Structure-Based Approach for the Study of Estrogen Receptor Binding Affinity and Subtype Selectivity

Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpa (hER alpha) and beta (hER beta). Because the levels and relative proportion of hER alpha and hER beta differ significantly in different target cells, selective hER ligands could target specific tissues or pathways regulated by one receptor subtype without affecting the other. To understand the structural and chemical basis by which small molecule modulators are able to discriminate between the two subtypes, we have applied three-dimensional target-based approaches employing a series of potent hER-ligands. Comparative molecular field analysis (CoMFA) studies were applied to a data set of 81 hER modulators, for which binding affinity values were collected for both hER alpha and hER beta. Significant statistical coefficients were obtained (hER alpha, q(2) = 0.76; hER beta, q(2) = 0.70), indicating the internal consistency of the models. The generated models were validated using external test sets, and the predicted values were in good agreement with the experimental results. Five hER crystal structures were used in GRID/PCA investigations to generate molecular interaction fields (MIF) maps. hER alpha and hER beta were separated using one factor. The resulting 3D information was integrated with the aim of revealing the most relevant structural features involved in hER subtype selectivity. The final QSAR and GRID/PCA models and the information gathered from 3D contour maps should be useful for the design or novel hER modulators with improved selectivity.

Quantitative structure-activity studies on a series of migrastatin analogs as inhibitors of cancer cell metastasis

Migrastatin, a macrolide natural product, and its structurally related analogs are potent inhibitors of cancer cell metastasis, invasion and migration. In the present work, a specialized fragment-based method was employed to develop QSAR models for a series of migrastatin and isomigrastatin analogs. Significant correlation coefficients were obtained (best model, q(2) = 0.76 and r(2) = 0.91) indicating that the QSAR models possess high internal consistency. The best model was then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results (R(2) (pred) = 0.85). The final model and the corresponding contribution maps, combined with molecular modeling studies, provided important insights into the key structural features for the anticancer activity of this family of synthetic compounds based on natural products.

Mode of operation and low-resolution structure of a multi-domain and hyperthermophilic endo-beta-1,3-glucanase from Thermotoga petrophila

1,3-beta-Glucan depolymerizing enzymes have considerable biotechnological applications including biofuel production, feedstock-chemicals and pharmaceuticals. Here we describe a comprehensive functional characterization and low-resolution structure of a hyperthermophilic laminarinase from Thermotoga petrophila (TpLam). We determine TpLam enzymatic mode of operation, which specifically cleaves internal beta-1,3-glucosidic bonds. The enzyme most frequently attacks the bond between the 3rd and 4th residue from the non-reducing end, producing glucose, laminaribiose and laminaritriose as major products. Far-UV circular dichroism demonstrates that TpLam is formed mainly by beta structural elements, and the secondary structure is maintained after incubation at 90 degrees C. The structure resolved by small angle X-ray scattering, reveals a multi-domain structural architecture of a V-shape envelope with a catalytic domain flanked by two carbohydrate-binding modules. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.

Expediting New Program Development: Meeting Market Demand and Leveraging Internal Resources

Expediting new program development can help universities meet student and employer demand while gaining an edge over competitors, but coordinating program development and approval requires careful preparation and execution. This report profiles strategies to measure market demand for new programs, choose programs for accelerated development, and leverage internal resources. The report also suggests ways to structure and staff program development to maximize speed and effectiveness.

Estimation and evaluation of dynamic properties as indicators of changes on soil structure in sugarcane fields of São Paulo State - Brazil

The indiscriminate management and use of soils without moisture control has changed the structure of it due to the increment of the traffic by agricultural machines through the years, causing in consequence, a soil compaction and yield reduction in the areas of intensive traffic. The purpose of this work was to estimate and to evaluate the performance of preconsolidation pressure of the soil and shear stress as indicators of changes on soil structure in fields cropped with sugarcane, as well as the impact of management processes in an Eutrorthox soil structure located in São Paulo State. The experimental field was located in Piracicaba's rural area (São Paulo State, Brazil) and has been cropped with sugarcane, in the second harvest cycle. The soil was classified by Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA) [Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA), 1999. Centro Nacional de Pesquisa de Solos. Sistema Brasileiro de Classificao de Solos, Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA), Brasilia, 412 pp.] as an Eutrorthox. Undisturbed samples were collected and georeferenced in a grid of 60 m x 60 m from two depths: 0-0.10 m (superficial layer - SL) and in the layer of greatest mechanical resistance (LGMR), previously identified by cone index (CI). The investigated variables were pressure preconsolidation (sigma(p)), apparent cohesion (c) and internal friction angle (phi). The conclusions from the results were that the SLSC was predicted satisfactorily from up as a function of soil moisture; thus, decisions about machinery size and loading (contact pressures) can be taken. Apparent cohesion (c), internal friction angle (phi) and the Coulomb equation were significantly altered by traffic intensity. The sigma(p), c and phi maps were shown to be important tools to localize and visualize soil compaction and mechanical resistance zones. They constitute a valuable resource to evaluate the traffic impact in areas cropped with sugarcane in State of São Paulo, Brazil. (C) 2008 Elsevier B.V. All rights reserved.

