Pulsed neutron source measurements in the subcritical ADS experiment YALINA-Booster

A subcritical zero-power source-driven coupled core, the YALINA-Booster, has been constructed for experimental investigations of neutron kinetics of source-driven systems. In this study, the reactivity of two subcritical configurations has been determined by the area ratio method. The prompt neutron decay constants have been evaluated through slope fitting of the prompt neutron decay as well as through the pulsed Rossi-α method. It is shown that the slope fitting method and the pulsed Rossi-α method give stable results whereas the area ratio method results show spatial dependence. The reasons for the spatial spread are addressed.     

Water Governance in Canada: Innovation and Fragmentation

This paper explores Canada's approach to water governance. It argues that fragmented governance has had negative impacts on Canada's ability to manage water resources adequately (particularly in the context of urbanization, agriculture and resource extraction), and to deal with new issues (such as climate change). Further, it argues that Canada's highly decentralized approach to water governance creates challenges of integration, coordination and data availability. The paper explores possible future strategies for innovations in water governance that may have the potential to improve water management outcomes.     

Temporal course of perfusion in human masseter muscle during isometric contraction assessed by arterial spin labeling at 3T

Object  

Examination of blood perfusion in the masseter muscle in the course of repetitive isometric contraction by arterial spin-labeling (ASL) MR imaging and additional T2 relaxation time measurements during and after masseter muscle activation.     

Influence of water on the generation of Strecker aldehydes from dry processed foods

Completeness of extraction, losses during isolation and, in particular, the formation of new constituents are challenges during the enrichment of volatiles for GC analysis. Especially the isolation of volatiles by simultaneous steam distillation/extraction has long been known to generate artifacts due to the hot water treatment. However, even a simple treatment of dry foods with cold water may already lead to the release of odour-active volatiles. After treatment of chocolate or cocoa beans with water, the concentrations of the four Strecker aldehydes 2- and 3-methylbutanal, 3-(methylthio)propanal and phenylacetaldehyde were increased by factors between 10 and 100. Also in other dry processed foods, such as malt or crackers, the concentrations of the Strecker aldehydes were substantially increased upon water addition. Although a physical release of the aldehydes weakly bound to, e.g. proteins or starch is possible, in a further experiment, it could be shown that a yet unknown precursor of 3-(methylthio)propanal and phenylacetaldehyde could be isolated by solvent extraction from caramalt and Munich malt. As a consequence, the presence or absence of water during the work-up procedure might either lead to an over- or underestimation of the relevance of the respective aroma compounds, which might also effect aroma formation and perception during the process of eating.     

Analysis of seed oil from ricinus communis and dimorphoteca pluvialis by gas and supercritical fluid chromatography

The seed oils from Dimorphoteca pluvialis and Ricinus communis contain hydroxy fatty acids. Dimorphoteca pluvialis contains Δ-9-hydroxy-10t, 12t-octadecadienoic acid (dimorphecolic acid) and R. communis contains Δ-12-hydroxy-9c-octadecenoic acid (ricinoleic acid). The oils were derivatized and analyzed to determine the content of hydroxy fatty acids. The trimethylsilyl fatty acid methyl ester (TMS-FAME) derivatives were analyzed by capillary gas chromatography (GC), and the free fatty acid (FFA) derivatives and the oils were analyzed by capillary supercritical fluid chromatography (SFC). Further, mass spectroscopy of the TMS-FAME derivatives was performed to check the purity of the derivatives. The results from the GC analyses of TMS-FAME corresponded to the results found by SFC analysis of the FFA. The content of ricinoleic acid in the glycerolipids of R. communis was 87.7 wt%, and the content of dimorphecolic acid in D. pluvialis was 54.0 wt%. The methods were evaluated with respect to the cost, ease, and time needed for sample preparation and analysis.     

