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OBJECTIVE: This article puts forward consensus recommendations from PROSEC North America regarding single indirect restorations made from ceramic and nonmetallic biomaterials in posterior teeth. OVERVIEW: The consensus process involved a multidisciplinary panel and three consensus workshops. A systematic literature review was conducted across five databases to gather evidence. The recommendations, informed by findings from systematic reviews and formulated based on a two-phase e-Delphi survey, emphasize a comprehensive treatment strategy that includes noninvasive measures alongside restorative interventions for managing dental caries and tooth wear. The recommendations advocate for selecting between direct and indirect restorations on a case-by-case basis, favoring inlays and onlays over crowns to align with minimally invasive dentistry principles. The recommendations highlight the critical role of selecting restorative biomaterials based on clinical performance, esthetic properties, and adherence to manufacturer guidelines. They emphasize the importance of precision in restorative procedures, including tooth preparation, impression taking, contamination control, and luting. Regular follow-up and maintenance tailored to individual patient needs are crucial for the longevity of ceramic and nonmetallic restorations. CONCLUSIONS: These PROSEC recommendations provide a framework for dental practitioners to deliver high-quality restorative care, advocating for personalized treatment planning and minimally invasive approaches to optimize oral health outcomes. CLINICAL SIGNIFICANCE: The PROSEC North America recommendations highlight the importance of minimally invasive techniques in posterior tooth restorations using ceramic and non-metallic biomaterials. These principles prioritize tooth structure conservation and personalized treatment planning, essential for enhancing clinical outcomes and long-term oral health.
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The aim of the present study is to provide an estimate of the number of white sharks Carcharodon carcharias that seasonally interact with ecotourism boats in Guadalupe Island using Schnabel's mark-recapture method and 6316 records of white sharks during 2012-2014. The results of the estimation highlight an abundance of 78 white sharks 95% C.I. (62.1, 105.6) interacting with ecotourism. The regulations regarding the number of tourists, boats and the monitoring of white sharks should be assessed to improve management decisions regarding the conservation and sustainable use of this threatened species.
Assuntos
Espécies em Perigo de Extinção , Tubarões/fisiologia , Turismo , Animais , Conservação dos Recursos Naturais/legislação & jurisprudência , Guadalupe , IlhasRESUMO
Saccharomycotina comprises a diverse group of yeasts that includes numerous species of industrial or clinical relevance. Opportunistic pathogens within this clade are often assigned to the genus Candida but belong to phylogenetically distant lineages that also comprise non-pathogenic species. This indicates that the ability to infect humans has evolved independently several times among Saccharomycotina. Although the mechanisms of infection of the main groups of Candida pathogens are starting to be unveiled, we still lack sufficient understanding of the evolutionary paths that led to a virulent phenotype in each of the pathogenic lineages. Deciphering what genomic changes underlie the evolutionary emergence of a virulence trait will not only aid the discovery of novel virulence mechanisms but it will also provide valuable information to understand how new pathogens emerge, and what clades may pose a future danger. Here we review recent comparative genomics efforts that have revealed possible evolutionary paths to pathogenesis in different lineages, focusing on the main three agents of candidiasis worldwide: Candida albicans, C. parapsilosis and C. glabrata We will discuss what genomic traits may facilitate the emergence of virulence, and focus on two different genome evolution mechanisms able to generate drastic phenotypic changes and which have been associated to the emergence of virulence: gene family expansion and interspecies hybridization.
