Development, characterization, and in vitro trials of chloroaluminum phthalocyanine-magnetic nanoemulsion to hyperthermia and photodynamic therapies on glioblastoma as a biological model

A glioblastoma multiforme (GBM) is the highest grade glioma tumor (grade IV) and is the most malignant form of astrocytomas. Grade IV tumors, which are the most malignant and aggressive, affect people between the ages of 45 and 70 years. A GBM exhibits remarkable characteristics that include excessive proliferation, necrosis, genetic instability, and chemoresistance. Because of these characteristics, GBMs are difficult to treat and have a poor prognosis with a median survival of less than one year. New methods to achieve widespread distribution of therapeutic agents across infiltrative gliomas significantly improve brain tumor therapy. Photodynamic therapy (PDT) and hyperthermia (HPT) are well-established tumor therapies with minimal side effects while acting synergistically. This study introduces a new promising nanocarrier for the synergistic application of PDT and magnetic hyperthermia therapy against human glioma cell line T98 G, with cellular viability reduction down to as low as 17% compared with the control. (C) 2012 American Institute of Physics. [doi:10.1063/1.3671775]

Biological evaluation of the bone healing process after application of two potentially osteogenic proteins: an animal experimental model

doi: 10.1111/j.1741-2358.2011.00526.x Biological evaluation of the bone healing process after application of two potentially osteogenic proteins: an animal experimental model Objective: The aim of this work was to analyse qualitatively and quantitatively the newly formed bone after insertion of rhBMP-2 and protein extracted from Hevea brasiliensis (P-1), associated or not with a carrier in critical bone defects created in Wistar rat calvarial bone, using histological and histomorphometrical analyses. Materials and methods: Eighty-four male Wistar rats were used, divided into two groups, according to the period of time until the sacrifice (2 and 6 weeks). Each one of these groups was subdivided into six groups with seven animals each, according to the treatments: (1) 5 mu g of pure rhBMP-2, (2) 5 mu g of rhBMP-2/monoolein gel, (3) pure monoolein gel, (4) 5 mu g of pure P-1, (5) 5 mu g of P-1/monoolein gel and (6) critical bone defect controls. The animals were euthanised and the calvarial bone tissue removed for histological and histomorphometrical analyses. Result and conclusion: The results showed an improvement in the bone healing process using the rhBMP-2 protein, associated or not with a material carrier in relation to the other groups, and this process demonstrated to be time dependent.

Bayesian model accounting for within-class biological variability in Serial Analysis of Gene Expression (SAGE)

Abstract Background An important challenge for transcript counting methods such as Serial Analysis of Gene Expression (SAGE), "Digital Northern" or Massively Parallel Signature Sequencing (MPSS), is to carry out statistical analyses that account for the within-class variability, i.e., variability due to the intrinsic biological differences among sampled individuals of the same class, and not only variability due to technical sampling error. Results We introduce a Bayesian model that accounts for the within-class variability by means of mixture distribution. We show that the previously available approaches of aggregation in pools ("pseudo-libraries") and the Beta-Binomial model, are particular cases of the mixture model. We illustrate our method with a brain tumor vs. normal comparison using SAGE data from public databases. We show examples of tags regarded as differentially expressed with high significance if the within-class variability is ignored, but clearly not so significant if one accounts for it. Conclusion Using available information about biological replicates, one can transform a list of candidate transcripts showing differential expression to a more reliable one. Our method is freely available, under GPL/GNU copyleft, through a user friendly web-based on-line tool or as R language scripts at supplemental web-site.

Height variability from the MIROC - IPCC model for the 20th century compared to that of the TOPEX/POSEIDON altimeter

Planetary waves are key to large-scale dynamical adjustment in the global ocean as they transfer energy from the east to the west side of oceanic basins; they connect the forcing in the ocean interior with the variability at its boundaries: and they change the local heat content, thus coupling oceanic, atmospheric, and biological processes. Planetary waves, mostly of the first baroclinic mode, are observed as distinctive patterns in global time series of sea surface height anomaly (SSHA) and heat storage. The goal of this study is to compare and validate large-scale SSHA signals from coupled ocean-atmosphere general circulation Model for Interdisciplinary Research on Climate (MIROC) with TOPEX/POSEIDON satellite altimeter observations. The last decade of the models` time series is selected for comparison with the altimeter data. The wave patterns are separated from the meso- and large-scale SSHA signals by digital filters calibrated to select the same spectral bands in both model and altimeter data. The band-wise comparison allows for an assessment of the model skill to simulate the dynamical components of the observed wave field. Comparisons regarding both the seasonal cycle and the Rossby wave Held differ significantly among basins. When carried within the same basin, differences can occur between equal latitudes in opposite hemispheres. Furthermore, at some latitudes the MIROC reproduces biannual, annual and semiannual planetary waves with phase speeds and average amplitudes similar to those observed by the altimeter, but with significant differences in phase. (C) 2008 Elsevier Ltd. All rights reserved.

