Cytotoxic and pro-apoptotic effects of Abrus precatorius L. on human metastatic breast cancer cell line, MDA-MB-231

Abrus precatorius is highly regarded as a universal panacea in the herbal medicine with diverse pharmacological activity spectra. This experimental study on the mechanism of the anticancer activity of A. precatorius leaf extracts, may offer new evidence for A. precatorius in the treatment of breast cancer in clinical practice. Cell death was determined by using MTT assay. Further analyses were carried out by doing DNA laddering, PARP cleavage, FACS, semi-quantitative RT-PCR and detection of cellular reactive oxygen species (ROS) by DCFDA assay. A. precatorius showed very striking inhibition on MDA-MB-231 cells. MTT assay showed more than 75 % inhibition of the cells and treated cells indicated visible laddering pattern with thick compact band. PARP cleavage produced 89 kDa cleavage product which was associated with apoptosis. Flow cytometer exhibited a sub-G0/G1 peak as an indicative of apoptosis. mRNA expression level of apoptosis-related genes p21 and p53 was markedly increased in cells treated with the extract as compared to control. The up-regulation of p21 and p53 may be the molecular mechanisms by which A. precatorius extract which induces apoptosis. An increase in the concentration of A. precatorius extract does not generate ROS, instead it reduces ROS formation in MDA-MB-231 cells, as evident from the shift in fluorescence below untreated control. This is the first report showing that A. precatorius leaf extract exhibits a growth inhibitory effect by induction of apoptosis in MDA-MB-231 cells. Our results contribute towards validation of the A. precatorius extract as a potentially effective chemopreventive or therapeutic agent against breast cancer.

Crystal-structure analysis of cis-X-pro-containing peptidomimetics: understanding the steric interactions at cis X-pro amide bonds

Catch the twist: The cis Piv-Pro conformer (Piv=pivaloyl) of peptides is no longer inaccessible. Any cis X-Pro tertiary-amide-bond conformer can be stabilized in crystals of peptides by accommodating the unavoidable distortion of the dihedral angle of the peptide bond to the carbonyl group of the Pro residue (see picture), in this case through ni−1→πi* interactions. Steric clashes were not observed in the cis Piv-Pro rotamers studied.

Steric and Electronic Interactions Controlling the cis/trans Isomer Equilibrium at X-Pro Tertiary Amide Motifs in Solution

A systematic understanding of the noncovalent interactions that influence the structures of the cis conformers and the equilibrium between the cis and the trans conformers, of the X-Pro tertiary amide motifs, is presented based on analyses of H-1-, C-13-NMR and FTIR absorption spectra of two sets of homologous peptides, X-Pro-Aib-OMe and X-Pro-NH-Me (where X is acetyl, propionyl, isobutyryl and pivaloyl), in solvents of varying polarities. First, this work shows that the cis conformers of any X-Pro tertiary amide motif, including Piv-Pro, are accessible in the new motifs X-Pro-Aib-OMe, in solution. These conformers are uniquely observable by FTIR spectroscopy at ambient temperatures and by NMR spectroscopy from temperatures as high as 273 K. This is made possible by the persistent presence of n(i-1i)* interactions at Aib, which also influence the disappearance of steric effects at these cis X-Pro rotamers. Second, contrary to conventional understanding, the energy contribution of steric effects to the cis/trans equilibrium at the X-Pro motifs is found to be nonvariant (0.54 +/- 0.02 kcal/mol) with increase in steric bulk on the X group. Third, the current studies provide direct evidence for the weak intramolecular interactions namely the n(i-1i)*, the N-Pro center dot center dot center dot Hi+1 (C(5)a), and the C-7 hydrogen bond that operate and influence the structures, stabilities, and dynamics between different conformational states of X-Pro tertiary amide motifs. NMR and IR spectral data suggest that the cis conformers of X-Pro motifs are ensembles of short-lived rotamers about the C-X-N-Pro bond. (c) 2013 Wiley Periodicals, Inc. Biopolymers 101: 66-77, 2014.

