Nitric oxide decreases intestinal haemorrhagic lesions in rat anaphylaxis independently of mast cell activation

The purpose of this study is to assess the role of nitric oxide (NO) in the intestinal lesions of passive anaphylaxis, since this experimental model resembles necrotizing enterocolitis. Sprague-Dawley rats were sensitized with IgE anti-dinitrophenol monoclonal antibody. Extravasation of protein-rich plasma and haemorrhagia were measured in the small intestine. Plasma histamine was measured to assess mast cell activation. The effect of exogenous NO on the lesions was assessed by using two structurally unrelated NO-donors: sodium nitroprusside and S-nitroso-Nacetyl-penicillamine (SNAP). An increased basal production of NO was observed in cells taken after anaphylaxis, associated with a reduced response to platelet-activating factor, interleukin 1beta, and IgE/DNP-bovine serum albumin complexes. The response to bacterial lipopolysaccharide and dibutyryl cyclic adenosine monophosphate (AMP) was enhanced 24 h after challenge, but at earlier times was not significantly different from that observed in controls. Treatment with either sodium nitroprusside or SNAP produced a significant reduction of the haemorrhagic lesions, which are a hallmark of rat anaphylaxis. The extravasation of protein-rich plasma was not influenced by NO-donors. The increase of plasma histamine elicited by the anaphylactic challenge was not influenced by SNAP treatment. NO-donors protect intestinal haemorrhagic lesions of rat anaphylaxis by a mechanism apparently independent of mast cell histamine release

Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP

The transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin-cytoskeleton-dependent and Hippo-kinase-independent mechanisms. RHO activity is necessary, but not sufficient, for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based small interfering RNA (siRNA) screens provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective extracellular matrix (ECM) remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications. Moreno-Vicente et al. report that CAV1, a key component of PM mechanosensing caveolae, mediates adaptation to ECM rigidity by modulating YAP activity through the control of actin dynamics and phosphorylation-dependent interaction of YAP with the 14-3-3-domain protein YWHAH. Cav1-dependent YAP regulation drives two pathophysiological processes: ECM remodeling and pancreatic ADM. © 2018 The Author

Anti-inflammatory, pro-proliferative and antimicrobial potential of the compounds isolated from Daemonorops draco (Willd.) Blume

Ethno-pharmacological relevance: Daemonorops draco (D. draco) commonly known as “Dragon's blood” is one of the most used plants by Momok, Anak Dalam and Talang Mamak tribes from Indonesia as a remedy for wound healing. Aim of the study: This study aimed to identify the extract, fractions and compounds responsible for the anti-inflammatory and pro-proliferative activities of the D. draco resin. Additionally, the antimicrobial activity against two bacteria and one yeast species was analysed. Materials and methods: Bio-guided isolation of compounds with anti-inflammatory, pro-proliferative and antimicrobial activities from the D. draco resin was carried out by measuring: the inhibition of NF-κB and activation of Nrf2 in THP-1, HaCaT, NIH-3T3 cells; cell proliferation in NIH-3T3 and HaCaT cells; and the antimicrobial effect on E. coli, S. aureus and C. albicans. Results: Guided isolation by bioassay gave rise to the isolation and characterisation by nuclear magnetic resonance and mass spectrometry of three compounds: 1 (Bexarotene), 2 (Taspine) and 3 (2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone). All compounds showed NF-κB inhibitory activity with IC50 values of 0.10–0.13, 0.22–0.24 and 3.75–4.78 μM, respectively, while the positive control, Celastrol, had an IC50 of 7.96 μM. Likewise, all compounds showed an activating effect of Nrf2 with EC50 values of 5.34–5.43, 163.20–169.20 and 300.82–315.56 nM, respectively, while the positive control, CDDO-Me, had an EC50 of 0.11 nM. In addition, concerning the pro-proliferative activity, compound 1 (IC50 = 8.62–8.71 nM) showed a capacity of 100%, compound 2 (IC50 = 166–171 nM) showed a capacity of 75%, and compound 3 (IC50 = 469–486 nM) showed a capacity of 65%, while FSB 10% (positive control) had a pro-proliferative activity of 100% in the NIH3T3 cell lines (fibroblasts) and HaCaT (keratinocytes). Finally, all the compounds showed antimicrobial activity with MIC values of 0.12–0.16, 0.31–0.39 and 3.96–3.99 μM, respectively, in S. aureus, E. coli and C. albicans strains, while the positive control, Ofloxacin, had a MIC of 27.65 μM. Conclusion: This study managed to isolate, for the first time, three compounds (Bexarotene, Taspine and 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone) from the resin of D. draco, with anti-inflammatory, and pro-proliferative as well as antimicrobial activitie

Participation and Influence of the libero in recepcion and defence, in volleyball U-19