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.

A palaeobiogeographic model for biotic diversification within Amazonia over the past three million years

Many hypotheses have been proposed to explain high species diversity in Amazonia, but few generalizations have emerged. In part, this has arisen from the scarcity of rigorous tests for mechanisms promoting speciation, and from major uncertainties about palaeogeographic events and their spatial and temporal associations with diversification. Here, we investigate the environmental history of Amazonia using a phylogenetic and biogeographic analysis of trumpeters (Aves: Psophia), which are represented by species in each of the vertebrate areas of endemism. Their relationships reveal an unforeseen 'complete' time-slice of Amazonian diversification over the past 3.0 Myr. We employ this temporally calibrated phylogeny to test competing palaeogeographic hypotheses. Our results are consistent with the establishment of the current Amazonian drainage system at approximately 3.0-2.0 Ma and predict the temporal pattern of major river formation over Plio-Pleistocene times. We propose a palaeobiogeographic model for the last 3.0 Myr of Amazonian history that has implications for understanding patterns of endemism, the temporal history of Amazonian diversification and mechanisms promoting speciation. The history of Psophia, in combination with new geological evidence, provides the strongest direct evidence supporting a role for river dynamics in Amazonian diversification, and the absence of such a role for glacial climate cycles and refugia.

Interaction of chitosan and mucin in a biomembrane model environment

Chitosans have been widely exploited in biological applications, including drug delivery and tissue engineering, especially owing to their mucoadhesive properties, but the molecular-level mechanisms for the chitosan action are not known in detail. It is believed that chitosan could affect the mucus by interacting with the proteins mucins, in a process mediated by the cell membrane. In this study we used Langmuir monolayers of dimyristoylphosphatidic acid (DMPA) as simplified membrane models to investigate the interplay between the activity of mucins and chitosan. Surface pressure and surface potential measurements were performed with DMPA monolayers onto which chitosan and/or mucin was adsorbed. We found that the expanding effect from mucin was considerably reduced when chitosan was injected after mucin had been adsorbed on the DMPA monolayer. The results were consistent with the formation of complexes between mucin and chitosan, thus highlighting the importance of electrostatic interactions. Furthermore, chitosan could remove mucin that was co-deposited along with DMPA in Langmuir-Blodgett (LB) films, which could be ascribed to molecular-level interactions between chitosan and mucin inferred from the FTIR spectra of the LB films. In conclusion, the results with Langmuir and LB films suggest that electrostatic interactions are crucial for the mucoadhesive mechanism, which is affected by the complexation between chitosan and mucin. (C) 2012 Elsevier Inc. All rights reserved.

Integrodifference model for blowfly invasion

We propose a stage-structured integrodifference model for blowflies' growth and dispersion taking into account the density dependence of fertility and survival rates and the non-overlap of generations. We assume a discrete-time, stage-structured, model. The spatial dynamics is introduced by means of a redistribution kernel. We treat one and two dimensional cases, the latter on the semi-plane, with a reflexive boundary. We analytically show that the upper bound for the invasion front speed is the same as in the one-dimensional case. Using laboratory data for fertility and survival parameters and dispersal data of a single generation from a capture-recapture experiment in South Africa, we obtain an estimate for the velocity of invasion of blowflies of the species Chrysomya albiceps. This model predicts a speed of invasion which was compared to actual observational data for the invasion of the focal species in the Neotropics. Good agreement was found between model and observations.

A model to explain spermatophore implantation in cephalopods (Mollusca: Cephalopoda) and a discussion on its evolutionary origins and significance

Male coleoid cephalopods produce spermatophores that can attach autonomously on the female's body during a complex process of evagination called the spermatophoric reaction, during which the ejaculatory apparatus and spiral filament of the spermatophore are everted and exposed to the external milieu. In some deepwater cephalopods, the reaction leads to the intradermal implantation of the spermatophore, a hitherto enigmatic phenomenon. The present study builds upon several lines of evidence to propose that spermatophore implantation is probably achieved through the combination of (1) an evaginating-tube mechanism performed by the everting ejaculatory apparatus and (2) the anchorage provided by the spiral filament's stellate particles. The proposed theoretical model assumes that, as it is exposed to the external milieu, each whorl of the spiral filament anchors to the surrounding tissue by means of its sharp stellate particles. As the ejaculatory apparatus tip continues evaginating, it grows in diameter and stretches lengthwise, enlarging the diameter of the whorl and propelling it, consequently tearing and pushing the anchored tissue outward and backward, and opening space for the next whorl to attach. After the ejaculatory apparatus has been everted and has perforated tissue, the cement body is extruded, possibly aiding in final attachment, and the sperm mass comes to lie inside the female tissue, encompassed by the everted ejaculatory apparatus tube. It is proposed that this unique, efficient spermatophore attachment mechanism possibly evolved in intimate relationship with the adoption of an active mode of life by coleoids. The possible roles of predation pressure and sperm competition in the evolution of this mechanism are also discussed. (c) 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105, 711726.

