Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension

Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs. 3.5 ± 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES−/− knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang II vs. 15 ± 4% in RANTES−/−), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8+ and double-negative CD3+CD4−CD8− T cells in perivascular space and reduced vascular oxidative stress while FoxP3+ T-regulatory cells were unaltered. IFN-γ ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = −0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.—Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P., Budzyn, K., Osmenda, G., Skiba, D., Sagan, A., Wu, J., Vinh, A., Marvar, P. J., Guzik, B., Podolec, J., Drummond, G., Lob, H. E., Harrison, D. G., Guzik, T. J. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension

The Council of Europe's Approach towards Ageism

In this chapter, I examine the degree of interest in ageism among Council of Europe members, and the degree of interest in its elimination through the Council of Europe forum. I also examine the interpretation of the concept of ageism by various Council of Europe institutions. Finally, I explore the Council’s willingness and ability to eliminate or at least mitigate ageism effect

Eating disorders: the current status of molecular genetic research

Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders characterized by disordered eating behavior where the patient’s attitude towards weight and shape, as well as their perception of body shape, are disturbed. Formal genetic studies on twins and families suggested a substantial genetic influence for AN and BN. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Hardly any of the positive findings achieved in these studies were unequivocally confirmed or substantiated in meta-analyses. This might be due to too small sample sizes and thus low power and/or the genes underlying eating disorders have not yet been analyzed. However, some studies that also used subphenotypes (e.g., restricting type of AN) led to more specific results; however, confirmation is as yet mostly lacking. Systematic genome-wide linkage scans based on families with at least two individuals with an eating disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4 (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region led to the (as yet unconfirmed) identification of certain variants associated with AN. Genome-wide association studies are under way and will presumably help to identify genes and pathways involved in these eating disorders. The elucidation of the molecular mechanisms underlying eating disorders might improve therapeutic approaches

TESS Cycle 1 observations of roAp stars with 2-min cadence data

We present the results of a systematic search for new rapidly oscillating Ap (roAp) stars using the 2-min cadence data collected by the Transiting Exoplanet Survey Satellite (TESS) during its Cycle 1 observations. We identify 12 new roAp stars. Amongst these stars we discover the roAp star with the longest pulsation period, another with the shortest rotation period, and six with multiperiodic variability. In addition to these new roAp stars, we present an analysis of 44 known roAp stars observed by TESS during Cycle 1, providing the first high-precision and homogeneous sample of a significant fraction of the known roAp stars. The TESS observations have shown that almost 60 per cent (33) of our sample of stars are multiperiodic, providing excellent cases to test models of roAp pulsations, and from which the most rewarding asteroseismic results can be gleaned. We report four cases of the occurrence of rotationally split frequency multiplets that imply different mode geometries for the same degree modes in the same star. This provides a conundrum in applying the oblique pulsator model to the roAp stars. Finally, we report the discovery of non-linear mode interactions in $\alpha$ Cir (TIC 402546736, HD 128898) around the harmonic of the principal mode -- this is only the second case of such a phenomenon...

TESS Cycle 2 observations of roAp stars with 2-min cadence data

We present the results of a systematic search of the Transiting Exoplanet Survey Satellite (TESS) 2-min cadence data for new rapidly oscillating Ap (roAp) stars observed during the Cycle 2 phase of its mission. We find seven new roAp stars previously unreported as such and present the analysis of a further 25 roAp stars that are already known. Three of the new stars show multiperiodic pulsations, while all new members are rotationally variable stars, leading to almost 70 per cent (22) of the roAp stars presented being α2 CVn-type variable stars. We show that targeted observations of known chemically peculiar stars are likely to overlook many new roAp stars, and demonstrate that multi-epoch observations are necessary to see pulsational behaviour changes. We find a lack of roAp stars close to the blue edge of the theoretical roAp instability strip, and reaffirm that mode instability is observed more frequently with precise, space-based observations. In addition to the Cycle 2 observations, we analyse TESS data for all known roAp stars. This amounts to 18 further roAp stars observed by TESS. Finally, we list six known roAp stars that TESS is yet to observe. We deduce that the incidence of roAp stars amongst the Ap star population is just 5.5 per cent, raising fundamental questions about the conditions required to excite pulsations in Ap stars. This work, coupled with our previous work on roAp stars in Cycle 1 observations, presents the most comprehensive, homogeneous study of the roAp stars in the TESS nominal mission, with a collection of 112 confirmed roAp stars in total