Internal Architecture and Population Size of Acromyrmex subterraneus molestans (Hymenoptera, Formicidae) Nests: Comparison Between a Rural and an Urban Area

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Structure and vascularization of the ventricular myocardium of Piaractus mesopotamicus and Clarias gariepinus (Teleostei)

The structural characteristics of the ventricular myocardium and the arterial distribution of the ventricular wall were studied in two freshwater teleost fish species (Piaractus mesopotamicus and Clarias gariepinus). The ventricular myocardium consists of two distinct layers, an external compact layer and an internal spongy layer. In Piaractus mesopotamicus the compact layer contains fibres with an external longitudinal arrangement and an internal circular arrangement. The arterial vascularization of the compact layer is provided by subepicardial vessels and their ramifications in both species.

Contribution to the study of aortic mural structure of opossum (Didelphis albiventris)

Opossum is considered one of the most primitive mammals, with transition evolutive characteristics. In mammals, the aorta artery is referred as the main body blood vessel. The arteries wall structural organization follows a basic pattern, being contituted of three tunics: Intima, Median and Adventicial. After euthanasia, three samples of opossum had segments from the aorta artery ascendent, thoracic descending and abdominal descending portions removed, fixed in phormalin at 10% for 48 hours. Then, the material was washed in alcohol 70% several times, dehydrated in alcohois of growing concentrations, diafanized in xylol and included in "paraplast". Cuts with 5 to 7 mu m of thickness were placed in histological laminae and submitted to color methods of Hematoxilin-Eosin, Masson, Mallory and Calleja Tricromics. It was observed that in the different portions ascendent, thoracic and abdominal descending of aorta, the intima tunic presents much thick, made up of a layer of smooth muscular cells and elastic fibers, forming a limiting internal elastic membrane. In the three portions studied, the median tunic was the most evident layer, constituted of colagen fibers, smooth muscular cells arranged in a circular manner and elastic fibers, showing a variation in the mural elements proportion. It was evidenced the presence of a external elastic lamina, marking the transition between the median and adventicial tunic, formed by elastic fibers condensation. The aortic adventicial tunic showed to be little organized, having in its structure predominantely colagen fibers beans with some isolated smooth muscular fibers or in small fascicules among a few elastic fibers.

Food bodies in Cissus verticillata (Vitaceae): ontogenesis, structure and functional aspects

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Short comments on self-synchronization of two non-ideal sources supported by a flexible portal frame structure

A practical problem of synchronization of a non-ideal (i.e. when the excitation is influenced by the response of the system) and non-linear vibrating system was posed and investigated by means of numerical simulations. Two rotating unbalanced motors compose the mathematical model considered here with limited power supply mounted on the horizontal beam of a simple portal frame. As a starting point, the problem is reduced to a four-degrees-of-freedom model and its equations of motion, derived elsewhere via a Lagrangian approach, are presented. The numerical results show the expected phenomena associated with the passage through resonance with limited power. Further, for a two-to-one relationship between the frequencies associated with the first symmetric mode and the sway mode, by using the variation of torque constants, the control of the self-synchronization and synchronization (in the system) are observed at certain levels of excitations.

Microscopic studies on the transition between the sigmoid sinus, the superior bulb of the jugular vein and the first portion of the internal jugular vein

The author studied the structure of the tissue components of the tunicae of the terminal segment of the sigmoid sinus, particularly at the level of the transition between the sigmoid sinus, the superior bulb of the jugular vein and the first portion of the human internal jugular vein; it was established that the transition between the sigmoid sinus and the first portion of the internal jugular vein occupies the whole extension of the superior bulb of the jugular vein up to the inferior third of the first portion of this vessel. These vascular walls exhibit a structure similar to that of the dura, i.e. the tunica adventitia is formed by fascicles of collagenic fibers which describe discontinuous spirals, more open proximal to the beginning of the first portion of the internal jugular vein. Approximately in the inferior third of the first portion of the internal jugular vein, there appear fascicles of smooth muscle fibers which are arranged similarly to those of the venous walls. The tunica intima of these vascular segments exhibits an endothelium resting on a network of elastic fibers which may play the role of an internal elastic lamina. From the bony border of the jugular foramen there originates a connective system whose fascicles of collagenic and elastic fibers incorporate to the wall of the internal jugular vein after describing a stretch in spiral around the vascular lumen.