Forced Desynchronization of Activity Rhythms in a Model of Chronic Jet Lag in Mice

We studied locomotor activity rhythms of C57/Bl6 mice under a chronic jet lag (CJL) protocol (ChrA(6/2)), which consisted of 6-hour phase advances of the light-dark schedule (LD) every 2 days. Through periodogram analysis, we found 2 components of the activity rhythm: a short-period component (21.01 +/- 0.04 h) that was entrained by the LD schedule and a long-period component (24.68 +/- 0.26 h). We developed a mathematical model comprising 2 coupled circadian oscillators that was tested experimentally with different CJL schedules. Our simulations suggested that under CJL, the system behaves as if it were under a zeitgeber with a period determined by (24 -[phase shift size/days between shifts]). Desynchronization within the system arises according to whether this effective zeitgeber is inside or outside the range of entrainment of the oscillators. In this sense, ChrA(6/2) is interpreted as a (24 - 6/2 = 21 h) zeitgeber, and simulations predicted the behavior of mice under other CJL schedules with an effective 21-hour zeitgeber. Animals studied under an asymmetric T = 21 h zeitgeber (carried out by a 3-hour shortening of every dark phase) showed 2 activity components as observed under ChrA(6/2): an entrained short-period (21.01 +/- 0.03 h) and a long-period component (23.93 +/- 0.31 h). Internal desynchronization was lost when mice were subjected to 9-hour advances every 3 days, a possibility also contemplated by the simulations. Simulations also predicted that desynchronization should be less prevalent under delaying than under advancing CJL. Indeed, most mice subjected to 6-hour delay shifts every 2 days (an effective 27-hour zeitgeber) displayed a single entrained activity component (26.92 +/- 0.11 h). Our results demonstrate that the disruption provoked by CJL schedules is not dependent on the phase-shift magnitude or the frequency of the shifts separately but on the combination of both, through its ratio and additionally on their absolute values. In this study, we present a novel model of forced desynchronization in mice under a specific CJL schedule; in addition, our model provides theoretical tools for the evaluation of circadian disruption under CJL conditions that are currently used in circadian research.

Chemical characterization and in vitro biological activity of four tropical legumes, Styzolobium aterrimum L., Styzolobium deeringianum, Leucaena leucocephala, and Mimosa caesalpiniaefolia, as compared with a tropical grass, Cynodon spp. for the use in ruminant diets

Leucaena leucocephala (LEU) and three under-utilized tanniferous legumes, Styzolobium aterrimum L. (STA), Styzolobium deeringianum (STD), and Mimosa caesalpiniaefolia Benth (MIC) were chemically characterized and the biological activity of tannins was evaluated using in vitro simulated ruminal fermentation through tannin-binding polyethylene glycol (PEG) and compared with a non-tanniferous tropical grass hay, Cynodon spp. (CYN). The Hohenheim gas test was used and gas production (GP) was recorded at 4, 8, 12, 24, 32, 48, 56, 72, 80, and 96 h incubation with and without PEG. Kinetic parameters were estimated by an exponential model. STA, STD, and LEU contained higher (P < 0.05) crude protein than MIC, which had greater neutral detergent fibre and acid detergent fibre. Total phenols, total tannins, and condensed tannins (CT) were consistently the highest in MIC. Gas production was the lowest from MIC (P < 0.05) and the highest in LEU and STA. MIC + PEG largely reduced (P < 0.05) the lag phase and the fractional rate of fermentation and increased potential GP. Kinetic parameters of STA + PEG and LEU + PEG were not affected. LEU + PEG produced greater gas increment (P < 0.05) than STD + PEG, although both legumes had the same CT. All legumes except MIC were more extensively degraded than CYN. However, fermentation of the legumes was differently affected by the presence and proportions of CT, indigestible fibre or both.

