. pallens Blanchard, 1851; and L. densicollis Moser, 1921 is a new synonym of L. opacicollis Fairmaire, 1892. Liogenys cribricollis Moser, 1921 species status is revalidated from its synonymy with L. densicollis. A neotype is designated for Liogenys mendozana incisa Frey, 1969, as well as lectotypes for: L. bruchi Moser, 1924; L. cribricollis, L. denticulata, L. denticeps, L. fulvescens, L. latitarsis Moser, 1918; L. mendozana Moser, 1918; L. obscura Blanchard, 1851; L. opacicollis; and L. pallens. Redescriptions and/or diagnoses and updated geographical distributions are provided for 16 species. Six species previously known only from Argentina have their distribution expanded to Bolivia (L. mendozana; L. opacicollis; L. rectangula Frey, 1969), Paraguay (L. nigrofusca Moser, 1918; L. pallens), or to both of these countries (L. latitarsis).


Assuntos
Besouros , Animais , Feminino
17.
Zootaxa ; 4990(2): 201226, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34186763

RESUMO

The biodiversity of northern South American and Central American Liogenys Guérin-Méneville, 1831 (Coleoptera: Scarabaeidae: Melolonthinae: Diplotaxini) is reviewed. Four new species are described: L. clipeosetosa Cherman, new species; L. genieri Smith Cherman, new species; L. granadina Cherman, new species; and L. schneiderae Cherman, new species. The male of L. quadridens (Fabricius, 1798) and the female of L. quadridentata Blanchard, 1851 are described for the first time. Liogenys gebieni Moser, 1921 is a new junior subjective synonym of L. macropelma Bates, 1887. The northernmost record of Liogenys is emended to Trinidad and Tobago for L. granadina Cherman, new species and L. schneiderae new species. Diplotaxis puberea cuprascens (Bates, 1887) new combination, Diplotaxis puberea puberea (Bates, 1887) new combination, and Diplotaxis pubisternis (Bates, 1887) new combination are all transferred from Liogenys to Diplotaxis Kirby, 1837. Lectotypes are designated for Liogenys gebieni Moser, 1921; Melolontha quadridens Fabricius, 1798; and Liogenys quadridentatus Blanchard, 1851. An identification key to northern South American Liogenys is presented.


Assuntos
Besouros/classificação , Animais , América Central , Feminino , Masculino , América do Sul
18.
Braz Dent J ; 32(5): 41-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34877977

RESUMO

This study reports the SARS-CoV-2 outbreak and its impact on dental practice and education in Brazil. A literature review involving medical and dental interests was performed based on recent general findings about the infection (research and relevant guidelines). COVID-19 is a high transmissible, unpredictable systemic disease, involving a viral replication phase, followed by an inflammatory phase that can evolve into hyperinflammation that leads to a cytokine storm and other serious issues including sepsis, shock and multiple organ failure. The dentists are directly impacted by the new coronavirus as they work with the oral cavity that is irrigated by the saliva and receive the respiratory aerosols and droplets from the patient. In conclusion, the world is facing a completely new situation that deserves the comprehension of the population and close attention of the authorities. Following protocols to attend patients can prevent the dissemination of the virus, cross-infection, and the contamination of health care professionals. New strategies need to be developed to enhance the existing teaching and learning protocols in Universities and to allow research to continue.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Boca , Aerossóis e Gotículas Respiratórios , Saliva
19.
Neurochem Res ; 35(11): 1700-7, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20632091

RESUMO

Previous studies have shown sex-specific oxidative changes in spinal cord of rats submitted to chronic stress, which may be due to gonadal hormones. Here, we assessed total radical-trapping potential (TRAP), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and lipid peroxidation (evaluated by the TBARS test) in the spinal cord of ovariectomized (OVX) female rats. Female rats were subjected to OVX, and half of the animals received estradiol replacement. Animals were subdivided into controls and chronically stressed (for 40 days). Our findings demonstrate that chronic stress decreased TRAP, and increased SOD activity in spinal cord homogenates from ovariectomized female rats and had no effect on GPx activity. On the other hand, groups receiving 17ß-estradiol replacement presented a decreased GPx activity, but no alteration in TRAP and in SOD activity. No differences in the TBARS test were found in any of the groups analyzed. In conclusion, our results support the idea that chronic stress induces an imbalance between SOD and GPx activities, additionally decreasing TRAP. Estradiol replacement did not reverse the effects of chronic stress, but induced a decrease in GPx activity. Therefore, estradiol replacement in ovariectomized chronically stressed rats could make the spinal cord more susceptible to oxidative injury.


Assuntos
Estradiol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Restrição Física/fisiologia , Medula Espinal/metabolismo , Estresse Psicológico/fisiopatologia , Animais , Feminino , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Ovariectomia , Ovário/fisiologia , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Superóxido Dismutase/metabolismo
20.
Zookeys ; 962: 123-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32904313

RESUMO

We report here a new species belonging to Nephus (Nephus) Mulsant. Nephus (Nephus) apoloniasp. nov. was collected in the Reunion Island (Mascarene Archipelago, Indian Ocean). We describe this new species and redescribe and illustrate three other Nephus species already known from Reunion: Nephus (Nephus) oblongosignatus Mulsant, 1850, Nephus (Geminosipho) reunioni (Fürsch, 1974) and Nephus (Nephus) voeltzkowi Weise, 1910. Furthermore, we present a phylogenetic tree for these four species and calculate the genetic distances between them, using high-throughput DNA sequencing of the mitochondrial genome. The similar external morphology of N. apolonia sp. nov. and N. voeltzkowi very probably explains why individuals from the first species have been mistakenly identified as the latter and were not recognized as different until now. Other than external and genitalia traits, the present study provides molecular evidence confirming these are indeed two different species.

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