Understanding intellectual disability through RASopathies

Intellectual disability, commonly known as mental retardation in the International Classification of Disease from World Health Organization, is the term that describes an intellectual and adaptive cognitive disability that begins in early life during the developmental period. Currently the term intellectual disability is the preferred one. Although our understanding of the physiological basis of learning and learning disability is poor, a general idea is that such condition is quite permanent. However, investigations in animal models suggest that learning disability can be functional in nature and as such reversible through pharmacology or appropriate learning paradigms. A fraction of the cases of intellectual disability is caused by point mutations or deletions in genes that encode for proteins of the RAS/MAP kinase signaling pathway known as RASopathies. Here we examined the current understanding of the molecular mechanisms involved in this group of genetic disorders focusing in studies which provide evidence that intellectual disability is potentially treatable and curable. The evidence presented supports the idea that with the appropriate understanding of the molecular mechanisms involved, intellectual disability could be treated pharmacologically and perhaps through specific mechanistic-based teaching strategies.Fil: San Martín, Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pagani, Mario Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

The Spacing Effect for Structural Synaptic Plasticity Provides Specificity and Precision in Plastic Changes

In contrast to trials of training without intervals (massed training), training trials spaced over time (spaced training) induce a more persistent memory identified as long-term memory (LTM). This phenomenon, known as the spacing effect for memory, is poorly understood. LTM is supported by structural synaptic plasticity; however, how synapses integrate spaced stimuli remains elusive. Here, we analyzed events of structural synaptic plasticity at the single-synapse level after distinct patterns of stimulation in motoneurons of Drosophila. We found that the spacing effect is a phenomenon detected at synaptic level, which determines the specificity and the precision in structural synaptic plasticity. Whereas a single pulse of stimulation (massed) induced structural synaptic plasticity, the same amount of stimulation divided in three spaced stimuli completely prevented it. This inhibitory effect was determined by the length of the interstimulus intervals. The inhibitory effect of the spacing was lost by suppressing the activity of Ras or mitogen-activated protein kinase, whereas the overexpression of Ras-WT enhanced it. Moreover, dividing the same total time of stimulation into five or more stimuli produced a higher precision in the number of events of plasticity. Ras mutations associated with intellectual disability abolished the spacing effect and led neurons to decode distinct stimulation patterns as massed stimulation. This evidence suggests that the spacing effect for memory may result from the effect of the spacing in synaptic plasticity, which appears to be a property not limited to neurons involved in learning and memory. We propose a model of spacing-dependent structural synaptic plasticity.Fil: San Martín, Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Gelb, Bruce. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Pagani, Mario Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Caracterizacion morfologica de biotipos de arroz rojo (Oryza sativa) presentes en Chile.

Resumen (Spanish, English)44 p.Para determinar la variabilidad entre las poblaciones de "arroz rojo" en el país se realizo la caracterización morfológica de 232 accesiones de "arroz rojo", colectadas en el área arrocera comprendida entre la VI y VIII regiones del país. Estas accesiones de "arroz rojo" fueron sembradas y caracterizadas en conjunto con las variedades comerciales de arroz Oro, DiamanteINIA y Brillante-INIA. Se definieron 18 características basados en la regla UPOV de 1985, los que mediante un análisis multivariado arrojaron como resultado 17 grupos de "arroz rojo", entre los que destaca el grupo n°1 que reúne a las variedades comerciales y que además cuenta con las únicas tres accesiones con algunas características de "arroz rojo" pero que presenta pericarpio de color blanco. Mediante el análisis de componentes principales se determinó que el 95,7% de la variación fue explicada por los tres primeros componentes. El componente principal 1 estuvo asociado a altura de plantas, largo de tallos y largo de panícula; el componente principal 2 estuvo asociado a largo de hoja bandera, largo de panícula y largo de tallo; el componente principal 3 a largo de panícula, largo de hoja bandera y largo de tallo. Este estudio constituye el primer esfuerzo en la identificación de los biotipos de esta maleza presente en el país, necesitándose la profundización de la identificación Palabras claves: arroz, malezas, "arroz rojo", análisis multivariad

The Phosphatase CSW Controls Life Span by Insulin Signaling and Metabolism Throughout Adult Life in Drosophila

