Complex networks: the key to systems biology

Though introduced recently, complex networks research has grown steadily because of its potential to represent, characterize and model a wide range of intricate natural systems and phenomena. Because of the intrinsic complexity and systemic organization of life, complex networks provide a specially promising framework for systems biology investigation. The current article is an up-to-date review of the major developments related to the application of complex networks in biology, with special attention focused on the more recent literature. The main concepts and models of complex networks are presented and illustrated in an accessible fashion. Three main types of networks are covered: transcriptional regulatory networks, protein-protein interaction networks and metabolic networks. The key role of complex networks for systems biology is extensively illustrated by several of the papers reviewed.

Neural networks and statistical analysis for classification of corneal videokeratography maps based on Zernike coefficients: a quantitative comparison

PURPOSE: The main goal of this study was to develop and compare two different techniques for classification of specific types of corneal shapes when Zernike coefficients are used as inputs. A feed-forward artificial Neural Network (NN) and discriminant analysis (DA) techniques were used. METHODS: The inputs both for the NN and DA were the first 15 standard Zernike coefficients for 80 previously classified corneal elevation data files from an Eyesys System 2000 Videokeratograph (VK), installed at the Departamento de Oftalmologia of the Escola Paulista de Medicina, São Paulo. The NN had 5 output neurons which were associated with 5 typical corneal shapes: keratoconus, with-the-rule astigmatism, against-the-rule astigmatism, "regular" or "normal" shape and post-PRK. RESULTS: The NN and DA responses were statistically analyzed in terms of precision ([true positive+true negative]/total number of cases). Mean overall results for all cases for the NN and DA techniques were, respectively, 94% and 84.8%. CONCLUSION: Although we used a relatively small database, results obtained in the present study indicate that Zernike polynomials as descriptors of corneal shape may be a reliable parameter as input data for diagnostic automation of VK maps, using either NN or DA.

Learning processes and the neural analysis of conditioning

Classical and operant conditioning principles, such as the behavioral discrepancy-derived assumption that reinforcement always selects antecedent stimulus and response relations, have been studied at the neural level, mainly by observing the strengthening of neuronal responses or synaptic connections. A review of the literature on the neural basis of behavior provided extensive scientific data that indicate a synthesis between the two conditioning processes based mainly on stimulus control in learning tasks. The resulting analysis revealed the following aspects. Dopamine acts as a behavioral discrepancy signal in the midbrain pathway of positive reinforcement, leading toward the nucleus accumbens. Dopamine modulates both types of conditioning in the Aplysia mollusk and in mammals. In vivo and in vitro mollusk preparations show convergence of both types of conditioning in the same motor neuron. Frontal cortical neurons are involved in behavioral discrimination in reversal and extinction procedures, and these neurons preferentially deliver glutamate through conditioned stimulus or discriminative stimulus pathways. Discriminative neural responses can reliably precede operant movements and can also be common to stimuli that share complex symbolic relations. The present article discusses convergent and divergent points between conditioning paradigms at the neural level of analysis to advance our knowledge on reinforcement.

Evaluation of follicular lymphoid depletion in the Bursa of Fabricius: an alternative methodology using digital image analysis and artificial neural networks

Fifty Bursa of Fabricius (BF) were examined by conventional optical microscopy and digital images were acquired and processed using Matlab® 6.5 software. The Artificial Neuronal Network (ANN) was generated using Neuroshell® Classifier software and the optical and digital data were compared. The ANN was able to make a comparable classification of digital and optical scores. The use of ANN was able to classify correctly the majority of the follicles, reaching sensibility and specificity of 89% and 96%, respectively. When the follicles were scored and grouped in a binary fashion the sensibility increased to 90% and obtained the maximum value for the specificity of 92%. These results demonstrate that the use of digital image analysis and ANN is a useful tool for the pathological classification of the BF lymphoid depletion. In addition it provides objective results that allow measuring the dimension of the error in the diagnosis and classification therefore making comparison between databases feasible.

