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The deficiency of galectin-3 in stromal cells leads to enhanced tumor growth and bone marrow metastasis
Abstract\ud
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Background\ud
Galectin-3 is a multifunctional β-galactoside-binding lectin that once synthesized, is expressed in the nucleus, cytoplasm, cell surface and in the extracellular environment. Because of its unique structure, galectin-3 can oligomerize forming lattice upon binding to multivalent oligossacharides and influence several pathologic events such as tumorigenesis, invasion and metastasis.\ud
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Methods\ud
In our study, balb/c Lgals3+/+ and Lgals3−/− female mice were inoculated in the fourth mammary fat pad with 4T1 breast cancer cell line. The primary tumor, inguinal lymph nodes and iliac bone marrow were evaluated 15, 21 and 28 days post-injection. The primary tumor growth was evaluated by measuring the external diameter, internal growth by ultrasound and weight of the excised tumor. The presence of cancer cells in the draining lymph nodes and iliac crest bone marrow were performed by immunohistochemistry, PCR and clonogenic metastatic assay.\ud
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Results\ud
In this study we demonstrated that the deletion of galectin-3 in the host affected drastically the in vivo growth rate of 4T1 tumors. The primary tumors in Lgals3−/− mice displayed a higher proliferative rate (p < 0,05), an increased necrotic area (p < 0,01) and new blood vessels with a wider lumen in comparison with tumors from Lgals3+/+ mice (P < 0,05). Moreover, we detected a higher number of 4T1-derived metastatic colonies in the lymph nodes and the bone marrow of Lgals3−/− mice (p < 0,05). Additionally, healthy Lgals3−/− control mice presented an altered spatial distribution of CXCL12 in the bone marrow, which may explain at least in part the initial colonization of this organ in Lgals3−/− injected with 4T1 cells.\ud
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Conclusions\ud
Taken together, our results demonstrate for the first time that the absence of galectin-3 in the host microenvironment favors the growth of the primary tumors, the metastatic spread to the inguinal lymph nodes and bone marrow colonization by metastatic 4T1 tumor cells.This work was supported by the Research Support Foundation of Rio de\ud
Janeiro (FAPERJ), Brazil. Grants n°: E-26/111.316/2011
A elaboração e utilização de um kit de triângulos modeláveis para atividades de ensino de classificações de triângulos
Estudos e documentos oficiais apontam o potencial de materiais manipuláveis como um recurso que pode tornar significativo o processo de ensino e aprendizagem de Matemática. Nesse sentido, bolsistas do grupo de Geometria do Programa Institucional de Bolsa de Iniciação à Docência (PIBID), da Matemática, ao elaborarem uma sequência didática, decidiram por utilizar um material manipulável. Dessa forma, esse relato de experiência trata da criação e reflexão sobre a aplicação desse, à saber no desenvolvimento de uma aula de classificações de triângulos. Para isso, a primeira autora desse trabalho desenvolveu um kit de triângulos modeláveis feitos de canudos e linhas, a fim de que os alunos pudessem explorar esse tema e se apropriarem dos conceitos envolvidos. A aplicação deste, junto a outros bolsistas, foi em nonos anos do ensino fundamental de uma escola estadual em São Carlos/SP, no primeiro bimestre de 2016, e foi avaliada no decorrer e posteriormente, por meio de exercícios e uma prova final. Através dessa experiência, foi possível verificar que é possível em baixo custo e em pouco tempo o desenvolvimento de materiais manipuláveis que agucem o interesse dos alunos, tornando a aula mais participativa, o que facilitou a abstração dos conceitos estudados.PIBID - CAPE
O olhar geométrico na atividade de ensino de trigonometria
Este texto relata as dificuldades que nós, bolsistas do PIBID Matemática USP encontramos ao propor atividades sobre o triângulo retângulo em três 2ª séries do ensino médio de uma escola pública estadual paulista. Foi necessário rever e propor atividades que possibilitassem aos alunos desenvolver um “olhar geométrico” para os elementos do triângulo retângulo, isto é, identificar os catetos, hipotenusa, ângulo reto e ângulos agudos em qualquer posição que o triângulo retângulo se encontre. Com o objetivo de desenvolver essa habilidade realizamos uma série de atividades que necessitavam de especial atenção do aluno para esses elementos. O replanejamento das atividades iniciais propostas nos auxiliou, enquanto futuros professores, a perceber as dificuldades dos alunos e as nossas próprias dificuldades na elaboração de atividades de ensino de geometria.PIBID CAPE
On the equivalence between algorithms for non-negative matrix factorization and latent Dirichlet allocation
LDA (Latent Dirichlet Allocation ) and NMF (Non-negative Matrix Factorization) are two popular techniques to extract topics in a textual document corpus. This paper shows that NMF with Kullback-Leibler divergence approximate the LDA model under a uniform Dirichlet prior, therefore the comparative analysis can be useful to elucidate the implementation of variational inference algorithm for LDA.FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Projeto 2011/23689-9
Novel homologous lactate transporter improves l-lactic acid production from glycerol in recombinant strains of Pichia pastoris
Abstract\ud
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Background\ud
Crude glycerol is the main byproduct of the biodiesel industry. Although it can have different applications, its purification is costly. Therefore, in this study a biotechnological route has been proposed for further utilization of crude glycerol in the fermentative production of lactic acid. This acid is largely utilized in food, pharmaceutical, textile, and chemical industries, making it the hydroxycarboxylic acid with the highest market potential worldwide. Currently, industrial production of lactic acid is done mainly using sugar as the substrate. Thus here, for the first time, Pichia pastoris has been engineered for heterologous l-lactic acid production using glycerol as a single carbon source. For that, the Bos taurus lactate dehydrogenase gene was introduced into P. pastoris. Moreover, a heterologous and a novel homologous lactate transporter have been evaluated for l-lactic acid production.\ud
