Targeting FRET-Based Reporters for cAMP and PKA Activity Using AKAP79

Fluorescence resonance energy transfer (FRET)-based sensors for 3′⁻5′cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) allow real-time imaging of cAMP levels and kinase activity in intact cells with high spatiotemporal resolution. The development of FRET-based sensors has made it possible to directly demonstrate that cAMP and PKA signals are compartmentalized. These sensors are currently widely used to dissect the organization and physiological function of local cAMP/PKA signaling events in a variety of cell systems. Fusion to targeting domains has been used to direct the sensors to a specific subcellular nanodomain and to monitor cAMP and PKA activity at specific subcellular sites. Here, we investigate the effects of using the A-kinase anchoring protein 79 (AKAP79) as a targeting domain for cAMP and PKA FRET-based reporters. As AKAP79 interacts with PKA itself, when used as a targeting domain, it can potentially impact on the amplitude and kinetics of the signals recorded locally. By using as the targeting domain wild type AKAP79 or a mutant that cannot interact with PKA, we establish that AKAP79 does not affect the amplitude and kinetics of cAMP changes or the level of PKA activity detected by the sensor

Diffusion coefficients of sodium dodecyl sulfate in water swollen cross-linked polyacrylamide membranes

http://www.sciencedirect.com/science/article/B6TWW-4603M7T-5/1/856606240860bfc6cbe86dfc5f5b4bf

The influence of basin slope and fluvial flow on deltaic built-up processes off mountainous, seasonal rivers

0,000

Nanotoxicología ambiental

Las nanopartículas son partículas cuyas dimensiones están entre 1 y 100 nanometros, que se producen de forma natural en caso de incendios forestales, erupciones volcánicas, etc., y se pueden fabricar e incorporar en diferentes procesos industriales, lo que ha dado lugar a una gran exposición de estos nanomateriales a nivel medioambiental. Las nanoparticulas presentan propiedades físicas y químicas únicas, las cuales difieren significativamente de las correspondientes al mismo material de mayor escala, por lo que no es posible predecir su perfil de toxicidad por extrapolación a partir de datos de sus equivalentes de mayor tamaño. El principal objetivo de este trabajo es realizar una valoración exhaustiva de los usos y de los posibles mecanismos de toxicidad de estas sustancias en el medio ambiente y en el hombre ya que actualmente no existe una legislación específica sobre nanomateriales. La investigación de este tema tiene gran actualidad ya que es necesario determinar la relación beneficio/riesgo de estos materiales para una correcta evaluación del riesgo siendo la investigación en esta área, una de las líneas prioritarias dentro del 7º Programa Marco de la Unión Europea en materia de salud.Nanoparticles are particles which dimensions are between 1 and 100 nanometers. This kind of particles can be produced under natural circumstances such as forest fires, volcanic eruptions, etc., or can be manufactured and included in different industrial processes, something which has caused an increase in the presence of these particles in the environment. Nanoparticles have unique physico-chemical properties which are significantly different from the same material at a bigger scale. This is the reason why it is not possible to predict its toxicity profile by extrapolation from their equivalents of bigger size. The main aim of this research is to conduct an exhaustive study of the uses and possible toxicity mechanism of these substances in the environment and in humans, due to the absence, nowadays, of specific legislation regarding nanomaterials. This item reseach is a current issue because it is necessary to determine the benefit/ risk balance for these materials, so we can develop a correct evaluation of the potential danger. This investigation area is one of the priorities in the Seventh Framework Programme of the European Community regarding to health matters

The evolution of the Guadalfeo submarine delta (northern Alboran Sea) during the last ca. 200 years

The Guadalfeo submarine delta is located on the northern Alboran Sea shelf in the western Mediterranean Sea. The sedimentary dynamics of the deltaic system is governed by the discharge of one of the major rivers in this area draining the western sector of the near-coastal Sierra Nevada Mountains. The area is under the influence of a Mediterranean climate, with high spatial and temporal (i.e., inter- and intra-annual) rain variability. Major anthropogenic forcing affected the river system during the 1930’s, with the deviation of the main river channel 2.5 km to the west, to its present position. More recently, the construction of Béznar (1977-1985) and Rules (1993-2003) dams have also contributed to limit the amount of sediments exported to the deltaic system. In order to understand the interaction between river discharges and the evolution of the submarine delta at different timescales, sediment cores were collected off the ancient (core 13) and present-day (cores12 and 15) river courses. A chronological framework was performed and combined with sedimentological and benthic foraminiferal analyses. Radiocarbon dating of plant debris from the base of the cores indicates that the sedimentary record goes back 200 years. In core 13, the variations between coarse and fine fractions along the core and the upward increase of benthic foraminiferal population density, would indicate that deposition possibly occurred until the deviation of the main river course to its present position. In the lower part of core 12, the strong alternation between coarse and fine sediment textures and the variable amounts of benthic foraminiferal species are interpreted as the result of an active fluvial regime. The upper part, with high percentages of fine sediments and high values of population density, could be attributed to the stabilization of the river course in its present-day location. Core 15, located at 11 m water depth, showed the highest content of gravel in the lower part of the core, high contents of silt at two core depths and increased percentages of sand to the top, indicating the strong influence of human interventions in the river basin and consequent changes in the sediment supply to the Guadalfeo submarine delta.info:eu-repo/semantics/publishedVersio

Substantia nigra neuromelanin as an imaging biomarker of disease progression in Parkinson’s Disease

