Glucose metabolism and oscillatory behavior of pancreatic islets

A variety of oscillations are observed in pancreatic islets.We establish a model, incorporating two oscillatory systems of different time scales: One is the well-known bursting model in pancreatic beta-cells and the other is the glucose-insulin feedback model which considers direct and indirect feedback of secreted insulin. These two are coupled to interact with each other in the combined model, and two basic assumptions are made on the basis of biological observations: The conductance g_{K(ATP)} for the ATP-dependent potassium current is a decreasing function of the glucose concentration whereas the insulin secretion rate is given by a function of the intracellular calcium concentration. Obtained via extensive numerical simulations are complex oscillations including clusters of bursts, slow and fast calcium oscillations, and so on. We also consider how the intracellular glucose concentration depends upon the extracellular glucose concentration, and examine the inhibitory effects of insulin.Comment: 11 pages, 16 figure

Caracterización de los sistemas palustres de Las Tablas de Daimiel durante el Cuaternario: textura y composición de sus barros micríticos

The National Park of Las Tablas de Daimiel contains a continuous record o f shallow-lacustrine and fluvial deposits, which was studied in a borehole, 38.5 m in depth. The borehole has three different parts that reflect important sedimentary changes. The lower part (17 m) consists of cal cite muds with some dolomite, gypsum moulds, gastropods, calcified root tissues and sponge spicules. It deposited in a shallow, mostly permanent lacustrine system of variable salinity. The middle part (8.6 m) is formed by calcitic muds with traces of dolomite and include diatoms, sponge spicules, ostracods and calcified filaments. It represents the sedimentation within a freshwater palustrine system. The upper part (12.9 m) is made of m¡critic muds with desiccation cracks, alveolar structures, gastropods, charophytes and intraclasts. It formed in a palustrine regime with clear desiccation events. Radiocarbon dating of samples situated between 8.1 and 12.6 m indicate an age of about 25,000 yr BP

Sequential Loading of Cohesin Subunits during the First Meiotic Prophase of Grasshoppers

A previous version of this article appeared as an Early Online Release on January 2, 2007 (doi:10.1371/journal.pgen.0030028.eor).The cohesin complexes play a key role in chromosome segregation during both mitosis and meiosis. They establish sister chromatid cohesion between duplicating DNA molecules during S-phase, but they also have an important role during postreplicative double-strand break repair in mitosis, as well as during recombination between homologous chromosomes in meiosis. An additional function in meiosis is related to the sister kinetochore cohesion, so they can be pulled by microtubules to the same pole at anaphase I. Data about the dynamics of cohesin subunits during meiosis are scarce; therefore, it is of great interest to characterize how the formation of the cohesin complexes is achieved in order to understand the roles of the different subunits within them. We have investigated the spatio-temporal distribution of three different cohesin subunits in prophase I grasshopper spermatocytes. We found that structural maintenance of chromosome protein 3 (SMC3) appears as early as preleptotene, and its localization resembles the location of the unsynapsed axial elements, whereas radiation-sensitive mutant 21 (RAD21) (sister chromatid cohesion protein 1, SCC1) and stromal antigen protein 1 (SA1) (sister chromatid cohesion protein 3, SCC3) are not visualized until zygotene, since they are located in the synapsed regions of the bivalents. During pachytene, the distribution of the three cohesin subunits is very similar and all appear along the trajectories of the lateral elements of the autosomal synaptonemal complexes. However, whereas SMC3 also appears over the single and unsynapsed X chromosome, RAD21 and SA1 do not. We conclude that the loading of SMC3 and the non-SMC subunits, RAD21 and SA1, occurs in different steps throughout prophase I grasshopper meiosis. These results strongly suggest the participation of SMC3 in the initial cohesin axis formation as early as preleptotene, thus contributing to sister chromatid cohesion, with a later association of both RAD21 and SA1 subunits at zygotene to reinforce and stabilize the bivalent structure. Therefore, we speculate that more than one cohesin complex participates in the sister chromatid cohesion at prophase I.This work was supported by grants BFU2005–05668-C03–01, BFU2006–06655, BFU2005–01266, BFU2005–02431, and BFU2006–04406 from Ministerio de Educación y Ciencia, España, and grants 1001160016 and 11/BCB/013 from Universidad Autónoma de Madrid and Comunidad de Madrid. The Department of Immunology and Oncology was founded and is supported by the Spanish Council for Scientific Research (CSIC).Peer reviewe