Assuntos
Ascomicetos/genética , Evolução Molecular , Genômica , Fatores de Virulência/genéticaRESUMO
BACKGROUND: The project selection process is a crucial step for healthcare organizations at the moment of implementing six sigma programs in both administrative and caring processes. However, six-sigma project selection is often defined as a decision making process with interaction and feedback between criteria; so that it is necessary to explore different methods to help healthcare companies to determine the Six-sigma projects that provide the maximum benefits. This paper describes the application of both ANP (Analytic Network process) and DEMATEL (Decision Making trial and evaluation laboratory)-ANP in a public medical centre to establish the most suitable six sigma project and finally, these methods were compared to evaluate their performance in the decision making process. METHODS: ANP and DEMATEL-ANP were used to evaluate 6 six sigma project alternatives under an evaluation model composed by 3 strategies, 4 criteria and 15 sub-criteria. Judgement matrixes were completed by the six sigma team whose participants worked in different departments of the medical centre. RESULTS: The improving of care opportunity in obstetric outpatients was elected as the most suitable six sigma project with a score of 0,117 as contribution to the organization goals. DEMATEL-ANP performed better at decision making process since it reduced the error probability due to interactions and feedback. CONCLUSIONS: ANP and DEMATEL-ANP effectively supported six sigma project selection processes, helping to create a complete framework that guarantees the prioritization of projects that provide maximum benefits to healthcare organizations. As DEMATEL- ANP performed better, it should be used by practitioners involved in decisions related to the implementation of six sigma programs in healthcare sector accompanied by the adequate identification of the evaluation criteria that support the decision making model. Thus, this comparative study contributes to choosing more effective approaches in this field. Suggestions of further work are also proposed so that these methods can be applied more adequate in six sigma project selection processes in healthcare.
Assuntos
Tomada de Decisões Gerenciais , Técnicas de Apoio para a Decisão , Pesquisa sobre Serviços de Saúde/métodos , Serviços de Saúde , Modelos Teóricos , HumanosRESUMO
A recent genome-wide association study reported five loci for which there was strong, but sub-genome-wide significant evidence for association with multiple sclerosis risk. The aim of this study was to evaluate the role of these potential risk loci in a large and independent data set of ≈ 20,000 subjects. We tested five single nucleotide polymorphisms rs228614 (MANBA), rs630923 (CXCR5), rs2744148 (SOX8), rs180515 (RPS6KB1), and rs6062314 (ZBTB46) for association with multiple sclerosis risk in a total of 8499 cases with multiple sclerosis, 8765 unrelated control subjects and 958 trios of European descent. In addition, we assessed the overall evidence for association by combining these newly generated data with the results from the original genome-wide association study by meta-analysis. All five tested single nucleotide polymorphisms showed consistent and statistically significant evidence for association with multiple sclerosis in our validation data sets (rs228614: odds ratio = 0.91, P = 2.4 × 10(-6); rs630923: odds ratio = 0.89, P = 1.2 × 10(-4); rs2744148: odds ratio = 1.14, P = 1.8 × 10(-6); rs180515: odds ratio = 1.12, P = 5.2 × 10(-7); rs6062314: odds ratio = 0.90, P = 4.3 × 10(-3)). Combining our data with results from the previous genome-wide association study by meta-analysis, the evidence for association was strengthened further, surpassing the threshold for genome-wide significance (P < 5 × 10(-8)) in each case. Our study provides compelling evidence that these five loci are genuine multiple sclerosis susceptibility loci. These results may eventually lead to a better understanding of the underlying disease pathophysiology.
Assuntos
Esclerose Múltipla/genética , Receptores CXCR5/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Fatores de Transcrição SOXE/genética , Fatores de Transcrição/genética , alfa-Manosidase/genética , Estudos de Casos e Controles , Bases de Dados Genéticas , Feminino , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Humanos , Masculino , Esclerose Múltipla/diagnóstico , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently. METHODS: We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments. RESULTS: Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively). CONCLUSION: Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.
Assuntos
Apolipoproteínas E/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Esclerose Múltipla/genética , Bases de Dados Genéticas , Humanos , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , População Branca/genéticaRESUMO
Empathy is understood as a multidimensional construct involving both cognitive and emotional factors for which, traditionally, gender differences have been reported. The Interpersonal Reactivity Index (Davis in Catalog Sel Documents Psychol 10:1-19, 1980) is an instrument made up of four subscales, each measuring a different dimension of the global concept of empathy. Attending to gender differences, the present study's objective is twofold. First, it aims to determine, conceptually speaking, whether or not the model analyzed by this instrument is equivalent for the two sexes. Second, it aims to determine which dimensions involved in empathy most strongly predict gender differences. The results convey that the proposed model is invariant between boys and girls, although the dimensions exhibited significant differences of magnitude as a function of sex. Mainly two variables (Considerate Social Style and Impassiveness) were capable of distinguishing between men and women. Possible reasons for these results are also discussed.
