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Although many fungal species are found in association with honey bees and their broader environment, the effects of these interactions on honey bee health are largely unknown. Here, we report the discovery that a yeast commonly found in the environment can be found at high levels in honey bee digestive tracts.

Cardiac homeostasis relies on the appropriate provision of nutrients and functional specialization of local endothelial cells. Previously we reported in this journal that the endothelial Eph-ephrin signalling, in particular the ligand EphB4, is required for the maintenance of vascular integrity and correct fatty acid transport uptake in the heart via regulating the caveolar trafficking of the fatty acid receptor CD36. In the mouse, endothelial specific loss-of-function of the receptor EphB4, or its ligand ephrin-B2, induces Dilated Cardiomyopathy (DCM) like defects (Luxán et al., 2019).Here, we have identified new rareEPHB4variants in a cohort of 573 DCM patients. Similar to what we had observed in the EphB4 mutant mice,EPHB4variants carrying patients show an altered expression pattern of CD36 and CAV1 in the myocardium.Our study confirms a crucial role of the Eph-ephrin signalling pathway, and in particular the receptor EPHB4, in the development of DCM in humans.

Background COVID-19 is characterized by emergency hematopoiesis with a dysregulated myeloid compartment, comprising proinflammatory and immunosuppressive immune cells. Preexisting cardiovascular disease (CVD) is a major risk factor for severe and fatal COVID-19 outcomes. Individuals with atherosclerosis are known to have a proinflammatory immune cell phenotype. However, the mechanisms of how CVD causes worse outcomes during SARS-Cov2 infection remain unknown. Purpose To investigate the mechanisms of how immune cells link atherosclerosis to worse COVID-19 outcomes Methods Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) derived from hospitalized SARS-Cov2 infected patients in an uncomplicated phase of the disease not requiring intensive-care treatment with (n=5) and without (n=6) preexisting atherosclerosis was performed. Results Baseline characteristics between the two groups were similar (atherosclerosis vs. no atherosclerosis: mean age 75 vs. 70 years, oxygen requirement 2.2 vs. 3.2 l/min, CRP 10.7 vs. 6.6 mg/dl, IL-6 61.6 vs. 60.6 pg/ml, all p>0.05). In accordance with previous COVID-19 scRNA-seq studies, we found low-density neutrophils, immature neutrophils, neutrophil like plasmablasts and mostly classical monocytes in the myeloid compartment. Low-density neutrophils from patients with atherosclerosis demonstrated an increased expression of proinflammatory (IL18R1 fold change (fc) = 3.3, IL18RAP fc=1.9, HMGB2 fc=1.8, S100A12 fc=1.7, TLR2 fc=1.5, S100A9 fc=1.4 C3AR1 fc=1.8, TLR4 fc= 1.4, all adjusted p-values Conclusions Our data show for the first time that patients with atherosclerosis have a dysregulated myeloid immune response already in the uncomplicated phase of SARS-CoV-2 infection. Upregulated genes and cell populations found in this study have previously been associated with severe COVID-19. Therefore, the enhanced inflammatory response may contribute to the worse outcome of patients with CVD and might be addressed by antiinflammatory drugs. Further efforts are needed to understand how atherosclerosis may control chromatin accessibility to predispose for an enhanced inflammatory response. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart Foundation

Introduction The pathophysiology of cardiac hypertrophy is multifactorial and is accompanied by the dysregulation of various signaling pathways contributing to cardiac dysfunction and heart failure. While the hypertrophic response of cardiomyocytes (CM) has been extensively studied, the interplay of CMs with the non-parenchymal cells in the heart is less explored. Here, we apply high-resolution transcriptomic analysis on single cell level allowing the identification of cellular responses and communication in the hypertrophic human heart. Results We analyzed single nuclei RNA sequencing data of cardiac tissues from five patients with aortic stenosis and cardiac hypertrophy and 13 matched healthy subjects. Bioinformatic data analysis of 88,536 nuclei followed by clustering led to the identification of specific heterogenic cell type signatures. Analyzing cell type specific gene expression signatures, we found the expected up-regulation of the cardiac stress MYH7 (4.15-fold), CMYA5 (4.89-fold) and XIRP2 (6.13-fold) in cardiomyocytes (CM) (all p Conclusion Investigating the cross-talk in cardiac hypertrophy reveals novel disturbed communication signatures, with a striking reduction in the intercellular communication pathways of CMs. Reduced expression of receptors of the Ephrin family, particularly Ephrin-B1, in CM may prevent cardioprotective signaling by the agonist Ephrin-B2, which is highly expressed in ECs, leading to inhibition of cardioprotective cross-talk between ECs and CMs in the hypertrophic heart. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Dr. Rolf M. Schwiete StiftungDie Deutsche ForschungsgemeinschaftGerman Center for Cardiovascular Research