"BACKGROUND: A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinson's disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression. OBJECTIVE: to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages. METHODS: A comparative cross-sectional study was performed, analyzing SN-NM MRI signal in LSPD (Schwab and England Activities of Daily Living Scale score 3), comparing this group with de novo, 2-5 year PD and controls. SN-NM signal area and CR values for the internal and lateral SN regions were obtained with semi-automated methods. RESULTS: 13 LSPD, 12 de novo patients with PD, 10 PD patients with a 2-5 year disease duration, and 10 controls were included. NM signal area was significantly decreased in LSPD compared to de novo PD (P-value = 0.005; sensitivity: 75%; specificity 92% and AUC: 0.86). In the lateral SN region, a decrease in the CR was detected in all PD groups compared to controls; despite not reaching statistical significance, a slight increment was observed comparing LSPD to 2-5 year PD. NM signal area significantly correlated with HY (R = -0.37; P < 0.05) and Movement disorder Society Unified Parkinson's Disease Rating Scale part II (MDS-UPDRS) (R = -0.4; P < 0.05) while a weak correlation was found with MDS-UPDRS part III (R = -0.26; P: 0.1). CONCLUSION: SN area evaluated by NM-sensitive MRI may be a promising biomarker of nigral degeneration and disease progression in PD patients."info:eu-repo/semantics/publishedVersio

Substantia nigra area evaluated by neuromelanin-sensitive MRI as an imaging biomarker of disease progression in Parkinson's disease

Poster presented at the International Congress of Parkinson's Disease and Movement Disorders. 4-8 June 2017, Vancouver, CanadaN/

Multi-proxy evidence of rainfall variability recorded in subaqueous deltaic deposits off the Adra River, southeast Iberian Peninsula

The Adra River deltaic system, southeast Iberian Peninsula, shows a steep topography and is subjected to strong climatic seasonality. This system has been affected by alternating wet and dry periods, and it has also undergone numerous anthropogenic activities such as deforestation, mining activities, river channel deviations and dam construction, particularly during the last two centuries. Two sediment cores were retrieved off the Adra River, from the western (MS_V9) and eastern (MS_V4) lobes of the subaqueous deltaic deposit. A multi-proxy study was carried out, including grain size, benthic foraminiferal assemblages, magnetic susceptibility and geochemical element analyses, in order to understand the sedimentary expression of recent climatic cycles and anthropogenic interventions in the river basin. Periods of increased deposition of coarse-grained sediments, low absolute abundance of benthic foraminifera and high elemental ratios indicative of terrigenous contributions, were interpreted as periods of increased sediment supply to the shelf. Four flooding events were recorded in core MS_V9 and three events on core MS_V4, of which two were observed in both cores. They were related to periods with major floods that were documented on the southern Iberian Peninsula around 1770e1810 and 1860 e1870 AD. On the other hand, sediment core intervals exhibiting increasing proportion of fine-grained sediments and higher abundances of foraminiferal species assigned as successful colonizers (Textularia earlandi) and opportunistic species that feed on bacteria or terrestrial organic matter (Bolivina ordinaria, Bulimina elongata, Eggerelloides scaber and Ammonia beccarii or tepida), indicate the establishment of new environments with new ecological constraints. They were related to significant decreases of terrigenous sediment input during low rainfall or dry periods. The increase of opportunistic species feeding on fresh phytodetritus (Nonionella iridea, Nonionella stella, Nonionella sp., Brizalina dilatata, Epistominella vitrea and Bolivinellina pseudopuntata), under more stable environmental conditions, also point to a stronger marine influence on the prodeltaic environments during these periods. The human interventions on the river basin after 1872 AD, with the deviation of the main river channel to the east, led to a drastic reduction of the sediment exported to the western delta lobe. This study showed that the sedimentation on the Adra subaqueous deltaic deposit was mainly controlled by rainfall variability from 1663 to 1872 AD, and afterwards by anthropogenic interventions.En prensa2,247

Submarine deltaic geometries linked to steep, mountainous drainage basins in the northern shelf of the Alboran Sea: Filling the gaps in the spectrum of deltaic deposition

A comprehensive analysis of small deltaic environments linked to short, mountainous, and seasonal fluvial systems in the northern shelf of the Alboran Sea was undertaken in order to define the controlling parameters of the geomorphological variability. The database includes multibeam and backscatter imagery, surficial sediment samples, and high-resolution seismic profiles. Additionally, geomorphological and hydrodynamic modeling and statistical analysis (principal component and cluster analysis) of hydrological and physiographic variables were performed.Most of the studied deltaic systems have high-gradient, coarse-grained deposits with preferential development of the submarine portions to the detriment of the deltaic plains. The geomorphological analysis identified three basic types of plan-viewdistributions according to the length-to-width ratios: elongate, linguoid and lobate. Cross-slope profiles evidence dominant concave-upward geometries, fewer occurrences of planar geometries, and no sigmoid profiles. Sediment depocenters are extremely thick in proximal locations, but thin out rapidly seawards. The geometric distribution patterns of the deltaic systems are characterized by a predictable pattern in plan-view according to the type of fluvial system, ranging from a relatively large river to ephemeral creeks. Prevailing concave and secondary planar profiles support strong sediment progradation in the submarine realmand lowsediment retention in the emerged deltaic environment. Two different types of systems are distinguished: (1) larger rivers,where deltaic deposition is largely controlled by basin dimensions, ultimately dictating themagnitude of water and sediment discharges; and (2) smaller rivers and creeks,where deltaic geometries are related to the basin slopes. The influence of hydrodynamic variables on defining the submarine deltaic geometry has been observed in the case of concave-upward geometries, where geomorphological boundaries are defined by medium- and high-energy wave conditions.Versión del editor2,520