Bisphosphonate Inhibition of Prostate Cancer Cell Invasion, Migration and Cytoskeletal Organization

Metastatic bone lesions are commonly associated with prostate cancer affecting approximately 60-80% of the patients. The progression of prostate cancer into an advanced stage is a complex process and its molecular mechanisms are poorly understood. So far, no curative treatment is available for advanced stages of prostate cancer. Bisphosphonates (BPs) are synthetic pyrophosphate analogues, which are used as therapeutics for various metabolic bone diseases because of their ability to inhibit osteoclastic bone resorption. Nitrogen-containing bisphosphonates block the function of osteoclasts by disturbing the vesicular traffic and the mevalonate pathway -related enzymes, for example farnesyl diphosphate synthase, which is involved in post-translational isoprenylation of small GTPases. In addition, the anti-proliferative, anti-invasive and pro-apoptotic effects of nitrogen-containing bisphosphonates on various cancer cell lines have been reported. The aim of this thesis work was to clarify the effects of bisphosphonates on prostate cancer cells, focusing on the mechanisms of adhesion, invasion and migration. Furthermore, the role of the mevalonate pathway and prenylation reactions in invasion and regulation of the cytoskeleton of prostate cancer cells were examined. Finally, the effects of alendronate on cytoskeleton- and actin-related proteins in prostate cancer cells were studied in vitro and in vivo. The results showed that the nitrogen-containing bisphosphonate alendronate inhibited the adhesion of prostate cancer cells to various extracellular matrix proteins and migration and invasion in vitro. Inhibition of invasion and migration was reversed by mevalonate pathway intermediates. The blockage of the prenylation transferases GGTase I and FTase inhibited the invasion, migration and actin organization of prostate cancer cells. The marked decrease of cofilin was observed by the prenylation inhibitors used. Inhibition of GGTase I also disrupted the regulation of focal adhesion kinase and paxillin. In addition, alendronate disrupted the cytoskeletal organization and decreased the level of cofilin in vitro and in vivo. The decrease of the cofilin level by alendronate could be one of the key mechanisms behind the observed inhibition of migration and invasion. Based on the effects of nitrogen-containing bisphosphonates on tumor cell invasion and cytoskeletal organization, they can be suggested to be developed as therapeutics for inhibiting prostate cancer metastasis.

Potential impact of the global climate changes on the spatial distribution of areas of risk for the occurrence of eucalyptus rust in Brazil

Rust, caused by Puccinia psidii, is one of the most important diseases affecting eucalyptus in Brazil. This pathogen causes disease in mini-clonal garden and in young plants in the field, especially in leaves and juvenile shoots. Favorable climate conditions for infection by this pathogen in eucalyptus include temperature between 18 and 25 ºC, together with at least 6-hour leaf wetness periods, for 5 to 7 consecutive days. Considering the interaction between the environment and the pathogen, this study aimed to evaluate the potential impact of global climate changes on the spatial distribution of areas of risk for the occurrence of eucalyptus rust in Brazil. Thus, monthly maps of the areas of risk for the occurrence of this disease were elaborated, considering the current climate conditions, based on a historic series between 1961 and 1990, and the future scenarios A2 and B2, predicted by IPCC. The climate conditions were classified into three categories, according to the potential risk for the disease occurrence, considering temperature (T) and air relative humidity (RH): i) high risk (18 < T < 25 ºC and RH > 90%); ii) medium risk (18 < T < 25 ºC and RH < 90%; T< 18 or T > 25 ºC and RH > 90%); and iii) low risk (T < 18 or T > 25 ºC and RH < 90%). Data about the future climate scenarios were supplied by GCM Change Fields. In this study, the simulation model Hadley Centers for Climate Prediction and Research (HadCm3) was adopted, using the software Idrisi 32. The obtained results led to the conclusion that there will be a reduction in the area favorable to eucalyptus rust occurrence, and such a reduction will be gradual for the decades of 2020, 2050 and 2080 but more marked in scenario A2 than in B2. However, it is important to point out that extensive areas will still be favorable to the disease development, especially in the coldest months of the year, i.e., June and July. Therefore, the zoning of areas and periods of higher occurrence risk, considering the global climate changes, becomes important knowledge for the elaboration of predicting models and an alert for the integrated management of this disease.

