Homocysteine alters the osteoprotegerin/RANKL system in the osteoblast to promote bone loss: pivotal role of the redox regulator forkhead O1

In this study we determined the molecular mechanisms of how homocysteine differentially affects receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) synthesis in the bone. The results showed that oxidative stress induced by homocysteine deranges insulin-sensitive FOXO1 and MAP kinase signaling cascades to decrease OPG and increase RANKL synthesis in osteoblast cultures. We observed that downregulation of insulin/FOXO1 and p38 MAP kinase signaling mechanisms due to phosphorylation of protein phosphatase 2 A (PP2A) was the key event that inhibited OPG synthesis in homocysteine-treated osteoblast cultures. siRNA knockdown experiments confirmed that FOXO1 is integral to OPG and p38 synthesis. Conversely homocysteine increased RANKL synthesis in osteoblasts through c-Jun/JNK MAP kinase signaling mechanisms independent of FOXO1. In the rat bone milieu, high-methionine diet-induced hyperhomocysteinemia lowered FOXO1 and OPG expression and increased synthesis of proresorptive and inflammatory cytokines such as RANKL, M-CSF, IL-1 alpha, IL-1 beta, G-CSF, GM-CSF, MIP-1 alpha, IFN-gamma, IL-17, and TNF-alpha. Such pathophysiological conditions were exacerbated by ovariectomy. Lowering the serum homocysteine level by a simultaneous supplementation with N-acetylcysteine improved OPG and FOXO1 expression and partially antagonized RANKL and proresorptive cytokine synthesis in the bone milieu. These results emphasize that hyperhomocysteinemia alters the redox regulatory mechanism in the osteoblast by activating PP2A and deranging FOXO1 and MAPK signaling cascades, eventually shifting the OPG:RANKL ratio toward increased osteoclast activity and decreased bone quality (C) 2013 Elsevier Inc. All rights reserved.

Tuning the parameters to establish Quenching and enhancement regimes in hybrid Gold nanoparticles and CdSe Quantum dots monolayer

The multi-component nanomaterials combine the individual properties and give rise to emergent phenomenon. Optical excitations in such hybrid nonmaterial's ( for example Exciton in semiconductor quantum dots and Plasmon in Metal nanomaterials) undergo strong weak electromagnetic coupling. Such exciton-plasmon interactions allow design of absorption and emission properties, control of nanoscale energy-transfer processes, and creation of new excitations in the strong coupling regime.This Exciton plasmon interaction in hybrid nanomaterial can lead to both enhancement in the emission as well as quenching. In this work we prepared close-packed hybrid monolayer of thiol capped CdSe and gold nanoparticles. They exhibit both the Quenching and enhancements the in PL emission.The systematic variance of PL from such hybrid nanomaterials monolayer is studied by tuning the Number ratio of Gold per Quantum dots, the surface density of QDs and the spectral overlap of emission spectrum of QD and absorption spectrum of Gold nanoparticles. Role of Localized surface Plasmon which not only leads to quenching but strong enhancements as well, is explored.

Co-evolution of specific amino acid in sigma 1.2 region and nucleotide base in the discriminator to act as sensors of small molecule effectors of transcription initiation in mycobacteria

The transcription from rrn and a number of other promoters is regulated by initiating ribonucleotides (iNTPs) and guanosine tetra/penta phosphate (p)ppGpp], either by strengthening or by weakening of the RNA polymerase (RNAP)-promoter interactions during initiation. Studies in Escherichia coli revealed the importance of a sequence termed discriminator, located between -10 and the transcription start site of the responsive promoters in this mode of regulation. Instability of the open complex at these promoters is attributed to the lack of stabilizing interactions between the suboptimal discriminator and the 1.2 region of sigma 70 (Sig70) in RNAP holoenzyme. We demonstrate a different pattern of interaction between the promoters and sigma A (SigA) of Mycobacterium tuberculosis to execute similar regulation. Instead of cytosine and methionine, thymine at three nucleotides downstream to -10 element and leucine 232 in SigA are found to be essential for iNTPs and pppGpp mediated response at the rrn and gyr promoters of the organism. The specificity of the interaction is substantiated by mutational replacements, either in the discriminator or in SigA, which abolish the nucleotide mediated regulation in vitro or in vivo. Specific yet distinct bases and the amino acids appear to have co-evolved' to retain the discriminator-sigma 1.2 region regulatory switch operated by iNTPs/pppGpp during the transcription initiation in different bacteria.

Overview of nano-drugs characteristics for clinical application: the journey from the entry to the exit point

The ever-increasing number of diseases worldwide requires comprehensive, efficient, and cost-effective modes of treatments. Among various strategies, nanomaterials fulfill most of these criteria. The unique physicochemical properties of nanoparticles have made them a premier choice as a drug or a drug delivery system for the purpose of treatment, and as bio-detectors for disease prognosis. However, the main challenge is the proper consideration of the physical properties of these nanomaterials, while developing them as potential tools for therapeutics and/or diagnostics. In this review, we focus mainly on the characteristics of nanoparticles to develop an effective and sensitive system for clinical purposes. This review will present an overview of the important properties of nanoparticles, through their journey from its route of administration until disposal from the human body after accomplishing targeted functionality. We have chosen cancer as our model disease to explain the potentiality of nano-systems for therapeutics and diagnostics in relation to several organs (intestine, lung, brain, etc.). Furthermore, we have discussed their biodegradability and accumulation probability which can cause unfavorable side effects in healthy human subjects.

