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USP2a alters chemotherapeutic response by modulating redox
Cancer cells are characterized by altered ubiquitination of many proteins. The ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme overexpressed in prostate adenocarcinomas, where it exhibits oncogenic behavior in a variety of ways including targeting c-Myc via the miR-34b/c cluster. Here we demonstrate that USP2a induces drug resistance in both immortalized and transformed prostate cells. Specifically, it confers resistance to typically pro-oxidant agents, such as cisplatin (CDDP) and doxorubicin (Doxo), and to taxanes. USP2a overexpression protects from drug-induced oxidative stress by reducing reactive oxygen species (ROS) production and stabilizing the mitochondrial membrane potential (ΔΨ), thus impairing downstream p38 activation and triggering of apoptosis. The molecular mediator of the USP2a protective function is the glutathione (GSH). Through miR-34b/c-driven c-Myc regulation, USP2a increases intracellular GSH content, thus interfering with the oxidative cascade triggered by chemotherapeutic agents. In light of these findings, targeting Myc and/or miR-34b/c might revert chemo-resistance
Effects of phase transitions in devices actuated by the electromagnetic vacuum force
We study the influence of the electromagnetic vacuum force on the behaviour
of a model device based on materials, like germanium tellurides, that undergo
fast and reversible metal-insulator transitions on passing from the crystalline
to the amorphous phase. The calculations are performed at finite temperature
and fully accounting for the behaviour of the material dielectric functions.
The results show that the transition can be exploited to extend the distance
and energy ranges under which the device can be operated without undergoing
stiction phenomena. We discuss the approximation involved in adopting the
Casimir expression in simulating nano- and micro- devices at finite
temperature
Analysis of Diterpens in Green and Roasted Coffee of Coffea arabica Cultivars Growing in the Same Edapho-Climatic Conditions.
Lipids are important components of coffee beverage flavor and aroma. Coffee oil is rich in diterpens of the kaurane family, mainly cafestol (C20H28O3) and kahweol (C20H26O3), which have increasingly received attention in recent years due to their physiological effects in human health. However, few studies have been conducted on the effects of the genetic variability for those lipids in Coffea arabica. In this work we initiate the characterization of cafestol and kahweol in different cultivars of Coffea arabica, growing in the same edaphoclimatic conditions. Mature coffee fruits from cultivars Catuaí, Icatu and three Catucaí derived the cultivars IPR 100, IPR 102 and IPR 106. They were harvested at the Agricultural Field Station of the Coop COCARI, Mandaguari, Paraná, Brazil, from May to July 2009. Although the time of harvesting was according to the maturation of each cultivar, harvesting and post-harvesting conditions were the same for all cultivars. The five samples were subjected to medium roasting for 8 to 11 minutes at 200-210 °C, until the degree of roasting light/media (L* around 28). The extraction of diterpens was carried out in green or roasted coffee by direct saponification with KOH, extraction with terc-butyl methyl ether, and clean up with water. A reverse-phase HPLC column with isocratic elution with acetonitrile/water (55/45 v/v) was used for detection and quantification of kahweol at 290 nm and cafestol at 220 nm. In green beans, the level of kahweol was higher than cafestol, for all three IPR cultivars. Meanwhile, the inverse was observed for green beans cultivars Catuaí and Icatu, where cafestol levels were higher than kahweol. The higher levels of kahweol in relation to cafestol were again observed in roasted coffee of the three IPR cultivars. In cultivars Icatu the values for kahweol and cafestol were similar (635 and 683 mg/100 g, respectively). The highest levels of kahweol were observed in cultivar IPR 106 (1096 mg/100 g). The cultivar IPR 102 showed the highest level of cafestol (394 mg/100g). Association of this data with gene expression profile can be useful to find genes involved in cafestol and kahweol metabolism as well as to develop molecular markers for diterpens in coffee
Shock Profiles for the Asymmetric Simple Exclusion Process in One Dimension
The asymmetric simple exclusion process (ASEP) on a one-dimensional lattice
is a system of particles which jump at rates and (here ) to
adjacent empty sites on their right and left respectively. The system is
described on suitable macroscopic spatial and temporal scales by the inviscid
