Alterations in pulmonary structure by elastase administration in a model of emphysema in mice is associated with functional disturbances

Several experimental studies of pulmonary emphysema using animal models have been described in the literature. However, only a few of these studies have focused on the assessment of ergometric function as a non-invasive technique to validate the methodology used for induction of experimental emphysema. Additionally, functional assessments of emphysema are rarely correlated with morphological pulmonary abnormalities caused by induced emphysema. The present study aimed to evaluate the effects of elastase administered by tracheal puncture on pulmonary parenchyma and their corresponding functional impairment. This was evaluated by measuring exercise capacity in C57Bl/6 mice in order to establish a reproducible and safe methodology of inducing experimental emphysema. Thirty six mice underwent ergometric tests before and 28 days after elastase administration. Pancreatic porcine elastase solution was administered by tracheal puncture, which resulted in a significantly decreased exercise capacity, shown by a shorter distance run (-30.5%) and a lower mean velocity (-15%), as well as in failure to increase the elimination of carbon dioxide. The mean linear intercept increased significantly by 50% in tracheal elastase administration. In conclusion, application of elastase by tracheal function in C57Bl/6 induces emphysema, as validated by morphometric analyses, and resulted in a significantly lower exercise capacity, while resulting in a low mortality rate. (C) 2011 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved.

Variations in Structure Explain the Viscometric Behavior of AOT Microemulsions at Low Water/AOT Molar Ratios

The viscosity of AOT/water/decane water-in-oil microemulsions exhibits a well-known maximum as a function of water/AOT molar ratio, which is usually attributed to increased attractions among nearly spherical droplets. The maximum can be removed by adding salt or by changing the oil to CCl4. Systematic small-angle X-ray scattering (SAXS) measurements have been used to monitor the structure of the microemulsion droplets in the composition regime where the maximum appears. On increasing the droplet concentration, the scattering intensity is found to scale with the inverse of the wavevector, a behavior which is consistent with cylindrical structures. The inverse wavevector scaling is not observed when the molar ratio is changed, moving the system away from the value corresponding to the viscosity maximum. It is also not present in the scattering from systems containing enough added salt to essentially eliminate the viscosity maximum. An asymptotic analysis of the SAXS data, complemented by some quantitative modeling, is consistent with cylindrical growth of droplets as their concentration is increased. Such elongated structures are familiar from related AOT systems in which the sodium counterion has been exchanged for a divalent one. However, the results of this study suggest that the formation of non-spherical aggregates at low molar ratios is an intrinsic property of AOT.

Water-in-Oil Micro-Emulsion Enhances the Secondary Structure of a Protein by Confinement

A scheme is presented in which an organic solvent environment in combination with surfactants is used to confine a natively unfolded protein inside an inverse microemulsion droplet. This type of confinement allows a study that provides unique insight into the dynamic structure of an unfolded, flexible protein which is still solvated and thus under near-physiological conditions. In a model system, the protein osteopontin (OPN) is used. It is a highly phosphorylated glycoprotein that is expressed in a wide range of cells and tissues for which limited structural analysis exists due to the high degree of flexibility and large number of post-translational modifications. OPN is implicated in tissue functions, such as inflammation and mineralisation. It also has a key function in tumour metastasis and progression. Circular dichroism measurements show that confinement enhances the secondary structural features of the protein. Small-angle X-ray scattering and dynamic light scattering show that OPN changes from being a flexible protein in aqueous solution to adopting a less flexible and more compact structure inside the microemulsion droplets. This novel approach for confining proteins while they are still hydrated may aid in studying the structure of a wide range of natively unfolded proteins.