Background & Aims T cells are central mediators of liver inflammation and represent potential treatment targets in cholestatic liver disease. Whereas emerging evidence shows that bile acids (BAs) affect T cell function, the role of T cells for the regulation of BA metabolism is unknown. In order to understand this interplay, we investigated the influence of T cells on BA metabolism in a novel mouse model of cholangitis. Methods Mdr2−/− mice were crossed with transgenic K14-OVAp mice, which express an MHC class I restricted ovalbumin peptide on biliary epithelial cells (Mdr2−/−xK14-OVAp). T cell-mediated cholangitis was induced by the adoptive transfer of antigen-specific CD8+ T cells. BA levels were quantified using a targeted liquid chromatography-mass spectrometry-based approach. Results T cell-induced cholangitis resulted in reduced levels of unconjugated BAs in the liver and significantly increased serum and hepatic levels of conjugated BAs. Genes responsible for BA synthesis and uptake were downregulated and expression of the bile salt export pump was increased. The transferred antigen-specific CD8+ T cells alone were able to induce these changes, as demonstrated using Mdr2−/−xK14-OVAp recipient mice on the Rag1−/− background. Mechanistically, we showed by depletion experiments that alterations in BA metabolism were partly mediated by the proinflammatory cytokines TNF and IFN-γ in an FXR-dependent manner, a process that in vitro required cell contact between T cells and hepatocytes. Conclusion Whereas it is known that BA metabolism is dysregulated in sepsis and related conditions, we have shown that T cells are able to control the synthesis and metabolism of BAs, a process which depends on TNF and IFN-γ. Understanding the effect of lymphocytes on BA metabolism will help in the design of combined treatment strategies for cholestatic liver diseases. Lay summary Dysregulation of bile acid metabolism and T cells can contribute to the development of cholangiopathies. Before targeting T cells for the treatment of cholangiopathies, it should be determined whether they exert protective effects on bile acid metabolism. Herein, we demonstrate that T cell-induced cholangitis resulted in decreased levels of harmful unconjugated bile acids. T cells were able to directly control synthesis and metabolism of bile acids, a process which was dependent on the proinflammatory cytokines TNF and IFN-γ. Understanding the effect of lymphocytes on bile acid metabolism will help in the design of combined treatment strategies for cholestatic liver diseases.

Endothelial cells can acquire a mesenchymal phenotype through a process called Endothelial-to-Mesenchymal transition (EndMT). This event is found in embryonic development, but also in pathological conditions. Blood vessels lose their ability to maintain vascular homeostasis and ultimately develop atherosclerosis, pulmonary hypertension, or fibrosis. An increase in inflammatory signals causes an upregulation of EndMT transcription factors, mesenchymal markers, and a decrease in endothelial markers. In our study, we show that the induction of EndMT results in an increase in long non-coding RNA AERRIE expression. JMJD2B, a known EndMT regulator, induces AERRIE and subsequently SULF1. Silencing of AERRIE shows a partial regulation of SULF1 but showed no effect on the endothelial and mesenchymal markers. Additionally, the overexpression of AERRIE results in no significant changes in EndMT markers, suggesting that AERRIE is marginally regulating mesenchymal markers and transcription factors. This study identifies AERRIE as a novel factor in EndMT, but its mechanism of action still needs to be elucidated.