Efetividade de programa de agentes comunitários na promoção da saúde bucal

OBJETIVO:Avaliar mudanças em conhecimentos, atitudes e acesso/utilização de serviços odontológicos decorrentes de um programa de promoção da saúde bucal com agentes comunitários de saúde. MÉTODOS:Um projeto de capacitação combinando ensino-aprendizagem, apoio e supervisão, foi desenvolvido entre os meses de julho de 2003 a agosto de 2004. As mudanças foram avaliadas por meio de entrevistas estruturadas em que participaram 36 agentes comunitários de saúde e uma amostra de 91 mulheres e mães, representativa de donas de casa com 25 a 39 anos de idade, alfabetizadas e residentes em domicílios de três a seis cômodos no município de Rio Grande da Serra (SP). Foram colhidos dados sobre conhecimentos de saúde-doença bucal, práticas e capacidades auto-referidas em relação ao auto-exame, higiene bucal, número de residentes e de escovas dentais individuais e coletivas em cada domicílio e acesso e uso de serviços odontológicos. Por meio do teste t de Student pareado, foram comparadas as médias dos valores obtidos antes e depois do programa para cada um dos grupos estudados. As respostas foram analisadas adotando-se um nível de significância de 5%. RESULTADOS: Foram observadas diferenças estatisticamente significativas para questões relativas ao conhecimento de saúde bucal entre os agentes e entre as mulheres antes e depois da capacitação (p<0,05). Desequilíbrio entre o número de escovas e de indivíduos em cada família diminuiu. A freqüência da escovação e do uso do fio dental se elevou depois da atuação dos agentes. Os valores de auto-avaliação da higiene bucal aumentaram. Modificação nas práticas e capacidades auto-referidas mostrou significativa elevação da auto-confiança. O acesso ao serviço foi mais fácil (p<0,000) e seu uso mais regular (p<0,000) entre mulheres. CONCLUSÕES: Houve mudanças positivas na percepção em relação a aspectos de saúde bucal, na auto-confiança e no acesso e uso de serviços odontológicos. Tais mudanças po

The Process of Simulation Authoring/Creation by Chemistry Teachers: A Service Learning Experience

Two case studies are presented to describe the process of public school teachers authoring and creating chemistry simulations. They are part of the Virtual Didactic Laboratory for Chemistry, a project developed by the School of the Future of the University of Sao Paulo. the documental analysis of the material produced by two groups of teachers reflects different selection process for both themes and problem-situations when creating simulations. The study demonstrates the potential for chemistry learning with an approach that takes students' everyday lives into account and is based on collaborative work among teachers and researches. Also, from the teachers' perspectives, the possibilities of interaction that a simulation offers for classroom activities are considered.

Students' collective knowledge construction in the virtual learning environment ""ToLigado - your school interactive newspaper""

Introduction. The ToLigado Project - Your School Interactive Newspaper is an interactive virtual learning environment conceived, developed, implemented and supported by researchers at the School of the Future Research Laboratory of the University of Sao Paulo, Brazil. Method. This virtual learning environment aims to motivate trans-disciplinary research among public school students and teachers in 2,931 schools equipped with Internet-access computer rooms. Within this virtual community, students produce collective multimedia research documents that are immediately published in the portal. The project also aims to increase students' autonomy for research, collaborative work and Web authorship. Main sections of the portal are presented and described. Results. Partial results of the first two years' implementation are presented and indicate a strong motivation among students to produce knowledge despite the fragile hardware and software infrastructure at the time. Discussion. In this new environment, students should be seen as 'knowledge architects' and teachers as facilitators, or 'curiosity managers'. The ToLigado portal may constitute a repository for future studies regarding student attitudes in virtual learning environments, students' behaviour as 'authors', Web authorship involving collective knowledge production, teachers' behaviour as facilitators, and virtual learning environments as digital repositories of students' knowledge construction and social capital in virtual learning communities.

Cooperation, interaction and learning in local production systems: Evidence in Brazilian firms

In a local production system (LPS), besides external economies, the interaction, cooperation, and learning are indicated by the literature as complementary ways of enhancing the LPS's competitiveness and gains. In Brazil, the greater part of LPSs, mostly composed by small enterprises, displays incipient relationships and low levels of interaction and cooperation among their actors. The size of the participating enterprises itself for specificities that engender organizational constraints, which, in turn, can have a considerable impact on their relationships and learning dynamics. For that reason, it is the purpose of this article to present an analysis of interaction, cooperation, and learning relationships among several types of actors pertaining to an LPS in the farming equipment and machinery sector, bearing in mind the specificities of small enterprises. To this end, the fieldwork carried out in this study aimed at: (i) investigating external and internal knowledge sources conducive to learning and (ii) identifying and analyzing motivating and inhibiting factors related to specificities of small enterprises in order to bring the LPS members closer together and increase their cooperation and interaction. Empirical evidence shows that internal aspects of the enterprises, related to management and infrastructure, can have a strong bearing on their joint actions, interaction and learning processes.

