Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition

O atendimento educacional especializado no processo de inclusão escolar, na rede municipal de ensino de Mossoró/RN

This dissertation aims to analyze the specialized educational services(AEE, Portuguese) implemented in four municipal schools of Mossoró/RN, with attention to the process of collaboration between regular classroom teachers and multifunctional resource classroom teachers. We use as theoretical reference the works of Vygotsky and others authors that write about education and collaboration. To accomplish the research we chose a qualitative approach, using as a methodological resources: study of cases, bibliographical, documental and field research. For the field research we make observations in regular and multifunctional classrooms. We produce group intervieus with regular and multifunctional teachers. From the analysis performed we identify that the concepts and the practices of teachers in regular classrooms changes, with integrationist predominance. The AEE s teachers had more inclusive conceptions and greater investment in continuing education than the regular classroom teachers. The practices of regular classroom teachers are more traditional, what makes the learning process more difficult for the students, even more for the students with disabilities and pervasive developmental disorders. Teachers of AEE was more interactive and creative, however, the attention to the students was more individual. In three of the four schools surveyed stand out the efforts of the teachers of specialist classroom to collaborate with regular school teachers, by notes, e-mails, phone calls and resource sharing. In one of the four was noted a good collaborative interactive between the AEE teachers and the regular school teachers. The school with the worst improvement was that in which the actions of the teachers of the AEE were limited to actions in multifunctional resource classroom. The resistance to these professionals was identified in the statements of the regular classroom teachers. Another issue raised was the lack of time for teachers to conduct AEE actions that contribute to the process of school students, because their working hours is restricted to the opposite turn in school. Transport difficulties for the students to attend the resource classroom multifunctional and the lack of dialogue with the health sector was challenges for the four schools. The families were with a practically constant interest to interact with the AEE teachers in the four schools. Thus, we believe that the presence of AEE school can make contributions to the educational process, however, it is necessary more attention to the collaborative process between teachers and the school community

Trilhas da inclusão escolar percorridas por uma aluna com paralisia cerebral na EJA: concepções e práticas

On this qualitative study, it has been discussed the school inclusion paths done by a student with cerebral palsy, who we call Liz, and who was also the reference and indirect subject for this study. For the representation of landscapes found, it follows throughout historical, political and pedagogical paths, getting through the case study method references on the current Brazilian educational context, analyzing, which concepts are attributed to the inclusion and which practices are developed by educational managers and teachers in a regular school of the City of Natal/RN. The theory which based this research is supported on Vygotsky's central ideas (1991, 1997, 2004) and his followers. Furthermore, it was essential to bring to this investigative journey a literature which could dialogue with the most relevant aspects of the cultural-historical approach, emphasizing the assumptions of a progressive education tendency, which promotes the subject involvement of his/her work in the world and for the world. This way, it was necessary to seek for theoretical support on assistive technology and on alternative communication, in order to show the importance of establishing other communications, which is, to break away from the conventional pattern established by the school. On this journey it was used procedures for the data construction, such as: observation, conducting semistructured interviews and questionnaires; and document analysis that supported and legitimized the inclusion, besides the permanent field diaries record. On the access paths to this landscape it entered in the Youth and Adults Education (Educação de Jovens e Adultos - EJA), seeking to establish a dialogue among Youth and Adult Education and Special Education. It was verified that, still, there are large gaps in these policies articulation. Among the results obtained it was raised discussions on new scenery, in which Youth and Adults Education (EJA) emerges as prominent mode of the established relationships throughout the school inclusion process. There were target reflections on: the planning and evaluation systematic, the pedagogical articulation among the Youth and Adults Education (EJA) teachers and the multifunctional resource room teacher's actions and the continuous training importance of the educators involved. It was considered, therefore, that the necessary mediations for school inclusion may be sustained if the walkers are involved in a permanent contact with the nature of a proposal from the Special Education inclusive perspective

A coordenação pedagógica e o processo de inclusão do aluno com necessidade educacionais especiais:Um estudo de caso

