Papel da proteína de reparo XPC na regulação das proteínas de reparo APE1, OGG1 e PARP-1 em células humanas e de camundongos

studies using UV as a source of DNA damage. However, even though unrepaired UV-induced DNA damages are related to mutagenesis, cell death and tumorigenesis, they do not explain phenotypes such as neurodegeneration and internal tumors observed in patients with syndromes like Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS) that are associated with NER deficiency. Recent evidences point to a role of NER in the repair of 8-oxodG, a typical substrate of Base Excision Repair (BER). Since deficiencies in BER result in genomic instability, neurodegenerative diseases and cancer, it was investigated in this research the impact of XPC deficiency on BER functions in human cells. It was analyzed both the expression and the cellular localization of APE1, OGG1 e PARP-1, the mainly BER enzymes, in different NER-deficient human fibroblasts. The endogenous levels of these enzymes are reduced in XPC deficient cells. Surprisingly, XP-C fibroblasts were more resistant to oxidative agents than the other NER deficient fibroblasts, despite presenting the highest of 8-oxodG. Furthermore, subtle changes in the nuclear and mitochondrial localization of APE1 were detected in XP-C fibroblasts. To confirm the impact of XPC deficiency in the regulation of APE1 and OGG1 expression and activity, we constructed a XPC-complemented cell line. Although the XPC complementation was only partial, we found that XPC-complemented cells presented increased levels of OGG1 than XPC-deficient cells. The extracts from XPC-complemented cells also presented an elevated OGG1 enzimatic activity. However, it was not observed changes in APE1 expression and activity in the XPCcomplemented cells. In addition, we found that full-length APE1 (37 kDa) and OGG1- α are in the mitochondria of XPC-deficient fibroblasts and XPC-complemented fibroblasts before and after induction of oxidative stress. On the other hand, the expression of APE1 and PARP-1 are not altered in brain and liver of XPC knockout mice. However, XPC deficiency changed the APE1 localization in hypoccampus and hypothalamus. We also observed a physical interaction between XPC and APE1 proteins in human cells. In conclusion, the data suggest that XPC protein has a role in the regulation of OGG1 expression and activity in human cells and is involved mainly in the regulation of APE1 localization in mice. Aditionally, the response of NER deficient cells under oxidative stress may not be only associated to the NER deficiency per se, but it may include the new functions of NER enzymes in regulation of expression and cell localization of BER proteins

Efeito agudo do exercício aeróbio vigoroso sobre as funções executivas em adolescentes

Executive functions are determinant cognitive processes for student success, since they execute and control complex cognitive activities such as reasoning, planning and solving problems. The development of the executive functions performances begin early at childhood going through the adolescence until adulthood, concomitant with the neuroanatomical, functional and blood perfusion changes over the brain. In this scenario, exercise has been considered an important environmental factor for neurodevelopment, as well as for the promotion of cognitive and brain health. However, there are no large scientific studies investigating the effects of a single vigorous aerobic exercise session on executive functions in adolescents. Objective: To verify the acute effect of vigorous aerobic exercise on executive functions in adolescents. Methods: A randomized controlled trial (RCT) with crossover design was used. 20 pubescent from both sexes/gender with age between 10 and 16 years were submitted to two sessions of 30min each: 1) The aerobic exercise session intensity was between 65 and 75% of heart rate reserve, in which 5min for warm-up, 20min at the target intensity and 5min of cool down; and 2) control session watching cartoons. The computerized Stroop test – Testinpacs and trail making test were used to evaluate the inhibitory control and cognitive flexibility assessment respectively, before and after both experimental and control sessions. The reaction time (RT) and number of errors (n) of Stroop test were recorded. The total time (TT) and the number of errors (n) of the trail making test were also recorded. Results: The control session’s RT did not present significant differences in the Stroop test. On the other hand, the exercise session’s RT decreased significantly (p<0.01) after the session. The number of errors made at the Stroop test had no significant differences in control and exercise sessions. The ΔTT of trail making test of exercise session was significantly (p<0.001) lower than the control session’s. Errors made in trail making test did not show significant differences between control and exercise sessions. Additionally, there was significant and positive association among the Stroop test ΔRT of exercise session with xiii chronological age (r= 0.635, p=0.001; r 2 = 0.404, p=0.003) and sexual maturation (rs= 0.580, p=0.007; r 2 = 0.408, p=0.002). Differently, there was no association among the control session ΔRT and chronological age (r= – 0.144, p=0.273; r 2 = 0.021, p=0.545) or sexual maturation (rs= –0.155, p=0.513; r 2 = 0.015, p=0.610). Conclusion: Vigorous aerobic exercise seems to improve acutely executive functions in adolescents. The effect of exercise on inhibitory control performance was associated to pubertal stage and chronological age. In other words, the benefits of exercise were more evident in early adolescence (↑ ΔRT) and its magnitude decreases along the growing up process.

