The role of type 4 phosphodiesterases in generating microdomains of cAMP: Large scale stochastic simulations

Cyclic AMP (cAMP) and its main effector Protein Kinase A (PKA) are critical for several aspects of neuronal function including synaptic plasticity. Specificity of synaptic plasticity requires that cAMP activates PKA in a highly localized manner despite the speed with which cAMP diffuses. Two mechanisms have been proposed to produce localized elevations in cAMP, known as microdomains: impeded diffusion, and high phosphodiesterase (PDE) activity. This paper investigates the mechanism of localized cAMP signaling using a computational model of the biochemical network in the HEK293 cell, which is a subset of pathways involved in PKA-dependent synaptic plasticity. This biochemical network includes cAMP production, PKA activation, and cAMP degradation by PDE activity. The model is implemented in NeuroRD: novel, computationally efficient, stochastic reaction-diffusion software, and is constrained by intracellular cAMP dynamics that were determined experimentally by real-time imaging using an Epac-based FRET sensor (H30). The model reproduces the high concentration cAMP microdomain in the submembrane region, distinct from the lower concentration of cAMP in the cytosol. Simulations further demonstrate that generation of the cAMP microdomain requires a pool of PDE4D anchored in the cytosol and also requires PKA-mediated phosphorylation of PDE4D which increases its activity. The microdomain does not require impeded diffusion of cAMP, confirming that barriers are not required for microdomains. The simulations reported here further demonstrate the utility of the new stochastic reaction-diffusion algorithm for exploring signaling pathways in spatially complex structures such as neurons

Efeito inibitório na germinação, induzido pelo extrato de couve (Brassica oleracea L. var. acephala DC.)

With the purpose of studying the possible allelopathy characteristics of the common kale (Brassica oleracea L. var. acephala DC.), an experiment was conducted in laboratory conditions, at E.S.A. "Luiz de Queiroz", in Piracicaba, São Paulo State. Tomato seeds (Lycopersicon esculentum Mill. cv. Santa Cruz) were put to germinate in solutions with different concentrations (0; 25; 50 and 100%) of the extract obtained from the air part (leaves) of the common kale. Effects pronouncedly inhibitories of the germination of the tomato seeds were found in the largest concentrations of the common kale extract. The seedlings which germinated in the parcels treated with the extract presented reduced growth morpfo-physiologically abnormal and with larger time for the beginning of the germination. All these characteristics were more pronounced in the parcels with larger concentrations of the extract.Com a finalidade de se estudar as possíveis propriedades alelopáticas da couve (Brassica oleracea L. var. acephala DC), foi conduzido um bioensaio, em condições de laboratório, na E.S.A."Luiz de Queiroz", em Piracicaba, SP. Foram utilizadas sementes de tomate (Lycopersicon esculentum Mill. cv.Santa Cruz) colocadas para germinar em soluções com diferentes concentrações (0; 25; 50 e 100%) do extrato obtido da parte aérea (folhas) da couve. Constataram-se efeitos pronunciadamente inibitórios de germinação das sementes de tomate nas maiores concentrações do extrato de couve. As plântulas que germinaram, nas parcelas tratadas com o extrato, mostraram-se com o crescimento reduzido, morfo-fisiologicamente anormais, e com maior tempo para o início da germinação. Todas essas características foram mais pronunciadas nas parcelas com maiores concentrações do extrato

Switch rates vary due to expected payoff but not due to individual risk tendency.

