0122: The serotonergic system in pathological human cardiac valves. What is the role of progenitors cells expressing the 5-HT2B receptor?

Many compounds (pergolide, cabergoline, fenfluramine, ectasy) were described as inducers of fibrotic valvular lesions, a rare but severe drug reaction. All these drugs share in common the pharmacological property to activate a serotonergic receptor subtype, the 5HT2B. Together with the well known “carcinoid heart” that is a valvulopathy due to high amounts of circulating serotonin, these observations lead to the hypothesis that cardiac valves express a “serotonergic system” that could be activated by 5-HT or 5-HTR agonists. The aim of this work was to characterize the pattern of expression of 5-HT2A,2B,4 receptors, the serotonin transporter (SERT) and the biosynthesis peripheral enzyme (Tph1) in various valvulopathies. Thirty degenerated human valves were collected: 11 calcified aortic valves (CAV), 5 sclerotic aortic valves (SAV), 11 dystrophic mitral valves (DMV). They were analyzed by RT-qPCR and immunohistochemistery. All samples express 5HT2A,2B,4 receptors, SERT and Tph1. In these valve tissues, the amount of 5HT2B receptor (5HT2B R) mRNA is higher than the 5HT2A one (5HT2A R) : Δ Ct (5HT2B R -18S) = 12,53±1,12 vs Δ Ct (5HT2A R -18S) = 15,95±2,37 for CAV, Δ Ct (5HT2B R -18S) = 13,04±2,62 vs Δ Ct (5HT2A R - 18S)=16,00±1,46 for SAV, Δ Ct (5HT2B R -18S) = 12,34±0,77 vs Δ Ct (5HT2A R -18S) = 16,14±0,86 for DMV. The amounts of SERT, Tph1 and 5HT4 receptor mRNA are negligible whatever valve and etiology. At a topographical point of view, 5HT2BR expression is found in endothelial cells (at the valve surface) but also inside valve lesions, by interstitial cells (smooth muscle α-actin and vimentin positive cells) located in an abundant glycosaminoglycan matrix. Characterization of these cells is in progress. In particular, we characterize the high amount CD34+ hematopoietic progenitors that are highly present in fibromyxoid lesions. To summarize, 5HT2A,2B,4 receptors, SERT and Tph1 are expressed in aortic and mitral diseased valves. The amounts of 5HT2A,2B R mRNA are equal between mitral and aortic valves. The contribution of the two 5-HT2 receptors in valve degeneration is now under investigation whatever the pathological process considered

Pharmacological hypothesis: A recombinant probiotic for taming bacterial β-glucuronidase in drug-induced enteropathy

Advances in pharmacomicrobiomics have shed light on the pathophysiology of drug-induced enteropathy associated with the therapeutic use of certain non-steroidal anti-inflammatory drugs, anticancer chemotherapies and immunosuppressants. The toxicity pathway results from the post-glucuronidation release and digestive accumulation of an aglycone generated in the context of intestinal dysbiosis characterized by the expansion of β-glucuronidase-expressing bacteria. The active aglycone could trigger direct or indirect inflammatory signaling on the gut epithelium. Therefore, taming bacterial β-glucuronidase (GUS) activity is a druggable target for preventing drug-induced enteropathy. In face of the limitations of antibiotic strategies that can worsen intestinal dysbiosis and impair immune functions, we hereby propose the use of a recombinant probiotic capable of mimicking repressive conditions of GUS through an inducible plasmid vector

Prevalence and Determinants of Sinus Problems in Farm and Non-Farm Populations of Rural Saskatchewan, Canada

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Canadian Institutes of Health Research - MOP-187209-POP-CCAA-11829Peer ReviewedAlthough sinus problems have long been recognized as the most common respiratory symptoms associated with agricultural work, there is a scarcity of recent studies and/or reliable estimates as to the true prevalence or risk factors of sinus problems related to farming. The aim of this study was to determine the prevalence of sinus problems in farming and non-farming rural populations and further investigate the association of individual (for example life-style, occupational), contextual (e.g., environmental), and important covariates (e.g., age, sex) with sinus problems. A large-scale cross-sectional study was conducted in farm and non-farm residents of rural Saskatchewan, Canada. A logistic regression model based on a generalized estimating equations approach were fitted to investigate the risk factors of sinus problems. Sinus problems were reported by 2755 (34.0%) of the 8101 subjects. Farm residents were more likely to spend their first year of life on farm compared with non-farm residents, and indicated a significantly lower risk of sinus problems. Meanwhile, occupational exposure to solvent and mold were associated with an increased risk of sinus problems. Some health conditions such as allergy and stomach acidity/reflux, family history, and female sex were also related to a higher risk of sinus problems. Farm residents had a significantly lower risk of sinus problems than non-farm residents, likely due to the exposure to farm specific environments in their early life

Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

Post-transplant diabetes mellitus (PTDM) is one of the most common and deleterious comorbidities after solid organ transplantation (SOT). Its incidence varies depending on the organs transplanted and can affect up to 40% of patients. Current research indicates that PTDM shares several common features with type 2 diabetes mellitus (T2DM) in non-transplant populations. However, the pathophysiology of PTDM is still poorly characterized. Therefore, ways should be sought to improve its diagnosis and therapeutic management. A clear correlation has been made between PTDM and the use of immunosuppressants. Moreover, immunosuppressants are known to induce gut microbiota alterations, also called intestinal dysbiosis. Whereas the role of intestinal dysbiosis in the development of T2DM has been well documented, little is known about its impacts on PTDM. Functional alterations associated with intestinal dysbiosis, especially defects in pathways generating physiologically active bacterial metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide, indole and kynurenine) are known to favour several metabolic disorders. This publication aims at discussing the potential role of intestinal dysbiosis and dysregulation of bacterial metabolites associated with immunosuppressive therapy in the occurrence of PTDM