Modelagem dos efeitos da irradiação luminosa no cérebro de camundongos e rastreamento de neurônios durante experimentos de microscopia de fluorescência

The fluorescent proteins are an essential tool in many fields of biology, since they allow us to watch the development of structures and dynamic processes of cells in living tissue, with the aid of fluorescence microscopy. Optogenectics is another technique that is currently widely used in Neuroscience. In general, this technique allows to activate/deactivate neurons with the radiation of certain wavelengths on the cells that have ion channels sensitive to light, at the same time that can be used with fluorescent proteins. This dissertation has two main objectives. Initially, we study the interaction of light radiation and mice brain tissue to be applied in optogenetic experiments. In this step, we model absorption and scattering effects using mice brain tissue characteristics and Kubelka-Munk theory, for specific wavelengths, as a function of light penetration depth (distance) within the tissue. Furthermore, we model temperature variations using the finite element method to solve Pennes’ bioheat equation, with the aid of COMSOL Multiphysics Modeling Software 4.4, where we simulate protocols of light stimulation tipically used in optogenetics. Subsequently, we develop some computational algorithms to reduce the exposure of neuron cells to the light radiation necessary for the visualization of their emitted fluorescence. At this stage, we describe the image processing techniques developed to be used in fluorescence microscopy to reduce the exposure of the brain samples to continuous light, which is responsible for fluorochrome excitation. The developed techniques are able to track, in real time, a region of interest (ROI) and replace the fluorescence emitted by the cells by a virtual mask, as a result of the overlay of the tracked ROI and the fluorescence information previously stored, preserving cell location, independently of the time exposure to fluorescent light. In summary, this dissertation intends to investigate and describe the effects of light radiation in brain tissue, within the context of Optogenetics, in addition to providing a computational tool to be used in fluorescence microscopy experiments to reduce image bleaching and photodamage due to the intense exposure of fluorescent cells to light radiation.

Papel da proteína de reparo XPC na regulação das proteínas de reparo APE1, OGG1 e PARP-1 em células humanas e de camundongos

studies using UV as a source of DNA damage. However, even though unrepaired UV-induced DNA damages are related to mutagenesis, cell death and tumorigenesis, they do not explain phenotypes such as neurodegeneration and internal tumors observed in patients with syndromes like Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS) that are associated with NER deficiency. Recent evidences point to a role of NER in the repair of 8-oxodG, a typical substrate of Base Excision Repair (BER). Since deficiencies in BER result in genomic instability, neurodegenerative diseases and cancer, it was investigated in this research the impact of XPC deficiency on BER functions in human cells. It was analyzed both the expression and the cellular localization of APE1, OGG1 e PARP-1, the mainly BER enzymes, in different NER-deficient human fibroblasts. The endogenous levels of these enzymes are reduced in XPC deficient cells. Surprisingly, XP-C fibroblasts were more resistant to oxidative agents than the other NER deficient fibroblasts, despite presenting the highest of 8-oxodG. Furthermore, subtle changes in the nuclear and mitochondrial localization of APE1 were detected in XP-C fibroblasts. To confirm the impact of XPC deficiency in the regulation of APE1 and OGG1 expression and activity, we constructed a XPC-complemented cell line. Although the XPC complementation was only partial, we found that XPC-complemented cells presented increased levels of OGG1 than XPC-deficient cells. The extracts from XPC-complemented cells also presented an elevated OGG1 enzimatic activity. However, it was not observed changes in APE1 expression and activity in the XPCcomplemented cells. In addition, we found that full-length APE1 (37 kDa) and OGG1- α are in the mitochondria of XPC-deficient fibroblasts and XPC-complemented fibroblasts before and after induction of oxidative stress. On the other hand, the expression of APE1 and PARP-1 are not altered in brain and liver of XPC knockout mice. However, XPC deficiency changed the APE1 localization in hypoccampus and hypothalamus. We also observed a physical interaction between XPC and APE1 proteins in human cells. In conclusion, the data suggest that XPC protein has a role in the regulation of OGG1 expression and activity in human cells and is involved mainly in the regulation of APE1 localization in mice. Aditionally, the response of NER deficient cells under oxidative stress may not be only associated to the NER deficiency per se, but it may include the new functions of NER enzymes in regulation of expression and cell localization of BER proteins