Noonan syndrome and related disorders are caused by mutations in genes encoding for proteins of the RAS-ERK1/2 signaling pathway, which affect development by enhanced ERK1/2 activity. However, the mutations’ effects throughout adult life are unclear. In this study, we identify that the protein most commonly affected in Noonan syndrome, the phosphatase SHP2, known in Drosophila as corkscrew (CSW), controls life span, triglyceride levels, and metabolism without affecting ERK signaling pathway. We found that CSW loss-of-function mutations extended life span by interacting with components of the insulin signaling pathway and impairing AKT activity in adult flies. By expressing csw-RNAi in different organs, we determined that CSW extended life span by acting in organs that regulate energy availability, including gut, fat body and neurons. In contrast to that in control animals, loss of CSW leads to reduced homeostasis in metabolic rate during activity. Clinically relevant gain-of-function csw allele reduced life span, when expressed in fat body, but not in other tissues. However, overexpression of a wild-type allele did not affect life span, showing a specific effect of the gain-of-function allele independently of a gene dosage effect. We concluded that CSW normally regulates life span and that mutations in SHP2 are expected to have critical effects throughout life by insulin-dependent mechanisms in addition to the well-known RAS-ERK1/2-dependent developmental alterations.Fil: Ruzzi, Leonardo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Schilman, Pablo Ernesto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: San Martín, Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Lew, Sergio Eduardo. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; ArgentinaFil: Gelb, Bruce D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Pagani, Mario Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Técnicas continuas de depuración extrarrenal. ¿Precoces o tardías? ¿Cuál es el momento idóneo para su inicio?

The development of acute kidney injury (AKI) is a frequent problem in critical care units (ICUs), specifically in subpopulations admitted with a diagnosis of sepsis or septic shock. In the literature, the indications for the application of CRRT are clear (both of renal and extrarenal origin). However, it seems unclear in any previously published study the ideal time of the beginning of these techniques, nor the impact this has on morbidity and mortality. The objective of this clinical trial is to analyze whether there are differences in mortality between 2 patients groups with AKI and septic shock, depending on the early or late onset of CRRT. It is open (no masking), and may fall into measurement bias during the measurement of the data. The study groups were homogeneous and randomized. However, they do not specify the type of CRRT mode used. The sample size initially calculated according to the power conferred on the study was not finally reached. The measurements were objective. Nonetheless, they do not clarify why they designate the early CRRT as early in the first 12 hours after the development of AKI and late 48 hours later. Results: There are no mortality differences at 90 days (P = 0.38, not significant). It seems that in the late group 38% did not receive CRRT, and 17% received it early. The late group presented significantly fewer days with CRRT. There were no differences in days of mechanical ventilation, vasopressors or ICU stay.El desarrollo de insuficiencia renal aguda (IRA) constituye una problemática frecuente en las unidades de cuidados críticos (UCI), concretamente en las subpoblaciones ingresadas con diagnóstico de sepsis o shock séptico. En la literatura, las indicaciones de aplicación de TCRR están claras (tanto de origen renal como extrarrenal). Sin embargo, no parece claro en ningún estudio publicado previamente el momento ideal del inicio de dichas técnicas, ni la repercusión que esto tiene en la morbimortalidad. El objetivo de este ensayo clínico es analizar si existen diferencias en la mortalidad entre 2 grupos de pacientes con lesión renal aguda y shock séptico, según el inicio precoz o tardío de las TCRR. Es abierto (no hay enmascaramiento), pudiendo caer en sesgo de medición durante la medición de los datos. Los grupos de estudio fueron homogéneos, con aleatorización al azar. Sin embargo, no especifican el tipo de modalidad de TCRR utilizada. El tamaño muestral calculado inicialmente según la potencia conferida al estudio no fue alcanzado finalmente. Las mediciones fueron objetivas. Sin embargo, no aclaran por qué designan como precoz al inicio de las TCRR en las primeras 12 horas desde el desarrollo de LRA y tardío a 48 horas después. Resultados: No hay diferencias de mortalidad a los 90 días (P=0.38, no significativo). Sin embargo, en el grupo tardío un 38% no recibieron TCRR, y 17 % lo recibieron precozmente. El grupo tardío presentó de forma significativa menos días con TCRR. No hubo diferencias en días de ventilación mecánica, vasopresores ni estancia en UCI

Geometric documentation and photogrammetric stereoplotting of Labraza walls (Álava, Spain)

[ES] Se han documentado unos 180 metros de muralla que corresponde a los alzados este y norte. También se incluye el interior de dos puertas de acceso, el muro exterior del cementerio y parte de los muros de la iglesia.La documentación se ha realizado mediante pares estereoscópicos en película (negativos y diapositivas) obtenidos con una cámara semimétrica de 6x6 cm.[EN] Around 180 metres of the western and northern wall were documented. The documentation also includes the inside of two entries, the wall of the graveyard and part of the walls of the church.The documentation was done by means of photogrammetric stereopairs taken with a semi-metric camera of 6x6 cm.Arabarri (Sociedad Anónima de Gestión de Los Centros Históricos de Álava)[ES] Memoria del proyecto (7 páginas en formato PDF) + 7 fotografías de documentación (JPEG).[EN] General report (7 pages in Spanish and PDF format) + 7 photographs for documentation purposes

Fluctuating nonlinear spring theory:Strength, deformability, and toughness of biological nanoparticles from theoretical reconstruction of force-deformation spectra