Burgers' equation; the latter has shock solutions with a discontinuous jump
from left density to right density , , which
travel with velocity . In the microscopic system we
may track the shock position by introducing a second class particle, which is
attracted to and travels with the shock. In this paper we obtain the time
invariant measure for this shock solution in the ASEP, as seen from such a
particle. The mean density at lattice site , measured from this particle,
approaches at an exponential rate as , with a
characteristic length which becomes independent of when
. For a special value of the
asymmetry, given by , the measure is
Bernoulli, with density on the left and on the right. In the
weakly asymmetric limit, , the microscopic width of the shock
diverges as . The stationary measure is then essentially a
superposition of Bernoulli measures, corresponding to a convolution of a
density profile described by the viscous Burgers equation with a well-defined
distribution for the location of the second class particle.Comment: 34 pages, LaTeX, 2 figures are included in the LaTeX file. Email:
[email protected], [email protected], [email protected]
Observation of Umklapp processes in non-crystalline materials
Umklapp processes are known to exist in cristalline materials, where they
control important properties such as thermal conductivity, heat capacity and
electrical conductivity. In this work we report the provocative observation of
Umklapp processes in a non-periodical system, namely liquid Lithium. The lack
of a well defined periodicity seems then not to prevent the existence of these
scattering processes mechanisms provided that the local order of the systems
i.e. the maxima of the static structure factor supply the equivalent of a
reciprocal lattice vector in the case of cristalline materials.Comment: 13 pages P
Determinismo genético e molecular do metabolismo de diterpenos em Coffea spp.
Cafestol e caveol são os dois principais diterpenos presentes nos frutos de café. Esses compostos específicos do cafeeiro têm se mostrado importantes na saúde humana, induzindo alterações no colesterol e ações anti-cancerígenas. Apesar da sua importância, há pouca informação sobre os princípios genéticos e moleculares de seu metabolismo. Análises fenotípicas através de HPLC, com cafés de diferentes espécies (vários genótipos por espécie), indicam uma variabilidade importante para cafestol, caveol e 16OMC. As análises in silico dos EST de Coffea permitiram identificar cDNAs parciais correspondente a um gene de CPS, dois de KO e um de KS. Análises de expressão desses genes por RTq-PCR quantitativa, em tecidos separados durante o desenvolvimento dos frutos, estão em andamento. Resultados preliminares indicam que os quatro genes alvos apresentam expressão diferencial durante o desenvolvimento dos tecidos do fruto. Os resultados de expressão serão discutidos considerando o interesse na identificação dos genes potencialmente envolvidos na regulação da concentração de cafestol e caveol
Static and Dynamic Properties of a Viscous Silica Melt Molecular Dynamics Computer Simulations
We present the results of a large scale molecular dynamics computer
simulation in which we investigated the static and dynamic properties of a
silica melt in the temperature range in which the viscosity of the system
changes from O(10^-2) Poise to O(10^2) Poise. We show that even at temperatures
as high as 4000 K the structure of this system is very similar to the random
tetrahedral network found in silica at lower temperatures. The temperature
dependence of the concentration of the defects in this network shows an
Arrhenius law. From the partial structure factors we calculate the neutron
scattering function and find that it agrees very well with experimental neutron
scattering data. At low temperatures the temperature dependence of the
diffusion constants shows an Arrhenius law with activation energies which
are in very good agreement with the experimental values. With increasing
temperature we find that this dependence shows a cross-over to one which can be
described well by a power-law, D\propto (T-T_c)^gamma. The critical temperature
T_c is 3330 K and the exponent gamma is close to 2.1. Since we find a similar
cross-over in the viscosity we have evidence that the relaxation dynamics of
the system changes from a flow-like motion of the particles, as described by
the ideal version of mode-coupling theory, to a hopping like motion. We show
that such a change of the transport mechanism is also observed in the product
of the diffusion constant and the life time of a Si-O bond, or the space and
time dependence of the van Hove correlation functions.Comment: 30 pages of Latex, 14 figure
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