Unraveling the structure of squids' spermatophores: a combined approach based on Doryteuthis plei (Blainville, 1823) (Cephalopoda: Loliginidae)

Marian, J.E.A.R. and Domaneschi, O. 2012. Unraveling the structure of squids spermatophores: a combined approach based on Doryteuthis plei (Blainville, 1823) (Cephalopoda: Loliginidae). Acta Zoologica (Stockholm) 93: 281307. Male coleoid cephalopods produce elaborate spermatophores, which function autonomously outside the male body during copulation, undergoing a complicated process of evagination. In order to contribute to the understanding of this unique structure, this study investigated the morphology of the spermatophore of Doryteuthis plei applying several microscopy techniques. A hitherto unreported, much more complex structural arrangement was revealed for the loliginid spermatophore, the most striking findings being: (1) the complex, layered structure of the middle membrane, which bears an additional, chemically distinct segment surrounding part of the cement body; (2) the presence of a space between the inner tunic and middle membrane filled with a fine reticulated material; (3) the presence of stellate particles not only embedded in the spiral filament, but also closely applied to the inner membrane at the level of the cement body; (4) the presence of a pre-oral chamber in the cap region; and (5) the complex organization of the cement body, formed by two distinct layers encompassing contents of different chemical and textural properties. Careful literature reassessment suggests several of these features are common to loliginids, and to some extent to other squids. Their possible functional implications are discussed in light of our knowledge of the spermatophoric reaction mechanics.

SPATIAL PATTERN OF FOUR FOREST COMMUNITIES BY RIPLEY'S K FUNCTION IN SAO PAULO STATE

Investigating tree's spatial patterns according to their size classes and according to their more abundant species can provide evidences about the structure of the vegetal community, since the spatial pattern is a key question for forestry ecology studies. The tree spatial organization patterns on the environment depend on several ecological processes and on the specific characteristics of each environment, so that the best understanding of this frame provides important elements for the knowledge on forestry formation. This paper aimed to study tree spatial patterns, according to the diameter classes and from four most abundant species in different forests, in order to provide evidences regarding to the ecology of each vegetal community. The spatial pattern description in each forestry formation was developed using Ripley's K function. The studied forestry formations were: Ombrophilous Forest, Cerradao, Seasonal Forest and Restinga Forest. In this work, a 10.24 ha plot was installed in each forestry formation, and every tree, with a circumference at breast height (CBH) larger than 15 cm were measured, georeferenced and identified. The obtained data highlights the aggregated character in tropical forests, as observed in every studied forest. The 'Cerraddo' and 'Restinga' forest trees showed close aggregate patterns. In the Ombrophilous forest, for all distance scales, the aggregate pattern was meaningful. In the seasonal forest, a random tendency was observed, although a meaningful aggregation was observed in all short distances. The spatial pattern by diameter classes was generally aggregated for trees smaller than 10 cm of diameter and between 10 and 20 cm and random for the others, proving the existence of a tendency which in young trees is more aggregated than in old ones. The spatial pattern of the dominant species is always strongly similar to the general pattern of each forestry formation. The differences between the spatial patterns of two or three coincident species, among the forestry formations, indicate that its pattern is influenced by each different environment. This stands out the importance of its self-ecology and of its ecological processes, intrinsic of each community that can explain the observed patterns.

Relationship between global structural parameters and Enzyme Commission hierarchy: Implications for function prediction

In protein databases there is a substantial number of proteins structurally determined but without function annotation. Understanding the relationship between function and structure can be useful to predict function on a large scale. We have analyzed the similarities in global physicochemical parameters for a set of enzymes which were classified according to the four Enzyme Commission (EC) hierarchical levels. Using relevance theory we introduced a distance between proteins in the space of physicochemical characteristics. This was done by minimizing a cost function of the metric tensor built to reflect the EC classification system. Using an unsupervised clustering method on a set of 1025 enzymes, we obtained no relevant clustering formation compatible with EC classification. The distance distributions between enzymes from the same EC group and from different EC groups were compared by histograms. Such analysis was also performed using sequence alignment similarity as a distance. Our results suggest that global structure parameters are not sufficient to segregate enzymes according to EC hierarchy. This indicates that features essential for function are rather local than global. Consequently, methods for predicting function based on global attributes should not obtain high accuracy in main EC classes prediction without relying on similarities between enzymes from training and validation datasets. Furthermore, these results are consistent with a substantial number of studies suggesting that function evolves fundamentally by recruitment, i.e., a same protein motif or fold can be used to perform different enzymatic functions and a few specific amino acids (AAs) are actually responsible for enzyme activity. These essential amino acids should belong to active sites and an effective method for predicting function should be able to recognize them. (C) 2012 Elsevier Ltd. All rights reserved.