Sequential Loading of Cohesin Subunits during the First Meiotic Prophase of Grasshoppers

The cohesin complexes play a key role in chromosome segregation during both mitosis and meiosis. They establish sister chromatid cohesion between duplicating DNA molecules during S-phase, but they also have an important role during postreplicative double-strand break repair in mitosis, as well as during recombination between homologous chromosomes in meiosis. An additional function in meiosis is related to the sister kinetochore cohesion, so they can be pulled by microtubules to the same pole at anaphase I. Data about the dynamics of cohesin subunits during meiosis are scarce; therefore, it is of great interest to characterize how the formation of the cohesin complexes is achieved in order to understand the roles of the different subunits within them. We have investigated the spatio-temporal distribution of three different cohesin subunits in prophase I grasshopper spermatocytes. We found that structural maintenance of chromosome protein 3 (SMC3) appears as early as preleptotene, and its localization resembles the location of the unsynapsed axial elements, whereas radiation-sensitive mutant 21 (RAD21) (sister chromatid cohesion protein 1, SCC1) and stromal antigen protein 1 (SA1) (sister chromatid cohesion protein 3, SCC3) are not visualized until zygotene, since they are located in the synapsed regions of the bivalents. During pachytene, the distribution of the three cohesin subunits is very similar and all appear along the trajectories of the lateral elements of the autosomal synaptonemal complexes. However, whereas SMC3 also appears over the single and unsynapsed X chromosome, RAD21 and SA1 do not. We conclude that the loading of SMC3 and the non-SMC subunits, RAD21 and SA1, occurs in different steps throughout prophase I grasshopper meiosis. These results strongly suggest the participation of SMC3 in the initial cohesin axis formation as early as preleptotene, thus contributing to sister chromatid cohesion, with a later association of both RAD21 and SA1 subunits at zygotene to reinforce and stabilize the bivalent structure. Therefore, we speculate that more than one cohesin complex participates in the sister chromatid cohesion at prophase I

Registro paleoclimático del Pleistoceno Medio en el valle del rio Tajo.

The central region of the Iberian Peninsula has specific climatic characteristics that have affected the vegetation evolution along the Quaternary period. The scarce available paleoclimatic information has shown that the vegetation evolution did not follow the valid patterns for other regions, not only those for Europe regions but also those for other regions into the Iberian Peninsula. We present in this work three palynological records from alluvial deposits of the river Tajo that correspond, by datation and/or correlation with other well-dated deposits, to the Middle Pleistocene. The vegetation during this period was open mediterranean formations made up of mainly evergreen Quercus, Olea, Juniperus and Cistaceae, indicating the existence of a dry mediterranean climate. The vegetation evolution along the Middle Pleistocene, reconstructed from the three palynological records, also shows the development of more humid or more arid pulses into a general trend of increasing aridity during the Middle Pleistocene

Caracterización climática de las etapas áridas del Pleistoceno Superior en la Región Central Peninsular

Evidences from different paleoclimatic records have shown the existence of arid periods during the Upper Pleistocene and the Holocene in the central Iberian Peninsula. We present the palynological records from two aeolian deposits of central Iberian Peninsula which were developed during two of that arid periods in the Upper Pleistocene. One deposit is a clay dune, dated by OSL/TL on 22-23 ka, corresponding to the Last Glacial Maximum. The second deposit is a sand formation with massive structure and facies loess-like, dated by IRSL on I I ka, corresponding to the Younger Dryas event. Both palynological records confirm the existence of arid periods at 22-23 ka and at Ilka, showing a vegetation made up of Pinus, Juniperus and steppe-like taxa. The differences between both records indicate that the cold-and-arid climatic conditions were more intense and longer during the Last Glacial Maximum than during the Younger Dryas

Quaternary fossil horses within the Prados-Guatén Depression (Pantoja de La Sagra, Toledo)