Enzymatic bioremediation of xenobiotics

Wciąż wzrastające zanieczyszczenie środowiska związane z częstym przedostawaniem się do środowiska toksycznych substancji jest jednym z największych problemów ekologicznych współczesnego świata. Wzrasta więc zainteresowanie nowymi, ekologicznymi technologiami remediacji, niewymagającymi dużych nakładów finansowych, pozwalającymi na całkowite lub częściowe oczyszczenie środowiska. Technologie bioremediacji, wykorzystujące potencjał mikroorganizmów, mogą być z powodzeniem wykorzystywane do usuwania ze środowiska zanieczyszczeń alifatycznymi bądź aromatycznymi związkami pochodzenia naftowego. Jednakże, w przypadku substancji o charakterze ksenobiotyków efektywność mikrobiologicznego rozkładu może ulec ograniczeniu. Wśród czynników biologicznych enzymy posiadają wysoki potencjał do efektywnego przekształcania i detoksykacji zanieczyszczeń i potencjalnie mogą one zostać wykorzystane do oczyszczania zanieczyszczonego środowiska. Celem pracy było przedstawienie, na podstawie literatury, niektórych grup enzymów zdolnych do przekształcania ksenobiotyków w nieszkodliwe związki. Znaczna uwaga została poświęcona enzymom pochodzącym z grzybów białej zgnilizny, charakteryzujących się wysokim potencjałem do efektywnego rozkładu ksenobiotyków. W artykule zestawiono zarówno zalety, jak i wady stosowania enzymów w bioremediacji zanieczyszczonego środowiska, a także perspektywy aplikacji in situ bioremediacji z wykorzystaniem enzymów.Environmental pollution is growing more and more due to the frequently deliberate release of hazardous, toxic substances into the environment and it has become one of the biggest ecological problems of the world. Therefore, a growing interest is being devoted to develop new, cost-effective and eco-friendly remediation technology capable of partial or total recovery of polluted environment. Bioremediation that uses naturally existing catabolic potential of microorganisms can be efficiently used to clean up certain pollutants such as aliphatic or aromatic hydrocarbons. However, for chemicals exhibiting high xenobiotic character, like polyaromatic hydrocarbons, chlorophenols, dioxines, PCBs, etc., microorganisms can turn out to be ineffective. Among biological agents, enzymes have a great potential to effectively transform and detoxify pollutants and are potentially suitable to restore polluted environments. Moreover, the use of enzymatic proteins may represent a good alternative for overcoming most disadvantages related to the use of microorganisms. They are active in the presence of microbial predators and antagonists, can be used under extreme conditions limiting microbial activity and are effective at low pollutant concentrations. This work will examine the possibility of using enzyme preparations as an element of bioremediation technology. The main terms which must be fulfilled while using this type of technology will be presented. This review will also examine some class of enzymes, mainly oxidoreductases and hydrolases, that are capable of transforming xenobiotics effectively into innocuous products. Particular attention will be devoted to enzymes from white-rot fungi, such as Mn-peroxidase, lignin proxidase and laccase, which have a great potential towards xenobiotic compounds transformation. Also the use of lipase in biodegradation of phtalanes and as an agent for monitoring of bioremediation progress will be discussed. The main advantages as well as disadvantages that are present in the application of enzymes in the bioremediation of polluted environments will be examined in details. The future perspective for the in situ application of enzymatic bioremediation of polluted with xenobiotics environments will be discussed