Reconstitution of Monocyte Subsets and PD-L1 Expression but Not T Cell PD-1 Expression in Obstructive Sleep Apnea Patients upon PAP Therapy

Obstructive sleep apnea (OSA) is characterized by nocturnal breathing intermissions resulting in oxidative stress and eventually, a low-grade systemic inflammation. The study aimed to investigate the impact of positive airway pressure (PAP) therapy on the inflammatory milieu as measured by monocyte and T cell phenotypic alterations. Participants were assessed for their OSA severity before PAP therapy and about six months later, including patient-reported outcome and therapy usage by telemetry readout. The distributions of the CD14/CD16-characterized monocyte subsets as well as the CD4/CD8-characterized effector T cell subsets with regard to their PD-1 and PD-L1 expression were analyzed by flow cytometry from blood samples. Data of 25 patients revealed a significant reconstitution of the monocyte subset distribution and a decrease in PD-L1 expression on pan-monocytes and CD8⁺ T cells without an association to initial AHI and overweight. The PD-1 expression was still increased on T cell subsets, especially on CD4⁺ TH17/22 cells. We conclude that PAP therapy might have a rapid effect on the monocyte phenotype and overall PD-L1 expression levels. However, T cell immune alterations especially on TH17/22 cells persist longer, indicating an ongoing disturbance of the adaptive immune system.     

Pathogenesis of Endometriosis: New Insights into Prospective Therapies

Endometriosis is a female reproductive disorder characterized by growth of uterine cells and tissue in distant sites. Around 2–10% of women experience this condition during reproductive age, 35–50% of whom encounter fertility issues or pain. To date, there are no established methods for its early diagnosis and treatment, other than surgical procedures and scans. It is difficult to identify the disease at its onset, unless symptoms such as infertility and/or pain are present. Determining the mechanisms involved in its pathogenesis is vital, not only to pave the way for early identification, but also for disease management and development of less invasive but successful treatment strategies. Endometriosis is characterized by cell proliferation, propagation, evasion of immunosurveillance, and invasive metastasis. This review reports the underlying mechanisms that are individually or collectively responsible for disease establishment and evolution. Treatment of endometriosis mainly involves hormone therapies, which may be undesirable or have their own repercussions. It is therefore important to devise alternative strategies that are both effective and cause fewer side effects. Use of phytochemicals may be one of them. This review focuses on pharmacological inhibitors that can be therapeutically investigated in terms of their effects on signaling pathways and/or mechanisms involved in the pathogenesis of endometriosis.     

Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells

The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE.     

The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies

Cardiomyopathies (CMPs) are a heterogeneous group of myocardial diseases accountable for the majority of cases of heart failure (HF) and/or sudden cardiac death (SCD) worldwide. With the recent advances in genomics, the original classification of CMPs on the basis of morphological and functional criteria (dilated (DCM), hypertrophic (HCM), restrictive (RCM), and arrhythmogenic ventricular cardiomyopathy (AVC)) was further refined into genetic (inherited or familial) and acquired (non-inherited or secondary) forms. Despite substantial progress in the identification of novel CMP-associated genetic variations, as well as improved clinical recognition diagnoses, the functional consequences of these mutations and the exact details of the signaling pathways leading to hypertrophy, dilation, and/or contractile impairment remain elusive. To date, global research has mainly focused on the genetic factors underlying CMP pathogenesis. However, growing evidence shows that alterations in molecular mediators associated with the diagnosis of CMPs are not always correlated with genetic mutations, suggesting that additional mechanisms, such as epigenetics, may play a role in the onset or progression of CMPs. This review summarizes published findings of inherited CMPs with a specific focus on the potential role of epigenetic mechanisms in regulating these cardiac disorders.     

Trans-Splicing Improvement by the Combined Application of Antisense Strategies

Spliceosome-mediated RNA trans-splicing has become an emergent tool for the repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans-splicing molecules (RTMs) are designed to induce a specific trans-splicing reaction via a binding domain for a respective target pre-mRNA region. A previously established reporter-based screening system allows us to analyze the impact of various factors on the RTM trans-splicing efficiency in vitro. Using this system, we are further able to investigate the potential of antisense RNAs (AS RNAs), presuming to improve the trans-splicing efficiency of a selected RTM, specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB). We have shown that co-transfections of the RTM and a selected AS RNA, interfering with competitive splicing elements on a COL7A1-minigene (COL7A1-MG), lead to a significant increase of the RNA trans-splicing efficiency. Thereby, accurate trans-splicing between the RTM and the COL7A1-MG is represented by the restoration of full-length green fluorescent protein GFP on mRNA and protein level. This mechanism can be crucial for the improvement of an RTM-mediated correction, especially in cases where a high trans-splicing efficiency is required.