Durante la primera reunión de campo del Grupo Madrileño de Cuaternario (GQM-AEQUA) se localizaron restos fragmentarios de dentición de caballos fósiles en los antiguos areneros de Pantoja de La Sagra (Toledo), actualmente en proceso de desmantelamiento y relleno. Ante la posibilidad de deterioro y pérdida los restos fueron recolectados y trasladados al Museo Nacional de Ciencias Naturales (CSIC, Madrid) donde se ha procedido a su análisis. Las piezas fósiles analizadas responden a un maxilar izquierdo con tres piezas dentales in situ (molares y premolares), y otras siete más aisladas. Todos los dientes aislados, junto con el fragmento de maxilar existente, corresponden a un adulto joven. Los restos fósiles se encontraban asociados a un nivel de arenas fluviales situado unos cuatro metros por debajo de la superficie de la Terraza de +15 m de la Depresión Prados-Guatén definida como un nivel perteneciente al tránsito Pleistoceno inferior-medio, del antiguo Sistema fluvial Manzanares-Guatén por Silva (1988). En concreto los niveles superiores de esta terraza han sido interpretados como resultado de la superposición de los últimos depósitos del antiguo sistema fluvial y los primeros asociados al relleno de la Depresión por tributarios de área fuente más local tras su abandono como consecuencia del proceso de captura del valle inferior del Manzanares por parte del Río Jarama al SW de la Ciudad de Madrid (Silva et al., 1988). Los caracteres morfológicos y morfométricos de las piezas dentarias permiten identificarlos como Equus ferus cf. mosbachensis cuya distribución bioestratigráfica abarca la parte final del Pleistoceno Medio (c.a. 500-200 ka B.P.). Junto a los restos fósiles aparecieron también escasos fragmentos líticos correspondientes a productos de lascado en sílex de difícil atribución tecnológica. Los restos fósiles analizados, indican que el depósito extensivo de arenas fluviales en el eje de la Depresión, culminó durante el final del Pleistoceno medio, y que la dinámica fluvial de la Depresión tras su proceso de abandono fue de hecho más activa de lo que se pensaba con la instalación de sistemas de arroyos relevantes alimentados por cabeceras locales antes del encajamiento definitivo actual de los arroyos Prados y Guatén.During the first field-meeting of the Madrid Quaternary Research Group (GQM-AEQUA) several fossil teeth remnants of horses were localised at the ancient sand-quarries of Pantoja de La Sagra (Toledo), which presently are abandoned and refilling in progress. The possibility of deterioration and loss of the localised fossils remnants induced by the quarry works, they were collected and taken away to the Museo Nacional de Ciencias Naturales (CSIC, Madrid) for their preservation and analysis. Fossil remains correspond to a left maxilla with two in situ molars, another one inset on its alveolar cavity, fragments of premolar cavities, as well as other seven more isolated teeth. These fossils were outcropping in a sandy level at four meters below the +15 m fluvial terrace surface of the axial sector of de Prados-Guatén Depression, which is considered the last fluvial level belonging to the ancient Manzanares-Guatén fluvial system during the Lower-Middle Pleistocene transit (Silva, 1988). In detail, the upper fluvial sediments of this particular terrace level were interpreted as the result of the overlapping between the last materials deposited by the ancient Manzanares-Guatén fluvial system and the first ones resulting from the readjustment of former tributaries after the abandonment of the Depression caused by fluvial capture of the Lower Manzanares Valley SW Madrid City. The morphological features of the oclusal surface of the horse teeth and morphometric comparative analyses indicate that they belong to the specie Equus ferus, and probably to the subspecie mosbachensis. However due to the bad definition of this group in Europe and the few individuals analysed the better classification is Equus ferus cf. mosbachensis. The bioestratigraphic distribution of this fossil horse group in Europe extends on the upper part of the Middle Pleistocene (c.a. 500-200 ka B.P.). Few lithic artefacts outcropped also associated to the fossil remains, constituted by laminar flakes of hard technological classification. Fossil remains analysed in this work joint to the unique previous quaternary fossil mammal described for the Prados-Guatén Depression constituted by Mammuthus meridionalis NESTI of the former quarry of Esquivias adjacent to the AVE railway line (Silva et al., 1988b; 1999). The chronostratigraphic attribution of the fossil horses (Upper Middle Pleistocene) described here indicate that fluvial sedimentary activity within the Depression was relevant after its abandonment. Ancient tributaries of the former Manzanares-Guatén fluvial system, feed by local-intrabasinal headwaters, reworked the previous sandy sediments triggering multiepisodic deposition during the upper part of the Middle Pleistocene, before the more recent eventual incision of present streams dissecting the Depression