Unconjugated Bilirubin exerts Pro-Apoptotic Effect on Platelets via p38-MAPK activation

Thrombocytopenia is one of the most frequently observed secondary complications in many pathological conditions including liver diseases, where hyperbilirubinemia is very common. The present study sought to find the cause of thrombocytopenia in unconjugated hyperbilirubinemic conditions. Unconjugated bilirubin (UCB), an end-product of heme catabolism, is known to have pro-oxidative and cytotoxic effects at high serum concentration. We investigated the molecular mechanism underlying the pro-apoptotic effect of UCB on human platelets in vitro, and followed it up with studies in phenylhydrazine-induced hyperbilirubinemic rat model and hyperbilirubinemic human subjects. UCB is indeed found to significantly induce platelet apoptotic events including elevated endogenous reactive oxygen species generation, mitochondrial membrane depolarization, increased intracellular calcium levels, cardiolipin peroxidation and phosphatidylserine externalization (p < 0.001) as evident by FACS analysis. The immunoblots show the elevated levels of cytosolic cytochrome c and caspase activation in UCB-treated platelets. Further, UCB is found to induce mitochondrial ROS generation leading to p38 activation, followed by downstream activation of p53, ultimately resulting in altered expression of Bcl-2 and Bax proteins as evident from immunoblotting. All these parameters conclude that elevated unconjugated bilirubin causes thrombocytopenia by stimulating platelet apoptosis via mitochondrial ROS-induced p38 and p53 activation.

Estudio de "gar" como marcador del discurso: "Pro corona" de Demóstenes

[ES] En este trabajo se estudia gár como marcador del discurso en un corpus del griego ático, el discurso Pro corona de Demóstenes. Gár introduce secciones informativas tanto en el nivel local como en el global. En el primero añade información complementaria, mientras que en el segundo indica la introducción de un nuevo tema como desarrollo de una información preliminar. La función común de gár en los dos casos es marcar la información que introduce como suplementaria.

Synthesis report with pro-poor trade research findings and policy recommandations

The purpose of the project was to investigate international trade in fisheries products and its relationship to poverty alleviation and livelihoods of poor aquatic resource users in developing countries in Asia, and to identify options to improve the effectiveness of poverty reduction through international seafood trade. The project directly addressed the EC-PREP priority area of trade and development, and indirectly provided valuable insight to two other priority areas: food security and sustainable rural development; and institutional capacity building. [PDF contains 60 pages.]

Missale romanum ex decreto sacrosancti concilii tridentini restitutum :cum omnibus aliorum sanctorum missis novissimè per summos pontifices enarratis, ac universis ditionibus fidelissimorum lusitaniae regum hucusquè pro utroque clero concessis locupletatum : PII V. Pont. Max. Jussu editum, Clementis VIII. et Urbani VIII. Auctoritate Recognitum

Pagina de rosto e texto impressos em vermelho e preto

Framework for a pro-poor regional strategy on sustainable aquatic resources management in Asia-Pacific: a statement of understanding and recommendations

This statement was prepared by the participants of the FAO/NACA-STREAM Workshop on Aquatic Resources and Livelihoods: Connecting Policy and People, 17-19 March 2005, in Los Baños, Laguna, Philippines. This was the concluding event of the FAO Technical Cooperation Program (TCP) project entitled “Assistance in Poverty Alleviation through Improved Aquatic Resources Management in Asia-Pacific.” The purpose of the workshop was to review and share experiences of the NACA-STREAM Initiative, build consensus on the value of livelihoods approaches in aquatic resources management and poverty alleviation, and identify ways of promoting livelihoods approaches throughout the region. (Pdf contains 2 pages).

Cartas enviadas por José Urbano Aguirre y Diego Joaquín Ibarbia (Comité Pro-Inmigración Vasca) a Justo Garate en 1940

3 cartas (mecanografiadas) ; entre 220x340mm y 220x310mm. Ubicación: Caja 1 - Carpeta 11

Suspensión trasera regulable para un a moto de competición: alternativa Pro-Link

El objetivo general que se pretende alcanzar con la realización de este proyecto, consiste en el diseño del sistema de suspensión trasera regulable y el prediseño de un basculante para una motocicleta de competición de 250cc y 4 tiempos, englobado dentro de la competición MotoStudent promovida por la Fundación Moto Engineering Foundation. Más concretamente se pretende diseñar un sistema de suspensión con un buen comportamiento dinámico que facilite el manejo de la moto, regulable para que se pueda adaptar a las características de los diferentes circuitos y a la forma de conducción de los pilotos, y el prediseño de un basculante con una buena relación rigidez - peso.

Pro und Kontra Industriefischerei

Bei ordnungsgemäßer Durchführung ist aus wissenschaftlicher Sicht gegen eine maßvolle Industriefischerei auch in der Nordsee nichts einzuwenden. Wichtige Kriterien sind allerdimgs, dass die genutzten Bestände wissenschaftlich überwacht werden und negative Effekte auf das Nahrungsnetz vermieden werden.