Structure and anomalous solubility for hard spheres in an associating lattice gas model

In this paper we investigate the solubility of a hard-sphere gas in a solvent modeled as an associating lattice gas. The solution phase diagram for solute at 5% is compared with the phase diagram of the original solute free model. Model properties are investigated both through Monte Carlo simulations and a cluster approximation. The model solubility is computed via simulations and is shown to exhibit a minimum as a function of temperature. The line of minimum solubility (TmS) coincides with the line of maximum density (TMD) for different solvent chemical potentials, in accordance with the literature on continuous realistic models and on the "cavity" picture. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4743635]

Ligand- and Structure-Based Drug Design Strategies and PPAR delta/alpha Selectivity

Peroxisome-proliferator-activated receptors are a class of nuclear receptors with three subtypes: a, ? and d. Their main function is regulating gene transcription related to lipid and carbohydrate metabolism. Currently, there are no peroxisome-proliferator-activated receptors d drugs being marketed. In this work, we studied a data set of 70 compounds with a and d activity. Three partial least square models were created, and molecular docking studies were performed to understand the main reasons for peroxisome-proliferator-activated receptors d selectivity. The obtained results showed that some molecular descriptors (log P, hydration energy, steric and polar properties) are related to the main interactions that can direct ligands to a particular peroxisome-proliferator-activated receptors subtype.

Intelligence systems methodology: a systemic approach to the organizational intelligence function

Organizational intelligence can be seen as a function of the viable structure of an organization. With the integration of the Viable System Model and Soft Systems Methodology (systemic approaches of organizational management) focused on the role of the intelligence function, it is possible to elaborate a model of action with a structured methodology to prospect, select, treat and distribute information to the entire organization that improves the efficacy and efficiency of all processes. This combination of methodologies is called Intelligence Systems Methodology (ISM) whose assumptions and dynamics are delimited in this paper. The ISM is composed of two simultaneous activities: the Active Environmental Mapping and the Stimulated Action Cycle. The elaboration of the formal ISM description opens opportunities for applications of the methodology on real situations, offering a new path for this specific issue of systems thinking: the intelligence systems. Knowledge Management Research & Practice (2012) 10, 141-152. doi:10.1057/kmrp.2011.44

Cyclosporin A causes impairment of the ventral prostate tissue structure of Wistar rats

Cyclosporin A (CsA) is an immunosuppressive drug widely used in medicine to reduce the immune system activity and, therefore, the risk of organ rejection after transplantation. However, many side effects can be related to its use, such as, reduction in serum testosterone levels due to damage of the testis structure and, consequently, male infertility. The present study aims to evaluate the effects of chronic CsA administration on the ventral prostate tissue ( 1 5 mg/kg per d, for 56 days). Stereological, morphometrical, morphological and ultrastructural observations were employed. The plasmatic testosterone and glucose levels were measured. An androgen receptor (AR) immunohistochemical method was applied on ventral prostate sections. Apoptosis was detected with the terminal deoxynucleotidyl transferase dUTP nick end labeling technique. CsA treatment caused reduction in plasmatic testosterone levels and an increase in glycemia. The volume of all ventral prostate tissue components (lumen, epithelium and muscular and nonmuscular stroma) and ventral prostate weight were reduced in the CsA-treated group. Light and transmission electron microscopy confirmed epithelium atrophy of treated animals. There was no alteration of AR expression or apoptotic index. CsA chronic treatment in the therapeutic doses caused damage to prostate tissue of adult Wistar rats, probably due to increase in the glucose levels and reduction in the plasmatic testosterone levels.