Background: Palliative care provides holistic supportive care for people with complex life-limiting disease including symptom relief, navigation of complex medical decisions and support for their unique psychological, social, and spiritual needs to enhance their quality of life. Children are distinct from adults in many ways including their diagnoses, disease trajectories, symptom burden, and spectrum of caregivers. As medical technologies improve, the number of children who are appropriate for pediatric palliative care (PPC) expertise is increasing. This project sought to characterize …

Significance Here we show that the histone demethylase JMJD2B is induced in endothelial cells by EndMT provoking stimuli and thereby contributes to the acquirement of a mesenchymal/smooth muscle phenotype. Silencing of JMJD2B inhibited EndMT in vitro and reduced the induction of EndMT after myocardial infarction in vivo. Inhibition of JMJD2B prevents the demethylation of repressive trimethylated histone H3 at lysine 9 (H3K9me3) at promoters of mesenchymal and EndMT-controlling genes, thereby reducing EndMT. Together, our study reports a crucial role for JMJD2B in controlling histone modifications during the transition of endothelial cells toward a mesenchymal phenotype., Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under proinflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional properties of endothelial cells. Here, we investigated the epigenetic control of EndMT. We show that the histone demethylase JMJD2B is induced by EndMT-promoting, proinflammatory, and hypoxic conditions. Silencing of JMJD2B reduced TGF-β2-induced expression of mesenchymal genes, prevented the alterations in endothelial morphology and impaired endothelial barrier function. Endothelial-specific deletion of JMJD2B in vivo confirmed a reduction of EndMT after myocardial infarction. EndMT did not affect global H3K9me3 levels but induced a site-specific reduction of repressive H3K9me3 marks at promoters of mesenchymal genes, such as Calponin (CNN1), and genes involved in TGF-β signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and Sulfatase 1 (SULF1). Silencing of JMJD2B prevented the EndMT-induced reduction of H3K9me3 marks at these promotors and further repressed these EndMT-related genes. Our study reveals that endothelial identity and function is critically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting, proinflammatory, and hypoxic conditions, and supports the acquirement of a mesenchymal phenotype.

Rationale: Long noncoding RNAs (lncRNAs) are emerging as important regulators of diverse biological functions. Their role in pulmonary arterial hypertension (PAH) remains to be explored. Objectives: To elucidate the role of TYKRIL (tyrosine kinase receptor–inducing lncRNA) as a regulator of p53/ PDGFRβ (platelet-derived growth factor receptor β) signaling pathway and to investigate its role in PAH. Methods: Pericytes and pulmonary arterial smooth muscle cells exposed to hypoxia and derived from patients with idiopathic PAH were analyzed with RNA sequencing. TYKRIL knockdown was performed in above-mentioned human primary cells and in precision-cut lung slices derived from patients with PAH. Measurements and Main Results: Using RNA sequencing data, TYKRIL was identified to be consistently upregulated in pericytes and pulmonary arterial smooth muscles cells exposed to hypoxia and derived from patients with idiopathic PAH. TYKRIL knockdown reversed the proproliferative (n = 3) and antiapoptotic (n = 3) phenotype induced under hypoxic and idiopathic PAH conditions. Owing to the poor species conservation of TYKRIL, ex vivo studies were performed in precision-cut lung slices from patients with PAH. Knockdown of TYKRIL in precision-cut lung slices decreased the vascular remodeling (n = 5). The number of proliferating cell nuclear antigen–positive cells in the vessels was decreased and the number of terminal deoxynucleotide transferase–mediated dUTP nick end label–positive cells in the vessels was increased in the LNA (locked nucleic acid)-treated group compared with control. Expression of PDGFRβ, a key player in PAH, was found to strongly correlate with TYKRIL expression in the patient samples (n = 12), and TYKRIL knockdown decreased PDGFRβ expression (n = 3). From the transcription factor–screening array, it was observed that TYKRIL knockdown increased the p53 activity, a known repressor of PDGFRβ. RNA immunoprecipitation using various p53 mutants demonstrated that TYKRIL binds to the N-terminal of p53 (an important region for p300 interaction with p53). The proximity ligation assay revealed that TYKRIL interferes with the p53–p300 interaction (n = 3) and regulates p53 nuclear translocation. Conclusions: TYKRIL plays an important role in PAH by regulating the p53/PDGFRβ axis.