Combining Productivity and Renewal in a Production Organization: a Case Study on Organizational Ambidexterity

This case study examined how productivity and renewal are combined in a production organization operating in process industry through the antecedents of organizational ambidexterity; structure, culture, and management. The empirical material consisted of semi-structured interviews, observations and case organization documents. The findings suggest that the case organization structurally separates exploitation and exploration to separate units. However, it was found that the units focusing on exploration also devote resources to exploitation. External networks, such as customers, suppliers, and other factories seemed to play a role in the exploration activities, as well as in learning activities, which were connected to renewal. Productivity was seen as a natural part of a production organization and pursued at manufacturing units. Process management techniques appeared to be spread across the organization and having positive impact on exploitation and negative impact on exploration. The managerial culture and management’s capability to communicate goals, vision and strategy was found to be unsatisfactory. This thesis contributes to the new research paradigm of organizational ambidexterity by providing unique results on how the antecedents of organizational ambidexterity are accomplished in a production organization. Furthermore, the thesis extends the previous research of organizational renewal capability by connecting it to the ambidexterity theory.

Impersonal trust within the organization: what, how and why?

It has been shown in organizational settings that trust is a crucial factor in different kinds of outcomes, and consequently, building employee trust in the employer is a goal for all kinds of organizations. Although it is recognized that trust in organizations operates on multiple levels, at present there is no clear consensus on the concept of trust within the organization. One can have trust in particular people (i.e. interpersonal trust) or in organized systems (i.e. impersonal trust). Until recently organizational trust has been treated mainly as an interpersonal phenomenon. However, the interpersonal approach is limited. Scholars studying organizational trust have thus far focused only on specific dimensions of impersonal trust, and none have taken a comprehensive approach. The first objective in this study was to develop a construct and a scale encompassing the impersonal element of organizational trust. The second objective was to examine the effects of various HRM practices on the impersonal dimensions of organizational trust. Moreover, although the “black box” model of HRM is widely studied, there have been only a few attempts to unlock the box. Previous studies on the HRM-performance link refer to trust, and this work contributes to the literature in considering trust an impersonal issue in the relationship between HRM, trust, and performance. The third objective was thus to clarify the role of impersonal trust in the relationship between HRM and performance. The study is divided into two parts comprising the Introduction and four separate publications. Each publication addresses a distinct sub-question, whereas the Introduction discusses the overall results in the light of the individual sub-questions. The study makes two major contributions to the research on trust. Firstly, it offers a framework describing the construct of impersonal trust, which to date has not been clearly articulated in the research on organizational trust. Secondly, a comprehensive, psychometrically sound, operationally valid scale for measuring impersonal trust was developed. In addition, the study makes an empirical contribution to the research on strategic HRM. First, it shows that HRM practices affect impersonal trust and the contribution is to consider the HRM-trust link in terms of impersonal organizational trust. It is shown that each of the six HRM practices in focus is connected to impersonal trust. A further contribution lies in unlocking the black box. The study explores the impersonal element of organizational trust and its mediating role between HRM practices and performance. The result is the identification of the path by which HRM contributes to performance through the mediator of impersonal trust. It is shown that the effect on performance of HRM designed specifically to enhance employees’ impersonal trust in the organization is positive.

POPULATION STRUCTURE AND SPATIAL DISTRIBUTION OF Bauhinia cheilantha (Bong.) Steud. IN TWO FRAGMENTS AT DIFFERENT REGENERATION STAGES IN THE CAATINGA, IN SERGIPE, BRAZIL

ABSTRACTThis study aimed to analyze the vertical and diameter structure and the spatial distribution pattern of Bauhinia cheilantha in two Caatinga fragments in Sergipe, Brazil, at different regeneration stages. Thirty plots were demarcated in area I (Canindé de São Francisco and Poço Redondo), which has vegetation regeneration, and 25 plots in area II (Porto da Folha) with preserved vegetation, both having 400 m2. All B. cheilanthaindividuals had their height and circumference (circumference at breast height > 6 cm) measured. Possible differences in height and diameter at breast height were tested in the two populations by using Student’s T-test. The distribution pattern of species was calculated through Payandeh’s index. We sampled 154 B. cheilantha individuals, equivalent to 33.3% of the plots in area I and in 1,027 individuals in area II, totaling 100% frequency. Height and the diameter of the two populations were statistically different, where AI achieved all values lower than AII. The spatial distribution pattern of B. cheilantha found in both areas was aggregate, with values of 11.85 and 9.00, respectively. Thus, it became clear that the population in AII is at a more advanced successional status than AI, due to its longer conservation time.