Assuntos
Emoções , Empatia , Relações Interpessoais , Caracteres Sexuais , Adolescente , Criança , Feminino , Humanos , Masculino , Autorrelato , Espanha , Inquéritos e QuestionáriosRESUMO
Myelin, an extension of the oligodendrocyte plasma membrane, wraps around axons to facilitate nerve conduction. Myelination is compromised in ATR-X intellectual disability syndrome patients, but the causes are unknown. We show that loss of ATRX leads to myelination deficits in male mice that are partially rectified upon systemic thyroxine administration. Targeted ATRX inactivation in either neurons or oligodendrocyte progenitor cells (OPCs) reveals OPC-intrinsic effects on myelination. OPCs lacking ATRX fail to differentiate along the oligodendrocyte lineage and acquire a more plastic state that favors astrocytic differentiation in vitro and in vivo. ATRX chromatin occupancy in OPCs greatly overlaps with that of the chromatin remodelers CHD7 and CHD8 as well as H3K27Ac, a mark of active enhancers. Overall, our data indicate that ATRX regulates the onset of myelination systemically via thyroxine, and by promoting OPC differentiation and suppressing astrogliogenesis. These functions of ATRX identified in mice could explain white matter pathogenesis observed in ATR-X syndrome patients.
Assuntos
Bainha de Mielina , Tiroxina , Proteína Nuclear Ligada ao X , Animais , Humanos , Masculino , Camundongos , Diferenciação Celular/fisiologia , Cromatina/metabolismo , Bainha de Mielina/metabolismo , Neurogênese , Oligodendroglia/metabolismo , Tiroxina/metabolismo , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismo , NeurogliaRESUMO
BACKGROUND AND OBJECTIVES: Ten genes previously showing different evidence of association with multiple sclerosis have been selected to validate. METHODS: Eleven polymorphisms were genotyped with the iPLEX™ Sequenom in a well-powered collection of Spanish origin including 2863 multiple sclerosis cases and 2930 controls. RESULTS: Replication extended to the following polymorphisms: PKN2 (rs305217), GTF2B (rs7538427), EPHA4 (rs1517440), YTHDF3 (rs12115114), ANKFN1 (rs17758761) and PTPRM (rs4798571), which did not reach the threshold of significance in a follow-up of the first genome-wide association study (GWAS) conducted in multiple sclerosis; TMEM39A (rs1132200), which appeared as a newly identified susceptibility gene in the same study; a gene previously reaching GWAS significance in Italy, CBLB (rs9657904); IL12B (rs6887695, rs10045431), a susceptibility gene shared by diverse autoimmune diseases and, finally, another gene showing inconclusive association with multiple sclerosis, CNR1 (rs1049353). CONCLUSIONS: Pooled analysis corroborated the effect on MS predisposition of three genes: TMEM39A [rs1132200: p(M-H)=0.001; OR(M-H) (95% CI)= 0.84 (0.75-0.93)], IL12B [rs6887695: p(M-H)=0.03; OR(M-H) (95% CI)= 1.09 (1.01-1.17)] and CBLB [rs9657904: p(M-H)=0.01; OR(M-H) (95% CI)= 0.89 (0.81-0.97)].
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença/genética , Subunidade p40 da Interleucina-12/genética , Proteínas de Membrana/genética , Esclerose Múltipla/genética , Proteínas Proto-Oncogênicas c-cbl/genética , Adulto , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: The objective of this study was to investigate the prevalence, clinical features, and factors related to personal protective-associated headaches. METHODS: We conducted a cross-sectional study among healthcare workers using an online questionnaire. RESULTS: We surveyed 305 participants. The N95 face-mask was the most used device by 93%. Of 305 respondents, 206 experienced headaches while wearing protective equipment; 36.06% suffered from a headache disorder before the pandemic. The prevalence of de novo headache was 39.01%. Gender, age, or exposure to coronavirus disease were not determining factors to develop headache. Headache intensity was higher in front-line healthcare workers and was correlated (r = 0.728) with the time wearing protective equipment. The more days per month the participants wore personal protective equipment the shorter the time to headache onset after donning equipment. CONCLUSION: Our study confirms the relationship between frequent and prolonged use of protection devices with headaches and reaffirms the implication of external pressure as a primary mechanism.