When switching between different tasks, the initiation of task switches may depend on task characteristics (difficulty, salient cues, etc.) or reasons within the person performing the task (decisions, behavioral variability, etc.). The reasons for variance in switching strategies, especially in paradigms where participants are free to choose the order of tasks and the amount of switching between tasks, are not well researched. In this study, we follow up the recent discussion that variance in switching strategies might be partly explained by the characteristics of the person fulfilling the task. We examined whether risk tendency and impulsiveness differentiate individuals in their response (i.e., switch rates and time spent on tasks) to different task characteristics on a tracking-while-typing paradigm. In detail, we manipulated two aspects of loss prospect (i.e., "payoff" as the amount of points that could be lost when tracking was unattended for too long, and "cursor speed" determining the likelihood of such a loss occurring). To account for between-subject variance and within-subject variability in the data, we employed linear mixed effect analyses following the model selection procedure (Bates, Kliegl, et al., 2015). Besides, we tested whether risk tendency can be transformed into a decision parameter which could predict switching strategies when being computationally modelled. We transferred decision parameters from the Decision Field Theory to model "switching thresholds" for each individual. Results show that neither risk tendency nor impulsiveness explain between-subject variance in the paradigm, nonetheless linear mixed-effects models confirmed that within-subject variability plays a significant role for interpreting dual-task data. Our computational model yielded a good model fit, suggesting that the use of a decision threshold parameter for switching may serve as an alternative means to classify different strategies in task switching. [Abstract copyright: Copyright © 2022. Published by Elsevier B.V.

Binding affinities and activation of Asp712Ala and Cys100Ser mutated kinin B1 receptor forms suggest a bimodal scheme for the molecule of bound-DABK

AbstractMutant forms of kinin B1 receptor (B1R) and analogs of the full agonist des-Arg9-bradykinin (DABK) were investigated aiming to verify the importance of selected receptor residues and of each agonist-peptide residue in the specific binding and activation. Linked by a specific disulfide bond (Cys100–Cys650), the N-terminal (Nt) and the EC3 loop C-terminal (Ct) segments of angiotensin II (AngII) receptor 1 (AT1R) have been identified to form an extracellular site for binding the agonist Nt segment (Asp1 and Arg2 residues). Asp712 residue at the receptor EC3 loop binds the peptide Arg2 residue. By homology, a similar site might be considered for DABK binding to B1R since this receptor contains the same structural elements for composing the site in AT1R, namely the disulfide bond and the EC3 loop Asp712 residue. DABK, Alan-DABK analogs (n=Ala1-, Ala2-, Ala3-, Ala4-, Ala5-, Ala6-, Ala7-, Ala8-DABK), and other analogs were selected to binding wild-type, Asp712Ala and Cys100Ser mutated B1R receptors. The results obtained suggested that the same bimodal scheme adopted for AngII-AT1R system may be applied to DABK binding to B1R. The most crucial similarity in the two cases is that the Nt segments of peptides equally bind to the homologous Asp712 residue of both AT1R and B1R extracellular sites. Confirming this preliminary supposition, mutation of residues located at the B1R extracellular site as EC3 loop Asp712 and Cys100 caused the same modifications in biological assays observed in AT1R submitted to homologous mutations, such as significant weakening of agonist binding and reduction of post-receptor-activation processes. These findings provided enough support for defining a site that determines the specific binding of DABK to B1R receptors

Cognitive performance of young and elderly subjects on the free word recall memory test: effect of presentation order on recall order

The influence of aging on memory has been extensively studied, but the importance of short-term memory and recall sequence has not. The objective of the current study was to examine the recall order of words presented on lists and to determine if age affects recall sequence. Physically and psychologically healthy male subjects were divided into two groups according to age, i.e., 23 young subjects (20 to 30 years) and 50 elderly subjects (60 to 70 years) submitted to the Wechsler Adult Intelligence Scale-Revised and the free word recall test. The order of word presentation significantly affected the 3rd and 4th words recalled (P < 0.01; F = 14.6). In addition, there was interaction between the presentation order and the type of list presented (P < 0.05; F = 9.7). Also, both groups recalled the last words presented from each list (words 13-15) significantly more times 3rd and 4th than words presented in all remaining positions (P < 0.01). The order of word presentation also significantly affected the 5th and 6th words recalled (P = 0.05; F = 7.5) and there was a significant interaction between the order of presentation and the type of list presented (P < 0.01; F = 20.8). The more developed the cognitive functions, resulting mainly from formal education, the greater the cognitive reserve, helping to minimize the effects of aging on the long-term memory (episodic declarative).Associação Fundo de Incentivo à Psicofarmacologia Instituto do SonoUniversidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUNIFESP, Depto. de PsicobiologiaSciEL