Spatial variability of leaf wetness duration in a 'Niagara Rosada' vineyard

Despite considerable efforts to develop accurate electronic sensors to measure leaf wetness duration (LWD), little attention has been given to studies about how is LWD variability in different positions of the crop canopy. In order to evaluate the influence of 'Niagara Rosada' (Vitis labrusca) grapevine structure on the spatial variability of LWD, the objective of this study was to determine the canopy position of the ‘Niagara Rosada’ table grape with longer LWD and its correlation with measured standard LWD over turfgrass. LWD was measured in four different canopy positions of the vineyard (sensors deployed at 45º with the horizontal): at the top of the plants, with sensors facing southwest and northeast (Top-SW and Top-NE), and at the grape bunches height, with sensors facing southwest and northeast (Bottom-SW and Bottom-NE). No significant difference was observed between the top (1.6 m) and the bottom (1.0 m) of the canopy and also between the southwest and northeast face of the plants. The relationship between standard LWD over turfgrass and crop LWD in different positions of the grape canopy showed a define correlation, with R² ranging from 0.86 to 0.89 for all period, from 0.72 to 0.77 for days without rain, and from 0.89 to 0.91 for days with rain.

Terrain forms and spatial variability of soil properties in an area cultivatedwith citrus

The technique of precision agriculture and soil-landscape allows delimiting areas for localized management, allowing a localized application of agricultural inputs and thereby may contribute to preservation of natural resources. Therefore, the objective of this work was to characterize the spatial variability of chemical properties and clay content in the context of soil-landscape relationship in a Latosol (Oxisol) under cultivation of citrus. Soil samples were collected at a depth of 0.0-0.2 m in an area of 83.5 ha planted with citrus, as a 50-m intervals grid, with 129 points in concave terrain and 206 points in flat terrain, totaling 335 points. Values for the variables that express the chemical characteristics and clay content of soil properties were analyzed with descriptive statistics and geostatistical modeling of semivariograms for making maps of kriging. The values of range and kriging maps indicated higher variability in the shape of concave topography (top segment) compared with the shape of flat topography (slope and hillside segments below). The identification of different forms of terrain proved to be efficient in understanding the spatial variability of chemical properties and clay content of soil under cultivation of citrus.

GPS receivers for georeferencing of spatial variability of soil attributes

The characterization of the spatial variability of soil attributes is essential to support agricultural practices in a sustainable manner. The use of geostatistics to characterize spatial variability of these attributes, such as soil resistance to penetration (RP) and gravimetric soil moisture (GM) is now usual practice in precision agriculture. The result of geostatistical analysis is dependent on the sample density and other factors according to the georeferencing methodology used. Thus, this study aimed to compare two methods of georeferencing to characterize the spatial variability of RP and GM as well as the spatial correlation of these variables. Sampling grid of 60 points spaced 20 m was used. For RP measurements, an electronic penetrometer was used and to determine the GM, a Dutch auger (0.0-0.1 m depth) was used. The samples were georeferenced using a GPS navigation receiver, Simple Point Positioning (SPP) with navigation GPS receiver, and Semi-Kinematic Relative Positioning (SKRP) with an L1 geodetic GPS receiver. The results indicated that the georeferencing conducted by PPS did not affect the characterization of spatial variability of RP or GM, neither the spatial structure relationship of these attributes.