This paper discusses the issue of differential item functioning (DIF) in international surveys. DIF is likely to occur in international surveys. What is needed is a statistical approach that takes DIF into account, while at the same time allowing for meaningful comparisons between countries. Some existing approaches are discussed and an alternative is provided. The core of this alternative approach is to define the construct as a large set of items, and to report in terms of summary statistics. Since the data are incomplete, measurement models are used to complete the incomplete data. For that purpose, different models can be used across countries. The method is illustrated with PISA’s reading literacy data. The results indicate that this approach fits the data better than the current PISA methodology; however, the league tables are nearly identical. The implications for monitoring changes over time are discussed.

Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under proinflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional properties of endothelial cells. Here, we investigated the epigenetic control of EndMT. We show that the histone demethylase JMJD2B is induced by EndMT-promoting, proinflammatory, and hypoxic conditions. Silencing of JMJD2B reduced TGF-β2-induced expression of mesenchymal genes, prevented the alterations in endothelial morphology and impaired endothelial barrier function. Endothelial-specific deletion of JMJD2B in vivo confirmed a reduction of EndMT after myocardial infarction. EndMT did not affect global H3K9me3 levels but induced a site-specific reduction of repressive H3K9me3 marks at promoters of mesenchymal genes, such as Calponin (CNN1), and genes involved in TGF-β signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and Sulfatase 1 (SULF1). Silencing of JMJD2B prevented the EndMT-induced reduction of H3K9me3 marks at these promotors and further repressed these EndMT-related genes. Our study reveals that endothelial identity and function is critically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting, proinflammatory, and hypoxic conditions, and supports the acquirement of a mesenchymal phenotype.

Aims Circulating immune cells have a significant impact on progression and outcome of heart failure. Long non-coding RNAs (lncRNAs) comprise novel epigenetic regulators which control cardiovascular diseases and inflammatory disorders. We aimed to identify lncRNAs regulated in circulating immune cells of the blood of heart failure patients. Methods and results Next-generation sequencing revealed 110 potentially non-coding RNA transcripts differentially expressed in peripheral blood mononuclear cells of heart failure patients with reduced ejection fraction. The up-regulated lncRNA Heat2 was further functionally characterized. Heat2 expression was detected in whole blood, PBMNCs, eosinophil and basophil granulocytes. Heat2 regulates cell division, invasion, transmigration and immune cell adhesion on endothelial cells. Conclusion Heat2 is an immune cell enriched lncRNA that is elevated in the blood of heart failure patients and controls cellular functions.

Objective— Endothelial cells play important roles in tissue homeostasis and vascularization, a function that is impaired by aging. Here, we aim to decipher the role of the microenvironment underlying the impairment of endothelial cell functions by aging. Approach and Results— RNA sequencing of isolated cardiac endothelial cells derived from young and 18-month-old mouse hearts revealed that aging affects the endothelial expression of genes encoding extracellular matrix proteins, specifically the laminin β1 ( Lamb1 ) and laminin β2 ( Lamb2 ) chains. Whereas Lamb1 was upregulated, Lamb2 was decreased in endothelial cells in old mice compared with young controls. A similar change in expression patterns was observed after induction of acute myocardial infarction. Mimicking aging and injury conditions by plating endothelial cells on laminin β1–containing laminin 411 matrix impaired endothelial cell adhesion, migration, and tube formation and augmented endothelial-to-mesenchymal transition and endothelial detachment compared with laminin 421, which contains the laminin β2 chain. Because laminins can signal via integrin receptors, we determined the activation of ITGB1 (integrin β1). Laminin 421 coating induced a higher activation of ITGB1 compared with laminin 411. siRNA-mediated silencing of ITGB1 reduced laminin β2–dependent adhesion, suggesting that laminin β2 more efficiently activates ITGB1. Conclusions— Mimicking age-related modulation of laminin β1 versus β2 chain expression changes the functional properties and phenotype of endothelial cells. The dysregulation of the extracellular matrix during vascular aging may contribute to age-associated impairment of organ function and fibrosis.