Preface

One of the current challenges in plant biology is the development of quantitative phenotyping approaches to link the genotype and the environment to plant structural, functional, and yield characteristics in order to meet the growing demands for sustainable food, feed, and fuel. The genotype of a plant consists of all of the hereditary information within the individual, whilst the phenotype, which represents the morphological, physiological, anatomical, and developmental characteristics, is the result of the interaction between the genotype and the environment. Understanding this interaction is one of the major challenges in plant sciences. In plant breeding, the ultimate goal is the improvement of traits of agricultural importance related to disease resistance, high yields, and the plant’s ability to grow in unfavourable environmental conditions. Currently, breeding approaches produce an annual yield increase of approximately 1% for major crops, which is below the over 2% increase needed to meet the global demands for food by 2050 (Ray et al., 2013).Rapid developments in plant molecular biology and in molecular-based breeding techniques have resulted in an increasing number of species being sequenced and large collections of mutants, accessions, and recombinant lines allowing detailed analysis of gene functions. High-definition genotyping can now be carried out on thousands of plants in an automated way at continuously decreasing costs, thereby facilitating association genetics and the determination of multi-parental quantitative trait loci (QTLs) (Poland and Rife, 2012). For transcriptomic, proteomic, and metabolomic analyses large, often robotized, platforms are available allowing detailed characterization of the biochemical status of plants at a reasonable cost (Ehrhardt and Frommer, 2012). By contrast, an understanding of the link between genotype and phenotype has progressed more slowly and is the major limiting step i

First discovery of Holocene Alaskan and Icelandic tephra in Polish peatlands

Despite the discovery of cryptotephra layers in over 100 peatlands across northern Europe, Holocene cryptotephra layers have not previously been reported from Polish peatlands. Here we present the first Holocene tephra findings from two peatlands in northern Poland. At Bagno Kusowo peatland we identify the most easterly occurrence of the AD 860 B tephra, recently correlated to the White River Ash (WRAe) derived from Mount Churchill, Alaska. A shorter core from Linje peatland contains tephra from the Askja 1875 eruption, extending the spatial distribution and regional importance of this Icelandic tephra in Eastern Europe. Our research indicates the potential of cryptotephra layers to date and correlate the growing number of palaeoenvironmental studies being conducted on Polish peatlands and contributes towards the development of a regional Holocene tephrostratigraphy for Poland

The presence of Holocene cryptotephra in Wales and southern England

There have been few detailed studies into the tephrostratigraphy of southern Britain. We report the tephrostratigraphy of two sites, one in southern England (Rough Tor, Cornwall) and one in Wales (Cors Fochno, west Wales). Our study extends the known southernmost reach of Icelandic cryptotephra in northern Europe. Given the large distance between sites in southern England and eruptive sources (e.g. Iceland 1500–1700 km distant), most of the cryptotephra layers consist of sparse numbers of shards, even by the standards of distal tephrostratigraphy (as low as 3 shards cm−1), each layer spanning only 1 or 2 cm in depth. We identify multiple cryptotephra layers in both sites, extending the known distribution of several tephra layers including the MOR-T4 tephra (∼AD 1000) most probably of Icelandic origin, and the AD 860 B tephra correlated to an eruption of Mount Churchill, Alaska. The two sites record contrasting tephrostratigraphies, illustrating the need for the inclusion of multiple sites in the construction of a regional tephrostratigraphic framework. The tephra layers we describe may provide important isochrons for the dating and correlation of palaeoenvironmental sequences in the south of Britain

“A very orderly retreat”: Democratic transition in East Germany, 1989-90

East Germany's 1989-90 democratisation is among the best known of East European transitions, but does not lend itself to comparative analysis, due to the singular way in which political reform and democratic consolidation were subsumed by Germany's unification process. Yet aspects of East Germany's democratisation have proved amenable to comparative approaches. This article reviews the comparative literature that refers to East Germany, and finds a schism between those who designate East Germany's transition “regime collapse” and others who contend that it exemplifies “transition through extrication”. It inquires into the merits of each position and finds in favour of the latter. Drawing on primary and secondary literature, as well as archival and interview sources, it portrays a communist elite that was, to a large extent, prepared to adapt to changing circumstances and capable of learning from “reference states” such as Poland. Although East Germany was the Soviet state in which the positions of existing elites were most threatened by democratic transition, here too a surprising number succeeded in maintaining their position while filing across the bridge to market society. A concluding section outlines the alchemy through which their bureaucratic power was transmuted into property and influence in the “new Germany”

First discovery of Holocene cryptotephra in Amazonia

The use of volcanic ash layers for dating and correlation (tephrochronology) is widely applied in the study of past environmental changes. We describe the first cryptotephra (non-visible volcanic ash horizon) to be identified in the Amazon basin, which is tentatively attributed to a source in the Ecuadorian Eastern Cordillera (0–1°S, 78-79°W), some 500-600 km away from our field site in the Peruvian Amazon. Our discovery 1) indicates that the Amazon basin has been subject to volcanic ash fallout during the recent past; 2) highlights the opportunities for using cryptotephras to date palaeoenvironmental records in the Amazon basin and 3) indicates that cryptotephra layers are preserved in a dynamic Amazonian peatland, suggesting that similar layers are likely to be present in other peat sequences that are important for palaeoenvironmental reconstruction. The discovery of cryptotephra in an Amazonian peatland provides a baseline for further investigation of Amazonian tephrochronology and the potential impacts of volcanism on vegetation