Spatial variability of soil physical properties in two management systems in sugarcane crop

The aim of this study was to characterize the spatial variability of soil bulk density (Bd), soil moisture content (θ) and total porosity (Tp) in two management systems of sugarcane harvesting, with or without burning, in a Haplustox soil, in the 0-0.20 m layer. The study area is located in Rio Brilhante, state of Mato Grosso do Sul, Brazil, in Eldorado Sugar Mill. The plots have presented 180 m length, and 145.6 m width, totaling 90 points distributed in the form of a grid of nine rows by ten columns, with points spaced 20 m from its neighbor. Soil samples were collected at 0-0.20 m layer in 2007/2008 and 2008/2009 crops. The harvest with burning system had a higher density compared to mechanized harvest, in the two study periods. The moisture content as well as the porosity increased proportionally with the decrease of the density of the harvest burning system compared to the mechanized.

Spatial variability of the rainfall erosive potential in the State of Mato Grosso do Sul, Brazil

Information about rainfall erosivity is important during soil and water conservation planning. Thus, the spatial variability of rainfall erosivity of the state Mato Grosso do Sul was analyzed using ordinary kriging interpolation. For this, three pluviograph stations were used to obtain the regression equations between the erosivity index and the rainfall coefficient EI30. The equations obtained were applied to 109 pluviometric stations, resulting in EI30 values. These values were analyzed from geostatistical technique, which can be divided into: descriptive statistics, adjust to semivariogram, cross-validation process and implementation of ordinary kriging to generate the erosivity map.Highest erosivity values were found in central and northeast regions of the State, while the lowest values were observed in the southern region. In addition, high annual precipitation values not necessarily produce higher erosivity values.

Spatial variability of noise level in agricultural machines

The knowledge of the spatial variability of noise levels and the build of kriging maps can help the evaluation of the salubrity of environments occupied by agricultural workers. Therefore, the objective of this research was to characterize the spatial variability of the noise level generated by four agricultural machines, using geostatistics, and to verify if the values are within the limits of human comfort. The evaluated machines were: harvester, chainsaw, brushcutter and tractor. The data were collected at the height of the operator's ear and at different distances. Through the results, it was possible to verify that the use of geostatistics, by kriging technique, made it possible to define areas with different levels for the data collected. With exception of the harvester, all of machines presented noise levels above than 85 dB (A) near to the operator, demanding the use of hearing protection.

Spatial variability of yield and other parameters associated with pear trees

In the last few years, precision agriculture has become commonly used with many crops, particularly cereals, and there is also interest in precision horticulture. Pear is a seasonal fruit and well appreciated by Brazilian people, although it is mostly imported. Brazilian farmers are nowadays trying to increase pear production. Thus, this research aimed at mapping the yield of pear trees in order to study the spatial variability of yield as well as its comparison with spatial variability of soil and plant attributes. The experimental field had 146 pear trees, variety 'Pêra d'água', distributed on a 1.24 ha. Four harvests were performed according to the fruit ripening and from each tree; only the ripe fruits were harvested. In each harvest, all the fruits were weighed and the total yield was obtained based on the sum of each harvest. The soil attributes analyzed were P, K, Ca, Mg, pH in CaCl2, C, Cu, Zn, Fe, Mn and base saturation, and the plant attributes were fruit length, diameter and yield. Yield had low correlation with soil and plant attributes. An index of spatial variability was suggested in this study and helped in classifying levels of spatial dependence of the various soil and plant attributes: very low (fruit length); low (P, fruit diameter), medium (Mg, pH, Cu, Zn, Fe), high (Ca, K, base saturation and yield), and very high (Mn and C).

Comparison of maps of spatial variability of soil resistance to penetration constructed with and without covariables using a spatial linear model

A study about the spatial variability of data of soil resistance to penetration (RSP) was conducted at layers 0.0-0.1 m, 0.1-0.2 m and 0.2-0.3 m depth, using the statistical methods in univariate forms, i.e., using traditional geostatistics, forming thematic maps by ordinary kriging for each layer of the study. It was analyzed the RSP in layer 0.2-0.3 m depth through a spatial linear model (SLM), which considered the layers 0.0-0.1 m and 0.1-0.2 m in depth as covariable, obtaining an estimation model and a thematic map by universal kriging. The thematic maps of the RSP at layer 0.2-0.3 m depth, constructed by both methods, were compared using measures of accuracy obtained from the construction of the matrix of errors and confusion matrix. There are similarities between the thematic maps. All maps showed that the RSP is higher in the north region.