Supressão do ruído de rolamento superficial utilizando a transformada Curvelet

Among the many types of noise observed in seismic land acquisition there is one produced by surface waves called Ground Roll that is a particular type of Rayleigh wave which characteristics are high amplitude, low frequency and low velocity (generating a cone with high dip). Ground roll contaminates the relevant signals and can mask the relevant information, carried by waves scattered in deeper regions of the geological layers. In this thesis, we will present a method that attenuates the ground roll. The technique consists in to decompose the seismogram in a basis of curvelet functions that are localized in time, in frequency, and also, incorporate an angular orientation. These characteristics allow to construct a curvelet filter that takes in consideration the localization of denoise in scales, times and angles in the seismogram. The method was tested with real data and the results were very good

Papel da localização da carga em determinação dos parâmetros do canal iônico

To aureus α-HL channel, we used the cysteine-scanning mutagenesis technique. Twenty-four mutants were produced from the substitution of a single aminoacid of the primary structure of the α-HL pro this yzed after the incorporation of a mutant channel in planar lipid bilayer membranes. The modified proteins were studied in the absence and presence of watersoluble specific sulphydryl-specific reagents, in order to introduce a strong positive or negative harge at positions of substitution. The introduction of a negative charge in the stem region onverted the selectivity of the channel from weak anionic to more cationic. However, the troduction of a positive charge increased its selectivity to the anion. The degree of these alterations was inversely dependent on the channel radius at the position of the introduced harge (selectivity). As to the asymmetry of the conductance-voltage, the influence of the harge was more complex. The introduction of the negative charge in the stem region (the trans art of the pore) provoked a decrease. The intensity of these alterations depended on the radius, and on the type of free charge at the pore entrance. These results suggest that the free charge at surrounds the pore wall is responsible for the cation-anion selectivity of the channel. The istribution of the charges between the entrances is crucial for determining the asymmetry of e conductance-voltage curves. We hope that these results serve as a model for studies with other nanometric channels, in biological or planar lipid bilayer membranes or in iotechnological applications

Dos movimentos sociais às funções institucionais: a Consolidação de uma geração política em Sergipe.

This study was presented to the Post-Graduation Program in Social Sciences at UFRN as part of the requisites for obtaining the title of Master in Social Sciences. It describes the results of the research From social movements to the institutional functions: the consolidation of a generation . Its main objective is to describe the history of a political generation that emerged from the social movements, in the 80 s, in Sergipe, and that nowadays occupies the main governmental positions in the State s political scenario. As its specific objectives, the research described the emerging of social movements in the 80s in Sergipe; it found in the social movements in Sergipe, in the 80s, the beginning of the history of a new political generation, and described the consolidation of this new political generation in institutional positions as the expression of a new group of power in Sergipe s politics. Among the social movements that gained visibility in that period and that projected their leadership into the political scenario of Sergipe, this study highlights: the students movement, teacher s movement, bank clercks movement, miners movement, and rural workers movement. It utilized as methodology the research in sites, magazines, and the use of testimonies from semi-structured interviews. The main leadership of the five movements that were analyzed is, nowadays, governing the state, administering the capital s city hall, and performing legislative work at the Legislative Assembly of Sergipe, and at the Chamber of City Councilmen of Aracaju. This study described the political history of the main leadership of that generation of militants and organizers of social movements, and of left party groups in Sergipe, highlighting that their consolidation in the political scenario of the State meant the consolidation of a new group of power in Sergipe s politics.

Perfis do controle jurisdicional de políticas publicas: parâmetros objetivos e tutela coletiva

This paper focuses on a study of public policy jurisdictional control as some effectiveness mechanism for cultural, economical, and social fundamental rights. It investigates the juridical profile of public policies based on premises of the current (Neo)Constitutional State model and the assertion of an essentially constitutionalist Law paradigm from its genesis to its most peculiar elements, and through tormenting issues, such as: its position between Law and Politics, the difference with reflective subjective rights, and the problem of high financial costs. Once its object is identified, it moves forward into the theme itself, which is that of jurisdictional control, investigating its legitimacy based on paradigmatic judicial precedents and the facing of themes such as: current role of the Judicial Power, the splitting of state functions, administrative discretion, financial affordability, illegal omissions, and budget control. Finally, it examines, as its study central object, objective parameters for definition control, execution, and transparency of public policies, as well as identifying the most appropriate collective jurisdictional tutoring to its purposes together with some of its law process means. Therefrom, it shows new perspectives for the recent study on jurisdictional control of public policies, building foundations for the fundamental rights effectiveness

Papéis e funções dos profissionais dos serviços e política de saúde mental em Natal (RN)