Structural Characterization of Pro-inflammatory and Anti-inflammatory Immunoglobulin G Fc Proteins

Immunoglobulin G (IgG) is central in mediating host defense due to its ability to target and eliminate invading pathogens. The fragment antigen binding (Fab) regions are responsible for antigen recognition; however the effector responses are encoded on the Fc region of IgG. IgG Fc displays considerable glycan heterogeneity, accounting for its complex effector functions of inflammation, modulation and immune suppression. Intravenous immunoglobulin G (IVIG) is pooled serum IgG from multiple donors and is used to treat individuals with autoimmune and inflammatory disorders such as rheumatoid arthritis and Kawasaki’s disease, respectively. It contains all the subtypes of IgG (IgG1-4) and over 120 glycovariants due to variation of an Asparagine 297-linked glycan on the Fc. The species identified as the activating component of IVIG is sialylated IgG Fc. Comparisons of wild type Fc and sialylated Fc X-ray crystal structures suggests that sialylation causes an increase in conformational flexibility, which may be important for its anti-inflammatory properties.

Although glycan modifications can promote the anti-inflammatory properties of the Fc, there are amino acid substitutions that cause Fcs to initiate an enhanced immune response. Mutations in the Fc can cause up to a 100-fold increase in binding affinity to activating Fc gamma receptors located on immune cells, and have been shown to enhance antibody dependent cell-mediated cytotoxicity. This is important in developing therapeutic antibodies against cancer and infectious diseases. Structural studies of mutant Fcs in complex with activating receptors gave insight into new protein-protein interactions that lead to an enhanced binding affinity.

Together these studies show how dynamic and diverse the Fc region is and how both protein and carbohydrate modifications can alter structure, leading to IgG Fc’s switch from a pro-inflammatory to an anti-inflammatory protein.

Diseño de sistema de suspensión progresiva Pro-Link

[ES]Mediante este trabajo se va a diseñar un mecanismo para crear un sistema de suspensión progresiva para la suspensión trasera de una motocicleta a partir de un muelle lineal. El muelle introducido en la suspensión será lineal, por lo tanto, tendrá una sola rigidez, constante y la cual delimita el muelle, pero gracias a un mecanismo diseñado especialmente para la suspensión trasera de una moto, se va conseguir que la rigidez varíe. El mecanismo utilizado para este trabajo se llama Pro-Link y la empresa que lo emplea es Honda. Para ello, se creará un esquema del mecanismo en sí y tras un análisis cinemático mediante el programa Creo Parametric, y haciendo varios cambios en el sistema para ajustarlo a la mejor progresividad posible, se obtendrá la gráfica en la que se observará la curva que marca la rigidez progresiva. Esto es, se verá la evolución de la nueva rigidez dependiendo de la oscilación vertical de la rueda. Por otra parte, gracias a un análisis dinámico del mismo programa se conseguirán las reacciones del sistema y se calcularán los elementos auxiliares de éste para el buen funcionamiento del mismo. Finalmente, se creará el diseño del triángulo y un diseño preliminar del basculante mediante el método de elementos finitos del programa.

AutoCAD及Pro/E间图形交互的应用

介绍AutoCAD和Pro/E软件相互间数据交换的方法,利用AutoCAD工程图在Pro/E环境中进行三维建模,避免Pro/E建模时的草图重绘;同时将Pro/E工程图导入AutoCAD中进行编辑,符合一般工程设计的习惯.整个过程以DWG和DXF数据文件为桥梁,并以设计实例进行说明.该方法明显提高了设计效率.

Suspensión trasera progresiva para moto Student: Alternativa Pro-link

El objetivo de este proyecto ha sido el de diseñar un sistema de suspensión englobado en el ámbito de la competición interuniversitaria MotoStudent. Además de la normativa de la competición, dicha suspensión debe cumplir una serie de requisitos extra impuestos por el equipo de MotoStudent de la ETSI de Bilbao. Las características principales de la suspensión en cuestión deben ser las siguientes:  La rigidez del sistema de suspensión debe ser progresiva, de forma que se comporte como una suspensión blanda a bajas solicitaciones, y como una suspensión dura a altas solicitaciones.  A fin de poder adaptar la suspensión de la moto a diferentes circuitos, el esta deberá estar dotada de un sistema de regulación. Para ello el sistema de suspensión elegido es el sistema por bieletas tipo Pro- Link, cuya principal característica es que, en dicha solución, el balancín no solo tiene movimiento angular, sino que tiene también movimiento lineal, de forma que es mucho más versátil a la hora de diseñar. Figura[