SYNGAP1: Mind the Gap

A cardinal feature of early stages of human brain development centers on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopment disorders affect 3-4% of the world population. The impact of these disorders presents a major challenge to clinicians, geneticists, and neuroscientists. Mutations that cause neurodevelopmental disorders are commonly found in genes encoding proteins that regulate synaptic function. Investigation of the underlying mechanisms using gain or loss of function approaches has revealed alterations in dendritic spine structure, function, and plasticity, consequently modulating the neuronal circuit formation and thereby raising the possibility of neurodevelopmental disorders resulting from synaptopathies. One such gene, SYNGAP1 (Synaptic Ras-GTPase-activating protein) has been shown to cause Intellectual Disability (ID) with comorbid Autism Spectrum Disorder (ASD) and epilepsy in children. SYNGAP1 is a negative regulator of Ras, Rap and of AMPA receptor trafficking to the postsynaptic membrane, thereby regulating not only synaptic plasticity, but also neuronal homeostasis. Recent studies on the neurophysiology of SYNGAP1, using Syngapl mouse models, have provided deeper insights into how downstream signaling proteins and synaptic plasticity are regulated by SYNGAP1. This knowledge has led to a better understanding of the function of SYNGAP1 and suggests a potential target during critical period of development when the brain is more susceptible to therapeutic intervention.

Cytokines and Blastocyst Hatching

Blastocyst implantation into the uterine endometrium establishes early pregnancy. This event is regulated by blastocyst- and/or endometrium-derived molecular factors which include hormones, growth factors, cell adhesion molecules, cytokines and proteases. Their coordinated expression and function are critical for a viable pregnancy. A rate-limiting event that immediately precedes implantation is the hatching of blastocyst. Ironically, blastocyst hatching is tacitly linked to peri-implantation events, although it is a distinct developmental phenomenon. The exact molecular network regulating hatching is still unclear. A number of implantation-associated molecular factors are expressed in the pre-implanting blastocyst. Among others, cytokines, expressed by peri-implantation blastocysts, are thought to be important for hatching, making blastocysts implantation competent. Pro-inflammatory (IL-6, LIF, GM-CSF) and anti-inflammatory (IL-11, CSF-1) cytokines improve hatching rates; they modulate proteases (MMPs, tPAs, cathepsins and ISP1). However, functional involvement of cytokines and their specific mediation of hatching-associated proteases are unclear. There is a need to understand mechanistic roles of cytokines and proteases in blastocyst hatching. This review will assess the available knowledge on blastocyst-derived pro-inflammatory and anti-inflammatory cytokines and their role in potentially regulating blastocyst hatching. They have implications in our understanding of early embryonic loss and infertility in mammals, including humans.

SYNGAP1: Mind the Gap

A cardinal feature of early stages of human brain development centers on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopment disorders affect 3-4% of the world population. The impact of these disorders presents a major challenge to clinicians, geneticists, and neuroscientists. Mutations that cause neurodevelopmental disorders are commonly found in genes encoding proteins that regulate synaptic function. Investigation of the underlying mechanisms using gain or loss of function approaches has revealed alterations in dendritic spine structure, function, and plasticity, consequently modulating the neuronal circuit formation and thereby raising the possibility of neurodevelopmental disorders resulting from synaptopathies. One such gene, SYNGAP1 (Synaptic Ras-GTPase-activating protein) has been shown to cause Intellectual Disability (ID) with comorbid Autism Spectrum Disorder (ASD) and epilepsy in children. SYNGAP1 is a negative regulator of Ras, Rap and of AMPA receptor trafficking to the postsynaptic membrane, thereby regulating not only synaptic plasticity, but also neuronal homeostasis. Recent studies on the neurophysiology of SYNGAP1, using Syngapl mouse models, have provided deeper insights into how downstream signaling proteins and synaptic plasticity are regulated by SYNGAP1. This knowledge has led to a better understanding of the function of SYNGAP1 and suggests a potential target during critical period of development when the brain is more susceptible to therapeutic intervention.