Interface state contribution to the photovoltaic effect in organic phototransistors:Photocapacitance measurements and optical sensing

Made available in DSpace on 2018-12-11T16:50:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Instituto Nacional de Ciência e Tecnologia em Eletrônica OrgânicaWe report the results of an investigation into the contribution that trapping in interface states makes to the photovoltaic effect observed in organic phototransistors. To isolate this effect from other processes that occur in the transistor structure when under illumination, we focus attention on the photo-response of metal-insulator-semiconductor (MIS) capacitors - the core structure of transistors. The capacitors comprised poly(3-hexylthiophene), (P3HT), as the active semiconductor in combination with one of three insulators, namely, poly(amide-imide), (PAI), SU-8 photoresist and polysilsesquioxane (PSQ). Following initial characterization in the dark, the capacitor response was measured both during and after irradiation with light in the wavelength range 400–700 nm. Three different approaches were employed to study the photo-response, each providing a different insight into the processes occurring. Capacitance-voltage sweeps before, during and after illumination provided direct evidence supporting the view that the photovoltaic effect occurred as a result of electron trapping in interface states of density up to ∼2 × 1012 cm−2 in the P3HT/PAI combination but lower for SU-8 and PSQ. The dynamic photo-response, in which device capacitance was held constant by changing the applied bias, showed a fast component related to optically induced photoconduction in the semiconductor and a slower component reflecting the dynamics of interface electron trapping. Finally, photo-induced capacitance changes occurring with constant applied voltage were used to demonstrate a simple 3 × 3 imaging array.School of Electronic Engineering Bangor University, Dean StreetBrazilian Nanotechnology National Laboratory (LNNano) Brazilian Centre of Research in Energy and Materials (CNPEM)Department of Physics São Paulo State University (UNESP), PO Box 266Institute of Physics of São Carlos University of São Paulo (USP), PO Box 369Catarinense Federal Institute of Education Science and Technology, PO Box 21Department of Physics São Paulo State University (UNESP), PO Box 26

Effects of air temperature on physiology and productive performance of pigs during growing and finishing phases

Thirty-six castrated male pigs were used to determine the influence of thermal environment and reduction of consumption on performance and carcass composition. Animals were housed in two climate chambers. In one, animals were in thermal comfort (TN) (22 °C), and in the other, pigs were under heat stress (HS) (34 °C). Animals were distributed in a randomized block design, making three treatments (TN, HS and animals in thermal comfort with food consumption paired with that observed in HS (PFTN)), with six replicates and two animals per experimental unit. Data were obtained on performance and carcass composition. The weight gains of HS and PFTN animals were reduced by 40.5% and 34.7%, respectively, reflecting a reduction of 13.2% in the final weight of PFTN animals. Triiodothyronine concentration was not affected by heat, but there was an increase in lymphocyte numbers in PFTN animals. The HS and PFTN animals showed lower hot carcass weight. However, there were no effects on hot carcass yield and relative weights of heart, lung and spleen. Heat stress compromised performance. The negative effects of high temperature on pigs include reduction in feed intake and changes in physiology.Keywords: Environment, heat stress, pair feed, pig growth, pig productio

Sexing freshwater turtles: penile eversion in Phrynops tuberosus (Testudines: Chelidae)

Here, we described a noninvasive method for sexing freshwater turtles by stimulating penile eversion. We immobilized the neck and limbs of animals using fingers and, after some seconds, turtles everted their penis. This method was tested in 33 male Phrynops tuberosus, and 28 everted the penis. The efficiency of the method was not dependent of animal size, which reinforces its applicability. Our method allows sexing turtles in the field, avoiding killing the animal or causing major injuries in order to assess the sex