Discriminating Different Classes of Biological Networks by Analyzing the Graphs Spectra Distribution

The brain's structural and functional systems, protein-protein interaction, and gene networks are examples of biological systems that share some features of complex networks, such as highly connected nodes, modularity, and small-world topology. Recent studies indicate that some pathologies present topological network alterations relative to norms seen in the general population. Therefore, methods to discriminate the processes that generate the different classes of networks (e. g., normal and disease) might be crucial for the diagnosis, prognosis, and treatment of the disease. It is known that several topological properties of a network (graph) can be described by the distribution of the spectrum of its adjacency matrix. Moreover, large networks generated by the same random process have the same spectrum distribution, allowing us to use it as a "fingerprint". Based on this relationship, we introduce and propose the entropy of a graph spectrum to measure the "uncertainty" of a random graph and the Kullback-Leibler and Jensen-Shannon divergences between graph spectra to compare networks. We also introduce general methods for model selection and network model parameter estimation, as well as a statistical procedure to test the nullity of divergence between two classes of complex networks. Finally, we demonstrate the usefulness of the proposed methods by applying them to (1) protein-protein interaction networks of different species and (2) on networks derived from children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) and typically developing children. We conclude that scale-free networks best describe all the protein-protein interactions. Also, we show that our proposed measures succeeded in the identification of topological changes in the network while other commonly used measures (number of edges, clustering coefficient, average path length) failed.

Medium Light and Medium Roast Paper-Filtered Coffee Increased Antioxidant Capacity in Healthy Volunteers: Results of a Randomized Trial

We compared the effects of medium light roast (MLR) and medium roast (MR) paper-filtered coffee on antioxidant capacity and lipid peroxidation in healthy volunteers. In a randomized crossover study, 20 volunteers consumed 482 +/- 61 ml/day of MLR or MR for four weeks. Plasma total antioxidant status (TAS), oxygen radical absorbance capacity (ORAC), oxidized LDL and 8-epi-prostaglandin F2 alpha, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activity were measured at baseline and after the interventions. MLR had higher chlorogenic acids-(CGA; 334 mg/150 mL) and less caffeine (231 mg/150 ml) than MR had (210 and 244 mg/150 ml, respectively). MLR also had fewer Maillard reaction products (MRP) than MR had. Compared with baseline, subjects had an increase of 21 and 26 % in TAS, 13 and 13 % in CAT, 52 and 75 % in SOD, and 62 and 49 % in GPx after MLR and MR consumption (P < 0.001), respectively. ORAC increased after MLR (P = 0.004). No significant alteration in lipid peroxidation biomarkers was observed. Both coffees had antioxidant effects. Although MLR contained more CGA, there were similar antioxidant effects between the treatments. MRP may have contributed as an antioxidant. These effects may be important in protecting biological systems and reducing the risk of diseases related to oxidative stress.

MODULARITY, NOISE, AND NATURAL SELECTION

Most biological systems are formed by component parts that are to some degree interrelated. Groups of parts that are more associated among themselves and are relatively autonomous from others are called modules. One of the consequences of modularity is that biological systems usually present an unequal distribution of the genetic variation among traits. Estimating the covariance matrix that describes these systems is a difficult problem due to a number of factors such as poor sample sizes and measurement errors. We show that this problem will be exacerbated whenever matrix inversion is required, as in directional selection reconstruction analysis. We explore the consequences of varying degrees of modularity and signal-to-noise ratio on selection reconstruction. We then present and test the efficiency of available methods for controlling noise in matrix estimates. In our simulations, controlling matrices for noise vastly improves the reconstruction of selection gradients. We also perform an analysis of selection gradients reconstruction over a New World Monkeys skull database to illustrate the impact of noise on such analyses. Noise-controlled estimates render far more plausible interpretations that are in full agreement with previous results.

Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development

Congenital heart disease (CHD) occurs in similar to 1% of newborns. CHD arises from many distinct etiologies, ranging from genetic or genomic variation to exposure to teratogens, which elicit diverse cell and molecular responses during cardiac development. To systematically explore the relationships between CHD risk factors and responses, we compiled and integrated comprehensive datasets from studies of CHD in humans and model organisms. We examined two alternative models of potential functional relationships between genes in these datasets: direct convergence, in which CHD risk factors significantly and directly impact the same genes and molecules and functional convergence, in which risk factors significantly impact different molecules that participate in a discrete heart development network. We observed no evidence for direct convergence. In contrast, we show that CHD risk factors functionally converge in protein networks driving the development of specific anatomical structures (e.g., outflow tract, ventricular septum, and atrial septum) that are malformed by CHD. This integrative analysis of CHD risk factors and responses suggests a complex pattern of functional interactions between genomic variation and environmental exposures that modulate critical biological systems during heart development.

