Inhibition of Mitogen-Activated Protein Kinase Erk1/2 Promotes Protein Degradation of ATP Binding Cassette Transporters A1 and G1 in CHO and in HuH7 cells.

Signal transduction modulates expression and activity of cholesterol transporters. We recently demonstrated that the Ras/mitogen-activated protein kinase (MAPK) signaling cascade regulates protein stability of Scavenger Receptor BI (SR-BI) through Proliferator Activator Receptor (PPARα) -dependent degradation pathways. In addition, MAPK (Mek/Erk 1/2) inhibition has been shown to influence liver X receptor (LXR) -inducible ATP Binding Cassette (ABC) transporter ABCA1 expression in macrophages. Here we investigated if Ras/MAPK signaling could alter expression and activity of ABCA1 and ABCG1 in steroidogenic and hepatic cell lines. We demonstrate that in Chinese Hamster Ovary (CHO) cells and human hepatic HuH7 cells, extracellular signal-regulated kinase 1/2 (Erk1/2) inhibition reduces PPARα-inducible ABCA1 protein levels, while ectopic expression of constitutively active H-Ras, K-Ras and MAPK/Erk kinase 1 (Mek1) increases ABCA1 protein expression, respectively. Furthermore, Mek1/2 inhibitors reduce ABCG1 protein levels in ABCG1 overexpressing CHO cells (CHO-ABCG1) and human embryonic kidney 293 (HEK293) cells treated with LXR agonist. This correlates with Mek1/2 inhibition reducing ABCG1 cell surface expression and decreasing cholesterol efflux onto High Density Lipoproteins (HDL). Real Time reverse transcriptase polymerase chain reaction (RT-PCR) and protein turnover studies reveal that Mek1/2 inhibitors do not target transcriptional regulation of ABCA1 and ABCG1, but promote ABCA1 and ABCG1 protein degradation in HuH7 and CHO cells, respectively. In line with published data from mouse macrophages, blocking Mek1/2 activity upregulates ABCA1 and ABCG1 protein levels in human THP1 macrophages, indicating opposite roles for the Ras/MAPK pathway in the regulation of ABC transporter activity in macrophages compared to steroidogenic and hepatic cell types. In summary, this study suggests that Ras/MAPK signaling modulates PPARα- and LXR-dependent protein degradation pathways in a cell-specific manner to regulate the expression levels of ABCA1 and ABCG1 transporters.

Activation of c-Jun in the nuclei of neurons of the CA-1 in thrombin preconditioning occurs via PAR-1.

Recently it has been shown that the c-Jun N-terminal kinase (JNK) plays a role in thrombin preconditioning (TPC) in vivo and in vitro. To investigate further the pathways involved in TPC, we performed an immunohistochemical study in hippocampal slice cultures. Here we show that the major target of JNK, the AP-1 transcription factor c-Jun, is activated by phosphorylation in the nuclei of neurons of the CA1 region by using phospho-specific antibodies against the two JNK phosphorylation sites. The activation is early and transient, peaking at 90 min and not present by 3 hr after low-dose thrombin administration. Treatment of cultures with a synthetic thrombin receptor agonist results in the same c-Jun activation profile and protection against subsequent OGD, both of which are prevented by specific JNK inhibitors, showing that thrombin signals through PAR-1 to JNK. By using an antibody against the Ser 73 phosphorylation site of c-Jun, we identify possible additional TPC substrates.

Variação diurno-noturna do potencial mátrico e gradiente de potencial total da água no solo

O potencial mátrico em solos não saturados é um importante componente do potencial total e, portanto, deve ser medido da melhor forma possível. Este trabalho teve por objetivo avaliar a influência da temperatura do solo sobre o potencial mátrico e o gradiente de potencial total, durante a redistribuição da água num Latossolo Vermelho-Amarelo, em Piracicaba, SP, a partir de dados coletados por tensiometria. Em uma parcela circular de 3 m de diâmetro, foram instalados 10 tensiômetros com transdutor de tensão, modelo SWT3 da Delta-T, nas profundidades de 0,10; 0,15; 0,20; 0,25; 0,30; 0,35; 0,40; 0,45; 0,50; e 0,55 m, com os quais foram obtidos os potenciais mátricos para essas profundidades e o gradiente de potencial total, (ΔΦm/Δz)+1, para a profundidade de 0,25 m, com Δz de 0,1; 0,2; e 0,3 m, utilizando os tensiômetros instalados nas profundidades de 0,20 e 0,30; 0,15 e 0,35; e 0,10 e 0,40 m para ΔΦm, respectivamente. Na mesma parcela, foram também instalados termopares tipo T na superfície e nas profundidades 0,025; 0,050; e 0,075 m de solo. Ambas as leituras dos tensiômetros e termopares foram armazenadas em um Datalogger, Modelo DL2, da Delta-T, a idênticos intervalos de tempo. As avaliações detectaram oscilações na leitura do potencial mátrico da água no solo ao longo do dia e nos efeitos diferenciados nos tensiômetros instalados em profundidades diferentes, ocasionando oscilações também no gradiente de potencial total da água no solo. Os melhores horários para a realização das leituras dos tensiômetros são nas primeiras sete horas do dia ou após às 18 h.

Spin-Peierls vs Peierls distortions in a family of conjugated polymers

Distortions in a family of conjugated polymers are studied using two complementary approaches: within a many-body valence bond approach using a transfer-matrix technique to treat the Heisenberg model of the systems, and also in terms of the tight-binding band-theoretic model with interactions limited to nearest neighbors. The computations indicate that both methods predict the presence or absence of the same distortions in most of the polymers studied.

Superconducting p-branes and extremal black holes

In Einstein-Maxwell theory, magnetic flux lines are "expelled" from a black hole as extremality is approached, in the sense that the component of the field strength normal to the horizon goes to zero. Thus, extremal black holes are found to exhibit the sort of ¿Meissner effect¿ which is characteristic of superconducting media. We review some of the evidence for this effect and present new evidence for it using recently found black hole solutions in string theory and Kaluza-Klein theory. We also present some new solutions, which arise naturally in string theory, which are non-superconducting extremal black holes. We present a nice geometrical interpretation of these effects derived by looking carefully at the higher dimensional configurations from which the lower dimensional black hole solutions are obtained. We show that other extremal solitonic objects in string theory (such as p-branes) can also display superconducting properties. In particular, we argue that the relativistic London equation will hold on the world volume of ¿light¿ superconducting p-branes (which are embedded in flat space), and that minimally coupled zero modes will propagate in the adS factor of the near-horizon geometries of "heavy," or gravitating, superconducting p-branes.

Exact gravitational shockwaves and Planckian scattering on branes

We obtain a solution describing a gravitational shock wave propagating along a Randall-Sundrum brane. The interest of such a solution is twofold: on the one hand, it is the first exact solution for a localized source on a Randall-Sundrum three-brane. On the other hand, one can use it to study forward scattering at Planckian energies, including the effects of the continuum of Kaluza-Klein modes. We map out the different regimes for the scattering obtained by varying the center-of-mass energy and the impact parameter. We also discuss exact shock waves in ADD scenarios with compact extra dimensions.

Cosmic rays as probes of large extra dimensions and TeV gravity

If there are large extra dimensions and the fundamental Planck scale is at the TeV scale, then the question arises of whether ultrahigh energy cosmic rays might probe them. We study the neutrino-nucleon cross section in these models. The elastic forward scattering is analyzed in some detail, hoping to clarify earlier discussions. We also estimate the black hole production rate. We study energy loss from graviton mediated interactions and conclude that they cannot explain the cosmic ray events above the GZK energy limit. However, these interactions could start horizontal air showers with characteristic profile and at a rate higher than in the standard model.

