Loss of ovarian function promotes angiogenesis in human ovarian carcinoma

We show here that elevated levels of gonadotropins (luteinizing hormone and follicle stimulating hormone), as found in menopause or after ovariectomy, promote growth of human ovarian carcinoma by induction of tumor angiogenesis. Human epithelial ovarian cancer tumors progressed faster in ovariectomized mice. This induced growth could be attributed to the elevated levels of gonadotropins associated with loss of ovarian function because direct administration of gonadotropins also was effective in promoting tumor progression in vivo. On the other hand, gonadotropins had no direct effect on the proliferation of human ovarian cancer cells in vitro. Using MRI, we demonstrated that ovariectomy significantly (P < 0.02) induces neovascularization of human ovarian carcinoma spheroids implanted in nude mice. Moreover, conditioned medium of gonadotropin-treated human ovarian carcinoma cells showed increased mitogenic activity to bovine endothelial cells, and this activity could be blocked by neutralizing antibodies against luteinizing hormone and against vascular endothelial growth factor. Accordingly, gonadotropin stimulation resulted in a dose-dependent-induced expression of vascular endothelial growth factor in monolayer culture as well as in the outer proliferating cells of human ovarian cancer spheroids. These results demonstrate the significance of the elevated levels of gonadotropins, as found in menopause and in all ovarian cancer patients, on the progression of ovarian cancer and could explain the protective effect of estrogen replacement therapy. Based on these results, we suggest that hormonal therapy aimed at lowering the circulating levels of gonadotropins may possibly prolong remission in ovarian cancer by extending tumor dormancy.

Evolution of genome–phenome diversity under environmental stress

The genomic era revolutionized evolutionary biology. The enigma of genotypic-phenotypic diversity and biodiversity evolution of genes, genomes, phenomes, and biomes, reviewed here, was central in the research program of the Institute of Evolution, University of Haifa, since 1975. We explored the following questions. (i) How much of the genomic and phenomic diversity in nature is adaptive and processed by natural selection? (ii) What is the origin and evolution of adaptation and speciation processes under spatiotemporal variables and stressful macrogeographic and microgeographic environments? We advanced ecological genetics into ecological genomics and analyzed globally ecological, demographic, and life history variables in 1,200 diverse species across life, thousands of populations, and tens of thousands of individuals tested mostly for allozyme and partly for DNA diversity. Likewise, we tested thermal, chemical, climatic, and biotic stresses in several model organisms. Recently, we introduced genetic maps and quantitative trait loci to elucidate the genetic basis of adaptation and speciation. The genome–phenome holistic model was deciphered by the global regressive, progressive, and convergent evolution of subterranean mammals. Our results indicate abundant genotypic and phenotypic diversity in nature. The organization and evolution of molecular and organismal diversity in nature at global, regional, and local scales are nonrandom and structured; display regularities across life; and are positively correlated with, and partly predictable by, abiotic and biotic environmental heterogeneity and stress. Biodiversity evolution, even in small isolated populations, is primarily driven by natural selection, including diversifying, balancing, cyclical, and purifying selective regimes, interacting with, but ultimately overriding, the effects of mutation, migration, and stochasticity.

Complex dynamics of multilocus systems subjected to cyclical selection.

Earlier we have shown that oscillations with a long period ("supercycles") may arise in two-locus systems experiencing cyclical selection with a short period. However, this mode of complex limiting behavior appeared to be possible for narrow ranges of parameters. Here we demonstrate that a multilocus system subjected to stabilizing selection with cyclically moving optimum can generate ubiquitous complex limiting behavior including supercycles, T-cycles, and chaotic-like phenomena. This mode of multilocus dynamics far exceeds the potential attainable under ordinary selection models resulting in simple behavior. It may represent a novel evolutionary mechanism increasing genetic diversity over long-term time periods.

Genetic supercycles caused by cyclical selection.

Typical behavior of a two-locus genetic system experiencing cyclical selection, includes fixation (in one or both loci) or a stable polymorphic cycle with a period equal to that of environmental changes. By considering the time scale in terms of environmental periods, the last case could be trivially classified as a polymorphic stable point. Here we report on some results showing the complex limiting behavior of diploid population trajectories resulting from selection in a cyclically changing environment. We found that simple cyclical selection could produce genetic supercycles composed of many hundreds of environmental periods.

New capabilities:can IT service providers leverage crowdsourcing?