Regulation of Growth, Cell Shape, Cell Division, and Gene Expression by Second Messengers (p)ppGpp and Cyclic Di-GMP in Mycobacterium smegmatis

The alarmone (p)ppGpp regulates transcription, translation, replication, virulence, lipid synthesis, antibiotic sensitivity, biofilm formation, and other functions in bacteria. Signaling nucleotide cyclic di-GMP (c-di-GMP) regulates biofilm formation, motility, virulence, the cell cycle, and other functions. In Mycobacterium smegmatis, both (p) ppGpp and c-di-GMP are synthesized and degraded by bifunctional proteins Rel(Msm) and DcpA, encoded by rel(Msm) and dcpA genes, respectively. We have previously shown that the Delta rel(Msm) and Delta dcpA knockout strains are antibiotic resistant and defective in biofilm formation, show altered cell surface properties, and have reduced levels of glycopeptidolipids and polar lipids in their cell wall (K. R. Gupta, S. Kasetty, and D. Chatterji, Appl Environ Microbiol 81:2571-2578, 2015, http://dx.doi.org/10.1128/AEM.03999-14). In this work, we have explored the phenotypes that are affected by both (p) ppGpp and c-di-GMP in mycobacteria. We have shown that both (p) ppGpp and c-di-GMP are needed to maintain the proper growth rate under stress conditions such as carbon deprivation and cold shock. Scanning electron microscopy showed that low levels of these second messengers result in elongated cells, while high levels reduce the cell length and embed the cells in a biofilm-like matrix. Fluorescence microscopy revealed that the elongated Delta rel(Msm) and Delta dcpA cells are multinucleate, while transmission electron microscopy showed that the elongated cells are multiseptate. Gene expression analysis also showed that genes belonging to functional categories such as virulence, detoxification, lipid metabolism, and cell-wall-related processes were differentially expressed. Our results suggests that both (p) ppGpp and c-di-GMP affect some common phenotypes in M. smegmatis, thus raising a possibility of cross talk between these two second messengers in mycobacteria. IMPORTANCE Our work has expanded the horizon of (p) ppGpp and c-di-GMP signaling in Gram-positive bacteria. We have come across a novel observation that M. smegmatis needs (p) ppGpp and c-di-GMP for cold tolerance. We had previously shown that the Delta rel(Msm) and Delta dcpA strains are defective in biofilm formation. In this work, the overproduction of (p) ppGpp and c-di-GMP encased M. smegmatis in a biofilm-like matrix, which shows that both (p) ppGpp and c-di-GMP are needed for biofilm formation. The regulation of cell length and cell division by (p) ppGpp was known in mycobacteria, but our work shows that c-di-GMP also affects the cell size and cell division in mycobacteria. This is perhaps the first report of c-di-GMP regulating cell division in mycobacteria.

Effective thermal conductivity of reactive packed beds of hydriding materials

Applications of hydriding materials for solid state hydrogen storage, hydrogen compression, thermal energy storage and sorption heating and cooling systems have been demonstrated successfully. However, the performance of these devices significantly depends upon heat and mass transfer characteristics of the reactive packed beds. One of the important parameters regulating heat and mass transfer in the hydriding bed is its effective thermal conductivity (ETC), which is dependent on several operating parameters such as pressure and temperature. ETC also varies significantly due to the variation of hydrogen concentration during the hydriding and dehydriding processes. Based on the extensive studies done by the authors on ETC of metal hydride beds, a review of experimental methods, mathematical studies and augmentation techniques is presented in this paper, with emphasis on the effects of operating parameters on ETC. (C) 2016 Elsevier Ltd. All rights reserved.

Transient potassium channels augment degeneracy in hippocampal active dendritic spectral tuning

Hippocampal pyramidal neurons express an intraneuronal map of spectral tuning mediated by hyperpolarization-activated cyclic-nucleotide-gated nonspecific-cation channels. Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map. To test this, we performed patch-clamp recordings from soma and dendrites of rat hippocampal pyramidal neurons, and measured spectral tuning before and after blocking KA channels using two structurally distinct pharmacological agents. Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk. Furthermore, across all measured locations, blocking KA channels enhanced temporal summation of postsynaptic potentials and critically altered the impedance phase profile, resulting in a significant reduction in total inductive phase. Finally, pair-wise correlations between intraneuronal percentage changes (after blocking KA channels) in different measurements were mostly weak, suggesting differential regulation of different physiological properties by KA channels. Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

Generation of long, laminar plasma jets at atmospheric pressure and effects of flow turbulence

Long, laminar plasma jets at atmospheric pressure of pure argon and a mixture of argon and nitrogen with jet length up to 45 fi,Hes its diameter could be generated with a DC are torch by! restricting the movement of arc root in the torch channel. Effects of torch structure, gas feeding, and characteristics of power supply on the length of plasma jets were experimentally examined. Plasma jets of considerable length and excellent stability could be obtained by regulating the generating parameters, including are channel geometry gas flow I ate, and feeding methods, etc. Influence of flow turbulence at the torch,nozzle exit on the temperature distribution of plasma jets was numerically simulated. The analysis indicated that laminar flow plasma with very low initial turbulent kinetic energy will produce a long jet, with low axial temperature gradient. This kind of long laminar plasma jet could greatly improve the controllability for materials processing, compared with a short turbulent are let.