OBJETIVO: Investigar la prevalencia, las características clínicas y los factores relacionados con las cefaleas asociadas al equipo de protección personal. MÉTODOS: Realizamos un estudio transversal entre trabajadores de la salud por medio de un cuestionario en línea. RESULTADOS: Encuestamos a 305 participantes. La mascarilla N95 fue el dispositivo más utilizado opor 93%. Del total de encuestados, 206 experimentaron cefalea mientras usaban el equipo de protección; el 36.06% padecía algun trastorno cefalálgico antes del inicio de la pandemia. La prevalencia de cefalea de novo fue del 39.01%. El género, la edad o la exposición a la enfermedad por coronavirus no fueron factores determinantes para desarrollar cefalea. La cefalea fue de mayor intensidad en los trabajadores de primera línea y se correlacionó (r = 0.728) con el tiempo que se uso el equipo de protección personal. Mientras más días por mes los participantes usaron el equipo de protección personal menor fue el tiempo de inicio de la cefalea tras la colocación del equipo cada vez. CONCLUSIONES: Nuestro estudio confirma la asociación del uso frecuente y prolongado de dispositivos de protección con el desarrollo de cefalea y reafirma la implicación de la compresión externa como mecanismo primario.
Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Estudos Transversais , Equipamento de Proteção Individual , Pessoal de Saúde , Cefaleia/epidemiologia , Cefaleia/etiologiaRESUMO
BACKGROUND: Recent technological developments have made genome sequencing and assembly highly accessible and widely used. However, the presence in sequenced organisms of certain genomic features such as high heterozygosity, polyploidy, aneuploidy, heterokaryosis, or extreme compositional biases can challenge current standard assembly procedures and result in highly fragmented assemblies. Hence, we hypothesized that genome databases must contain a nonnegligible fraction of low-quality assemblies that result from such type of intrinsic genomic factors. FINDINGS: Here we present Karyon, a Python-based toolkit that uses raw sequencing data and de novo genome assembly to assess several parameters and generate informative plots to assist in the identification of nonchanonical genomic traits. Karyon includes automated de novo genome assembly and variant calling pipelines. We tested Karyon by diagnosing 35 highly fragmented publicly available assemblies from 19 different Mucorales (Fungi) species. CONCLUSIONS: Our results show that 10 (28.57%) of the assemblies presented signs of unusual genomic configurations, suggesting that these are common, at least for some lineages within the Fungi.
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Genoma , Genômica , Aneuploidia , Mapeamento Cromossômico , Fungos/genética , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNARESUMO
BACKGROUND: Isolation of cell types of interest from the brain for molecular applications presents several challenges, including cellular damage during tissue dissociation or enrichment procedures, and low cell number in the tissue in some cases. Techniques have been developed to enrich distinct cell populations using immunopanning or fluorescence activated cell/nuclei sorting. However, these techniques often involve fixation, immunolabeling and DNA staining steps, which could potentially influence downstream omics applications. NEW METHOD: Taking advantage of readily available genetically modified mice with fluorescent-tagged nuclei, we describe a technique for the purification of cell-type specific brain nuclei, optimized to decrease sample preparation time and to limit potential artefacts for downstream omics applications. We demonstrate the applicability of this approach for the purification of glial cell nuclei and show that the resulting cell-type specific nuclei obtained can be used effectively for omics applications, including ATAC-seq and RNA-seq. RESULTS: We demonstrate excellent enrichment of fluorescently-tagged glial nuclei, yielding high quality RNA and chromatin. We identify several critical steps during nuclei isolation that help limit nuclei rupture and clumping, including quick homogenization, dilution before filtration and loosening of the pellet before resuspension, thus improving yield. Sorting of fluorescent nuclei can be achieved without fixation, antibody labelling, or DAPI staining, reducing potential artifactual results in RNA-seq and ATAC-seq analyses. We show that reproducible glial cell type-specific profiles can be obtained in transcriptomic and chromatin accessibility assays using this rapid protocol. COMPARISON WITH EXISTING METHODS: Our method allows for rapid enrichment of glial nuclei populations from the mouse brain with minimal processing steps, while still providing high quality RNA and chromatin required for reliable omics analyses. CONCLUSIONS: We provide a reproducible method to obtain nucleic material from glial cells in the mouse brain with a quick and limited sample preparation.