Technological advancements enable new sourcing models in software development such as cloud computing, software-as-a-service, and crowdsourcing. While the first two are perceived as a re-emergence of older models (e.g., ASP), crowdsourcing is a new model that creates an opportunity for a global workforce to compete with established service providers. Organizations engaging in crowdsourcing need to develop the capabilities to successfully utilize this sourcing model in delivering services to their clients. To explore these capabilities we collected qualitative data from focus groups with crowdsourcing leaders at a large technology organization. New capabilities we identified stem from the need of the traditional service provider to assume a "client" role in the crowdsourcing context, while still acting as a "vendor" in providing services to the end client. This paper expands the research on vendor capabilities and IS outsourcing as well as offers important insights to organizations that are experimenting with, or considering, crowdsourcing.

Primary vendor capabilities in a mediated outsourcing model:can IT service providers leverage crowdsourcing?

Crowdsourcing platforms that attract a large pool of potential workforce allow organizations to reduce permanent staff levels. However managing this "human cloud" requires new management models and skills. Therefore, Information Technology (IT) service providers engaging in crowdsourcing need to develop new capabilities to successfully utilize crowdsourcing in delivering services to their clients. To explore these capabilities we collected qualitative data from focus groups with crowdsourcing leaders at a large multinational technology organization. New capabilities we identified stem from the need of the traditional service provider to assume a "client" role in the crowdsourcing context, while still acting as a "vendor" in providing services to the end-client. This paper expands the research on vendor capabilities and IT outsourcing as well as offers important insights to organizations that are experimenting with, or considering, crowdsourcing. © 2014 Elsevier B.V. All rights reserved.

Expressão imuno-histoquímica das proteínas E-Caderina e BCL2 e nevos melanociticos orais e cutâneos

Melanocytic nevi (MNs) are benign melanocytic proliferations of cells, which can be found in the skin and mucous coat, including the oral mucosa. However, skin NMs are more common when compared to those that affect the oral mucosa. The molecular mechanisms involved in the development of nevi and the factors that can influence the migration pattern of the nevus cells are little explored. The aim of this study was to analyze the immunohistochemical expression of E-cadherin protein and Bcl-2 in oral / skin NMs and relate them to the clinical characteristics (gender, age, location, exposure to solar radiation) and histopathological types. 36 cases of oral NMs and 34 Skin NMs were analyzed. The immunohistochemistry was used of the protein E-cadherin and bcl-2, which were analyzed the intensity (weak, moderate and strong) and distribution marking (diffuse and focal). The immunoreactivity also analyzed as to the types of nevus cells (epithelioid cells -A, -B lymphocyte and fibroblast-like -C). Statistical analysis was performed using the chi-square tests of Pearson and Spearman correlation with significance level set at 5%. Of the 70 cases of NMs, 82.9% were female, 48.6% aged 26-50 years, 51.4% were diagnosed histologically as intradermal / intramucosal nevi and 80% were NMs acquired. Immunohistochemical expression of BCL2 and E-cadherin were variables in the sample and showed no association with clinical parameters. The expression of bcl-2 and E-cadherin were variable according to the types of nevus cells (A, B and C) (P = 0.001). The expression of bcl-2 was more diffuse in congenital MNs (p = 0.002). E-cadherin was positive in 83.3% of MNs <1cm (p = 0.001) and exhibited weak staining in 73.9% of MNs that were in exposed areas (p = 0.010). Based on these results, it is suggested that the E-cadherin has a modulating effect on the migratory properties of NMs, and bcl-2 is a marker of MNs with increased proliferative capacity.

Automated Equation Formulation for Causal Loop Diagrams

The annotation of Business Dynamics models with parameters and equations, to simulate the system under study and further evaluate its simulation output, typically involves a lot of manual work. In this paper we present an approach for automated equation formulation of a given Causal Loop Diagram (CLD) and a set of associated time series with the help of neural network evolution (NEvo). NEvo enables the automated retrieval of surrogate equations for each quantity in the given CLD, hence it produces a fully annotated CLD that can be used for later simulations to predict future KPI development. In the end of the paper, we provide a detailed evaluation of NEvo on a business use-case to demonstrate its single step prediction capabilities.

Caso dermatológico

O nevo do tecido conjuntivo (NTC) é um hamartoma que pode estar associada a várias síndromes, como esclerose tube- rosa, síndrome de Buschke-Ollendorf ou síndrome de Proteus. Casos familiares de NTC têm sido relacionados com maior risco de patologia cardíaca. A apresentação clínica típica caracteriza-se pelo aparecimento de múltiplas placas cor de pele ou amareladas, confluentes no tronco e/ou nos membros, assintomáticas. São geralmente identificados na infância, sem predileção de género. O diagnóstico é confirmado por biopsia cutânea. Estudos adicionais podem ser necessários, de acordo com a presença de sinais ou sintomas sugestivos de uma doença subjacente.