Rationale: Vascularization is critical to maintain organ function. Although many molecular pathways were shown to control vessel growth, the genuine process of capillary formation under different conditions is unclear. Objective: Here, we elucidated whether clonal expansion contributes to vessel growth by using Confetti mice for genetic tracing of clonally expanding endothelial cells (ECs). Methods and Results: In postnatal retina angiogenesis, we predominantly observed random distribution of fluorescence labeled ECs indicative of random integration or cell mixing. However, in models of pathophysiological angiogenesis (retinopathy of prematurity), as well as ischemia-induced angiogenesis in limbs and hearts, clonally expanded ECs were significantly more abundant (≤69%). Inhibition of VEGFR2 (vascular endothelial growth factor receptor 2) reduced clonal expansion after ischemia. To determine the mechanism underlying clonal expansion in vivo, we assessed gene expression specifically in clonally expanded ECs selected by laser capture microscopy. Clonally expanded ECs showed an enrichment of genes involved in endothelial-to-mesenchymal transition. Moreover, hypoxia-induced clonal expansion and endothelial-to-mesenchymal transition in ECs in vitro suggesting that hypoxia-enhanced endothelial-to-mesenchymal transition might contribute to vessel growth under ischemia. Conclusions: Our data suggest that neovascularization after ischemia is partially mediated by clonal expansion of ECs. Identification of the pathways that control clonal expansion may provide novel tools to augment therapeutic neovascularization or treat pathological angiogenesis.

Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial–mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function., LncRNAs influence endothelial cell function via a number of mechanisms. Here the authors show that the lncRNA GATA6-AS regulates endothelial gene expression through interaction with the nuclear deaminase LOXL2, with functional consequences on endothelial-mesenchymal transition and angiogenesis.

The current study provides specificity data on a large sample (n = 115) of young to middle-aged, male, monolingual Spanish speakers of lower educational level and low acculturation to mainstream US culture for four neurocognitive performance validity tests (PVTs): the Dot Counting, the b Test, Rey Word Recognition, and Rey 15-Item Plus Recognition. Individuals with 0 to 6 years of education performed more poorly than did participants with 7 to 10 years of education on several Rey 15-Item scores (combination equation, recall intrusion errors, and recognition false positives), Rey Word Recognition total correct, and E-score and omission errors on the b Test, but no effect of educational level was observed for Dot Counting Test scores. Cutoff scores are provided that maintain approximately 90% specificity for the education subgroups separately. Some of these cutoffs match, or are even more stringent than, those recommended for use in US test takers who are primarily Caucasian, are tested in English, and have a higher educational level (i.e., Rey Word Recognition correct false-positive errors; Rey 15-Item recall intrusions and recognition false-positive errors; b Test total time; and Dot Counting E-score and grouped dot counting time). Thus, performance on these PVT variables in particular appears relatively robust to cultural/language/educational factors.

Seit einigen Jahren lobt der VDI jährlich einen Ideenwettbewerb für Studenten aus. Im Wettbewerb für 2014 bestand die Aufgabenstellung darin, ein nachhaltiges Holzhotel in Berlin zu entwerfen, wobei ein besonderes Augenmerk auf die integrale Bearbeitung und eine gesamtheitliche Konzeption gelegt wurde. Durch Teambildung mit Studierenden aus mehreren Fachbereichen sollte eine umfassende Zusammenarbeit im Hinblick auf Entwurf, technische Ausstattung, nachhaltige Holzkonstruktion sowie Statik erreicht werden. Das zu bearbeitende Grundstück ist in Berlin in direkter Nähe zum Ostbahnhof am Ufer der Spree gelegen. Im vorliegenden Beitrag wird der Entwurf des Studententeams von der RWTH Aachen beschrieben, der im Wettbewerb den ersten Platz erreichte. Darüber hinaus wird auch ein Ausblick über weiterführende Untersuchungen gegeben. Hierbei wurde überprüft, ob und mit welchen Konsequenzen es möglich ist, mithilfe visueller Programmierung einen Entwurf automatisch auf andere Grund- stücke mit ihren individuellen Anforderungen zu übertragen und zeitgleich die gemeinsamen identitätsstiftenden Entwurfsmerkmale zu erhalten.

