Bradykinin -induced vasodilatation : Role of age, ACE1-inhibitory peptide, mas- and bradykinin receptors

Bradykinin exerts its vascular actions via two types of receptors, the non-constitutively expressed bradykinin receptor type 1 (BR1) and the constitutive type 2 receptor (BR2). Bradykinin-induced vasorelaxation is age-dependent, a phenomenon related to the varying amounts of BR1 and BR2 in the vasculature. Isoleucine-proline-proline (Ile-Pro-Pro), a bioactive tripeptide, lowers elevated blood pressure and improves impaired endothelium-dependent vasorelaxation in hypertensive rats. It inhibits angiotensin converting enzyme 1 (ACE1). Other mechanisms of action have also been postulated. The aims of the study were to clarify the underlying mechanisms of the age-dependency of bradykinin-induced vasodilatation such as the roles of the two bradykinin receptors, themas-receptor and synergism with Ile-Pro-Pro. The vascular response studies were conducted using mesenteric artery and aorta rings from normotensive 6 wk. (young) and 22 wk. (old) Wistar rats. Cumulative dosing of acetylcholine, bradykinin and angiotensin(1-7) (Ang(1-7))were tested in phenylephrine-induced vasoconstriction with or without 10 min pre-incubation with antagonists against BR1-, BR2- or mas-receptors,Ang(1-7) or ACE1-inhibitors captopril and Ile-Pro-Pro. The bradykinin-induced vasorelaxation in vitro was age-dependent and it was improved by pre incubation with Ile-Pro-Pro, especially in old rats with endothelial dysfunction. The mas-receptor antagonist, D-Pro7-Ang(1-7) abolished bradykinin-induced relaxation totally. Interestingly, BR1 and BR2 antagonists only slightly reduced bradykinin-induced vasorelaxation, as an evidence for the involvement of other mechanisms in addition to receptor activation. In conclusion, bradykinin-induced vasorelaxation was age -dependent and He-Pro-Pro improved it. Mas receptor antagonist abolished relaxation while bradykinin receptor antagonist only slightly reduced it, suggesting that bradykinin-induced vasorelaxation is regulated also by other mechanisms than the classical BR1/BR2 pathway. (C) 2016 Elsevier Inc: All rights reserved.Peer reviewe

Expression of 6 Biomarkers in Liver Grafts After Pediatric Liver Transplantation : Correlations with Histology, Biochemistry, and Outcome

Background: Subclinical graft inflammation and fibrosis after pediatric liver transplantation (LT) are common. Biomarkers are needed that precede and are associated with these changes and graft outcome. Material/Methods: We evaluated immunohistochemical expression of 6 biomarkers [alpha-smooth muscle actin (alpha-SMA), collagen I, decorin, vimentin, P-selectin glycoprotein ligand-1 (PSGL-1), and CD34] in biopsies taken intraoperatively at LT (baseline) (n=29) and at 11.3 years after LT (first follow-up) (n=51). Liver biochemistry and graft histology were assessed at the first follow-up and at final assessment (19.6 years after LT) (n=48). Second follow-up biopsies for histology were available from 24 patients. The immunostainings were correlated with liver histology, biochemistry, and outcome at these time-points. Results: Baseline levels of the biomarkers were unrelated to presence of fibrosis at follow-up. Increased a-SMA, collagen I levels, decorin, and vimentin were associated with simultaneous fibrosis at the first follow-up (p=0.001-0.027). Increased SMA, collagen I, decorin, vimentin, PSGL-1, and CD34 expression at first follow-up were associated with simultaneous portal inflammation (p=0.001-0.025). alpha-SMA, decorin, and vimentin expression were increased in patients without fibrosis at the first follow-up but who developed fibrosis in second follow-up (p=0.014 p=0.024 and p=0.024). Significant fibrosis (F2) and markedly increased alpha-SMA, collagen I, decorin, and vimentin levels at first follow-up were associated with suboptimal liver status at the final assessment (p=0.002-0.042). Conclusions: The expression of the biomarkers at LT was unrelated to later development of graft fibrosis. alpha-SMA, decorin, and vimentin were associated with later graft fibrosis and suboptimal liver status.Peer reviewe

Alkuopetuksen luokanopettajien kokemuksia toiminnallisten opetusmenetelmien hyödyntämisestä LeaDo-oppimiskeskuksen käytön yhteydessä