Imaging Cyclic AMP Changes in Pancreatic Islets of Transgenic Reporter Mice

Cyclic AMP (cAMP) and Ca2+ are two ubiquitous second messengers in transduction pathways downstream of receptors for hormones, neurotransmitters and local signals. The availability of fluorescent Ca2+ reporter dyes that are easily introduced into cells and tissues has facilitated analysis of the dynamics and spatial patterns for Ca2+ signaling pathways. A similar dissection of the role of cAMP has lagged because indicator dyes do not exist. Genetically encoded reporters for cAMP are available but they must be introduced by transient transfection in cell culture, which limits their utility. We report here that we have produced a strain of transgenic mice in which an enhanced cAMP reporter is integrated in the genome and can be expressed in any targeted tissue and with tetracycline induction. We have expressed the cAMP reporter in β-cells of pancreatic islets and conducted an analysis of intracellular cAMP levels in relation to glucose stimulation, Ca2+ levels, and membrane depolarization. Pancreatic function in transgenic mice was normal. In induced transgenic islets, glucose evoked an increase in cAMP in β-cells in a dose-dependent manner. The cAMP response is independent of (in fact, precedes) the Ca2+ influx that results from glucose stimulation of islets. Glucose-evoked cAMP responses are synchronous in cells throughout the islet and occur in 2 phases suggestive of the time course of insulin secretion. Insofar as cAMP in islets is known to potentiate insulin secretion, the novel transgenic mouse model will for the first time permit detailed analyses of cAMP signals in β-cells within islets, i.e. in their native physiological context. Reporter expression in other tissues (such as the heart) where cAMP plays a critical regulatory role, will permit novel biomedical approaches

Deepint.net: A rapid deployment platform for smart territories

This paper presents an efficient cyberphysical platform for the smart management of smart territories. It is efficient because it facilitates the implementation of data acquisition and data management methods, as well as data representation and dashboard configuration. The platform allows for the use of any type of data source, ranging from the measurements of a multi-functional IoT sensing devices to relational and non-relational databases. It is also smart because it incorporates a complete artificial intelligence suit for data analysis; it includes techniques for data classification, clustering, forecasting, optimization, visualization, etc. It is also compatible with the edge computing concept, allowing for the distribution of intelligence and the use of intelligent sensors. The concept of smart cities is evolving and adapting to new applications; the trend to create intelligent neighbourhoods, districts or territories is becoming increasingly popular, as opposed to the previous approach of managing an entire megacity. In this paper, the platform is presented, and its architecture and functionalities are described. Moreover, its operation has been validated in a case study where the bike renting service of Paris—Vélib’ Métropole has been managed. This platform could enable smart territories to develop adapted knowledge management systems, adapt them to new requirements and to use multiple types of data, and execute efficient computational and artificial intelligence algorithms. The platform optimizes the decisions taken by human experts through explainable artificial intelligence models that obtain data from IoT sensors, databases, the Internet, etc. The global intelligence of the platform could potentially coordinate its decision-making processes with intelligent nodes installed in the edge, which would use the most advanced data processing techniques.This work has been partially supported by the European Regional Development Fund (ERDF) through the Interreg Spain-Portugal V-A Program (POCTEP) under grant 0677_DISRUPTIVE_2_E, the project My-TRAC: My TRAvel Companion (H2020-S2RJU-2017), the project LAPASSION, CITIES (CYTED 518RT0558) and the company DCSC. Pablo Chamoso’s research work has been funded through the Santander Iberoamerican Research Grants, call 2020/2021, under the direction of Paulo Novais