X-ray diffraction and theoretical investigation of the Gedunin crystal structure

The Gedunin compound (C28H34O6) is a natural product extracted from Trichilia pallida that has shown a wide activity. The crystallographic structure shows two conformers in the asymmetric unit, which differ in a rotation of the furan group. To understand this molecular arrangement, the density functional calculations. Molecular Electrostatic Potential (MEP) and thermodynamic function calculation have been performed at the B3LYP/6-311++g(d,p) level. Both conformers were optimized and the agreement with the experimental structure was very good, making possible further theoretical analysis of the structure. The inter-conversion between two conformers depends on the energy barrier. This process is studied in the vacuum and shows two transition states with a low energetic barrier for a potential energy curve scanning rigid around furan group: 4.37 kcal/mol and 16.52 kcal/mol. As the first transition state has a notably lower energetic barrier, the preferred inter-conversion pathway between the conformers involves the first rather than the second transition state. Understanding this transition state in detail led us to perform its optimization, showing an energetic barrier around 3.66 kcal/mol. The negative free energy and low enthalpy confirm that the process is spontaneous and exothermic. The results show that this requirement makes the existence of the two conformers in the asymmetric unit possible. The structure of molecules in the asymmetric unit is better understood when the MEP is used on the interaction between molecules. For Gedunin, both molecules have shown MEP with well-defined regions, and this behavior contributes to the observed link between molecules and for the negative regions complementing positive regions of another molecule. (C) 2011 Elsevier B.V. All rights reserved.

Variability in light absorption and scattering of phytoplankton in Patagonian waters: Role of community size structure and pigment composition

Intense phytoplankton blooms were observed along the Patagonian shelf-break with satellite ocean color data, but few in situ optical observations were made in that region. We examine the variability of phytoplankton absorption and particulate scattering coefficients during such blooms on the basis of field data. The chlorophyll-a concentration, [Chla], ranged from 0.1 to 22.3 mg m−3 in surface waters. The size fractionation of [Chla] showed that 80% of samples were dominated by nanophytoplankton (N-group) and 20% by microphytoplankton (M-group). Chlorophyll-specific phytoplankton absorption coefficients at 440 and 676 nm, a*ph(440) and a*ph(676), and particulate scattering coefficient at 660 nm, b*p(660), ranged from 0.018 to 0.173, 0.009 to 0.046, and 0.031 to 2.37 m2 (mg Chla)−1, respectively. Both a*ph(440) and a*ph(676) were statistically higher for the N-group than M-group and also considerably higher than expected from global trends as a function of [Chla]. This result suggests that size of phytoplankton cells in Patagonian waters tends to be smaller than in other regions at similar [Chla]. The phytoplankton cell size parameter, Sf, derived from phytoplankton absorption spectra, proved to be useful for interpreting the variability in the data around the general inverse dependence of a*ph(440), a*ph(676), and b*p(660) on [Chla]. Sf also showed a pattern along the increasing trend of a*ph(440) and a*ph(676) as a function of the ratios of some accessory pigments to [Chla]. Our results suggest that the variability in phytoplankton absorption and scattering coefficients in Patagonian waters is caused primarily by changes in the dominant phytoplankton cell size accompanied by covariation in the concentrations of accessory pigments.

Electronic Structure Calculations in a 2D SixGe1-x Alloy Under an Applied Electric Field.

The recent advances and promises in nanoscience and nanotechnology have been focused on hexagonal materials, mainly on carbon-based nanostructures. Recently, new candidates have been raised, where the greatest efforts are devoted to a new hexagonal and buckled material made of silicon, named Silicene. This new material presents an energy gap due to spin-orbit interaction of approximately 1.5 meV, where the measurement of quantum spin Hall effect(QSHE) can be made experimentally. Some investigations also show that the QSHE in 2D low-buckled hexagonal structures of germanium is present. Since the similarities, and at the same time the differences, between Si and Ge, over the years, have motivated a lot of investigations in these materials. In this work we performed systematic investigations on the electronic structure and band topology in both ordered and disordered SixGe1-x alloys monolayer with 2D honeycomb geometry by first-principles calculations. We show that an applied electric field can tune the gap size for both alloys. However, as a function of electric field, the disordered alloy presents a W-shaped behavior, similarly to the pure Si or Ge, whereas for the ordered alloy a V-shaped behavior is observed.