Characterisation of cell adhesion to substrate materials and the resistance to enzymatic and mechanical cell-removal

Cell-implant adhesive strength is important for prostheses. In this paper, an investigation is described into the adhesion of bovine chondrocytes to Ti6Al4V-based substrates with different surface roughnesses and compositions. Cells were cultured for 2 or 5 days, to promote adhesion. The ease of cell removal was characterised, using both biochemical (trypsin) and mechanical (accelerated buoyancy and liquid flow) methods. Computational fluid dynamics (CFD) modelling has been used to estimate the shear forces applied to the cells by the liquid flow. A comparison is presented between the ease of cell detachment indicated using these methods, for the three surfaces investigated. © 2008 Materials Research Society.

Reseña bibliográfica : poor economics. A radical rethinking of the way to fight global poverty

El libro recientemente publicado Poor Economics -y la técnica de evaluaciones aleatorias que dan sustento a sus conclusionestienen el potencial para cambiar radicalmente la manera de diseñar políticas para combatir la pobreza en el mundo. El libro fue escrito por Abhijit Banerjee y Esther Duflo, dos jóvenes reconocidos economistas del MIT (Massachusetts Institute of Technology). Duflo, nacida en Francia y educada en el École Normale Supérieure de Paris y MIT, fue ganadora en 2010 del premio John Bates Clark al mejor economista menor de 40 años y considerada por la revista Foreign Policy como una de los 100 intelectuales más influyentes del mundo. Abhijit Banerjee educado en la Universidad de Calcuta (su ciudad de origen) y la Universidad de Harvard también es ganador de numerosos premios.

Final report of the Support to Regional Aquatic Resources Management (STREAM): a NACA networking initiative

The governing council of Naca has resolved to effect a shift in emphasis from aquaculture development to aquaculture for development. This will require engaging partners from a broad spectrum of government and development agencies, the nature of the information that will need to be gathered and the strategies used for disseminating information and initiating action. The vehicle for operationalising this shift is STREAM - Support to Regional Aquatic Resources Management. This report outlines the nature of the STREAM network, its relationship to NACA's vision, mission, objectives and operating principles, and how STREAM differs from previous NACA's networks. Because STREAM is different, a theoretical basis for network communication is presented along with an outline of the preliminary steps in getting the network up and running. (Pdf contains 33 pages).

Mechanisms Responsible for the Trophic Effect of Beta-Adrenoceptors on the I-to Current Density in Type 1 Diabetic Rat Cardiomyocytes

Background/Aims: In diabetic ventricular myocytes, transient outward potassium current (I-to) amplitude is severely reduced because of the impaired catecholamine release that characterizes diabetic autonomic neuropathy. Sympathetic nervous system exhibits a trophic effect on I-to since incubation of myocytes with noradrenaline restores current amplitude via beta-adrenoceptor (beta AR) stimulation. Here, we investigate the intracellular signalling pathway though which incubation of diabetic cardiomyocytes with the beta AR agonist isoproterenol recovers I-to amplitude to normal values. Methods: Experiments were performed in ventricular myocytes isolated from streptozotocin-diabetic rats. I-to current was recorded by using the patch-clamp technique. Kv4 channel expression was determined by immunofluorescence. Protein-protein interaction was determined by coimmunoprecipitation. Results: Stimulation of beta AR activates first a G alpha s protein, adenylyl cyclase and Protein Kinase A. PKA-phosphorylated receptor then switches to the G alpha i protein. This leads to the activation of the beta AR-Kinase-1 and further receptor phosphorylation and arrestin dependent internalization. The internalized receptor-arrestin complex recruits and activates cSrc and the MAPK cascade, where Ras, c-Raf1 and finally ERK1/2 mediate the increase in Kv4.2 and Kv4.3 protein abundance in the plasma membrane. Conclusion: beta(2)AR stimulation activates a G alpha s and G alpha i protein dependent pathway where the ERK1/2 modulates the Ito current amplitude and the density of the Kv4.2 and Kv4.2 channels in the plasma membrane upon sympathetic stimulation in diabetic heart.

Effect of Molecular Flexibility on the Nematic-to-Isotropic Phase Transition for Highly Biaxial Molecular Non-Symmetric Liquid Crystal Dimers

In this work, a study of the nematic (N)-isotropic (I) phase transition has been made in a series of odd non-symmetric liquid crystal dimers, the alpha-(4-cyanobiphenyl-4'-yloxy)-omega-(1-pyrenimine-benzylidene-4'-oxy) alkanes, by means of accurate calorimetric and dielectric measurements. These materials are potential candidates to present the elusive biaxial nematic (N-B) phase, as they exhibit both molecular biaxiality and flexibility. According to the theory, the uniaxial nematic (N-U)-isotropic (I) phase transition is first-order in nature, whereas the N-B-I phase transition is second-order. Thus, a fine analysis of the critical behavior of the N-I phase transition would allow us to determine the presence or not of the biaxial nematic phase and understand how the molecular biaxiality and flexibility of these compounds influences the critical behavior of the N-I phase transition.