A assistência psiquiátrica e as políticas de atenção à saúde mental passaram por diversas transformações, marcadas ora por avanços, ora por retrocessos centrados no estigma, desinteresse e preconceito que ainda permeiam a sociedade e o senso comum. Este estudo objetivou analisar o processo de reforma psiquiátrica e a política de saúde mental do Município de Natal/RN a partir dos papéis e funções dos profissionais de nível superior dos serviços substitutivos em saúde mental. Trata-se de uma pesquisa analítica, transversal, com dados quantitativos e qualitativos, realizada nos sete serviços substitutivos de saúde mental de Natal, entre os meses de março a agosto de 2013, após aprovação do estudo pelo Comitê de Ética em Pesquisa da Universidade Federal do Rio Grande do Norte, Parecer nº 217.808, CAAE: 10650612.8.1001.5537, em 01 de março de 2013. A amostra por conveniência compôs-se por 65 profissionais de nível superior das equipes de saúde mental. Utilizou-se um questionário com questões fechadas e semiabertas sobre o perfil socioeconômico, as políticas, as práticas e a formação em saúde mental. Tabularam-se e submeteram-se as respostas das questões fechadas do questionário no programa estatístico SPSS versão 20.0, analisando-os por meio de estatística descritiva, com a formulação de gráficos e tabelas. Para verificar o nível de significância, adotando-se p-valor<0,05, optou-se pela aplicação dos testes qui-quadrado e exato de Fisher. Submeteram-se os dados das questões semiabertas ao software ALCESTE e à luz da análise de conteúdo de Bardin. O perfil dos participantes caracterizou-se por maioria do sexo feminino (79%), faixa etária de 36 a 55 anos (52%), média de 42 anos, carga horária de 40 horas semanais (62%), tempo de conclusão da graduação de 6 a 15 anos (57%), trabalhavam na área de saúde mental há menos de 10 anos (72%) e na instituição pesquisada há 5 anos ou menos (52%). Da amostra estudada, 86% atendiam grupos de usuários, 97% realizavam atendimento individual, 94% observavam o comportamento do paciente, 92% realizavam atendimento familiar, utilizando, principalmente, a abordagem cognitiva (28%). Os dados qualitativos originaram cinco categorias: Formação acadêmica e atuação em saúde mental; Ausência de capacitação e supervisão em saúde mental; Dificuldades da prática profissional nos serviços substitutivos de saúde mental; Trabalho em equipe: entre acertos e conflitos; Política Nacional de Saúde Mental: uma realidade ainda distante. Detectou-se adequabilidade dos papéis e funções dos profissionais quanto ao tempo de trabalho na saúde mental e na instituição pesquisada; no atendimento e atividades individuais; na promoção de ações visando à autonomia do paciente; no atendimento em grupo de pacientes; e, em parte, à família/familiar dos portadores de transtorno mental, havendo inadequação quanto ao atendimento aos grupos de familiares (52.3%), à formação especializada em saúde mental (69.2%; p=0,02) e às dificuldades de trabalho nos serviços (87.7%). Evidenciou-se adequação nos papéis e nas funções d esenvolvidas pelos profissionais nos serviços substitutivos em saúde mental de Natal, embora convivendo em seu cotidiano com inúmeras dificuldades encontradas no desenvolvimento de suas práticas profissiona is frente às condições de trabalho

Proposta de localização de uma unidade de tratamento de óleo e gordura residual de fritura na cidade do Natal/RN para produção de biodiesel

This work addresses biodiesel by transesterification from the use of waste frying oil as a possible technological alternative for both reducing greenhouse gas emissions and by presenting themselves as an environmental call to designate a rational use of oil when no longer played in the environment to become renewable energy. It has proposed location of a residual oil and fat treatment plant to produce biodiesel, using models of Location and Routing for the improvement of routes. To achieve the goal, questionnaires were administered in establishments that use oil or vegetable fat in their productive activities in order to quantify the residue, to analyze actions and environmental perception of people who work directly with the residue on the destination you are being given to oil and fat used. It has indicated using of two single setup location, the method of Center of Gravity and the model of Ardalan, a geographical point that minimizes the costs of transporting waste to the treatment plant. Actions have been proposed for the improvement of collection routes this residue using the Routing Method of Scanning, as an illustration. The results demonstrated the lack of knowledge of the people who deal directly with large amounts of waste, on the environmental impacts caused by their incorrect disposal. The models used were uniform since point out to neighborhoods in similar regions. The neighborhoods of Lagoa Nova / Morro Branco (Ardalan) and Nova Descoberta (Center of Gravity) as ideal for the installation of treatment plant. However, it is suggested to be tested other models that take into account new variables than those used (supply of waste and the distance between points). The routing through the method of scanning has shown that it is possible, in a simple way to optimize routes in order to reduce distances and therefore the logistics costs in the collection of such waste. Introducing a route as a test to gather the twenty largest oil suppliers used in sample frying, using as a main factor time 8 hour of working shift every day