The school inclusion presents a number of challenges that has been mobilizing initiatives and studies about its effectiveness. If on one hand in such studies and initiatives it becomes important to emphasize on the role and training of teachers, on the other, there is few studies about the role (and performance) of the pedagogical coordination in face of this process. In this sense, this research focuses on the role of educational coordination in face of the school inclusion of students with Special Educational Needs (SEN) and it undertakes the following study s questions: has the action by the coordinator contributed to the process of including students with Special Educational Needs? How is it presented in the process of inclusion of students with SEN in regular education? And it aims to: investigate the role of the pedagogical coordinator in the process of inclusion of students with Special Educational Needs of Primary Education at regular schools; and to analyze the limits and possibilities of the coordinator actions in the process of inclusion of students with SEN. For the effectiveness of the research, a state school of Elementary School located at the city of Natal/RN was taken as an empiric field. It was selected as research subjects 4 coordinators, 2 teachers of the Multifunctional Resources Room and 2 teachers of 6th to 9th grades. The methodological approach that was used in this research is consistent with the qualitative approach, and it is configured as a case study, as it is understood that this type of research responds to the objective of the study, assuming the observation of everyday school life, the educational document analysis and interviews with the subjects as procedures and tools to build data. The construction and analysis of the data were followed by a dialogue with the literature dedicated to coordinating education and school enrollment. Considering the responsibilities of the contemporary pedagogical coordination due to the challenges and possibilities of schooling for all students, specially regarding to what is referred as collaborative work and ongoing training of teachers, this study points out to the lack of an articulated action related to the school inclusion process, considering the monitoring of the teaching activity and its dialogue with the Multifunctional Resources Room. Moreover, the emphasis on meeting the daily school routines and the compliance with bureaucratic procedures, put it into second, restructuring of the Political-Pedagogical and the possibility of mobilization of school around the problematization and systematization of an inclusive school project. The effectiveness of school s inclusion, therefore, implies the scaling of the functions of the pedagogical coordination, as well as the reorganization of the school it self, to ensure the mediation of collaborative actions, contemplating the teachers continuing education, having as a landmark difficulties, problems and experiences constructed in the school context

Análise tribológica das malhas multifuncionais obtidas por multicamadas

The present work consists in the analysis of tribologycal properties of basic and multifunctional knitted fabrics. This knowledge has fundamental importance for the textile industry since it can quantify, in an objective way, the tactil. The fabrics used were characterized by friction and mechanical tests for determining the viscoelastic region, wear resistance and friction coefficient of the fabrics used. The stress-strain curve was obtained by the method Kawabata, KES-FB1. Wear tests performed with the aid of equipment Martindale. The measurement of friction coefficient, two methods were used and analyzed comparatively. The first was a method already established worldwide known as KES-FB4 and the second was an innovative method called FRICTORQ, developed by the University of Minho. These two methods were compared taking into account the relative motion between the tribologycal pairs are different from each method. While the first motion is translational, the second is rotational. It was formal that the knitted had a multifunctional fabrics tribologycal performance which was better than the basic knitted fabrics, as the viscoelastic region, was laager highlighting a multifunctional structure, with greater wear resistance mainly on the back side of the knitted fabrics and lower friction coefficient. Performing a comparative analysis between two methods used to measure the friction coefficient, it was formal that both methods were consistent in terms of results. In operational terms, the FRICTORQ showed ease of operation and increased reproducibility of results

As construções adverbiais em mente: análise funcionalista e implicações para o ensino de língua materna

This research aims at investigating the constructions with adverbials in ly, based on the view of contemporaneous linguistic functionalism, such as proposed by Givón, Hopper, Thompson, Traugott, Furtado da Cunha, as well as the cognitivist notion of language, through construction grammar support upon the patterns of Goldberg and the prototypes theory. The cognitive functional approach adopted here considers the change as a proper and inherent phenomenon of language and understands the linguistic phenomenon as resulting from effective use of language. Another aspect to be considered to the realization of this study is the fact that the formation adjective + ly is a word construction mechanism really productive, which generates interests on linguistic description. In a particular way, our leading objective is to exam the constructions with adverbials in ly in the context of language in use, in its oral and written forms, looking for to apprehend the meaning multiple manifestations forged in the use. Bearing this in mind, we worked with data from the Corpus Discurso & Gramática (Natal). There are, in the data, adverbs ended in ly that take the signification of mode, as foreseen in traditional models, but there are also other significations, for instance, the modalizador in its different manifestations. The results show that this adverb is a linguistic mark that carries in its constitution the multissêmico and multifunctional character, which interferes extremely in the ordination of this category, assuming a position sometimes pre-verbal, sometimes post-verbal. Other aspect observed refers to the relationship between the adverb and the verb, with emphasis on the compatibility or restriction between them, option which is related to the semantic aspect. The data in analysis legitimate the use in different constructions with adverb ended in ly in various genres, as follows: personal experience narrative, retold narrative, local description, proceeding account, opinion account, both in oral as in written language