Chromatin Remodeling by BRG1 and SNF2H : Biochemistry and Function

Chromatin is a highly dynamic, regulatory component in the process of transcription, repair, recombination and replication. The BRG1 and SNF2H proteins are ATP-dependent chromatin remodeling proteins that modulate chromatin structure to regulate DNA accessibility for DNA-binding proteins involved in these processes. The BRG1 protein is a central ATPase of the SWI/SNF complexes involved in chromatin remodeling associated with regulation of transcription. SWI/SNF complexes are biochemically hetero-geneous but little is known about the unique functional characteristics of the various forms. We have shown that SWI/SNF activity in SW13 cells affects actin filament organization dependent on the RhoA signaling pathway. We have further shown that the biochemical composition of SWI/SNF complexes qualitatively affects the remodeling activity and that the composition of biochemically purified SWI/SNF complexes does not reflect the patterns of chromatin binding of individual subunits. Chromatin binding assays (ChIP) reveal variations among subunits believed to be constitutive, suggesting that the plasticity in SWI/SNF complex composition is greater than suspected. We have also discovered an interaction between BRG1 and the splicing factor Prp8, linking SWI/SNF activity to mRNA processing. We propose a model whereby parts of the biochemical heterogeneity is a result of function and that the local chromatin environment to which the complex is recruited affect SWI/SNF composition. We have also isolated the novel B-WICH complex that contains WSTF, SNF2H, the splicing factor SAP155, the RNA helicase II/Guα, the transcription factor Myb-binding protein 1a, the transcription factor/DNA repair protein CSB and the RNA processing factor DEK. The formation of this complex is dependent on active transcription and links chromatin remodeling by SNF2H to RNA processing. By linking chromatin remodeling complexes with RNA processing proteins our work has begun to build a bridge between chromatin and RNA, suggesting that factors in chromatin associated assemblies translocate onto the growing nascent RNA.

Analyzing the dependence structure of microarray data: a copula–based approach

The main aim of this Ph.D. dissertation is the study of clustering dependent data by means of copula functions with particular emphasis on microarray data. Copula functions are a popular multivariate modeling tool in each field where the multivariate dependence is of great interest and their use in clustering has not been still investigated. The first part of this work contains the review of the literature of clustering methods, copula functions and microarray experiments. The attention focuses on the K–means (Hartigan, 1975; Hartigan and Wong, 1979), the hierarchical (Everitt, 1974) and the model–based (Fraley and Raftery, 1998, 1999, 2000, 2007) clustering techniques because their performance is compared. Then, the probabilistic interpretation of the Sklar’s theorem (Sklar’s, 1959), the estimation methods for copulas like the Inference for Margins (Joe and Xu, 1996) and the Archimedean and Elliptical copula families are presented. In the end, applications of clustering methods and copulas to the genetic and microarray experiments are highlighted. The second part contains the original contribution proposed. A simulation study is performed in order to evaluate the performance of the K–means and the hierarchical bottom–up clustering methods in identifying clusters according to the dependence structure of the data generating process. Different simulations are performed by varying different conditions (e.g., the kind of margins (distinct, overlapping and nested) and the value of the dependence parameter ) and the results are evaluated by means of different measures of performance. In light of the simulation results and of the limits of the two investigated clustering methods, a new clustering algorithm based on copula functions (‘CoClust’ in brief) is proposed. The basic idea, the iterative procedure of the CoClust and the description of the written R functions with their output are given. The CoClust algorithm is tested on simulated data (by varying the number of clusters, the copula models, the dependence parameter value and the degree of overlap of margins) and is compared with the performance of model–based clustering by using different measures of performance, like the percentage of well–identified number of clusters and the not rejection percentage of H0 on . It is shown that the CoClust algorithm allows to overcome all observed limits of the other investigated clustering techniques and is able to identify clusters according to the dependence structure of the data independently of the degree of overlap of margins and the strength of the dependence. The CoClust uses a criterion based on the maximized log–likelihood function of the copula and can virtually account for any possible dependence relationship between observations. Many peculiar characteristics are shown for the CoClust, e.g. its capability of identifying the true number of clusters and the fact that it does not require a starting classification. Finally, the CoClust algorithm is applied to the real microarray data of Hedenfalk et al. (2001) both to the gene expressions observed in three different cancer samples and to the columns (tumor samples) of the whole data matrix.