Tiivistelmä. Tämän tutkimuksen tarkoituksena oli selvittää alkuopetuksen luokanopettajien kokemuksia toiminnallisten opetusmenetelmien hyödyntämisestä LeaDo-oppimiskeskuksen käytön yhteydessä. Tutkimus perustuu kiinnostukseemme toiminnallista opetusta kohtaan, johon pääsimme tutustumaan uutta pedagogista innovaatiota tutkiessamme. Tutkimuksessa haluttiin selvittää LeaDo-oppimiskeskuksen käytön yhteydessä käytettyjä toiminnallisen opetuksen menetelmiä, sekä opettajien kokemia mahdollisuuksia, vahvuuksia, heikkouksia ja uhkia. LeaDo-oppimiskeskuksen tavoitteena on parantaa peruskoulun luokkien työrauhaa sekä helpottaa opettajan ja oppilaiden työskentelyä. Keräsimme aineistomme haastattelemalla LeaDo-oppimiskeskuksen perustajaa Lea Tornbergia sekä viittä alkuopetuksen opettajaa. Lea Tornbergin haastattelu toteutettiin teemahaastatteluna etäyhteyksiä hyödyntäen ja alkuopetuksen opettajien aineisto kerättiin Webropol-lomakkeen avulla. Kaikilla viidellä opettajalla oli käytössä LeaDo-oppimiskeskus Ilo. Tutkimuksessamme hyödynnettiin fenomenologista lähestymistapaa. Tutkimuksen tuloksia analysoitiin kahdella eri tutkimusmetodilla: sisällönanalyysillä ja SWOT-analyysillä. Tutkimustulokset olivat pääasiassa myönteisiä. LeaDo-oppimiskeskuksen yhteydessä käytettiin monipuolisesti erilaisia toiminnallisen opetuksen menetelmiä ja niiden koettiin toiminallistavan opetusta luonnollisella tavalla. Oppimiskeskuksessa koettiin olevan mahdollisuuksia ja vahvuuksia huomattavasti enemmän kuin heikkouksia ja uhkia. Teoreettinen viitekehys tukee tutkimuksesta saatuja tuloksia. Tutkimuksen luotettavuudesta ja eettisyydestä huolehdittiin koko tutkimusprosessin ajan. Aineisto kerättiin anonyymisti ja sitä säilytettiin asianmukaisella tavalla

Closed-loop optimization of transcranial magnetic stimulation with electroencephalography feedback

Background: Transcranial magnetic stimulation (TMS) is widely used in brain research and treatment of various brain dysfunctions. However, the optimal way to target stimulation and administer TMS therapies, for example, where and in which electric field direction the stimuli should be given, is yet to be determined. Objective: To develop an automated closed-loop system for adjusting TMS parameters (in this work, the stimulus orientation) online based on TMS-evoked brain activity measured with electroencephalography (EEG). Methods: We developed an automated closed-loop TMS-EEG set-up. In this set-up, the stimulus parameters are electronically adjusted with multi-locus TMS. As a proof of concept, we developed an algorithm that automatically optimizes the stimulation orientation based on single-trial EEG responses. We applied the algorithm to determine the electric field orientation that maximizes the amplitude of the TMS-EEG responses. The validation of the algorithm was performed with six healthy volunteers, repeating the search twenty times for each subject. Results: The validation demonstrated that the closed-loop control worked as desired despite the large variation in the single-trial EEG responses. We were often able to get close to the orientation that maximizes the EEG amplitude with only a few tens of pulses. Conclusion: Optimizing stimulation with EEG feedback in a closed-loop manner is feasible and enables effective coupling to brain activity. (C) 2022 The Author(s). Published by Elsevier Inc.Peer reviewe

Ice nucleation by viruses and their potential for cloud glaciation

In order to effectively predict the formation of ice in clouds we need to know which subsets of aerosol particles are effective at nucleating ice, how they are distributed and where they are from. A large proportion of ice-nucleating particles (INPs) in many locations are likely of biological origin, and some INPs are extremely small, being just tens of nanometres in size. The identity and sources of such INPs are not well characterized. Here, we show that several different types of virus particles can nucleate ice, with up to about 1 in 20 million virus particles able to nucleate ice at -20 degrees C. In terms of the impact on cloud glaciation, the ice-nucleating ability (the fraction which are ice nucleation active as a function of temperature) taken together with typical virus particle concentrations in the atmosphere leads to the conclusion that virus particles make a minor contribution to the atmospheric ice-nucleating particle population in the terrestrial-influenced atmosphere. However, they cannot be ruled out as being important in the remote marine atmosphere. It is striking that virus particles have an ice-nucleating activity, and further work should be done to explore other types of viruses for both their ice-nucleating potential and to understand the mechanism by which viruses nucleate ice.Peer reviewe

Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning

The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617–0.824) than in muscle (r = 0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.Peer reviewe

Structural and functional alterations in the brain gray matter among first-degree relatives of schizophrenia patients : A multimodal meta-analysis of fMRI and VBM studies

Objective: We conducted a multimodal coordinate-based meta-analysis (CBMA) to investigate structural and functional brain alterations in first-degree relatives of schizophrenia patients (FRs). Methods: We conducted a systematic literature search from electronic databases to find studies that examined differences between FRs and healthy controls using whole-brain functional magnetic resonance imaging (fMRI) or voxel-based morphometry (VBM). A CBMA of 30 fMRI (754 FRs; 959 controls) and 11 VBM (885 FRs; 775 controls) datasets were conducted using the anisotropic effect-size version of signed differential mapping. Further, we conducted separate meta-analyses about functional alterations in different cognitive tasks: social cognition, executive functioning, working memory, and inhibitory control. Results: FRs showed higher fMRI activation in the right frontal gyrus during cognitive tasks than healthy controls. In VBM studies, there were no differences in gray matter density between FRs and healthy controls. Furthermore, multi-modal meta-analysis obtained no differences between FRs and healthy controls. By utilizing the BrainMap database, we showed that the brain region which showed functional alterations in FRs (i) overlapped only slightly with the brain regions that were affected in the meta-analysis of schizophrenia patients and (ii) correlated positively with the brain regions that exhibited increased activity during cognitive tasks in healthy individuals. Conclusions: Based on this meta-analysis, FRs may exhibit only minor functional alterations in the brain during cognitive tasks, and the alterations are much more restricted and only slightly overlapping with the regions that are affected in schizophrenia patients. The familial risk did not relate to structural alterations in the gray matter. (C) 2019 Elsevier B.V. All rights reserved.Peer reviewe