Algoritmos para o problema de localização de uma facilidade com distâncias limitadas e restrições de atendimento

The objective in the facility location problem with limited distances is to minimize the sum of distance functions from the facility to the customers, but with a limit on each distance, after which the corresponding function becomes constant. The problem has applications in situations where the service provided by the facility is insensitive after a given threshold distance (eg. fire station location). In this work, we propose a global optimization algorithm for the case in which there are lower and upper limits on the numbers of customers that can be served

Algoritmos de otimização para decisões de localização de facilidades e distribuição em sistemas multiníveis de transporte rodoviário de carga

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Um protocolo de comunicação multicast na camada de aplicação com Consciência de Localização

Internet applications such as media streaming, collaborative computing and massive multiplayer are on the rise,. This leads to the need for multicast communication, but unfortunately group communications support based on IP multicast has not been widely adopted due to a combination of technical and non-technical problems. Therefore, a number of different application-layer multicast schemes have been proposed in recent literature to overcome the drawbacks. In addition, these applications often behave as both providers and clients of services, being called peer-topeer applications, and where participants come and go very dynamically. Thus, servercentric architectures for membership management have well-known problems related to scalability and fault-tolerance, and even peer-to-peer traditional solutions need to have some mechanism that takes into account member's volatility. The idea of location awareness distributes the participants in the overlay network according to their proximity in the underlying network allowing a better performance. Given this context, this thesis proposes an application layer multicast protocol, called LAALM, which takes into account the actual network topology in the assembly process of the overlay network. The membership algorithm uses a new metric, IPXY, to provide location awareness through the processing of local information, and it was implemented using a distributed shared and bi-directional tree. The algorithm also has a sub-optimal heuristic to minimize the cost of membership process. The protocol has been evaluated in two ways. First, through an own simulator developed in this work, where we evaluated the quality of distribution tree by metrics such as outdegree and path length. Second, reallife scenarios were built in the ns-3 network simulator where we evaluated the network protocol performance by metrics such as stress, stretch, time to first packet and reconfiguration group time

Localização e mapeamento simultâneos de ambientes planos usando visão monocular e representação híbrida do ambiente

The goal of this work is to propose a SLAM (Simultaneous Localization and Mapping) solution based on Extended Kalman Filter (EKF) in order to make possible a robot navigates along the environment using information from odometry and pre-existing lines on the floor. Initially, a segmentation step is necessary to classify parts of the image in floor or non floor . Then the image processing identifies floor lines and the parameters of these lines are mapped to world using a homography matrix. Finally, the identified lines are used in SLAM as landmarks in order to build a feature map. In parallel, using the corrected robot pose, the uncertainty about the pose and also the part non floor of the image, it is possible to build an occupancy grid map and generate a metric map with the obstacle s description. A greater autonomy for the robot is attained by using the two types of obtained map (the metric map and the features map). Thus, it is possible to run path planning tasks in parallel with localization and mapping. Practical results are presented to validate the proposal

Dedução de Funções de Alívio para Priorização de Variantes de Chaveamento Adequadas à Eliminação de Sobrecargas

Eventually, violations of voltage limits at buses or admissible loadings of transmission lines and/or power transformers may occur by the power system operation. If violations are detected in the supervision process, corrective measures may be carried out in order to eliminate them or to reduce their intensity. Loading restriction is an extreme solution and should only be adopted as the last control action. Previous researches have shown that it is possible to control constraints in electrical systems by changing the network topology, using the technique named Corrective Switching, which requires no additional costs. In previous works, the proposed calculations for verifying the ability of a switching variant in eliminating an overload in a specific branch were based on network reduction or heuristic analysis. The purpose of this work is to develop analytical derivation of linear equations to estimate current changes in a specific branch (due to switching measures) by means of few calculations. For bus-bar coupling, derivations will be based on short-circuit theory and Relief Function methodology. For bus-bar splitting, a Relief Function will be derived based on a technique of equivalent circuit. Although systems of linear equations are used to substantiate deductions, its formal solution for each variant, in real time does not become necessary. A priority list of promising variants is then assigned for final check by an exact load flow calculation and a transient analysis using ATP Alternative Transient Program. At last, results obtained by simulation in networks with different features will be presented