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Results\ud
Batch fermentation of the P. pastoris X-33 strain producing LDHb allowed for lactic acid production in this yeast. Although P. pastoris is known for its respiratory metabolism, batch fermentations were performed with different oxygenation levels, indicating that lower oxygen availability increased lactic acid production by 20 %, pushing the yeast towards a fermentative metabolism. Furthermore, a newly putative lactate transporter from P. pastoris named PAS has been identified by search similarity with the lactate transporter from Saccharomyces cerevisiae Jen1p. Both heterologous and homologous transporters, Jen1p and PAS, were evaluated in one strain already containing LDH activity. Fed-batch experiments of P. pastoris strains carrying the lactate transporter were performed with the batch phase at aerobic conditions followed by an aerobic oxygen-limited phase where production of lactic acid was favored. The results showed that the strain containing PAS presented the highest lactic acid titer, reaching a yield of approximately 0.7 g/g.\ud
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Conclusions\ud
We showed that P. pastoris has a great potential as a fermentative organism for producing l-lactic acid using glycerol as the carbon source at limited oxygenation conditions (below 0.05 % DO in the bioreactor). The best strain had both the LDHb and the homologous lactate transporter encoding genes expressed, and reached a titer 1.5 times higher than the strain with the S. cerevisiae transporter. Finally, it was also shown that increased lactic acid production was concomitant to reduction of acetic acid formation by half.This work was supported by the Brazilian National Council of Technological\ud
and Scientific Development (CNPq). Grant numbers are 473473/2011-9 and\ud
456452/2012-5. The Fundação de Amparo a Pesquisa do Estado de São Paulo\ud
(FAPESP), Brazil, provided funding for GHG and TFR
Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets
Abstract\ud
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Background\ud
Although males contribute half of the embryo’s genome, only recently has interest begun to be directed toward the potential impact of paternal experiences on the health of offspring. While there is evidence that paternal malnutrition may increase offspring susceptibility to metabolic diseases, the influence of paternal factors on a daughter’s breast cancer risk has been examined in few studies.\ud
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Methods\ud
Male Sprague-Dawley rats were fed, before and during puberty, either a lard-based (high in saturated fats) or a corn oil-based (high in n-6 polyunsaturated fats) high-fat diet (60 % of fat-derived energy). Control animals were fed an AIN-93G control diet (16 % of fat-derived energy). Their 50-day-old female offspring fed only a commercial diet were subjected to the classical model of mammary carcinogenesis based on 7,12-dimethylbenz[a]anthracene initiation, and mammary tumor development was evaluated. Sperm cells and mammary gland tissue were subjected to cellular and molecular analysis.\ud
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Results\ud
Compared with female offspring of control diet-fed male rats, offspring of lard-fed male rats did not differ in tumor latency, growth, or multiplicity. However, female offspring of lard-fed male rats had increased elongation of the mammary epithelial tree, number of terminal end buds, and tumor incidence compared with both female offspring of control diet-fed and corn oil-fed male rats. Compared with female offspring of control diet-fed male rats, female offspring of corn oil-fed male rats showed decreased tumor growth but no difference regarding tumor incidence, latency, or multiplicity. Additionally, female offspring of corn oil-fed male rats had longer tumor latency as well as decreased tumor growth and multiplicity compared with female offspring of lard-fed male rats. Paternal consumption of animal- or plant-based high-fat diets elicited opposing effects, with lard rich in saturated fatty acids increasing breast cancer risk in offspring and corn oil rich in n-6 polyunsaturated fatty acids decreasing it. These effects could be linked to alterations in microRNA expression in fathers’ sperm and their daughters’ mammary glands, and to modifications in breast cancer-related protein expression in this tissue.\ud
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Conclusions\ud
Our findings highlight the importance of paternal nutrition in affecting future generations’ risk of developing breast cancer.This study was supported by the Brazilian National Council for Scientific and\ud
Technological Development (CNPq; process 153478/2012-8), the São Paulo\ud
State Research Funding Agency (FAPESP; process 2011/23259-4), the National\ud
Cancer Institute (grant R01 CA164384 to LHC), and the Prevent Cancer\ud
Foundation (research grant 299045 to SdA)
Texture analysis using complex system models: fractal dimension, swarm systems and non-linear diffusion
Texture is one of the primary visual attributes used to describe patterns found in nature. Several texture analysis methods have been used as powerful tools for real applications involving computer vision. However, existing methods do not successfully discriminate the complexity of texture patterns. Such methods disregard the possibility of describing image structures by fractal dimension. Fractality-based measures allow a noninteger geometric interpretation with applications in areas such as mathematics, physics, and biology. The central hypothesis of this work is that textures can be described as irregular fractal surfaces due to their complex geometry. Pushing the limits of the state-of-the-art, the results achieved in the four methodologies described in this work demonstrated the potential of using texture features in tasks of pattern recognition. The contributions of this work shall support significant advances in materials engineering, computer vision, and agriculture.FAPESP (grant 2011/02918-0)CNPq (grant 142098/2011-6