Cholesterol and Fatty Acids Regulate Dynamic Caveolin Trafficking through the Golgi Complex and between the Cell Surface and Lipid Bodies

Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. The results suggest that cholesterol is a rate-limiting component for caveolin trafficking. Changes in caveolin flux through the exocytic pathway can therefore be an indicator of cellular cholesterol and fatty acid levels.

The dynamic adjustment of local government budgets : Does Spain behave differently?

[spa] El objetivo de este trabajo es analizar si los municipios españoles se ajustan en presencia de un shock presupuestario y (si es así) qué elementos del presupuesto son los que realizan el ajuste. La metodología utilizada para contestar estas preguntas es un mecanismo de corrección del error, VECM, que estimamos con un panel de datos de los municipios españoles durante el período 1988-2006. Nuestros resultados confirman que, en primer lugar, los municipios se ajustan en presencia de un shock fiscal (es decir, el déficit es estacionario en el largo plazo). En segundo lugar, obtenemos que cuando el shock afecta a los ingresos el ajuste lo soporta principalmente el municipio reduciendo el gasto, las transferencias tienen un papel muy reducido en este proceso de ajuste. Por el contrario, cuando el shock afecta al gasto, el ajuste es compartido en términos similares entre el municipio – incrementado los impuestos – y los gobiernos de niveles superiores – incrementando las transferencias. Estos resultados sugieren que la viabilidad de las finanzas pública locales es factible con diferentes entornos institucionales.

Nonlinear inverse dynamic models of gas sensing systems based on chemical sensor arrays for quantitative measurements

Gas sensing systems based on low-cost chemical sensor arrays are gaining interest for the analysis of multicomponent gas mixtures. These sensors show different problems, e.g., nonlinearities and slow time-response, which can be partially solved by digital signal processing. Our approach is based on building a nonlinear inverse dynamic system. Results for different identification techniques, including artificial neural networks and Wiener series, are compared in terms of measurement accuracy.

The dynamic adjustment of local government budgets : Does Spain behave differently?

[spa] El objetivo de este trabajo es analizar si los municipios españoles se ajustan en presencia de un shock presupuestario y (si es así) qué elementos del presupuesto son los que realizan el ajuste. La metodología utilizada para contestar estas preguntas es un mecanismo de corrección del error, VECM, que estimamos con un panel de datos de los municipios españoles durante el período 1988-2006. Nuestros resultados confirman que, en primer lugar, los municipios se ajustan en presencia de un shock fiscal (es decir, el déficit es estacionario en el largo plazo). En segundo lugar, obtenemos que cuando el shock afecta a los ingresos el ajuste lo soporta principalmente el municipio reduciendo el gasto, las transferencias tienen un papel muy reducido en este proceso de ajuste. Por el contrario, cuando el shock afecta al gasto, el ajuste es compartido en términos similares entre el municipio – incrementado los impuestos – y los gobiernos de niveles superiores – incrementando las transferencias. Estos resultados sugieren que la viabilidad de las finanzas pública locales es factible con diferentes entornos institucionales.

High-Momentum Response of Liquid 3He

A final-state-effects formalism suitable to analyze the high-momentum response of Fermi liquids is presented and used to study the dynamic structure function of liquid 3He. The theory, developed as a natural extension of the Gersch-Rodriguez formalism, incorporates the Fermi statistics explicitly through a new additive term which depends on the semidiagonal two-body density matrix. The use of a realistic momentum distribution, calculated using the diffusion Monte Carlo method, and the inclusion of this additive correction allows for good agreement with available deep-inelastic neutron scattering data.

Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry

We describe the use of dynamic combinatorial chemistry (DCC) to identify ligands for the stem-loop structure located at the exon 10-5'-intron junction of Tau pre-mRNA, which is involved in the onset of several tauopathies including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). A series of ligands that combine the small aminoglycoside neamine and heteroaromatic moieties (azaquinolone and two acridines) have been identified by using DCC. These compounds effectively bind the stem-loop RNA target (the concentration required for 50% RNA response (EC(50)): 2-58 μM), as determined by fluorescence titration experiments. Importantly, most of them are able to stabilize both the wild-type and the +3 and +14 mutated sequences associated with the development of FTDP-17 without producing a significant change in the overall structure of the RNA (as analyzed by circular dichroism (CD) spectroscopy), which is a key factor for recognition by the splicing regulatory machinery. A good correlation has been found between the affinity of the ligands for the target and their ability to stabilize the RNA secondary structure.

Dynamic range extension of SiPM detectors with the time-gated operation

The silicon photomultiplier (SiPM) is a novel detector technology that has undergone a fast development in the last few years, owing to its single-photon resolution and ultra-fast response time. However, the typical high dark count rates of the sensor may prevent the detection of low intensity radiation fluxes. In this article, the time-gated operation with short active periods in the nanosecond range is proposed as a solution to reduce the number of cells fired due to noise and thus increase the dynamic range. The technique is aimed at application fields that function under a trigger command, such as gated fluorescence lifetime imaging microscopy.

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

Visual realism enhances realistic response in an immersive virtual environment - Part2

Does realistic lighting in an immersive virtual reality application enhance presence, where participants feel that they are in the scene and behave correspondingly? Our previous study indicated that presence is more likely with real-time ray tracing compared with ray casting, but we could not separate the effects of overall quality of illumination from the dynamic effects of real-time shadows and reflections. Here we describe an experiment where 20 people experienced a scene rendered with global or local illumination. However, in both conditions there were dynamically changing shadows and reflections. We found that the quality of illumination did not impact presence, so that the earlier result must have been due to dynamic shadows and reflections. However, global illumination resulted in greater plausibility - participants were more likely to respond as if the virtual events were real. We conclude that global illumination does impact the responses of participants and is worth the effort.

Dynamic range extension of SiPM detectors with the time-gated operation

The silicon photomultiplier (SiPM) is a novel detector technology that has undergone a fast development in the last few years, owing to its single-photon resolution and ultra-fast response time. However, the typical high dark count rates of the sensor may prevent the detection of low intensity radiation fluxes. In this article, the time-gated operation with short active periods in the nanosecond range is proposed as a solution to reduce the number of cells fired due to noise and thus increase the dynamic range. The technique is aimed at application fields that function under a trigger command, such as gated fluorescence lifetime imaging microscopy.