A graph-theoretical approach in brain functional networks. Possible implications in EEG studies

Abstract Background Recently, it was realized that the functional connectivity networks estimated from actual brain-imaging technologies (MEG, fMRI and EEG) can be analyzed by means of the graph theory, that is a mathematical representation of a network, which is essentially reduced to nodes and connections between them. Methods We used high-resolution EEG technology to enhance the poor spatial information of the EEG activity on the scalp and it gives a measure of the electrical activity on the cortical surface. Afterwards, we used the Directed Transfer Function (DTF) that is a multivariate spectral measure for the estimation of the directional influences between any given pair of channels in a multivariate dataset. Finally, a graph theoretical approach was used to model the brain networks as graphs. These methods were used to analyze the structure of cortical connectivity during the attempt to move a paralyzed limb in a group (N=5) of spinal cord injured patients and during the movement execution in a group (N=5) of healthy subjects. Results Analysis performed on the cortical networks estimated from the group of normal and SCI patients revealed that both groups present few nodes with a high out-degree value (i.e. outgoing links). This property is valid in the networks estimated for all the frequency bands investigated. In particular, cingulate motor areas (CMAs) ROIs act as ‘‘hubs’’ for the outflow of information in both groups, SCI and healthy. Results also suggest that spinal cord injuries affect the functional architecture of the cortical network sub-serving the volition of motor acts mainly in its local feature property. In particular, a higher local efficiency El can be observed in the SCI patients for three frequency bands, theta (3-6 Hz), alpha (7-12 Hz) and beta (13-29 Hz). By taking into account all the possible pathways between different ROI couples, we were able to separate clearly the network properties of the SCI group from the CTRL group. In particular, we report a sort of compensatory mechanism in the SCI patients for the Theta (3-6 Hz) frequency band, indicating a higher level of “activation” Ω within the cortical network during the motor task. The activation index is directly related to diffusion, a type of dynamics that underlies several biological systems including possible spreading of neuronal activation across several cortical regions. Conclusions The present study aims at demonstrating the possible applications of graph theoretical approaches in the analyses of brain functional connectivity from EEG signals. In particular, the methodological aspects of the i) cortical activity from scalp EEG signals, ii) functional connectivity estimations iii) graph theoretical indexes are emphasized in the present paper to show their impact in a real application.

Modularity and evolutionary constraints in a baculovirus gene regulatory network

Abstract Background The structure of regulatory networks remains an open question in our understanding of complex biological systems. Interactions during complete viral life cycles present unique opportunities to understand how host-parasite network take shape and behave. The Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) is a large double-stranded DNA virus, whose genome may encode for 152 open reading frames (ORFs). Here we present the analysis of the ordered cascade of the AgMNPV gene expression. Results We observed an earlier onset of the expression than previously reported for other baculoviruses, especially for genes involved in DNA replication. Most ORFs were expressed at higher levels in a more permissive host cell line. Genes with more than one copy in the genome had distinct expression profiles, which could indicate the acquisition of new functionalities. The transcription gene regulatory network (GRN) for 149 ORFs had a modular topology comprising five communities of highly interconnected nodes that separated key genes that are functionally related on different communities, possibly maximizing redundancy and GRN robustness by compartmentalization of important functions. Core conserved functions showed expression synchronicity, distinct GRN features and significantly less genetic diversity, consistent with evolutionary constraints imposed in key elements of biological systems. This reduced genetic diversity also had a positive correlation with the importance of the gene in our estimated GRN, supporting a relationship between phylogenetic data of baculovirus genes and network features inferred from expression data. We also observed that gene arrangement in overlapping transcripts was conserved among related baculoviruses, suggesting a principle of genome organization. Conclusions Albeit with a reduced number of nodes (149), the AgMNPV GRN had a topology and key characteristics similar to those observed in complex cellular organisms, which indicates that modularity may be a general feature of biological gene regulatory networks.

Morphological alterations and gene and protein expression profiling of bladder tumor cells after treatment with gemcitabine.

