The ROCK inhibitor Fasudil prevents chronic restraint stress-induced depressive-like behaviors and dendritic spine loss in rat hippocampus

Indexación: Web of Science; Scopus.Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudiltreated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity.https://academic.oup.com/ijnp/article/20/4/336/263217

Razas autóctonas de las islas canarias: pasado, presente y futuro

We describe the means developed by official and private institutions for the conservation of Canary Breeds. We evaluate the response to concrete actions comparing the evolution of their census with presented at the Warwick Conference (1989).Se describen la evolución de las Razas autóctonas canarias y las medidas que se han de tomar de cara al futuro, tanto por organismos oficiales como por entidades particulares, para evitar el peligro de desaparición de dichas razas

Conservation program for the canarian creole cattle

The Cattle census of the Canary Islands is about 20500 animals, of this the Canary Creole Cattle Breed is only the 15.8 p.100. The other part of the census is formed by another selected breeds for milk production. Until the beginning of this decade this authochtonous breed became into danger of extinction because the competence of these imported breeds. In many cases the local population were absorbed and the total number decreased. At present, with the participation of an specific farmer association (Asociación Canaria de Arrastre) and the Official Institutions, the census are stabilised and is possible to see the future survival of the breed. In this paper we present the results of the main studies that had been made for the official acknowledgement of the Breeders Association, the standard of the breed and the situation of the Conservation program.El censo de ganado vacuno en Canarias es de unas 20500 cabezas, el 15,8 p.100 de raza Canaria y el resto, en su mayoría, es ganado selecto de aptitud lechera. Hasta principios de los años noventa esta raza se vio en grave peligro de extinción por la presión que sobre ella ejercieron otras razas más seleccionadas. A partir de entonces, gracias al esfuerzo de la Asociación Canaria de Arrastre y el apoyo de las distintas administraciones de la Comunidad Autónoma Canaria, los censos se han estabilizado e inician su recuperación. En esta comunicación se recopilan los resultados de los principales trabajos llevados a cabo para el reconocimiento de la Asociación de Criadores de esta raza, su estándar racial, así como el programa para su conservación

AXA: a computer program for the management of the Canary Goat Group milking control programs

A computer program, developed in Clipper, for the management of the genealogical and productive information from the Canary Goat Group, is described. The two first sections of this program are planned for the males and females genealogical data arrangement. Third section is devised for the productive data storage. Fourth section is constructed for the emission of reports and finally, fifth section is a miscellaneous of utilities, where the connection with other programs must be highlighted. Also an exit control is enclosed. The basic purposes of this program aim the emission of official production reports for the Administration and farmers, and the information processing for its analysis in programs of genetic selection.Se describe un programa de ordenador, desarrollado en Clipper, para la gestión de la información genealógica y productiva de la Agrupación Caprina Canaria. Sus dos primeras secciones se ocupan de la organización de la información genealógica de machos y de hembras; la tercera de la información productiva; la cuarta de la elaboración de informes y la quinta es una miscelánea de utilidades y un control de salida, con conexión con otros programas. Las misiones básicas del programa se centran en la emisión de informes productivos oficiales, destinados a la administración y a los ganaderos, y la preparación de la información para su análisis en programas de selección genética

Improvement of a System for Catchment, Pretreatment and Treatment of Runoff Water Using PIV Tests and Numerical Simulation

This paper studies how to improve the efficiency of a new system for catchment, pretreatment, and treatment of runoff water (SCPT). This system is integrated into an urban sustainable gravity settler that can decrease diffusive pollution. This study provides important advantages for the ecosystem by improving new sustainable drainage to clean runoff water. In this paper, an investigation methodology known as hybrid engineering (HE) was used. HE combines experimental tests and numerical simulations, both of them conducted on a 1:4-scale prototype. In this study, numerical simulations by the finite-volume method (FVM) and experimental tests by particle image velocimetry (PIV) were compared. A strong correlation between the numerical and experimental analysis was found. Next, the efficiency of the SCPTwas optimized by design of experiments (DOE). Analysis of experimental and numerical results and their comparison are presented in this paper.The authors wish to express their gratitude to the Spanish Ministry of Economy and Competitiveness for the research project BIA2009-08272 funding

Novel intravesical bacterial immunotherapy induces rejection of BCG-unresponsive established bladder tumors

Background Intravesical BCG is the gold-standard therapy for non-muscle invasive bladder cancer (NMIBC); however, it still fails in a significant proportion of patients, so improved treatment options are urgently needed. Methods Here, we compared BCG antitumoral efficacy with another live attenuated mycobacteria, MTBVAC, in an orthotopic mouse model of bladder cancer (BC). We aimed to identify both bacterial and host immunological factors to understand the antitumoral mechanisms behind effective bacterial immunotherapy for BC. Results We found that the expression of the BCG-absent proteins ESAT6/CFP10 by MTBVAC was determinant in mediating bladder colonization by the bacteria, which correlated with augmented antitumoral efficacy. We further analyzed the mechanism of action of bacterial immunotherapy and found that it critically relied on the adaptive cytotoxic response. MTBVAC enhanced both tumor antigen-specific CD4 + and CD8 + T-cell responses, in a process dependent on stimulation of type 1 conventional dendritic cells. Importantly, improved intravesical bacterial immunotherapy using MBTVAC induced eradication of fully established bladder tumors, both as a monotherapy and specially in combination with the immune checkpoint inhibitor antiprogrammed cell death ligand 1 (anti PD-L1). Conclusion These results contribute to the understanding of the mechanisms behind successful bacterial immunotherapy against BC and characterize a novel therapeutic approach for BCG-unresponsive NMIBC cases. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Variations on the Pear Tree Experiment : different variables, new results?

Inspired by the Pear Stories Project, the Pear Tree Project has investigated how different cultures and languages describe the same film in order to apply its findings to audio description (AD). Participants from different countries were asked to "write down what they saw" in a controlled setting. This article proposes an alternative experiment, also based on the original Pear Stories Project, which aims to shed light on two issues: how different describer profiles (translation students with AD training/without AD training) and different instructions concerning the target audience profiles (blind/non-blind) could alter the final production. The results are analysed in this paper, taking into account the elements covered in the original Pear Stories Project as well as some additional elements proposed by the authors

The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi

Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1−/− mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1−/− mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-γ production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-γ in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection

Prostaglandin E2 and T cells: friends or foes?

Our understanding of the key players involved in the differential regulation of T-cell responses during inflammation, infection and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. With respect to this, the inhibitory role of the lipid mediator prostaglandin E2 (PGE2) in T-cell immunity has been documented since the 1970s. Studies that ensued investigating the underlying mechanisms substantiated the suppressive function of micromolar concentrations of PGE2 in T-cell activation, proliferation, differentiation and migration. However, the past decade has seen a revolution in this perspective, since nanomolar concentrations of PGE2 have been shown to potentiate Th1 and Th17 responses and aid in T-cell proliferation. The understanding of concentration-specific effects of PGE2 in other cell types, the development of mice deficient in each subtype of the PGE2 receptors (EP receptors) and the delineation of signalling pathways mediated by the EP receptors have enhanced our understanding of PGE2 as an immune-stimulator. PGE2 regulates a multitude of functions in T-cell activation and differentiation and these effects vary depending on the micro-environment of the cell, maturation and activation state of the cell, type of EP receptor involved, local concentration of PGE2 and whether it is a homeostatic or inflammatory scenario. In this review, we compartmentalize the various aspects of this complex relationship of PGE2 with T lymphocytes. Given the importance of this molecule in T-cell activation, we also address the possibility of using EP receptor antagonism as a potential therapeutic approach for some immune disorders