Evaluación de variables lineales y de crecimiento en becerros y becerras de la raza brahman y sus cruces en la finca San Miguel, Barranca de Upía, Meta

Tesis (Zootecnista). -- Universidad de La Salle. Facultad de Ciencias Agropecuarias. Programa de Zootecnia, 2014

Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.

Expression of c-ets-1 mRNA is associated with an invasive, EMT-derived phenotype in breast carcinoma cell lines

We have previously observed in vitro that some stromal proteinases (MMP- 2, MT1-MMP) were expressed or activated by invasive carcinoma cell lines exhibiting mesenchymal features, presumably acquired through an epithelial to mesenchymal transition (EMT). To examine the potential contribution of c- ets-1 to this phenotype, we have compared here the expression of c-ets-1 with invasiveness in vitro and expression of vimentin, E-cadherin, uPA, MMP-1 and MMP-3 in a panel of human breast cancer cell lines. Our results clearly demonstrate an association between c-ets-1 expression and the invasive, EMT- derived phenotype, which is typified by the expression of vimentin and the lack of E-cadherin. While absent from the two non-invasive, vimentin-negative cell lines, c-ets-1 was abundantly expressed in all the four vimentin- positive lines. However, we could not find a clear quantitative or qualitative relationship between the expression of c-ets-1 and the three proteinases known to he regulated by c-ets-1, except that when they were expressed, it was only in the invasive c-ets-1-positive lines. UPA mRNAs were found in three of the four vimentin-positive lines, MMP-1 in two of the four, and MMP-3 could not be detected in any of the cell lines. Intriguingly, MDA- MB-435 cells, which exhibit the highest metastatic potential of these cell lines in nude mice, expressed vimentin and c-ets-1, but lacked expression of these three proteinases, at least under the culture conditions employed. Taken together, our results show that c-ets-1 expression is associated with an invasive, EMT-derived phenotype in breast cancer cells, although it is apparently not sufficient to ensure the expression of uPA, MMP-1 or MMP-3, in the vimentin-positive cells. Such proteases regulation is undoubtedly qualified by the cellular context. This study therefore advances our understanding of the molecular regulation of invasiveness in EMT-associated carcinoma progression, and suggests that c-ets-1 may contribute to the invasive phenotype in carcinoma cells.

The role of lysine-41 in RNase A catalysis - A quantum chemical study on the active site ligand complex

Several mechanisms have been proposed to explain the action of enzymes at the atomic level. Among them, the recent proposals involving short hydrogen bonds as a step in catalysis by Gerlt and Gassman [1] and proton transfer through low barrier hydrogen bonds (LBHBs) [2, 3] have attracted attention. There are several limitations to experimentally testing such hypotheses, Recent developments in computational methods facilitate the study of active site-ligand complexes to high levels of accuracy, Our previous studies, which involved the docking of the dinucleotide substrate UpA to the active site of RNase A [4, 5], enabled us to obtain a realistic model of the ligand-bound active site of RNase A. From these studies, based on empirical potential functions, we were able to obtain the molecular dynamics averaged coordinates of RNase A, bound to the ligand UpA. A quantum mechanical study is required to investigate the catalytic process which involves the cleavage and formation of covalent bonds. In the present study, we have investigated the strengths of some of the hydrogen bonds between the active site residues of RNase A and UpA at the ab initio quantum chemical level using the molecular dynamics averaged coordinates as the starting point. The 49 atom system and other model systems were optimized at the 3-21G level and the energies of the optimized systems were obtained at the 6-31G* level. The results clearly indicate the strengthening of hydrogen bonds between neutral residues due to the presence of charged species at appropriate positions. Such a strengthening manifests itself in the form of short hydrogen bonds and a low barrier for proton transfer. In the present study, the proton transfer between the 2'-OH of ribose (from the substrate) and the imidazole group from the H12 of RNase A is influenced by K41, which plays a crucial role in strengthening the neutral hydrogen bond, reducing the barrier for proton transfer.