Assuntos
Núcleo Celular , Cromatina , Animais , Encéfalo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Cromatina/metabolismo , Camundongos , RNA-SeqRESUMO
When neural cells are exposed to paraquat, nitric oxide generation increases primarily due to an increase in the expression of the inducible isoform of nitric oxide synthase. The nitric oxide generated has controversial actions in paraquat exposure, as both protective and harmful effects have been described previously. While the actions mediated by nitric oxide in neural cells have been well described, there is evidence that nitric oxide may also be an important modulator of the expression of several genes during paraquat exposure. To better understand the actions of nitric oxide and its potential role in paraquat-induced gene expression, we examined changes in GCH1, ARG1, ARG2, NOS1, NOS2, NOS3, NOSTRIN, NOSIP, NOS1AP, RASD1, DYNLL1, GUCY1A3, DDAH1, DDAH2 and CYGB genes whose expression is controlled by or involved in signaling by the second messenger nitric oxide, in rat mesencephalic cells after 3, 6, 12 and 24h of paraquat exposure. A qPCR strategy targeting these genes was developed using a SYBR green I-based method. The mRNA levels of all the genes studied were differentially regulated during exposure. These results demonstrate that nitric oxide-related genes are regulated following paraquat exposure of mesencephalic cells and provide the basis for further studies exploring the physiological and functional significance of nitric oxide-sensitive genes in paraquat-mediated neurotoxicity.
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Regulação da Expressão Gênica/efeitos dos fármacos , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/fisiologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/metabolismo , Análise de Variância , Animais , Linhagem Celular Transformada , Guanilato Ciclase/genética , Guanilato Ciclase/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Mesencéfalo/metabolismo , Óxido Nítrico Sintase/genética , Paraquat , Proteínas/genética , Proteínas/metabolismo , Ratos , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Guanilil Ciclase SolúvelRESUMO
Paraquat, a cationic herbicide, produces degenerative lesions in the lung and in the nervous system after systemic administration to man and animals. Many cases of acute poisoning and death have been reported over the past few decades. Although a definitive mechanism of toxicity of paraquat has not been delineated, a cyclic single electron reduction/oxidation is a critical mechanistic event. The redox cycling of paraquat has two potentially important consequences relevant to the development of toxicity: the generation of the superoxide anion, which can lead to the formation of more toxic reactive oxygen species which are highly reactive to cellular macromolecules; and the oxidation of reducing equivalents (e.g., NADPH, reduced glutathione), which results in the disruption of important NADPH-requiring biochemical processes necessary for normal cell function. Nitric oxide is an important signaling molecule that reacts with superoxide derived from the paraquat redox cycle, to form the potent oxidant peroxynitrite, which causes serious cell damage. Although nitric oxide has been involved in the mechanism of paraquat-mediated toxicity, the role of nitric oxide has been controversial as both protective and harmful effects have been described. The present review summarizes recent findings in the field and describes new knowledge on the role of nitric oxide in the paraquat-mediated toxicity.
Assuntos
Herbicidas/toxicidade , Óxido Nítrico/metabolismo , Paraquat/toxicidade , Animais , Glutationa/metabolismo , Humanos , Pulmão/patologia , NADP/metabolismo , Oxirredução , Ácido Peroxinitroso/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismoRESUMO
The presence of a symptomatic and recurrent unilateral pleural effusion should alert physicians to consider thoracentesis with mindful use of biomarkers not only for therapeutic purposes, but also for diagnosis of both benign and malignant etiologies.
