Differential cAMP signaling at hippocampal output synapses

cAMP is a critical second messenger involved in synaptic transmission and synaptic plasticity. Here, we show that activation of the adenylyl cyclase by forskolin and application of the cAMP-analog Sp-5,6-DCl-cBIMPS both mimicked and occluded tetanus-induced long-term potentiation (LTP) in subicular bursting neurons, but not in subicular regular firing cells. Furthermore, LTP in bursting cells was inhibited by protein kinase A (PKA) inhibitors Rp-8-CPT-cAMP and H-89. Variations in the degree of EPSC blockade by the low-affinity competitive AMPA receptor-antagonist {gamma}-d-glutamyl-glycine ({gamma}-DGG), analysis of the coefficient of variance as well as changes in short-term potentiation suggest an increase of glutamate concentration in the synaptic cleft after expression of LTP. We conclude that presynaptic LTP in bursting cells requires activation of PKA by a calcium-dependent adenylyl cyclase while LTP in regular firing cells is independent of elevated cAMP levels. Our results provide evidence for a differential role of cAMP in LTP at hippocampal output synapses

Production of n-propyl acetate by reactive distillation : experimental and theoretical study

First steps of the development of a catalytic reactive distillation process for the production of n-propyl acetate based on experiments and simulations are proposed. The kinetics for homogeneously (sulphuric acid) and heterogeneously (Amberlyst 15) catalysed reaction were investigated and the constants for a pseudo-homogeneous model are presented. Pilot plant experiments were performed using a homogeneous strong acid catalyst in a packed column. A top-column decanter is used to withdraw the aqueous phase and to reflux the organic phase. Simulation results are in good agreement with experimental data. Thermodynamics nonidealities are taken into account using VLE and LLE NRTL interaction parameters. Alcohol conversion and n-propyl acetate purity may be dramatically increased just by adding to the pilot plant a stripping section in an additional column: six different configurations are identified to achieve such a production. The startup is studied in order to determine the best strategy to achieve steady-state conditions. The strong influence of the composition of the initial charging in the decanter can be seen and an initial charging of the two-phase top product leads to the fastest startup

Role of amyloid-β glycine 33 in oligomerization, toxicity, and neuronal plasticity

The aggregation of the amyloid-{beta} (Abeta) peptide plays a pivotal role in the pathogenesis of Alzheimer's disease, as soluble oligomers are intimately linked to neuronal toxicity and inhibition of hippocampal long-term potentiation (LTP). In the C-terminal region of Abeta there are three consecutive GxxxG dimerization motifs, which we could previously demonstrate to play a critical role in the generation of Abeta. Here, we show that glycine 33 (G33) of the central GxxxG interaction motif within the hydrophobic Abeta sequence is important for the aggregation dynamics of the peptide. Abeta peptides with alanine or isoleucine substitutions of G33 displayed an increased propensity to form higher oligomers, which we could attribute to conformational changes. Importantly, the oligomers of G33 variants were much less toxic than Abeta(42) wild type (WT), in vitro and in vivo. Also, whereas Abeta(42) WT is known to inhibit LTP, Abeta(42) G33 variants had lost the potential to inhibit LTP. Our findings reveal that conformational changes induced by G33 substitutions unlink toxicity and oligomerization of Abeta on the molecular level and suggest that G33 is the key amino acid in the toxic activity of Abeta. Thus, a specific toxic conformation of Abeta exists, which represents a promising target for therapeutic interventions

Multisensory causal inference in the brain

At any given moment, our brain processes multiple inputs from its different sensory modalities (vision, hearing, touch, etc.). In deciphering this array of sensory information, the brain has to solve two problems: (1) which of the inputs originate from the same object and should be integrated and (2) for the sensations originating from the same object, how best to integrate them. Recent behavioural studies suggest that the human brain solves these problems using optimal probabilistic inference, known as Bayesian causal inference. However, how and where the underlying computations are carried out in the brain have remained unknown. By combining neuroimaging-based decoding techniques and computational modelling of behavioural data, a new study now sheds light on how multisensory causal inference maps onto specific brain areas. The results suggest that the complexity of neural computations increases along the visual hierarchy and link specific components of the causal inference process with specific visual and parietal regions

Acceleration of generalized hypergeometric functions through precise remainder asymptotics

We express the asymptotics of the remainders of the partial sums {s_n} of the generalized hypergeometric function q+1_F_q through an inverse power series z^n n^l \sum_k c_k/n^k, where the exponent l and the asymptotic coefficients {c_k} may be recursively computed to any desired order from the hypergeometric parameters and argument. From this we derive a new series acceleration technique that can be applied to any such function, even with complex parameters and at the branch point z=1. For moderate parameters (up to approximately ten) a C implementation at fixed precision is very effective at computing these functions; for larger parameters an implementation in higher than machine precision would be needed. Even for larger parameters, however, our C implementation is able to correctly determine whether or not it has converged; and when it converges, its estimate of its error is accurate.Comment: 36 pages, 6 figures, LaTeX2e. Fixed sign error in Eq. (2.28), added several references, added comparison to other methods, and added discussion of recursion stabilit

Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass: Five-year follow-up of a randomized trial

ObjectiveIn a randomized trial of 223 patients undergoing coronary artery surgery with cardiopulmonary bypass, we have reported a neuroprotective effect of mild hypothermia. To determine whether the beneficial effect of mild hypothermia was long-lasting, we repeated the psychometric tests in 131 patients after 5 years.MethodsPatients were cooled to 32°C during aortic crossclamping and then randomized to rewarming to either 34°C or 37°C, with no further rewarming until arrival in intensive care unit. Cognitive function was measured preoperatively and 1 week and 5 years postoperatively with a battery of 11 psychometric tests interrogating verbal memory, attention, and psychomotor speed and dexterity.ResultsPatients who had greater cognitive decline 1 week after surgery showed poorer performance 5 years later. The magnitude of cognitive decline over 5 years was modest. The incidence of deficits defined as a 1 standard deviation [SD] decline in at least 1 of 3 factors was not different between temperature groups. Fewer patients in the hypothermic group had deficits that persisted over the 5 years, but this difference did not attain statistical significance (RR = 0.64, P = .16).ConclusionsThe effect of surgery on cognitive function observed early after surgery is an important predictor of cognitive performance 5 years later. Although there was evidence of a neuroprotective effect of mild hypothermia early after surgery in the original cohort, the results after 5 years were inconclusive. In general, the magnitude of cognitive changes over 5 years was modest. We believe that further trials investigating the efficacy of mild hypothermia in patients having cardiac surgery are warranted

Collective Animal Behavior from Bayesian Estimation and Probability Matching

Animals living in groups make movement decisions that depend, among other factors, on social interactions with other group members. Our present understanding of social rules in animal collectives is based on empirical fits to observations and we lack first-principles approaches that allow their derivation. Here we show that patterns of collective decisions can be derived from the basic ability of animals to make probabilistic estimations in the presence of uncertainty. We build a decision-making model with two stages: Bayesian estimation and probabilistic matching.
In the first stage, each animal makes a Bayesian estimation of which behavior is best to perform taking into account personal information about the environment and social information collected by observing the behaviors of other animals. In the probability matching stage, each animal chooses a behavior with a probability given by the Bayesian estimation that this behavior is the most appropriate one. This model derives very simple rules of interaction in animal collectives that depend only on two types of reliability parameters, one that each animal assigns to the other animals and another given by the quality of the non-social information. We test our model by obtaining theoretically a rich set of observed collective patterns of decisions in three-spined sticklebacks, Gasterosteus aculeatus, a shoaling fish species. The quantitative link shown between probabilistic estimation and collective rules of behavior allows a better contact with other fields such as foraging, mate selection, neurobiology and psychology, and gives predictions for experiments directly testing the relationship between estimation and collective behavior

Gender roles and couple conflicts: gender stereotypes in couples therapy in Mendoza City

Introducción: las concepciones sobre los roles de género se han modificado profundamente en las últimas décadas. Conllevan asignaciones diferenciales de poder y estatus, foco de los cuestionamientos feministas que en la actualidad impactan en la construcción de la subjetividad y en las expectativas de rol. En el ámbito de la vida privada confluyen los estereotipos de género tradicionales junto a nuevas concepciones de los mismos, lo cual podría generar conflictos al interior de las parejas y la vida familiar afectando también el sano desarrollo de niños, niñas y adolescentes cuando estas dificultades no son resueltas y llegan a tener manifestaciones violentas. El efecto de estas modificaciones en la vida íntima y su influencia en las consultas psicológicas de pareja ha sido escasamente estudiado

How Haptic Size Sensations Improve Distance Perception

Determining distances to objects is one of the most ubiquitous perceptual tasks in everyday life. Nevertheless, it is challenging because the information from a single image confounds object size and distance. Though our brains frequently judge distances accurately, the underlying computations employed by the brain are not well understood. Our work illuminates these computions by formulating a family of probabilistic models that encompass a variety of distinct hypotheses about distance and size perception. We compare these models' predictions to a set of human distance judgments in an interception experiment and use Bayesian analysis tools to quantitatively select the best hypothesis on the basis of its explanatory power and robustness over experimental data. The central question is: whether, and how, human distance perception incorporates size cues to improve accuracy. Our conclusions are: 1) humans incorporate haptic object size sensations for distance perception, 2) the incorporation of haptic sensations is suboptimal given their reliability, 3) humans use environmentally accurate size and distance priors, 4) distance judgments are produced by perceptual “posterior sampling”. In addition, we compared our model's estimated sensory and motor noise parameters with previously reported measurements in the perceptual literature and found good correspondence between them. Taken together, these results represent a major step forward in establishing the computational underpinnings of human distance perception and the role of size information.National Institutes of Health (U.S.) (NIH grant R01EY015261)University of Minnesota (UMN Graduate School Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship)University of Minnesota (UMN Doctoral Dissertation Fellowship)National Institutes of Health (U.S.) (NIH NRSA grant F32EY019228-02)Ruth L. Kirschstein National Research Service Awar