Carotid arteries in the dog: Structure and histophysiology

Light microscopy analysis of the mural structure of the common carotid artery, internal carotid artery and external carotid artery in mongrel dog revealed variability in the middle values of vascular diameter and thickness of the intimal plus medial coats and adventitial coat. The vascular diameter did not differ between the internal carotid artery and external carotid artery, but was significantly increased in the common carotid artery from which the other two arteries had origin. The increased thickness of the intimal plus medial coats of the common carotid artery revealed the constant mechanical adjustment of the arterial wall and local shearing stress that occurred among the arterial coats. The adventitial coat of the internal carotid artery was significantly thicker than those of the common carotid and external carotid arteries, with no significant difference noted between the latter arteries. These histomorphometric results were related to the qualitative observations regarding the mural structure of the three arteries analyzed, especially regarding to the increased thickness and structural complexity of the adventitial coat of the internal carotid artery. Perhaps it acted as an external protective sheath of the vascular wall during its long course until the carotid channel. © 2006 Sociedad Chilena de Anatomía.

Low-frequency high-temperature internal friction in Ti-13Nb-13Zr alloy

Recent studies have been done to achieve biomedical alloys containing non-toxic elements and presenting low elastic moduli. It has been reported that Ti-Nb-Zr alloys rich in beta phase, especially Ti-13Nb-13Zr, have potential characteristics for substituting conventional materials such as Ti-6Al-4V, stainless steel and Co alloys. The aim of this work is to study the internal friction (IF) of Ti-13Nb-13Zr (TNZ) alloy due to the importance of the absorption impacts in orthopedic applications. The internal friction of this alloy produced by arc melting was measured using an inverted torsion pendulum with the free decay method. The measurements were performed from 77 to 700 K with heating rate of 1 K/min, in a vacuum better than 10-5 mBar. The results show a relaxation structure at high temperature strongly dependent on microstructure of the material. Qualitative discussions are presented for the experimental results, and the possibility of using the TNZ as a high damping material is briefly mentioned.

The influence of the flame structure on the combustion oscillations in a cylindrical chamber

An experimental study has been conducted with the objective of investigating the effects of the flame structure in the combustion oscillation conditions into a laboratorial scale cylindrical chamber. The experiments were conducted in a water-jacketed 1-m long by 25-cm internal diameter stainless steel vertical tube. The combustor operated with liquefied petroleum gas (LPG) in both oscillatory and non oscillatory conditions, under the same input conditions. Part of the reactant mixture was excited acoustically, before the burner exit, by a speaker positioned strategically. The burner was aligned with the chamber longitudinal axis and positioned at its bottom. The experiments were conducted for 0.16 g/s of LPG burning in stoichiometric equivalence ratio. To analyze the flame structure the image tomographic reconstruction process were used, and the resultant images were associated to the oscillatory conditions (frequency and amplitude) into the combustion chamber. The main conclusions were: 1) when the flame premixed condition increase, for example 60% of the total air flow rate is premixed with LPG, the region of intense energy released is close to burner exit and strong amplitudes of oscillation (close to 50 mbar) were obtained into the chamber; 2) for long flames, predominantly diffusive flames, just weak amplitudes were detected, in the spite of the speaker exiting the premixed flow; 3) when the energy is released distributed through the combustion chamber, the long flame acts like a baffle. Copyright © 2006 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.

Composition of functional ecological guilds of the fish fauna of the internal sector of the Amazon Estuary, Pará, Brazil

O presente estudo descreve a estrutura espacial e temporal da comunidade de peixes estuarinos da porção interna do estuário Amazônico. Amostras foram obtidas no canal principal e canais de maré das Baías do Guajará e Marajó e rio Guamá. Foram coletados um total de 41.516 espécimes, correspondendo 136 espécies, 38 famílias e 12 ordens. Na estação seca, a salinidade média no canal principal aumentou ao longo do gradiente limnico–marinho, entre o rio Guamá e a Baía do Marajó. A riqueza de espécies foi mais baixa na foz do rio Guamá e na margem direita da baía do Guajará. A composição das espécies e as guildas ambientais diferiram significativamente entre as áreas: Migrantes e Ocasionais de água doce foram dominantes no rio Guamá e na Baía do Guajará, enquanto Estuarinas, Marinhas Migrantes e Ocasionais dominaram na Baía do Marajó. Contudo, as guildas tróficas foram relativamente bem balanceadas, em termos funcionais. Piscívoros e Zoobentívoros foram os grupos alimentares dominantes em todas as áreas. Neste estudo, a avaliação da comunidade e o uso da abordagem com guildas foram eficientes para descrever a estrutura e o funcionamento das assembleias de peixes estuarinos e também como ferramenta na avaliação das pressões antrópicas na área.