RESUMO
The question of how phenotypic and genomic complexity are inter-related and how they are shaped through evolution is a central question in biology that historically has been approached from the perspective of animals and plants. In recent years, however, fungi have emerged as a promising alternative system to address such questions. Key to their ecological success, fungi present a broad and diverse range of phenotypic traits. Fungal cells can adopt many different shapes, often within a single species, providing them with great adaptive potential. Fungal cellular organizations span from unicellular forms to complex, macroscopic multicellularity, with multiple transitions to higher or lower levels of cellular complexity occurring throughout the evolutionary history of fungi. Similarly, fungal genomes are very diverse in their architecture. Deep changes in genome organization can occur very quickly, and these phenomena are known to mediate rapid adaptations to environmental changes. Finally, the biochemical complexity of fungi is huge, particularly with regard to their secondary metabolites, chemical products that mediate many aspects of fungal biology, including ecological interactions. Herein, we explore how the interplay of these cellular, genomic and metabolic traits mediates the emergence of complex phenotypes, and how this complexity is shaped throughout the evolutionary history of Fungi.
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Fungos , Genoma Fúngico , Adaptação Fisiológica , Animais , Fungos/genética , Genômica , Plantas/genéticaRESUMO
BACKGROUND: The Mediterranean mussel Mytilus galloprovincialis is an ecologically and economically relevant edible marine bivalve, highly invasive and resilient to biotic and abiotic stressors causing recurrent massive mortalities in other bivalves. Although these traits have been recently linked with the maintenance of a high genetic variation within natural populations, the factors underlying the evolutionary success of this species remain unclear. RESULTS: Here, after the assembly of a 1.28-Gb reference genome and the resequencing of 14 individuals from two independent populations, we reveal a complex pan-genomic architecture in M. galloprovincialis, with a core set of 45,000 genes plus a strikingly high number of dispensable genes (20,000) subject to presence-absence variation, which may be entirely missing in several individuals. We show that dispensable genes are associated with hemizygous genomic regions affected by structural variants, which overall account for nearly 580 Mb of DNA sequence not included in the reference genome assembly. As such, this is the first study to report the widespread occurrence of gene presence-absence variation at a whole-genome scale in the animal kingdom. CONCLUSIONS: Dispensable genes usually belong to young and recently expanded gene families enriched in survival functions, which might be the key to explain the resilience and invasiveness of this species. This unique pan-genome architecture is characterized by dispensable genes in accessory genomic regions that exceed by orders of magnitude those observed in other metazoans, including humans, and closely mirror the open pan-genomes found in prokaryotes and in a few non-metazoan eukaryotes.
Assuntos
Genoma , Mytilus/genética , Animais , Sequência de Bases , Evolução Biológica , Feminino , Genômica , Humanos , Imunidade Inata , Masculino , Mytilus/anatomia & histologia , Fator 1 de Elongação de Peptídeos , Proteínas Citotóxicas Formadoras de PorosRESUMO
The role of autophagy as a survival strategy of cells constitutes an emerging topic in the study of the pathogenesis of several diseases with autophagic changes being described in a number of age-related neurodegenerative disorders, including Parkinson's disease (PD). Although the etiology of PD is still unknown, both environmental (for example, paraquat exposure) and genetic factors have been investigated as putative causes of the disease. In the latter case, mutations or changes in the protein DJ-1 have been reported to be associated with autosomal recessive, early-onset parkinsonism. In this paper we established a model system to study the involvement of the DJ-1 protein in paraquat-induced autophagy. When human neuroblastoma SH-SY5Y cells were transfected with DJ-1-specific small interfering RNAs and exposed to paraquat, we observed (i) sensitization additive with paraquat-induced apoptotic cell death, (ii) inhibition of the cytoplasmic accumulation of autophagic vacuoles as well as the recruitment of LC3 fusion protein to the vacuoles, (iii) exacerbation of apoptotic cell death in the presence of the autophagy inhibitor 3-methyladenine, and (iv) an increase in mammalian target of rapamycin phosphorylation. Taken together, these findings suggest an active role for DJ-1 in the autophagic response produced by paraquat, providing evidence for the role of PD-related proteins in the autophagic degradation pathway, a factor that should be considered in the design of potential therapies for the treatment of the disease.