El objetivo fue conocer la participación e influencia líbero en fase de ataque y defensa, en etapas de formación. La muestra fueron 6948 acciones de juego, realizadas por los jugadores de los 21 equipos del Campeonato de España Juvenil masculino. Las variables fueron: función del receptor/defensor, zona de recepción/defensa en profundidad y lateralidad, eficacia de recepción/defensa, zona donde se realiza colocación en recepción/defensa, zona hacia donde se realiza la colocación en recepción/defensa, tiempo de ataque/contraataque y eficacia de ataque/contraataque. En recepción, existió asociación significativa entre función del receptor y zona de recepción en profundidad-lateralidad, y zona donde se realiza la colocación. En defensa, existió asociación significativa entre función del defensor y zona de defensa en profundidad-lateralidad, eficacia de defensa, zona donde se realiza la colocación, zona hacia donde se realiza la colocación y tiempo de contraataque. La influencia del líbero, en estas etapas, se manifiesta más en defensa que en recepciónThe aim was to know the participation and influence of the libero in side-out phase and counter-attack, in young athletes. The sample was 6948 game actions, carried out by the players of the 21 teams that participate in the Under-19 Spanish Championship. The variables were: player that intervened in reception/dig, depth and laterality reception/dig zone, reception/dig efficacy, setting zone in reception/dig, set´s area in reception/dig, tempo of attack/counterattack and attack/counterattack efficacy. In reception, showed significant association between player that intervened in reception, depth-laterality reception zone and the setting zone. In defense, showed significant association between the player that intervened in dig and the depth-laterality dig zone, dig efficacy, setting zone, set´s area and tempo of counterattack. The influence of the participation of the libero, in young athletes, appeared more often in defense than in the receptio

Systematic Review On Bullying Situations And Intervention Programs In Early Childhood Education

Background: Bullying is a traumatic event that is observed from the early stages of the educational system. Ensuring an adequate socioemotional development through the implementation of activities or intervention programs based on the work of Emotional Intelligence in the Early Childhood Education stage where empathy, assertiveness, emotional intelligence, social skills, values... are worked on, with the aim of preventing/eradicating situations of violence in educational environments, is essential to put an end to this problem. Goal: To find out whether there is evidence of bullying at the early childhood education (ECE) stage and to investigate whether bullying prevention work is carried out at this educational stage. Method: A systematic review, following the PRISMA 2020 Declaration, was carried out in the Web of Science (WoS) and Scopus (SJR) databases from January to March 2023. The search terms used were: "Children", "Health Education" and "Bullying". Only articles in Spanish and English published from 2013 to 2023 were selected, in which bullying in the ECE stage is analyzed. The last filter applied was related with research areas of Psychology and Education. The sample is composed of a total of 4 articles, most of them published abroad. Findings: According to the studies reviewed, there is little concern about bullying at the ECE stage, and there is little concern about the implementation of prevention programs for this proble

Coevolution of teaching activity promotes cooperation

Evolutionary games are studied where the teaching activity of players can evolve in time. Initially all players following either the cooperative or defecting strategy are distributed on a square lattice. The rate of strategy adoption is determined by the payoff difference and a teaching activity characterizing the donor's capability to enforce its strategy on the opponent. Each successful strategy adoption process is accompanied with an increase in the donor's teaching activity. By applying an optimum value of the increment this simple mechanism spontaneously creates relevant inhomogeneities in the teaching activities that support the maintenance of cooperation for both the prisoner's dilemma and the snowdrift game.Comment: 10 pages, 4 figures; accepted for publication in New Journal of Physic

Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast

Background: Bulk segregant analysis (BSA) coupled to high throughput sequencing is a powerful method to map genomic regions related with phenotypes of interest. It relies on crossing two parents, one inferior and one superior for a trait of interest. Segregants displaying the trait of the superior parent are pooled, the DNA extracted and sequenced. Genomic regions linked to the trait of interest are identified by searching the pool for overrepresented alleles that normally originate from the superior parent. BSA data analysis is non-trivial due to sequencing, alignment and screening errors. Results: To increase the power of the BSA technology and obtain a better distinction between spuriously and truly linked regions, we developed EXPLoRA (EXtraction of over-rePresented aLleles in BSA), an algorithm for BSA data analysis that explicitly models the dependency between neighboring marker sites by exploiting the properties of linkage disequilibrium through a Hidden Markov Model (HMM). Reanalyzing a BSA dataset for high ethanol tolerance in yeast allowed reliably identifying QTLs linked to this phenotype that could not be identified with statistical significance in the original study. Experimental validation of one of the least pronounced linked regions, by identifying its causative gene VPS70, confirmed the potential of our method. Conclusions: EXPLoRA has a performance at least as good as the state-of-the-art and it is robust even at low signal to noise ratio's i.e. when the true linkage signal is diluted by sampling, screening errors or when few segregants are available