O turismo de base local como um possível indutor de desenvolvimento rural: uma análise da realidade e das potencialidades no distrito de dondo-moçambique

The current debate on rural development focuses on the territorial approach, recognizing the multifunctional character of rural areas. Emphasize the use of endogenous forces, the need of implement policies which valorize local specificities, the participation of social actors in revitalization of rural areas. In this context tourism enters as a means to induce a new dynamic to rural areas, since the activity is regarded as a channel for the upgrading of the natural and cultural resources and the rural way of life. This study focuses on local-based tourism as a promoter of rural development, giving an analysis of the social reality and potential for this tourism in the district of Dondo. In it, is proposed to analyze the potential for development of local-based tourism in the district of Dondo, assessing the extent to which local reality enables the inclusion of the community in the management of local tourism resources. For this, was showed the inclusion of local-based tourism in the current context of rural development, was identified and organized systematically the factors that influence the implementation of local-based tourism in the study area and was verified as far as possible the study area corresponds to the constraints identified, showing how local-based tourism can best been encouraged. Was adopted a qualitative methodological approach to both the procedures and data processing, but also by critical approach, using bibliographical research, semi-structured interviews that fell on the group of public administrators who work in tourism and community leaders. The critical analysis was based on the principles of sustainability o Sachs particular ecological, social, cultural, economic, space, beyond the analysis of political and institutional aspects. The survey results show that the district of Dondo has a potential for implementing a model of tourism development on a local basis, since it is rich in natural and cultural research, benefits from good network accessibility in the context of the market in the region, the population live according to their habits and customs and value their identity. There is also a good cooperation between community members, although not in tourism, a fact which is observed through the lever of community participation in associations, cooperatives, working in areas such as agriculture, fishing, environment, civic education etc. It also has public funding sources to augment or stimulate local investment. Despite obstacles such as inexistence of policies and local plans for tourism development, lack of awareness of tourism, lack of basic infrastructure, as well as equipment and facilities to support tourism, the results shows that these problems can be solved through a public commitment from both government, and community through a joint planning and participation

Estudo in silico das interações da protease NS3-NS2B de DENV-2 com o inibidor peptídico Bz-nKRR-H com finalidades terapêuticas

Dengue virus is an important patogen that causes Dengue desease in all world, and belongs to Flavivirus gender. The virus consists of enveloped RNA with a single strand positive sense, 11Kb genome. The RNA is translated into a polyprotein precursor, wich is cleaved into 3 structural proteins (C, prM e E) and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B e NS5). The NS3 is a multifunctional protein, that besides to promote the polyprotein precursor cleavage, also have NTPase, helicase and RTPase activity. The NS3 needs a hydrophilic segment of 40 residues from the transmembrane NS2B protein (who acts like cofator) to realize this functions. Actually, there's no vacines available on the market, and the treatment are just symptomatic. The tetrapeptide inhibitor Bz-Nle-Lys-Arg-Arg-H (Ki de 5,8-7,0 M) was showed as a potent inhibitor μ for NS3prot in Dengue virus. That is a inteligent alternative to treat the dengue desease. The present work aimed analyse the interactions of the ligand bounded to the activity site to provid a clear and depth vision of that interaction. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant = 20 ε and 80 was used. The results demonstrate that the interaction energy of the system reached convergence at 13.5 A. Within a radius of 13,5A the most important residues were identified. Met49, Met84 and Asp81 perform interactions of hydrogen with the ligant. The Asp79 and Asp75 residues present high energy of attraction. Arg54, Arg85 and Lys 131 perform hydrogen interactions with the ligand, however, appear in BIRD graph having high repulsion energy with the inhibitor. The data also emphasizes the importance of residue Tyr161 and the involvement of the catalytic triad composed by Asp75, His51 and Ser135