Fully Connected PLL Networks: How Filter Determines the Number of Nodes

Synchronization plays an important role in telecommunication systems, integrated circuits, and automation systems. Formerly, the masterslave synchronization strategy was used in the great majority of cases due to its reliability and simplicity. Recently, with the wireless networks development, and with the increase of the operation frequency of integrated circuits, the decentralized clock distribution strategies are gaining importance. Consequently, fully connected clock distribution systems with nodes composed of phase-locked loops (PLLs) appear as a convenient engineering solution. In this work, the stability of the synchronous state of these networks is studied in two relevant situations: when the node filters are first-order lag-lead low-pass or when the node filters are second-order low-pass. For first-order filters, the synchronous state of the network shows to be stable for any number of nodes. For second-order filter, there is a superior limit for the number of nodes, depending on the PLL parameters. Copyright (C) 2009 Atila Madureira Bueno et al.

A reliable measure of similarity based on dependency for short time series: an application to gene expression networks

Background: Microarray techniques have become an important tool to the investigation of genetic relationships and the assignment of different phenotypes. Since microarrays are still very expensive, most of the experiments are performed with small samples. This paper introduces a method to quantify dependency between data series composed of few sample points. The method is used to construct gene co-expression subnetworks of highly significant edges. Results: The results shown here are for an adapted subset of a Saccharomyces cerevisiae gene expression data set with low temporal resolution and poor statistics. The method reveals common transcription factors with a high confidence level and allows the construction of subnetworks with high biological relevance that reveals characteristic features of the processes driving the organism adaptations to specific environmental conditions. Conclusion: Our method allows a reliable and sophisticated analysis of microarray data even under severe constraints. The utilization of systems biology improves the biologists ability to elucidate the mechanisms underlying celular processes and to formulate new hypotheses.

Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students

Souza MA, Souza MH, Palheta RC Jr, Cruz PR, Medeiros BA, Rola FH, Magalhaes PJ, Troncon LE, Santos AA. Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students. Adv Physiol Educ 33: 343-348, 2009; doi: 10.1152/advan.90176.2008.-Current medical curricula devote scarce time for practical activities on digestive physiology, despite frequent misconceptions about dyspepsia and dysmotility phenomena. Thus, we designed a hands-on activity followed by a small-group discussion on gut motility. Male awake rats were randomly submitted to insulin, control, or hypertonic protocols. Insulin and control rats were gavage fed with 5% glucose solution, whereas hypertonic-fed rats were gavage fed with 50% glucose solution. Insulin treatment was performed 30 min before a meal. All meals (1.5 ml) contained an equal mass of phenol red dye. After 10, 15, or 20 min of meal gavage, rats were euthanized. Each subset consisted of six to eight rats. Dye recovery in the stomach and proximal, middle, and distal small intestine was measured by spectrophotometry, a safe and reliable method that can be performed by minimally trained students. In a separate group of rats, we used the same protocols except that the test meal contained (99m)Tc as a marker. Compared with control, the hypertonic meal delayed gastric emptying and gastrointestinal transit, whereas insulinic hypoglycemia accelerated them. The session helped engage our undergraduate students in observing and analyzing gut motor behavior. In conclusion, the fractional dye retention test can be used as a teaching tool to strengthen the understanding of basic physiopathological features of gastrointestinal motility.

Assessment of Preclinical Learning on Oral Surgery Using Three Instructional Strategies

The purpose of this investigation was to evaluate three learning methods for teaching basic oral surgical skills Thirty predoctoral dental students without any surgical knowledge or previous surgical experience were divided Into three groups (n=10 each) according to instructional strategy Group 1, active learning Group 2, text reading only, and Group 3, text reading and video demonstration After instruction, the apprentices were allowed to practice incision dissection and suture maneuvers in a bench learning model During the students' performance, a structured practice evaluation test to account for correct or incorrect maneuvers was applied by trained observers Evaluation tests were repeated after thirty and sixty days Data from resulting scores between groups and periods were considered for statistical analysis (ANOVA and Tukey Kramer) with a significant level of a=0 05 Results showed that the active learning group presented the significantly best learning outcomes related to immediate assimilation of surgical procedures compared to other groups All groups results were similar after sixty days of the first practice Assessment tests were fundamental to evaluate teaching strategies and allowed theoretical and proficiency learning feedbacks Repetition and interactive practice promoted retention of knowledge on basic oral surgical skills