The distribution, abundance, and ecology of larval tunas from the entrance to the Gulf of California

ENGLISH: This study is based on collections of larvae of Thunnus albacares, Euthynnus llneatus, and Auxis sp. obtained from surface and oblique net tows made during seven cruises, each along a comparable track in the entrance of the Gulf of California and each during a different month. Concomitant measurements of surface temperature, salinity, and zooplankton were made at each of the plankton stations. The catches of larval Auxis sp. were examined by analysis of variance techniques to determine which environmental features were associated with the spawning of this tuna as indicated by the distribution of larvae and to gain some insight into the behavior of the larvae themselves. The testing indicated that the spawning of Auxis sp. varied significantly among the different months of the cruises. The testing also indicated that if the larvae were capable of avoiding the sampling apparatus, this ability was not related to features associated with time of day such as light conditions. The analysis did not detect any change in the vertical distribution of the larvae among the months of the experiment. It was concluded that the larvae did not exhibit a diel vertical movement. The measurements of temperature, salinity, and zooplankton volumes were treated as covariates in the analysis. The surface temperature proved to be a highly important factor in explaining the distribution of larvae, but salinity and zooplankton volumes were not. Catches of Thunnus albaeares and Euthynnus lineatus were rare during the course of the study; these are discussed in qualitative terms with respect to the time of the year and the surface temperature. The distribution of larval tunas in the area of study was compared with the distribution of surface water masses. It appeared that these masses had no influence per se on the distribution of larvae. SPANISH: Este estudio está basado en las recolecciones de larvas de Thunnus albacares, Eutbynnus lineatus, y Auxis sp. obtenidas según los arrastres superficiales y oblicuos de la red, realizados durante siete cruceros, cada uno a la entrada del Golfo de California a lo largo de un derrotero comparable, y cada uno durante distintos meses. Las mediciones correspondientes de la temperatura superficial, salinidad y de zooplancton se realizaron en cada una de las estaciones de plancton. Las capturas de larvas Auxís sp. fueron examinadas mediante el análisis de la varianza para determinar cuales características ambientales se encontraban asociadas con el desove de este atún según lo indicaba la distribución de las larvas, y para obtener alguna idea del comportamiento de las larvas en sí mismas. Las pruebas indicaron que el desove de Auxis sp. varió significativamente entre los diferentes meses de los cruceros; indicaron también que si las larvas eran capaces de evitar el aparato de muestreo, esta habilidad no se relacionaba a las características asociadas con la hora del día de acuerdo a las condiciones de luz. El análisis no demostró ningún cambio en la distribución vertical de las larvas durante los meses del experimento. Se determinó que las larvas no exhiben un movimiento vertical diario. Las mediciones de temperatura, salinidad, y de los volúmenes de zooplancton fueron tratadas como covariables en el análisis. La temperatura superficial demostró ser un factor altamente importante en la explicación de la distribución de las larvas, pero la salinidad y los volúmenes de zooplancton no lo fueron. Las capturas de Thunnus albacares y Eutbynnus lineatus fueron pocas durante el curso de este estudio; éstas se discuten en términos cualitativos respecto a la época del año y a la temperatura superficial. La distribución de los atunes larvales en el área de estudio fue comparada con la distribución de las masas superficiales de agua. Parece que estas masas no tienen influencia per se en la distribución de las larvas. (PDF contains 40 pages.)

Adaptation of coastal communities in the Philippines to the impacts climate change

The Quedan and Rural Credit Guarantee Corporation (Quedancor) of the Philippine Department of Agriculture has the critical responsibility of providing and improving credit assistance to fishers, it also has the task of helping its beneficiaries meet the repayment obligations of their loans. One reason for defaults can be attributed to the devastating impact of natural calamities. Schemes in place are still insufficient to help safeguard lending programs and operations from non-repayment of loans due to production losses and damages to personal properties.(PDF contains 5 pages) Natural calamities include the uncertainties and vagaries of weather and climate that bring about typhoons, floods, and drought; earthquakes; volcanic eruption as well as pests and diseases that affect the productivity of fisheries. When natural calamities occur, small fishers are unable to pay their loans from Quedancor, moreover they have difficulty renewing their loan applications from Quedancor or accessing credit from other sources. Failure to access credit could disable them to continue venture on fishing activities and could eventually jeopardize the welfare of their entire household. The inability of creditors to pay their loans and meet their obligations also impair, to a large extent, the financial operation and viability of the lending institutions. Risk management schemes currently employed include price stabilization measures, targeted relief` to typhoons and drought victims, and crop insurance systems, to name a few. Some of these schemes are becoming very expensive to implement. Moreover, they fail to enable fishers regain sufficient resources so that they may continue production.