Avaliação do efeito da inibição do reparo de sítios abásicos na resposta inflamatória celular

Base excision repair (BER) proteins has been associated with functions beyond DNA repair. Apurynic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein involved in a plethora of cellular activities, such as redox activation of transcription factors, RNA processing and DNA repair. Some studies have described the action of the protein 8-oxoguanine (OGG1) in correcting oxidized lesions in promoters as a step in the transcription of pro-inflammatory cytokines. Despite being especially important in redox activation of transcription factors such as nuclear factor κB (NF-κB) and AP- 1, the repair activity of APE1 has not yet been associated with the inflammatory response. In this study, experimental and bioinformatic analysis approaches have been used to investigate the relationship between inhibition of the repair of abasic sites in DNA by MX, a synthetic molecule designed to inhibt the repair activity of APE1, and the modulation of the inflammatory response. The results showed that treatment of monocytes with lipopolysaccharide (LPS) and MX reduced the expression of cytokines, chemokines and toll-like receptors, and negatively regulated biological immune processes, as macrophages activation, and NF-κB and tumor necrosis factor (TNF-α) and interferon pathways, without inducing cell death. The transcriptomic analysis suggests that LPS/MX treatment induces mitochondrial dysfunction, endoplasmic reticulum stress and activation of autophagy pathways, probably activated by impairment of cellular energy and/or the accumulation of nuclear and mitochondria DNA damage. Additionally, it is proposed that the repair activity of APE1 is required for transcription of inflammatory genes by interaction with abasic sites at specific promoters and recruitment of transcriptional complexes during inflammatory signaling. This work presents a new perspective on the interactions between the BER activity and the modulation of inflammatory response, and suggests a new activity for APE1 protein as modulator of the immune response in a redox-independent manner.

Desenvolvimento de um material têxtil termosenssível com micro/nanocápsulas imobilizadas em fibras regeneradas

Intelligent and functional Textile Materials have been widely developed and researched with the purpose of being used in several areas of science and technology. These fibrous materials require different chemical and physical properties to obtain a multifunctional material. With the advent of nanotechnology, the techniques developed, being used as essential tools to characterize these new materials qualitatively. Lately the application of micro and nanomaterials in textile substrates has been the objective of many studies, but many of these nanomaterials have not been optimized for their application, which has resulted in increased costs and environmental pollution, because there is still no satisfactory effluent treatment available for these nanomaterials. Soybean fiber has low adsorption for thermosensitive micro and nanocapsules due to their incompatibility of their surface charges. For this reason, in this work initially chitosan was synthesized to functionalise soybean fibres. Chitosan is a natural polyelectrolyte with a high density of positive charges, these fibres have negative charges as well as the micro/nanocápsules, for this reason the chitosan acts as auxiliary agent to cationize in order to fix the thermosensitive microcapsules in the textile substrate. Polyelectrolyte was characterized using particle size analyses and the measurement of zeta potential. For the morphological analysis scanning Electron Microscopy (SEM) and x-Ray Diffraction (XRD) and to study the thermal properties, thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Near Infrared Spectroscopy analysis in the Region of the Fourier Transform Infrared (FTIR), colourimetry using UV-VIS spectrum were simultaneously performed on the substrate. From the measurement of zeta potential and in the determination of the particle size, stability of electrostatic chitosan was observed around 31.55mV and 291.0 nm respectively. The result obtained with (GD) for chitosan extracted from shrimp was 70 %, which according to the literature survey can be considered as chitosan. To optimize the dyeing process a statistical software, Design expert was used. The surface functionalisation of textile substrate with 2% chitosan showed the best result of K/S, being the parameter used for the experimental design, in which this showed the best response of dyeing absorbance in the range of 2.624. It was noted that soy knitting dyed with the thermosensitive micro andnanocapsules property showed excellent washing solidity, which was observed after 25 home washes, and significant K/S values.

Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition