ß-Catenin Regulation during the Cell Cycle: Implications in G2/M and Apoptosis

ß-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. ß-Catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems ß-catenin also acts as a positive modulator of apoptosis. To get additional insights into the role of ß-Catenin in the regulation of the cell cycle and apoptosis, we have analyzed the levels and subcellular localization of endogenous ß-catenin and its relation with adenomatous polyposis coli (APC) during the cell cycle in S-phase¿synchronized epithelial cells. ß-Catenin levels increase in S phase, reaching maximum accumulation at late G2/M and then abruptly decreasing as the cells enter into a new G1 phase. In parallel, an increased cytoplasmic and nuclear localization of ß-catenin and APC is observed during S and G2 phases. In addition, strong colocalization of APC with centrosomes, but not ß-catenin, is detected in M phase. Interestingly, overexpression of a stable form of ß-catenin, or inhibition of endogenous ß-catenin degradation, in epidermal keratinocyte cells induces a G2 cell cycle arrest and leads to apoptosis. These results support a role for ß-catenin in the control of cell cycle and apoptosis at G2/M in normal and transformed epidermal keratinocytes.

Assembly and disassembly of the Golgi Complex: two prodesses arranged in a cis to trans direction

We have studied the disassembly and assembly of two morphologically and functionally distinct parts of the Golgi complex, the cis/middle and trans cisterna/trans network compartments. For this purpose we have followed the redistribution of three cis/middle- (GMPc-1, GMPc-2, MG 160) and two trans- (GMPt-1 and GMPt-2) Golgi membrane proteins during and after treatment of normal rat kidney (NRK) cells with brefeldin A (BFA). BFA induced complete disassembly of the cis/middle- and trans-Golgi complex and translocation of GMPc and GMPt to the ER. Cells treated for short times (3 min) with BFA showed extensive disorganization of both cis/middle- and trans-Golgi complexes. However, complete disorganization of the trans part required much longer incubations with the drug. Upon removal of BFA the Golgi complex was reassembled by a process consisting of three steps: (a) exist of cis/middle proteins from the ER and their accumulation into vesicular structures scattered throughout the cytoplasm; (b) gradual relocation and accumulation of the trans proteins in the vesicles containing the cis/middle proteins; and (c) assembly of the cisternae, and reconstruction of the Golgi complex within an area located in the vicinity of the centrosome from which the ER was excluded. Reconstruction of the cis/middle-Golgi complex occurred under temperature conditions inhibitory of the reorganization of the trans-Golgi complex, and was dependent on microtubules. Reconstruction of the trans-Golgi complex, disrupted with nocodazole after selective fusion of the cis/middle-Golgi complex with the ER, occurred after the release of cis/middle-Golgi proteins from the ER and the assembly of the cis/middle cisternae.

Stochastic resonance in noisy nondynamical systems

We have analyzed the effects of the addition of external noise to nondynamical systems displaying intrinsic noise, and established general conditions under which stochastic resonance appears. The criterion we have found may be applied to a wide class of nondynamical systems, covering situations of different nature. Some particular examples are discussed in detail.

The determinants of social spending in Spain (1880-1960): Is Lindert right?

[spa] El principal objetivo de este artículo se centra en analizar los orígenes del Estado de Bienestar en España a partir del marco teórico elaborado por Peter Lindert. Con este fin, se ofrece un análisis econométrico de los factores que determinaron la evolución del gasto social público en este país entre 1880 y 1960. Utilizando nueva evidencia cuantitativa, se construyó un panel de datos por quinquenios con el porcentaje de gasto social respecto al PIB desagregado en tres partidas: sanidad, seguridad social y beneficencia. El análisis permite insertar el caso español en el debate internacional y los resultados revelan interesantes singularidades de este país.

Stochastic resonance in noisy nondynamical systems

We have analyzed the effects of the addition of external noise to nondynamical systems displaying intrinsic noise, and established general conditions under which stochastic resonance appears. The criterion we have found may be applied to a wide class of nondynamical systems, covering situations of different nature. Some particular examples are discussed in detail.

Divergent signal-to-noise ratio and stochastic resonance in monostable systems

We present a class of systems for which the signal-to-noise ratio always increases when increasing the noise and diverges at infinite noise level. This new phenomenon is a direct consequence of the existence of a scaling law for the signal-to-noise ratio and implies the appearance of stochastic resonance in some monostable systems. We outline applications of our results to a wide variety of systems pertaining to different scientific areas. Two particular examples are discussed in detail.

Stochastic multiresonance

We present a class of systems for which the signal-to-noise ratio as a function of the noise level may display a multiplicity of maxima. This phenomenon, referred to as stochastic multiresonance, indicates the possibility that periodic signals may be enhanced at multiple values of the noise level, instead of at a single value which has occurred in systems considered up to now in the framework of stochastic resonance.

Spatiotemporal stochastic resonance in the Swift-Hohenberg equation

We show the appearance of spatiotemporal stochastic resonance in the Swift-Hohenberg equation. This phenomenon emerges when a control parameter varies periodically in time around the bifurcation point. By using general scaling arguments and by taking into account the common features occurring in a bifurcation, we outline possible manifestations of the phenomenon in other pattern-forming systems.

Noise suppression by noise

We have analyzed the interplay between an externally added noise and the intrinsic noise of systems that relax fast towards a stationary state, and found that increasing the intensity of the external noise can reduce the total noise of the system. We have established a general criterion for the appearance of this phenomenon and discussed two examples in detail.

Noise and periodic modulations in neural excitable medium

We have analyzed the interplay between noise and periodic modulations in a mean field model of a neural excitable medium. For this purpose, we have considered two types of modulations, namely, variations of the resistance and oscillations of the threshold. In both cases, stochastic resonance is present, irrespective of whether the system is monostable or bistable.

Effect of the output of the system in signal detection

We analyze the consequences that the choice of the output of the system has in the efficiency of signal detection. It is shown that the output signal and the signal-to-noise ratio (SNR), used to characterize the phenomenon of stochastic resonance, strongly depend on the form of the output. In particular, the SNR may be enhanced for an adequate output.

The determinants of social spending in Spain (1880-1960): Is Lindert right?

[spa] El principal objetivo de este artículo se centra en analizar los orígenes del Estado de Bienestar en España a partir del marco teórico elaborado por Peter Lindert. Con este fin, se ofrece un análisis econométrico de los factores que determinaron la evolución del gasto social público en este país entre 1880 y 1960. Utilizando nueva evidencia cuantitativa, se construyó un panel de datos por quinquenios con el porcentaje de gasto social respecto al PIB desagregado en tres partidas: sanidad, seguridad social y beneficencia. El análisis permite insertar el caso español en el debate internacional y los resultados revelan interesantes singularidades de este país.

Spectrum of gluten sensitive enteropathy in first degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

Background: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. Aims: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. Patients and methods: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. Results: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II¿III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p=0.002). Marsh I relatives had more severe abdominal pain (p=0.006), severe distension (p=0.047) and anaemia (p=0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). Conclusions: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

European guidelines for the development of mechanisms/tools supporting the individual demand for training through use of training Vouchers

El projecte de TAV es basa en la transferència d'un sistema de vals de capacitació, i en com aquest sistema de vals és adaptable a altres països o regions. En el document s'analitzen diferents conceptes teòrics sobre la conveniència o no de la implantació d'aquest sistema. A més a més, aquest document és una guia per a les organitzacions interessades en l'adaptació del sistema de vals formatius al seu territori, mostrant els passos a seguir i oferint eines útils per aconseguir-ho.