Generalized Weyl solutions

It was shown by Weyl that the general static axisymmetric solution of the vacuum Einstein equations in four dimensions is given in terms of a single axisymmetric solution of the Laplace equation in three-dimensional flat space. Weyls construction is generalized here to arbitrary dimension D>~4. The general solution of the D-dimensional vacuum Einstein equations that admits D-2 orthogonal commuting non-null Killing vector fields is given either in terms of D-3 independent axisymmetric solutions of Laplaces equation in three-dimensional flat space or by D-4 independent solutions of Laplaces equation in two-dimensional flat space. Explicit examples of new solutions are given. These include a five-dimensional asymptotically flat black ring with an event horizon of topology S1S2 held in equilibrium by a conical singularity in the form of a disk.

Radiative isotropic cosmologies with extra dimensions

We solve Einsteins equations in an n-dimensional vacuum with the simplest ansatz leading to a Friedmann-Robertson-Walker (FRW) four-dimensional space time. We show that the FRW model must be of radiation. For the open models the extra dimensions contract as a result of cosmological evolution. For flat and closed models they contract only when there is one extra dimension.

Cosmic strings in extra dimensions

The Einstein equations coupled with a cloud of geometric strings for a five-dimensional Bianchi type-I cosmological model are studied. The cosmological consequences of having strings along the fifth dimension are examined. Particular solutions with dynamical compactifications of the extra dimensions and compatibility with expanding three-dimensional spaces are presented.

Simple-sugar meals target GLUT2 at enterocyte apical membranes to improve sugar absorption: a study in GLUT2-null mice.

The physiological significance of the presence of GLUT2 at the food-facing pole of intestinal cells is addressed by a study of fructose absorption in GLUT2-null and control mice submitted to different sugar diets. Confocal microscopy localization, protein and mRNA abundance, as well as tissue and membrane vesicle uptakes of fructose were assayed. GLUT2 was located in the basolateral membrane of mice fed a meal devoid of sugar or containing complex carbohydrates. In addition, the ingestion of a simple sugar meal promoted the massive recruitment of GLUT2 to the food-facing membrane. Fructose uptake in brush-border membrane vesicles from GLUT2-null mice was half that of wild-type mice and was similar to the cytochalasin B-insensitive component, i.e. GLUT5-mediated uptake. A 5 day consumption of sugar-rich diets increased fructose uptake fivefold in wild-type tissue rings when it only doubled in GLUT2-null tissue. GLUT5 was estimated to contribute to 100 % of total uptake in wild-type mice fed low-sugar diets, falling to 60 and 40 % with glucose and fructose diets respectively; the complement was ensured by GLUT2 activity. The results indicate that basal sugar uptake is mediated by the resident food-facing SGLT1 and GLUT5 transporters, whose mRNA abundances double in long-term dietary adaptation. We also observe that a large improvement of intestinal absorption is promoted by the transient recruitment of food-facing GLUT2, induced by the ingestion of a simple-sugar meal. Thus, GLUT2 and GLUT5 could exert complementary roles in adapting the absorption capacity of the intestine to occasional or repeated loads of dietary sugars.

Reheating in inflationary cosmologies: Geometric coupling of the "inflaton" to quantum fields

We propose a simple geometrical prescription for coupling a test quantum scalar field to an "inflaton" (classical scalar field) in the presence of gravity. When the inflaton stems from the compactification of a Kaluza-Klein theory, the prescription leaves no arbitrariness and amounts to a dimensional reduction of the Klein-Gordon equation. We discuss the possible relevance of this coupling to "reheating" in inflationary cosmologies.

Gravity in the Randall-Sundrum brane world

We discuss the weak gravitational field created by isolated matter sources in the Randall-Sundrum brane world. For the case of a single wall of positive tension, the field stays localized near the wall if the source is stationary. We calculate the leading Kaluza-Klein corrections to the linearized gravitational field of a nonrelativistic spherical object, which is different from the Schwarzschild solution at large distances. In the case of two branes of opposite tension, linearized Brans-Dicke (BD) gravity is recovered on either wall, with different BD parameters. On the wall with positive tension the BD parameter is larger than 3000 provided that the separation between walls is larger than 4 times the AdS radius. The gravitational field due to shadow matter is also considered.