'A responsible nuclear weapons power' : Nuclear Weapons and Indian Foreign Policy

This thesis examines the interrelationship and dynamics between the Indian United Progressive Alliance government’s foreign policy and its nuclear weapons policy. The purpose of the study is to situate nuclear policy within a foreign policy framework, and the fundamental research problem is thus how does the Indian nuclear policy reflect and respond to the Indian foreign policy? The study examines the intentions in the Indian foreign and nuclear policies, and asks whether these intentions are commensurable or incommensurable. Moreover, the thesis asks whether the UPA government differs from its predecessors, most notably the Bharatiya Janata Party-led National Democratic Alliance government in its foreign and nuclear policies. Answers to these questions are based on the interpretation of political texts and speeches as suggested by Quentin Skinner’s notion of meaning3, what does a writer or speaker mean by what he or she says in a given text, and by J.L. Austin’s speech act theory. This linguistic perspective and the approach of intertextualizing, place the political acts within their contingent intellectual and political contexts. The notion of strategic culture is therefore introduced to provide context for these juxtapositions. The thesis firstly analyses the societal, historical and intellectual context of India’s foreign and nuclear policy. Following from this analysis the thesis then examines the foreign and nuclear policies of Prime Minister Manmo-han Singh’s UPA government. This analysis focuses on the texts, speeches and statements of Indian authorities between 2004 and 2008. This study forwards the following claims: firstly, the UPA Government conducts a foreign policy that is mainly and explicitly inclusive, open and enhancing, and it conducts a nuclear policy that is mainly and implicitly excluding, closed and protective. Secondly, despite the fact that the notion of military security is widely appreciated and does not, as such, necessarily collide with foreign policy, the UPA Government conducts a nuclear policy that is incommensurable with its foreign policy. Thirdly, the UPA Gov-ernment foreign and nuclear policies are, nevertheless, commensurable re-garding their internal intentions. Finally, the UPA Government is conduct-ing a nuclear policy that is gradually leading India towards having a triad of nuclear weapons with various platforms and device designs and a function-ing and robust command and control system encompassing political and military planning, decision-making and execution. Regarding the question of the possible differences between the UPA and NDA governments this thesis claims that, despite their different ideological roots and orientations in domestic affairs, the Indian National Congress Party conducts, perhaps surprisingly, quite a similar foreign and nuclear policy to the Bharatiya Janata Party.

Interaction of substrate uridyl 3',5'-adenosine with ribonuclease A:a molecular dynamics study

A wealth of information available from x-ray crystallographic structures of enzyme-ligand complexes makes it possible to study interactions at the molecular level. However, further investigation is needed when i) the binding of the natural substrate must be characterized, because ligands in the stable enzyme-ligand complexes are generally inhibitors or the analogs of substrate and transition state, and when ii) ligand binding is in part poorly characterized. We have investigated these aspects i? the binding of substrate uridyl 3',5'-adenosine (UpA) to ribonuclease A (RNase A). Based on the systematically docked RNase A-UpA complex resulting from our previous study, we have undertaken a molecular dynamics simulation of the complex with solvent molecules. The molecular dynamics trajectories of this complex are analyzed to provide structural explanations for varied experimental observations on the ligand binding at the B2 subsite of ribonuclease A. The present study suggests that B2 subsite stabilization can be effected by different active site groups, depending on the substrate conformation. Thus when adenosine ribose pucker is O4'-endo, Gln69 and Glu111 form hydrogen-bonding contacts with adenine base, and when it is C2'-endo, Asn71 is the only amino acid residue in direct contact with this base. The latter observation is in support of previous mutagenesis and kinetics studies. Possible roles for the solvent molecules in the binding subsites are described. Furthermore, the substrate conformation is also examined along the simulation pathway to see if any conformer has the properties of a transition state. This study has also helped us to recognize that small but concerted changes in the conformation of the substrate can result in substrate geometry favorable for 2',3' cyclization. The identified geometry is suitable for intraligand proton transfer between 2'-hydroxyl and phosphate oxygen atom. The possibility of intraligand proton transfer as suggested previously and the mode of transfer before the formation of cyclic intermediate during transphosphorylation are discussed.