Hybrid Scaffolds Built From PET and Collagen as a Model For Vascular Graft Architecture

A hybrid material with excellent mechanical and biological properties is produced by electrospinning a co-solution of PET and collagen. The fibers are mapped using SEM, confocal Raman microscopy and collagenase digestion assays. Fibers of different compositions and morphologies are intermingled within the same membrane, resulting in a heterogeneous scaffold. The collagen distribution and exposure are found to depend on the PET/collagen ratio. The materials are chemically and mechanically characterized and biologically tested with fibroblasts (3T3-L1) and a HUVEC culture in vitro. All of the hybrid scaffolds show better cell attachment and proliferation than PET. These materials are potential candidates to be used as vascular grafts.

STOCHASTIC MODEL FOR SIMULATING MAIZE YIELD

Maize is one of the most important crops in the world. The products generated from this crop are largely used in the starch industry, the animal and human nutrition sector, and biomass energy production and refineries. For these reasons, there is much interest in figuring the potential grain yield of maize genotypes in relation to the environment in which they will be grown, as the productivity directly affects agribusiness or farm profitability. Questions like these can be investigated with ecophysiological crop models, which can be organized according to different philosophies and structures. The main objective of this work is to conceptualize a stochastic model for predicting maize grain yield and productivity under different conditions of water supply while considering the uncertainties of daily climate data. Therefore, one focus is to explain the model construction in detail, and the other is to present some results in light of the philosophy adopted. A deterministic model was built as the basis for the stochastic model. The former performed well in terms of the curve shape of the above-ground dry matter over time as well as the grain yield under full and moderate water deficit conditions. Through the use of a triangular distribution for the harvest index and a bivariate normal distribution of the averaged daily solar radiation and air temperature, the stochastic model satisfactorily simulated grain productivity, i.e., it was found that 10,604 kg ha(-1) is the most likely grain productivity, very similar to the productivity simulated by the deterministic model and for the real conditions based on a field experiment.

Molecular mapping of the regenerative niche in a murine model of myocardial infarction

Adult stem cells are distributed through the whole organism, and present a great potential for the therapy of different types of disease. For the design of efficient therapeutic strategies, it is important to have a more detailed understanding of their basic biological characteristics, as well as of the signals produced by damaged tissues and to which they respond. Myocardial infarction (MI), a disease caused by a lack of blood flow supply in the heart, represents the most common cause of morbidity and mortality in the Western world. Stem cell therapy arises as a promising alternative to conventional treatments, which are often ineffective in preventing loss of cardiomyocytes and fibrosis. Cell therapy protocols must take into account the molecular events that occur in the regenerative niche of MI. In the present study, we investigated the expression profile of ten genes coding for chemokines or cytokines in a murine model of MI, aiming at the characterization of the regenerative niche. MI was induced in adult C57BL/6 mice and heart samples were collected after 24 h and 30 days, as well as from control animals, for quantitative RT-PCR. Expression of the chemokine genes CCL2, CCL3, CCL4, CCL7, CXCL2 and CXCL10 was significantly increased 24 h after infarction, returning to baseline levels on day 30. Expression of the CCL8 gene significantly increased only on day 30, whereas gene expression of CXCL12 and CX3CL1 were not significantly increased in either ischemic period. Finally, expression of the IL-6 gene increased 24 h after infarction and was maintained at a significantly higher level than control samples 30 days later. These results contribute to the better knowledge of the regenerative niche in MI, allowing a more efficient selection or genetic manipulation of cells in therapeutic protocols.

Sperm head morphometry in ejaculates of adult marmosets (Callithrix jacchus): a model for studying sperm subpopulations and among-donor variations

In humans and other mammals, sperm morphology has been considered one of the most important predictive parameters of fertility. The objective was to determine the presence and distribution of sperm head morphometric subpopulations in a nonhuman primate model (Callithrix jacchus), using an objective computer analysis system and principal component analysis (PCA) methods to establish the relationship between the subpopulation distribution observed and among-donor variation. The PCA method revealed a stable number of principal components in all donors studied, that represented more than 85% of the cumulative variance in all cases. After cluster analysis, a variable number (from three to seven) sperm morphometric subpopulations were identified with defined sperm dimensions and shapes. There were differences in the distribution of the sperm morphometric subpopulations (P < 0.001) in all ejaculates among the four donors analyzed. In conclusion, in this study, computerized sperm analysis methods combined with PCA cluster analyses were useful to identify, classify, and characterize various head sperm morphometric subpopulations in nonhuman primates, yielding considerable biological information. In addition, because all individuals were kept in the same conditions, differences in the distribution of these subpopulations were not attributed to external or management factors. Finally, the substantial information derived from subpopulation analyses provided new and relevant biological knowledge which may have a practical use for future studies in human and nonhuman primate ejaculates, including identifying individuals more suitable for assisted reproductive technologies. (c) 2012 Elsevier Inc. All rights reserved.