Background & Aims Reduced numbers of regulatory T cells (Treg) have been reported in patients with primary sclerosing cholangitis (PSC); therefore, Treg expansion might serve as a therapeutic approach. Here, we explored whether treatment with IL-2/IL-2 monoclonal antibody complex (IL-2/IL-2Ab complex) could provide in vivo Treg expansion and treatment of experimental sclerosing cholangitis. Methods Treg were expanded by repeated injection of IL-2/IL-2Ab complex in mouse models of cholangitis ( Mdr2 −/− , DDC) or colitis (dextran sulfate sodium [DSS]) as control. In vitro suppressive capacity and gene expression were analyzed in isolated hepatic and splenic Treg. Results In vivo expansion resulted in a 5-fold increase in hepatic Treg, which localized within the inflamed portal tracts. However, although Treg expansion was associated with reduced pro-inflammatory IL-17 and increased anti-inflammatory IL-10 production by hepatic lymphocytes, the severity of cholangitis was not reduced. In contrast, DSS-induced colitis could be improved by Treg expansion, suggesting a selectively reduced functionality of intrahepatic Treg. Indeed, hepatic Treg manifested reduced Foxp3 expression and reduced suppressive capacity compared to splenic Treg. Hepatic Treg dysfunction could be linked to increased IL-12 signaling due to an upregulation of the IL-12 receptor. Accordingly, IL-12 receptor beta 2 knockout mice ( IL-12rb2 −/− ) were able to maintain hepatic Treg functionality. Conclusions Hepatic Treg expanded in vivo failed to improve the course of cholangitis, which was related to the effects of hepatic IL-12 on Treg. Therefore, neutralization of IL-12 should be considered as part of treatment strategies targeting Treg in sclerosing cholangitis. Lay summary Primary sclerosing cholangitis (PSC) is associated with a paucity of regulatory T cells (Treg) that have a particular ability to control immune responses; therefore, in vivo expansion of Treg might serve as a treatment of cholangitis. However, in a mouse model of PSC, we show that Treg enrichment in the liver was not sufficient to provide effective control of cholangitis, as the suppressive functionality of hepatic Treg was significantly limited by IL-12 signals. Thus, neutralization of IL-12 should be considered as part of treatment strategies to improve the efficacy of Treg-based treatments for liver diseases. Data accession number: GSE 87898.

The discovery of materials that combine selectively, controllably, and reversibly with CO2 is a key challenge for realizing practical carbon capture from flue gas and other point sources. We report the design of ionic liquids (ILs) with properties tailored to this CO2 separation problem. Atomistic simulations predict that suitably substituted aprotic heterocyclic anions, or “AHAs,” bind CO2 with energies that can be controlled over a wide range suitable to gas separations. Further, unlike all previously known CO2-binding ILs, the AHA IL viscosity is predicted to be insensitive to CO2. Spectroscopic, temperature-dependent absorption, rheological, and calorimetric measurements on trihexyl(tetradecyl)-phosphonium 2-cyanopyrrolide ([P66614][2-CNpyr]) show CO2 uptakes close to prediction as well as insignificant changes in viscosity in the presence of CO2. A pyrazolide-based AHA IL behaves qualitatively similarly but with weaker binding energy. The results demonstrate the intrinsic design advantages of ILs as ...

Objective— Jumonji C (JmjC) domain–containing proteins modify histone and nonhistone proteins thereby controlling cellular functions. However, the role of JmjC proteins in angiogenesis is largely unknown. Here, we characterize the expression of JmjC domain–containing proteins after inducing endothelial differentiation of murine embryonic stem cells and study the function of JmjC domain–only proteins in endothelial cell (EC) functions. Approach and Results— We identified a large number of JmjC domain–containing proteins regulated by endothelial differentiation of murine embryonic stem cells. Among the family of JmjC domain–only proteins, Jmjd8 was significantly upregulated on endothelial differentiation. Knockdown of Jmjd8 in ECs significantly decreased in vitro network formation and sprouting in the spheroid assay. JMJD8 is exclusively detectable in the cytoplasm, excluding a function as a histone-modifying enzyme. Mass spectrometry analysis revealed JMJD8-interacting proteins with known functions in cellular metabolism like pyruvate kinase M2. Accordingly, knockdown of pyruvate kinase M2 in human umbilical vein ECs decreased endothelial sprouting in the spheroid assay. Knockdown of JMJD8 caused a reduction of EC metabolism as measured by Seahorse Bioscience extracellular flux analysis. Conversely, overexpression of JMJD8 enhanced cellular oxygen consumption rate of ECs, reflecting an increased mitochondrial respiration. Conclusions— Jmjd8 is upregulated during endothelial differentiation and regulates endothelial sprouting and metabolism by interacting with pyruvate kinase M2.