Molecular dynamics studies on nucleoside 2',3'-cyclic phosphates

2',3'-cyclic nucleotides are intermediates and substrates of Ribonuclease (RNase)-catalysed reactions. The characterization of the equilibrium conformation as well as the flexibility inherent in these molecules helps in understanding the enzymatic action of RNases. The present study explores parameters like phase angle, glycosydic torsion angle and hydrogen bond to find possible interrelationship between them through Molecular Dynamics (MD) simulations on 3'-GMP, 3'-UMP, A>p, G>p, U>p, C>p, GpA>p and UpA>p. Interesting results of the effect of cyclisation and other constraints such as hydrogen bond between certain groups on the equilibrium ribose conformation have emerged from this study.

Nonlinear static and dynamic damped response of a composite rectangular plate resting on a two-parameter elastic foundation

Nonlinear static and dynamic response analyses of a clamped. rectangular composite plate resting on a two-parameter elastic foundation have been studied using von Karman's relations. Incorporating the material damping, the governing coupled, nonlinear partial differential equations are obtained for the plate under step pressure pulse load excitation. These equations have been solved by a one-term solution and by applying Galerkin's technique to the deflection equation. This yields an ordinary nonlinear differential equation in time. The nonlinear static solution is obtained by neglecting the time-dependent variables. Thc nonlinear dynamic damped response is obtained by applying the ultraspherical polynomial approximation (UPA) technique. The influences of foundation modulus, shear modulus, orthotropy, etc. upon the nonlinear static and dynamic responses have been presented.

La equidad de género en la toma de decisiones a nivel de la Unidad de Producción Agropecuaria y de la Comunidad de Nandarola. Municipio de Nandaime (2013-2014)

La presente investigación se realizó en la comunidad de Nandarola, municipio de Nandaime, Nicaragua. 2013-2014. Los objetivos que se persiguieron fueron: analizar los diferentes factores que inciden en la equidad de género a través de los roles, la poca participación de la mujer en las labores agrícolas y sociales, así como capacitaciones, asistencia técnica, y la distribución del trabajo que desempeñan los miembros de cada unidad de producción agropecuaria, y en la Comunidad. Analizar el nivel de participación e integración de la mujer en la agricultura y labores domésticas. Conocer el grado de participación en la toma de decisiones de los recursos físicos y los cambios que se han venido dando en las diferentes épocas en el trabajo agropecuario. La metodología que se utilizó para la investigación fue tipo cualitativo-cuantitativo. En los métodos cualitativos se realizaron 17 entrevistas de preguntas abiertas para analizar el comportamiento y actitudes de hombres y mujeres, el grado de participación de la mujer en los procesos productivos en la agricultura, también se aplicaron como método cualitativo el grupo focal para conocer las diferentes expresiones de inequidad que ha vivido la mujer en la década de los ´80 y en la actualidad. En el análisis cuantitativo se realizaron 103 encuestas. En los resultados más importantes se encontró que el 8.33 % de las mujeres fueron beneficiados por la reforma agraria en la distribución de tierra, y los hombres con un 91.67%. Los problemas que enfrenta la población femenina es la falta de participación, en la toma de decisiones y el control de los recursos en la parte agropecuaria la mujer está ocupando apenas el 20 % en cambio el hombre con un 60%, dado que la mujer se limita a las actividades agrícolas y a la inserción del mercado. En el área pecuaria (ganado menor) la mujer colabora con un 71.43% y el hombre apenas aporta el 14.29%. En el aspecto organizativo las mujeres representan solamente el 20% del total de los miembros de las cooperativas, porque no tienen el tiempo suficiente de participar y son sometidas al conyugue. Otro dato importante que encontramos en la UPA como en la jefatura en el hogar el hombre representa un 63% y la mujer representa el 37%. La triple jornada (trabajo productivo, doméstico y reproductivo) de la mujer es uno de los problemas que enfrenta para participar de manera más sistemática en los diferentes ámbitos de su vida. En conclusión la mujer tiene menos acceso a los recursos físicos, por la falta de participación en las actividades agrícolas, también existe un dominio del hombre en todas las tomas de decisiones, tanto en el trabajo agropecuario como en el uso de los recursos de la unidad de producción agropecuaria, comunitario, y doméstico. Así mismo la distribución del trabajo familiar, lo doméstico está destinado para las hijas mujeres desde la temprana edad, y los hijos varones a las labores agrícolas y obreras.