Chemical agents used in cancer therapy are associated with cell cycle arrest, activation or deactivation of mechanisms associated to DNA repair and apoptosis. However, due to the complexity of biological systems, the molecular mechanisms responsible for these activities are not fully understood. Thus, studies about gene and protein expression have shown promising results for understanding the mechanisms related to cellular responses and regression of cancer after chemotherapy. This study aimed to evaluate the gene and protein expression profiling in bladder transitional cell carcinoma (TCC) with different TP53 status after gemcitabine (1.56 μM) treatment. The RT4 (grade 1, TP53 wild type), 5637 (grade 2, TP53 mutated) and T24 (grade 3, TP53 mutated) cell lines were used. PCR arrays and mass spectrometry were used to analyze gene and protein expression, respectively. Morphological alterations were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results of PCR array showed that gemcitabine activity was mainly related to CDKN1A, GADD45A and SERTDA1 overexpression, and BAX overexpression only in the wild type TP53 cells. Mass spectrometry demonstrated that gemcitabine modulated the protein expression, especially those from genes related to apoptosis, transport of vesicles and stress response. Analyses using SEM and TEM showed changes in cell morphology independently on the cell line studied. The observed decreased number of microvillus suggests low contact among the cells and between cell and extracellular matrix; irregular forms might indicate actin cytoskeleton deregulation; and the reduction in the amount of organelles and core size might indicate reduced cellular metabolism. In conclusion, independently on TP53 status or grade of bladder tumor, gemcitabine modulated genes related to the cell cycle and apoptosis, that reflected in morphological changes indicative of future cell death.

Optical storage in azobenzene-containing epoxy polymers processed as Langmuir Blodgett films

In this study, azocopolymers containing different main-chain segments have been synthesized with diglycidyl ether of bisphenol A (DGEBA, DER 332, n=0.03) and the azochromophore Disperse Orange 3 (DO3) cured with twomonoamines, viz. benzylamine (BA) and m-toluidine (MT). The photoinduced birefringence was investigated in films produced with these azopolymers using the spin coating (SC) and Langmuir Blodgett (LB) techniques. In the LB films, birefringence increased with the content of azochromophore and the film thickness, as expected. The nanostructured nature of the LB films led to an enhanced birefringence and faster dynamics in the writing process, compared to the SC films. In summary, the combination of azocopolymers and the LBmethod may allow materials with tuned properties for various optical applications, including in biological systems were photoisomerization may be used to trigger actions such as drug delivery.

Biological evolution of replicator systems: towards a quantitative approach

The aim of this work is to study the features of a simple replicator chemical model of the relation between kinetic stability and entropy production under the action of external perturbations. We quantitatively explore the different paths leading to evolution in a toy model where two independent replicators compete for the same substrate. To do that, the same scenario described originally by Pross (J Phys Org Chem 17:312–316, 2004) is revised and new criteria to define the kinetic stability are proposed. Our results suggest that fast replicator populations are continually favored by the effects of strong stochastic environmental fluctuations capable to determine the global population, the former assumed to be the only acting evolution force. We demonstrate that the process is continually driven by strong perturbations only, and that population crashes may be useful proxies for these catastrophic environmental fluctuations. As expected, such behavior is particularly enhanced under very large scale perturbations, suggesting a likely dynamical footprint in the recovery patterns of new species after mass extinction events in the Earth’s geological past. Furthermore, the hypothesis that natural selection always favors the faster processes may give theoretical support to different studies that claim the applicability of maximum principles like the Maximum Metabolic Flux (MMF) or Maximum Entropy Productions Principle (MEPP), seen as the main goal of biological evolution.

Evaluation of Microbicidal Activity of Oxygen-Containing Plasmas using Biological Monitors with Different Lumen Calibers

New technologies and sterilization agents for heat-sensitive materials are under intense investigation. Plasma sterilization, an atoxic low-temperature substitute for conventional sterilization, uses various gases that are activated by an electrical discharge, generating reactive species that promote lethality in microorganisms. Here, assays were performed using pure O-2 and O-2 + H2O2 mixture gas plasmas against a standard load of Bacillus atrophaeus spores inoculated on glass carriers inside PVC catheters. The sterilization efficiency was studied as a function of plasma system (reactive ion etching or inductively coupled plasma), biological monitor lumen diameter, gas, radio frequency power, and sub-lethal exposition time. After sterilization, the biological monitors were disassembled and the surviving bacteria were grown in trypticase soy broth using the most probable number technique. Plasma antimicrobial activity depended on the catheter's internal diameter and radio frequency powers. The N-2 + H2O2 mixture exhibited higher microbial efficacy than pure N-2 in both plasma systems.

