Bioinformatics and mathematical modelling in the study of receptor-receptor interactions and receptor oligomerization: focus on adenosine receptors.

none8sìThe concept of intra-membrane receptor-receptor interactions (RRIs) between different types of G protein-coupled receptors (GPCRs) and evidence for their existence was introduced by Agnati and Fuxe in 1980/81 through the biochemical analysis of the effects of neuropeptides on the binding characteristics of monoamine receptors in membrane preparations from discrete brain regions and functional studies of the interactions between neuropeptides and monoamines in the control of specific functions such as motor control and arterial blood pressure control in animal models. Whether GPCRs can form high-order structures is still a topic of an intense debate. Increasing evidence, however, suggests that the hypothesis of the existence of high-order receptor oligomers is correct. A fundamental consequence of the view describing GPCRs as interacting structures, with the likely formation at the plasma membrane of receptor aggregates of multiple receptors (Receptor Mosaics) is that it is no longer possible to describe signal transduction simply as the result of the binding of the chemical signal to its receptor, but rather as the result of a filtering/integration of chemical signals by the Receptor Mosaics (RMs) and membrane-associated proteins. Thus, in parallel with experimental research, significant efforts were spent in bioinformatics and mathematical modelling. We review here the main approaches that have been used to assess the interaction interfaces allowing the assembly of GPCRs and to shed some light on the integrative functions emerging from the complex behaviour of these RMs. Particular attention was paid to the RMs generated by adenosine A(2A), dopamine D-2, cannabinoid CB1, and metabotropic glutamate mGlu(5) receptors (A(2A). D-2, CB1, and mGlu(5), respectively), and a possible approach to model the interplay between the D-2-A(2A)-CB1 and D-2-A(2A)-mGlu(5) trimers is proposed. This article is part of a Special Issue entitled: "Adenosine Receptors". (C) 2010 Elsevier B.V. All rights reserved.openD. GUIDOLIN; F. CIRUELA; S. GENEDANI; M. GUESCINI; C. TORTORELLA; G. ALBERTIN; K. FUXE; L.F. AGNATID., Guidolin; F., Ciruela; S., Genedani; Guescini, Michele; C., Tortorella; G., Albertin; K., Fuxe; L. F., Agnat

Estimativas de parâmetros genéticos para características reprodutivas e de crescimento em bovinos da raça Canchim.

Estudou-se neste trabalho dados referentes às características de idade ao segundo parto (ISP), perímetro escrotal aos 420 dias de idade (PE420) e peso aos 420 dias de idade de machos e fêmeas (P420) de animais da raça Canchim, para as quais foram obtidas estimativas de herdabilidade e correlações genéticas. No modelo animal, foram incluídos os efeitos fixos de grupo de contemporâneos e os efeitos aleatórios aditivos diretos e residuais. Utilizou-se o método da máxima verossimilhança restrita em análise bi-característica. As médias de ISP, PE420 e P420 foram iguais a 57,07±8,69 meses, 24,63±3,84 cm e 260,37±46,5l kg, respectivamente. As estimativas de herdabilidade foram 0,07±0,01, 0,2l±0,05 e 0,24±0,03, respectivamente para ISP, PE420 e P420. As correlações genéticas foram iguais a -0,47 (ISPXPE420) e 0,10 (ISPxP420). A seleção direta para perímetro escrotal aos 420 dias de idade poderá resultar em progresso genético favoráveis na assiduidade reprodutiva de fêmeas da raça Canchim, considerando que o PE420 apresentou correlação genética aditiva com idade ao segundo parto

Estimativas de componentes de variância e herdabilidade para características reprodutivas e de crescimento em bovinos da raça Canchim.