Serviço social: cotidiano profissional nas unidades de pronto atendimento geridas por organizações sociais no município do Rio de Janeiro

O presente trabalho objetiva analisar o exercício profissional dos assistentes sociais inseridos nas unidades de pronto atendimento (UPA) municipais da cidade do Rio de Janeiro geridas por Organizações Sociais (OS), no sentido de identificar os reais limites e possibilidades colocados para a efetivação do projeto ético-político do Serviço Social brasileiro como horizonte da prática nesses espaços. Na busca por restaurar suas taxas de lucro, o capital avança sobre o fundo público e tem as políticas sociais como seu lócus privilegiado. A satanização de tudo que é público e a suposta busca por qualidade e eficiência justifica a gestão privada dos serviços públicos. Assim, impõe-se a lógica do lucro, da produtividade, do foco no quantitativo ao setor público. No município do Rio de Janeiro, a expansão da rede de saúde vem se dando por meio da gestão dessas instituições qualificadas como Organizações Sociais (OS). É o caso das UPA que, focadas nos atendimentos de urgência e emergência dentro de uma rede de saúde precarizada que não prioriza ações de prevenção e promoção, são pouco resolutivas e quando geridas por OS estão focadas em números de altas e de transferências. Nesse contexto, o assistente social, um dos profissionais que responde por essa produtividade, uma vez que com prioridade operacionaliza burocraticamente o processo de transferência e alta, fragilizado teoricamente e pelo vínculo precário, não tem sido capaz de criar estratégias e alternativas para uma prática embasada pelo projeto ético-político, ou seja, que caminhe na direção das necessidades e interesses da classe trabalhadora.

猕猴精浆纤溶酶原激活因子的来源及在精子获能中的作用

猕猴附睾、前列腺和精囊均表达tPA、uPA和PAI-1 mRNAs。加入uPA能维持精子的活力,使精子产生超激活运动,诱导顶体反应的发生,并使精子获得激活卵子的能力。这说明猕猴精浆PA除来源于睾丸外,可能主要来源于附睾及附性腺;在体外,uPA,而不是tPA,可能诱导精子获能。

纤溶酶原激活因子与猕猴精子运动力的关系及其在附睾和附性腺中的表达调节

原位杂交的结果表明11酸睾酮诱导少精子症和弱精子症,tPA mRNA的表达在附睾头、精囊及前列腺减少,而在附睾体升高,附睾尾表达基本无变化;uPA mRNA的表达在附睾头、附睾体、前列腺减少,而在精囊升高,附睾尾表达基本无变化;PAI-1 mRNA的表达在附睾头、附睾体、精囊下降,而在前列腺升高,附睾尾表达无显著变化。单侧隐睾手术不影响tPA、uPA和PAI-1 mRNA的表达。结果提示附睾头和附睾体分泌的uPA可能与精子前向运动能力的获得相关。tPA、uPA和PAI-1 mRNA在猕猴附睾头部和体部、前列腺和精囊中的表达可能受睾酮的调节,但不受睾丸分泌因子及温度的影响,且在不同部位睾酮的调节具不同的特征,而附睾尾tPA、uPA和PAI-1的表达则可能是组成性表达。