Assuntos
Autofagia/efeitos dos fármacos , Herbicidas/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Oncogênicas/metabolismo , Paraquat/farmacologia , Análise de Variância , Anexina A5/metabolismo , Autofagia/fisiologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Citometria de Fluxo/métodos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Neuroblastoma/patologia , Proteínas Oncogênicas/antagonistas & inibidores , Proteínas Oncogênicas/genética , Proteína Desglicase DJ-1 , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Transfecção , Vacúolos/efeitos dos fármacos , Vacúolos/patologiaRESUMO
Studies of human native C-reactive protein (nCRP) in mice have shown effects ranging from proatherogenic, to antiatherogenic, to no effect. It is likely that these disparities are related to (a) the use, in some studies, of contaminated nCRP, or to (b) variation in CRP levels associated with either its episodic administration or the use of CRP-transgenic mice. In our study, 12-week-old male apolipoprotein E-deficient (apoE (-/-)) mice, maintained on a Western diet, received azide- and endotoxin-free nCRP (n = 23) or placebo (n = 23) continuously via osmotic pumps (20.4 microg/day) for 4 weeks. CRP-treated and control mice developed similar atherosclerotic lesions in whole aortas (nCRP: 10.4 +/- 4.7% vs. controls: 11.7 +/- 4.4%, P = 0.76) and aortic roots (nCRP: 65.0 +/- 7.8% vs. controls: 64.7 +/- 9.7%, P = 0.94). No differences were observed in macrophage or T-lymphocyte infiltrates and there was no meaningful change in VCAM-1 or IL-6 expression, in the levels of soluble VCAM-1, or in circulating proinflammatory (IL-1 beta, IL-6, IL-12p40, IL-12p70, TNF-alpha, and INF-gamma), or anti-inflammatory (IL-4 and IL-10) cytokines. We conclude that continuous infusion of uncontaminated nCRP in apoE (-/-) mice is not associated with increased atherosclerosis, does not alter systemic or local inflammation, and does not affect endothelial activation. These observations suggest that alternative approaches to study CRP (perhaps using different pentraxins in the mouse model or using a rabbit model instead of a mouse model) are needed to evaluate the effects of pentraxins on atherosclerosis.
Assuntos
Apolipoproteínas E , Aterosclerose/metabolismo , Proteína C-Reativa/farmacologia , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/genética , Aterosclerose/patologia , Proteína C-Reativa/efeitos adversos , Citocinas/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Knockout , Coelhos , Linfócitos T/metabolismo , Linfócitos T/patologia , Fatores de Tempo , Molécula 1 de Adesão de Célula Vascular/biossínteseRESUMO
The fungal kingdom comprises a hyperdiverse clade of heterotrophic eukaryotes characterized by the presence of a chitinous cell wall, the loss of phagotrophic capabilities and cell organizations that range from completely unicellular monopolar organisms to highly complex syncitial filaments that may form macroscopic structures. Fungi emerged as a 'Third Kingdom', embracing organisms that were outside the classical dichotomy of animals versus vegetals. The taxonomy of this group has a turbulent history that is only now starting to be settled with the advent of genomics and phylogenomics. We here review the current status of the phylogeny and taxonomy of fungi, providing an overview of the main defined groups. Based on current knowledge, nine phylum-level clades can be defined: Opisthosporidia, Chytridiomycota, Neocallimastigomycota, Blastocladiomycota, Zoopagomycota, Mucoromycota, Glomeromycota, Basidiomycota and Ascomycota. For each group, we discuss their main traits and their diversity, focusing on the evolutionary relationships among the main fungal clades. We also explore the diversity and phylogeny of several groups of uncertain affinities and the main phylogenetic and taxonomical controversies and hypotheses in the field.