Methane emission from soil under long-term no-till cropping systems

Methane (CH4) emission from agricultural soils increases dramatically as a result of deleterious effect of soil disturbance and nitrogen fertilization on methanotrophic organisms; however, few studies have attempted to evaluate the potential of long-term conservation management systems to mitigate CH4 emissions in tropical and subtropical soils. This study aimed to evaluate the long-term effect (>19 years) of no-till grass- and legume-based cropping systems on annual soil CH4 fluxes in a formerly degraded Acrisol in Southern Brazil. Air sampling was carried out using static chambers and CH4 analysis by gas chromatography. Analysis of historical data set of the experiment evidenced a remarkable effect of high C- and N-input cropping systems on the improvement of biological, chemical, and physical characteristics of this no-tilled soil. Soil CH4 fluxes, which represent a net balance between consumption (-) and production (+) of CH4 in soil, varied from -40 +/- 2 to +62 +/- 78 mu g C m(-2) h(-1). Mean weighted contents of ammonium (NH4+-N) and dissolved organic carbon (DOC) in soil had a positive relationship with accumulated soil CH4 fluxes in the post-management period (r(2) = 0.95, p = 0.05), suggesting an additive effect of these nutrients in suppressing CH4 oxidation and stimulating methanogenesis, respectively, in legume-based cropping systems with high biomass input. Annual CH4 fluxes ranged from -50 +/- 610 to +994 +/- 105 g C ha(-1), which were inversely related to annual biomass-C input (r(2) = 0.99, p = 0.003), with the exception of the cropping system containing pigeon pea, a summer legume that had the highest biologically fixed N input (>300 kg ha(-1) yr(-1)). Our results evidenced a small effect of conservation management systems on decreasing CH4 emissions from soil, despite their significant effect restoring soil quality. We hypothesized that soil CH4 uptake strength has been off-set by an injurious effect of biologically fixed N in legume-based cropping systems on soil methanotrophic microbiota, and by the methanogenesis increase as a result of the O-2 depletion in niches of high biological activity in the surface layer of the no-tillage soil. (C) 2012 Elsevier B.V. All rights reserved.

THE CONVERSION OF THE ATLANTIC FOREST IN ANTHROPOGENIC LANDSCAPES: LESSONS FOR THE CONSERVATION OF BIOLOGICAL DIVERSITY OF TROPICAL FORESTS

The Brazilian Atlantic forest has been an excellent laboratory for investigations regarding tropical forest ecology and the fragility of tropical ecosystems in face of human disturbances. In this article, we present a synthesis about the spatial distribution of Atlantic forest biodiversity and forest response to human disturbances, as well as the ongoing conservation efforts based on a review of several investigations in this biota. In general, studies have documented an uneven distribution of biodiversity throughout the Atlantic forest region, revealing alarming rates of habitat loss at low altitudes, while protected areas concentrate at higher altitudes. It has been suggested that the remaining forest habitat is moving towards an early-successional systems across human-modified landscapes. Such regressive forest succession increases the threats for several animals and plant groups. Based on these findings, we propose seven guidelines in order to enhance the provision of ecosystem services and the conservation value of human-modified landscapes, reducing the species extinction risk in the Atlantic forest and in other irreplaceable tropical biotas.

Physical-chemical and microbiological changes in Cerrado Soil under differing sugarcane harvest management systems

Background: Sugarcane cultivation plays an important role in Brazilian economy, and it is expanding fast, mainly due to the increasing demand for ethanol production. In order to understand the impact of sugarcane cultivation and management, we studied sugarcane under different management regimes (pre-harvest burn and mechanical, unburnt harvest, or green cane), next to a control treatment with native vegetation. The soil bacterial community structure (including an evaluation of the diversity of the ammonia oxidizing (amoA) and denitrifying (nirK) genes), greenhouse gas flow and several soil physicochemical properties were evaluated. Results: Our results indicate that sugarcane cultivation in this region resulted in changes in several soil properties. Moreover, such changes are reflected in the soil microbiota. No significant influence of soil management on greenhouse gas fluxes was found. However, we did find a relationship between the biological changes and the dynamics of soil nutrients. In particular, the burnt cane and green cane treatments had distinct modifications. There were significant differences in the structure of the total bacterial, the ammonia oxidizing and the denitrifying bacterial communities, being that these groups responded differently to the changes in the soil. A combination of physical and chemical factors was correlated to the changes in the structures of the total bacterial communities of the soil. The changes in the structures of the functional groups follow a different pattern than the physicochemical variables. The latter might indicate a strong influence of interactions among different bacterial groups in the N cycle, emphasizing the importance of biological factors in the structuring of these communities. Conclusion: Sugarcane land use significantly impacted the structure of total selected soil bacterial communities and ammonia oxidizing and denitrifier gene diversities in a Cerrado field site in Central Brazil. A high impact of land use was observed in soil under the common burnt cane management. The green cane soil also presented different profiles compared to the control soil, but to at a lesser degree.

A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems

Abstract Background Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. Results This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. Conclusions This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.

What ethologically based models have taught us about the neural systems underlying fear and anxiety

Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.