La beneficencia en Lleida durante el trienio liberal

La Guerra de la Independencia generó miseria y ruina, aumentando la pobreza material y el descenso del poder adquisitivo de la población. Fruto de este negativo contexto económico los ayuntamientos solamente pudieron destinar una décima parte de su presupuesto a la beneficencia. Los efectos de la contienda bélica contra Napoleón también afectaron a la Iglesia, institución que tradicionalmente mediante diversos organismos eclesiásticos tuvo que atender las enormes carestías sociales que asolaban al pueblo, como por ejemplo, otorgar limosna, atender a los enfermos en los hospitales, acoger a los huérfanos en los hospicios o educar a los más jóvenes. En el caso de Lleida durante el régimen liberal cabe destacar la organización de diversas juntas de caridad, de sanidad y de beneficencia destinadas a socorrer a los más necesitados.

La caridad como amor de amistad

Resumen: En este artículo queremos explicar un aspecto de la concepción tomista de la caridad. Verla como amor de amistad. Para ello, primero vamos a investigar la teoría aristotélica de la amistad, como la expone en la Ética a Eudemo y la Ética a Nicómaco. Recurrimos a Aristóteles, ya que es la culminación griega acerca de la reflexión sobre la amistad. Santo Tomás se servirá de la noción aristotélica de la amistad, para explicar la caridad como amor de amistad. Explica que la caridad permite vivir una amistad intensa con Dios y con el prójimo. El acto propio de la caridad, así como sus efectos interiores y exteriores, se entienden más plenamente al captarlos como otros tantos actos de amistad

The circadian oscillator gene GIGANTEA mediates a long-term response of the Arabidopsis thaliana circadian clock to sucrose.

Circadian clocks are 24-h timing devices that phase cellular responses; coordinate growth, physiology, and metabolism; and anticipate the day-night cycle. Here we report sensitivity of the Arabidopsis thaliana circadian oscillator to sucrose, providing evidence that plant metabolism can regulate circadian function. We found that the Arabidopsis circadian system is particularly sensitive to sucrose in the dark. These data suggest that there is a feedback between the molecular components that comprise the circadian oscillator and plant metabolism, with the circadian clock both regulating and being regulated by metabolism. We used also simulations within a three-loop mathematical model of the Arabidopsis circadian oscillator to identify components of the circadian clock sensitive to sucrose. The mathematical studies identified GIGANTEA (GI) as being associated with sucrose sensing. Experimental validation of this prediction demonstrated that GI is required for the full response of the circadian clock to sucrose. We demonstrate that GI acts as part of the sucrose-signaling network and propose this role permits metabolic input into circadian timing in Arabidopsis.

La Eucaristía, primicia y fundamento de un orden social verdaderamente justo : un aporte con ocasión del Congreso Eucarístico Nacional

Resumen: Con motivo de la celebración del Congreso Eucarístico Nacional, el autor propone volver a la inspiración original de esos congresos, poniendo de relieve la dimensión salvífica social de la Eucaristía de cara a los desafíos que presenta la realidad argentina. Uno de ellos es, sin duda, el establecimiento de un orden social más justo. Como aporte en vista de ese fin, el artículo intenta profundizar en la relación entre Eucaristía y justicia. Esto se hace en un desarrollo en cinco momentos: una clarificación de la noción de justicia, desde el punto de vista jurídico-filosófico y desde la perspectiva bíblica; una relectura de las fuentes bíblicas relativas al signo y al significado de la Eucaristía, donde se pone de manifiesto que ésta es el sacramentum caritatis; un momento especulativo que busca explicitar la relación entre caridad y justicia, y la relación de ésta con la Eucaristía; la verificación de esa interpretación en la praxis sacramental cristiana de los primeros siglos; y, por último, la recuperación de algunos textos claves del Magisterio de la Iglesia que han desarrollado el tema. Esto permite concluir que la Eucaristía señala de modo eminente lo que significa ser cristiano, razón por la cual su celebración exige una cierta conducta ética. La Eucaristía rememora así que en Cristo la justicia de Dios ha sido definitivamente realizada y un nuevo orden ha sido instaurado; ella manifiesta e incentiva a establecer una verdadera “contra-cultura” donde prevalezcan la justicia y la solidaridad; y es signo profético de la realización de los “cielos nuevos y la tierra nueva”. Por eso el significado de la leitourgia del Pueblo de Dios se verá verificado en la diakonía y la martyria.