We developed the Fluctuating Nonlinear Spring (FNS) model to describe the dynamics of mechanical deformation of biological particles, such as virus capsids. The theory interprets the force-deformation spectra in terms of the “Hertzian stiffness” (non-linear regime of a particle's small-amplitude deformations), elastic constant (large-amplitude elastic deformations), and force range in which the particle's fracture occurs. The FNS theory enables one to quantify the particles’ elasticity (Young's moduli for Hertzian and bending deformations), and the limits of their strength (critical forces, fracture toughness) and deformability (critical deformations) as well as the probability distributions of these properties, and to calculate the free energy changes for the particle's Hertzian, elastic, and plastic deformations, and eventual fracture. We applied the FNS theory to describe the protein capsids of bacteriophage P22, Human Adenovirus, and Herpes Simplex virus characterized by deformations before fracture that did not exceed 10–19% of their size. These nanoshells are soft (~1–10-GPa elastic modulus), with low ~50–480-kPa toughness – a regime of material behavior that is not well understood, and with the strength increasing while toughness decreases with their size. The particles’ fracture is stochastic, with the average values of critical forces, critical deformations, and fracture toughness comparable with their standard deviations. The FNS theory predicts 0.7-MJ/mol free energy for P22 capsid maturation, and it could be extended to describe uniaxial deformation of cylindrical microtubules and ellipsoidal cellular organelles

Geometric documentation of the archaeological excavations at Santa Maria Cathedral (Vitoria-Gasteiz, Álava, Spain). May 2000 / June 2003

[ES] Información sobre este proyecto ha servido de base a los siguientes artículos:● LDGP_art_007: "Elementos auxiliares en fotogrametría de objeto cercano", http://hdl.handle.net/10810/9463● LDGP_car_002: "Documentación geométrica de excavaciones arqueológicas", http://hdl.handle.net/10810/6281[ES] Information from this project was included in the following papers:● LDGP_art_007: "Elementos auxiliares en fotogrametría de objeto cercano", http://hdl.handle.net/10810/9463● LDGP_car_002: "Documentación geométrica de excavaciones arqueológicas", http://hdl.handle.net/10810/6281[ES]Excavación arqueológica en parte del interior del templo (gran parte de la nave, capillas y cripta) y la plaza exterior.Toma de pares fotogramétricos con cámara semimétrica en película fotográfica (principalmente diapositiva de 6x6 cm), la mayoría de ellos –correspondientes a la superficie excavada- se han tomado utilizando una estructura portátil para la elevación de la cámara unos 4 metros sobre el terreno. La colección consta de 1.560 pares, todos ellos, clasificados, con su correspondiente apoyo (en el sistema local de coordenadas del proyecto). En campo las fotografías se toman por duplicado, razón por la que existen dos copias de la colección de negativos (diapositivas): la que se encuentra en el Fundación Catedral de Santa María y la copia almacenada en el Laboratorio de Documentación Geométrica del Patrimonio (UPV/EHU).[EN] Archaeological excavation of the most part of the nave (including chapels and crypt) and the square outside.Photogrammetric pairs (stereoscopic) taken with a semi-metric camera (6x6 cm film). Most of the photographs are had been taken by means of a portable structure to held the camera 4 meters above the ground. The collection is composed by 1560 stereoscopic pairs with control points (the project uses a local system for the coordinates). Due to the fact that, during the fieldwork, the photographs are taken twice, there are two copies of the collection: the one at the Fundación Catedral de Santa María de Vitoria and a copy kept at the Laboratorio de Documentación Geométrica del Patrimonio (UPV/EHU).Fundación Catedral de Santa María de Vitoria[ES] 1 documento PDF con la memoria (192 pp)+ 4 documentos con las 1560 fichas correspondientes a los pares fotogramétricos (también en PDF).[EN] General report (192 pp. in PDF) + 4 PDF documents containing 1560 sketches of stereoscopic pairs

Burden of herpes zoster requiring hospitalization in Spain during a seven-year period (1998–2004)

<p>Abstract</p> <p>Background</p> <p>A thorough epidemiological surveillance and a good understanding of the burden of diseases associated to VZV are crucial to asses any potential impact of a prevention strategy. A population-based retrospective epidemiological study to estimate the burden of herpes zoster requiring hospitalization in Spain was conducted.</p> <p>Methods</p> <p>This study was conducted by using data from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos (CMBD). Records of all patients admitted to hospital with a diagnosis of herpes zoster (ICD-9-MC codes 053.0–053.9) during a 7-year period (1998–2004) were selected.</p> <p>Results</p> <p>A total of 23,584 hospitalizations with a primary or secondary diagnosis of herpes zoster in patients ≥ 30 years of age were identified during the study period. Annually there were 13.4 hospitalizations for herpes zoster per 100,000 population in patients ≥ 30 years of age. The rate increases with age reaching a maximum in persons ≥ 80 years of age (54.3 admissions per 100,000 population >80 years of age). The mean cost of a hospitalization for herpes zoster in adult patients was 3,720 €. The estimated annual cost of hospitalizations for herpes zoster in patients ≥ 30 years of age in Spain was 12,731,954 €.</p> <p>Conclusion</p> <p>Herpes zoster imposes an important burden of hospitalizations and result in large cost expenses to the Spanish National Health System, especially in population older than 50 years of age</p