Estudou-se neste trabalho dados referentes às características de idade ao primeiro parto (lPP), idade ao segundo parto (ISP), perímetro escrotal aos 420 dias de idade (PE420) e peso aos 420 dias de idade de machos e fêmeas (P420) de animais da raça Canchim, para as quais foram obtidas estimativas de herdabilidade. No modelo animal, foram incluídos os efeitos fixos de grupo de contemporâneos e os efeitos aleatórios aditivos diretos e residuais. Empregou-se o método da máxima verossimilhança restrita em análise uni-característica. As médias observadas de IPP, ISP, PE420 e P420 foram iguais a 39,47±7,20 meses, 57,08±8,79 meses, 24,63±3,84 cm e 260,37±46,5l kg, respectivamente. As herdabilidades foram iguais a 0,03±0,Ol, 0,07±0,Ol, 0,22±0,05 e 0,24±0,03 para IPP, ISP, PE420 e P420, respectivamente. Dentre as características reprodutivas e de crescimento estudadas o perímetro escrotal e o peso aos 420 dias de idade apresentaram estimativas de herdabilidade de moderada magnitude, indicando que a seleção para estas características poderá contribuir para o melhoramento genético da raça Canchim

Different spatial distribution of inflammatory cells in the tumor microenvironment of ABC and GBC subgroups of diffuse large B cell lymphoma

Diffuse Large B-Cell Lymphoma (DLBCL) presents a high clinical and biological heterogeneity, and the tumor microenvironment chracteristics are important in its progression. The aim of this study was to evaluate tumor T, B cells, macrophages and mast cells distribution in GBC and ABC DLBCL subgroups through a set of morphometric parameters allowing to provide a quantitative evaluation of the morphological features of the spatial patterns generated by these inflammatory cells. Histological ABC and GCB samples were immunostained for CD4, CD8, CD68, CD 163, and tryptase in order to determine both percentage and position of positive cells in the tissue characterizing their spatial distribution. The results evidenced that cell patterns generated by CD4-, CD8-, CD68-, CD163- and tryptase-positive cell profiles exhibited a significantly higher uniformity index in ABC than in GCB subgroup. The positive-cell distributions appeared clustered in tissues from GCB, while in tissues from ABC such a feature was lower or absent. The combinations of spatial statistics-derived parameters can lead to better predictions of tumor cell infiltration than any classical morphometric method providing a more accurate description of the functional status of the tumor, useful for patient prognosis

Heterodimer of A2A and Oxytocin Receptors Regulating Glutamate Release in Adult Striatal Astrocytes

Background: Roles of astrocytes in the modulatory effects of oxytocin (OT) in central nervous system are increasingly considered. Nevertheless, OT effects on gliotransmitter release have been neglected. Methods: In purified astrocyte processes from adult rat striatum, we assessed OT receptor (OTR) and adenosine A2A receptor expression by confocal analysis. The effects of receptors activation on glutamate release from the processes were evaluated; A2A-OTR heteromerization was assessed by co-immunoprecipitation and PLA. Structure of the possible heterodimer of A2A and OT receptors was estimated by a bioinformatic approach. Results: Both A2A and OT receptors were expressed on the same astrocyte processes. Evidence for A2A-OTR receptor-receptor interaction was obtained by measuring the release of glutamate: OT inhibited the evoked glutamate release, while activation of A2A receptors, per se ineffective, abolished the OT effect. Biochemical and bio-physical evidence for A2A-OTR heterodimers on striatal astrocytes was also obtained. The residues in the transmembrane domains 4 and 5 of both receptors are predicted to be mainly involved in the heteromerization. Conclusions: When considering effects of OT in striatum, modulation of glutamate release from the astrocyte processes and of glutamatergic synapse functioning, and the interaction with A2A receptors on the astrocyte processes should be taken into consideration

Grupo genético pantaneiro.

bitstream/item/219042/1/CNPC-2020-Art-51.pd

Option prices under Bayesian learning: implied volatility dynamics and predictive densities

This paper shows that many of the empirical biases of the Black and Scholes option pricing model can be explained by Bayesian learning effects. In the context of an equilibrium model where dividend news evolve on a binomial lattice with unknown but recursively updated probabilities we derive closed-form pricing formulas for European options. Learning is found to generate asymmetric skews in the implied volatility surface and systematic patterns in the term structure of option prices. Data on S&P 500 index option prices is used to back out the parameters of the underlying learning process and to predict the evolution in the cross-section of option prices. The proposed model leads to lower out-of-sample forecast errors and smaller hedging errors than a variety of alternative option pricing models, including Black-Scholes and a GARCH model