Statistical Simulation of Rarefied Gas Flows in Micro-Channels

Rarefied gas flows through micro-channels are simulated using particle approaches, named as the information preservation (IP) method and the direct simulation Monte Carlo (DSMC) method. In simulating the low speed flows in long micro-channels the DSMC method encounters the problem of large sample size demand and the difficulty of regulating boundary conditions at the inlet and outlet. Some important computational issues in the calculation of long micro-channel flows by using the IP method, such as the use the conservative form of the mass conservation equation to guarantee the adjustment of the inlet and outlet boundary conditions and the super-relaxation scheme to accelerate the convergence process, are addressed. Stream-wise pressure distributions and mass fluxes through micro-channels given by the IP method agree well with experimental data measured in long micro-channels by Pong et al. (with a height to length ratio of 1.2:3000), Shih et al. (l.2:4800), Arkilic et al. and Arkilic (l.3:7500), respectively. The famous Knudsen minimum of normalized mass flux is observed in IP and DSMC calculations of a short micro-channel over the entire flow regime from continuum to free molecular, whereas the slip Navier-Stokes solution fails to predict it.

Quantifying Cell Binding Kinetics Mediated By Surface-Bound Blood Type B Antigen To Immobilized Antibodies

Cell adhesion is crucial to many biological processes, such as inflammatory responses, tumor metastasis and thrombosis formation. Recently a commercial surface plasmon resonance (SPR)-based BIAcore biosensor has been extended to determine cell binding mediated by surface-bound biomolecular interactions. How such cell binding is quantitatively governed by kinetic rates and regulating factors, however, has been poorly understood. Here we developed a novel assay to determine the binding kinetics of surface-bound biomolecular interactions using a commercial BIAcore 3000 biosensor. Human red blood cells (RBCs) presenting blood group B antigen and CM5 chip bearing immobilized anti-B monoclonal antibody (mAb) were used to obtain the time courses of response unit, or sensorgrams, when flowing RBCs over the chip surface. A cellular kinetic model was proposed to correlate the sensorgrams with kinetic rates. Impacts of regulating factors, such as cell concentration, flow duration and rate, antibody-presenting level, as well as pH value and osmotic pressure of suspending medium were tested systematically, which imparted the confidence that the approach can be applied to kinetic measurements of cell adhesion mediated by surface-bound biomolecular interactions. These results provided a new insight into quantifying cell binding using a commercial SPR-based BIAcore biosensor.

El sistema político rionegrino frente a la desnacionalización política: 1983-2011

Resumen: Las pautas que regulan la competencia por el acceso al poder son aspectos centrales para abordar el funcionamiento del sistema político democrático, las cuales se multiplican en un sistema federal o multinivel. Tras la apertura democrática el sistema político argentino redefinió su funcionamiento frente a la mayor autoridad de las provincias en materia de implementación de políticas públicas, recursos fiscales e independencia electoral respecto de la esfera nacional. La territorialización de la política (o desnacionalización) en parte explica los cambios sufridos por el bipartidismo nacional (PJ-UCR), el surgimiento de nuevos partidos políticos y la construcción de nuevas identidades políticas. Hasta el 2011, Río Negro fue de los pocos distritos con partido predominante diferente al partido predominante a nivel nacional, y el único que gobernó la Unión Cívica Radical de forma ininterrumpida desde 1983. El presente trabajo busca explorar el funcionamiento del sistema político rionegrino en el contexto de desnacionalización a partir de los siguientes interrogantes. ¿Cuán congruente o incongruente es el sistema de partido rionegrino al nacional? ¿Qué niveles registra la competencia partidaria en ambos sistemas? ¿Qué efectos tuvieron las reformas electorales sobre el funcionamiento del sistema de partidos subnacional en Río Negro? Dando respuesta a estas preguntas, este artículo busca aportar al estudio de la interaccion del sistema de partidos nacional y un sistema de partidos subnacional, en el marco de los sistemas políticos federales o multinivel

San Vicente de Paúl y la oración

Resumen: San Vicente de Paúl se revela no sólo como el santo defensor de los pobres, sino como un maestro de oración. Este artículo quiere detenerse en este último aspecto. Veremos cómo plantea San Vicente la vida de oración y de devoción. Como es un santo minucioso, propio del barroco del siglo XVII, nos señalará detalladamente como se puede mejorar la práctica de la oración. Al mismo tiempo, hará hincapié en que una vida de oración demuestra su coherencia en la medida que se abre a la caridad fraterna y al servicio a los hermanos que padecen. De tal modo, la oración nos capacita para cumplir cabalmente la Voluntad de Dios. Idea que se puede resumir en su frase: “Denme un hombre de oración y será capaz de todo”.