E-Learning Used in a Training Course on Atraumatic Restorative Treatment (ART) for Brazilian Dentists

The purpose of this study was to assess the benefits of using e-learning resources in a dental training course on Atraumatic Restorative Treatment (ART). This e-course was given in a DVD format, which presented the ART technique and philosophy. The participants were twenty-four dentists from the Brazilian public health system. Prior to receiving the DVD, the dentists answered a questionnaire regarding their personal data, previous knowledge about ART, and general interest in training courses. The dentists also participated in an assessment process consisting of a test applied before and after the course. A single researcher corrected the tests, and intraexaminer reproducibility was calculated (kappa=0.89). Paired t-tests were carried out to compare the means between the assessments, showing a significant improvement in the performance of the subjects on the test taken after the course (p<0.05). A linear regression model was used with the difference between the means as the outcome. A greater improvement on the test results was observed among female dentists (p=0.034), dentists working for a shorter period of time in the public health system (p=0.042), and dentists who used the ART technique only for urgent and/or temporary treatment (p=0.010). In conclusion, e-learning has the potential of improving the knowledge that dentists working in the public health system have about ART, especially those with less clinical experience and less knowledge about the subject.

The Missing Part of Seed Dispersal Networks: Structure and Robustness of Bat-Fruit Interactions

Mutualistic networks are crucial to the maintenance of ecosystem services. Unfortunately, what we know about seed dispersal networks is based only on bird-fruit interactions. Therefore, we aimed at filling part of this gap by investigating bat-fruit networks. It is known from population studies that: (i) some bat species depend more on fruits than others, and (ii) that some specialized frugivorous bats prefer particular plant genera. We tested whether those preferences affected the structure and robustness of the whole network and the functional roles of species. Nine bat-fruit datasets from the literature were analyzed and all networks showed lower complementary specialization (H(2)' = 0.3760.10, mean 6 SD) and similar nestedness (NODF = 0.5660.12) than pollination networks. All networks were modular (M=0.32 +/- 0.07), and had on average four cohesive subgroups (modules) of tightly connected bats and plants. The composition of those modules followed the genus-genus associations observed at population level (Artibeus-Ficus, Carollia-Piper, and Sturnira-Solanum), although a few of those plant genera were dispersed also by other bats. Bat-fruit networks showed high robustness to simulated cumulative removals of both bats (R = 0.55 +/- 0.10) and plants (R = 0.68 +/- 0.09). Primary frugivores interacted with a larger proportion of the plants available and also occupied more central positions; furthermore, their extinction caused larger changes in network structure. We conclude that bat-fruit networks are highly cohesive and robust mutualistic systems, in which redundancy is high within modules, although modules are complementary to each other. Dietary specialization seems to be an important structuring factor that affects the topology, the guild structure and functional roles in bat-fruit networks.

Social Networks Shape the Transmission Dynamics of Hepatitis C Virus

Hepatitis C virus (HCV) infects 170 million people worldwide, and is a major public health problem in Brazil, where over 1% of the population may be infected and where multiple viral genotypes co-circulate. Chronically infected individuals are both the source of transmission to others and are at risk for HCV-related diseases, such as liver cancer and cirrhosis. Before the adoption of anti-HCV control measures in blood banks, this virus was mainly transmitted via blood transfusion. Today, needle sharing among injecting drug users is the most common form of HCV transmission. Of particular importance is that HCV prevalence is growing in non-risk groups. Since there is no vaccine against HCV, it is important to determine the factors that control viral transmission in order to develop more efficient control measures. However, despite the health costs associated with HCV, the factors that determine the spread of virus at the epidemiological scale are often poorly understood. Here, we sequenced partial NS5b gene sequences sampled from blood samples collected from 591 patients in Sao Paulo state, Brazil. We show that different viral genotypes entered Sao Paulo at different times, grew at different rates, and are associated with different age groups and risk behaviors. In particular, subtype 1b is older and grew more slowly than subtypes 1a and 3a, and is associated with multiple age classes. In contrast, subtypes 1a and 3b are associated with younger people infected more recently, possibly with higher rates of sexual transmission. The transmission dynamics of HCV in Sao Paulo therefore vary by subtype and are determined by a combination of age, risk exposure and underlying social network. We conclude that social factors may play a key role in determining the rate and pattern of HCV spread, and should influence future intervention policies.