Previous studies have demonstrated impairments in attention, memory and executive functions in euthymic bipolar patients (BP) as well as their unaffected first-degree relatives, albeit in an attenuated form. Subsequently, cognitive deficits are discussed as a possible endophenotype of bipolar disorder. However, recent studies showed that only a subgroup of BP shows cognitive impairments. The aim of the present study was to investigate cognitive functioning in relatives compared to BP, to find out if the differentiation in a cognitive deficit vs. non-deficit subgroup is valid for relatives of BP, too. Therefore, the performance of 27 unaffected relatives of BP, 27 euthymic BP and 27 HC were compared using a neuropsychological test battery. The results showed that BP exhibited a reduced psychomotor speed and deficits in working memory compared to relatives and HC. Relatives performed significantly slower (psychomotor speed) as compared to HC (p = 0.024); performance in the other test measures lie between BP and HC. Furthermore, a detailed evaluation of the data indicated that only subgroups of BP and relatives exhibited cognitive impairments in the implemented tests. However, the deficit and non-deficit groups did not differ in sociodemographic and clinical variables from each other, possibly due to the small sample size. In conclusion, our results suggest that reduced psychomotor speed could serve as a potential endophenotype for bipolar disorder which should be investigated along the developmental trajectory of this disorder, also to examine whether abnormalities therein precede onset of the first mood episode. Furthermore, the division of relatives into subgroups aids in the identification of stable trait markers and high-risk bipolar groups and could enable early prevention strategies. As to that more research using distinct and homogeneous subgroups is necessary.

Even though the earliest prosthetic devices date to the Ancient Egyptian Empire and iconographic sources attest their use in the Greco-Roman world, archaeological evidence for this practice prior to 2nd millennium AD is very scant. In 2013, a skeleton dating to the Frankish period (6th century AD) was excavated at the Hemmaberg in southern Austria. The middle adult male was missing his left foot from above the ankle. In its place, an iron-ring and wooden remains were recovered and interpreted as a prosthesis replacing the lost foot. This represents one of the oldest examples of prosthetic limb replacement associated with the skeleton of its wearer in Europe to date. Analysis through macroscopic assessment, radiography and CT-scanning revealed healing of the lesion even though it may have initially been complicated by osteomyelitis. Atrophy of the left lower leg further indicates immobilisation and suggests survival of several years. Osteoarthritis in the knees and shoulder girdle provides tentative indications towards the functionality of the prosthesis, perhaps aided through a crutch. These findings are set against the historic, archaeological, bioarchaeological and social context of the man in order to discuss whether removal of the foot was due to medical, punitive or traumatic causes.

Objective: To enact a model of collaborative communication, demonstrate communication as coordinated management of meaning, to require active listening during the final, and to help students think through a complex social issue Course: Introduction to Public-Speaking

Course: Mass Media Objectives: Students will be able to distinguish between advertising and editorial content; compare the economic differences among magazines; analyze the relationships among articles, advertising, and audience; and practice content analysis

Recent research in bipolar disorder (BD) points to the relevance and persistence of cognitive deficits even in euthymia. Up to now, the mechanisms behind why some bipolar patients (BP) do not reach their former level of cognitive performance and psychosocial functioning while others remit completely, are not understood. In this study we aimed to identify a “cognitive deficit” vs. “non-deficit” subgroup within BD by using an extensive neuropsychological test battery. The test performance of 70 euthymic outpatients (BD-I and II, recruited as a sample of convenience from our bipolar disorder programme) was compared to 70 matched, healthy controls (HC). Furthermore, we investigated the association between demographic/clinical variables and the cognitive performance of BP. As expected, our sample of euthymic BP performed significantly worse than HC in psychomotor speed, divided attention, working memory, verbal memory, word fluency and problem solving. However, 41.4% of the patients did not have any neurocognitive deficits at all, and whether or not a patient belonged to the non-deficit group was not influenced by disease severity. Instead, our results demonstrate that patients suffering from persistent sleep disturbances and sub-threshold depressive symptomatology show more severe cognitive dysfunctions. In addition, antipsychotic treatment and comorbid anxiety disorder were associated with cognitive deficits. In sum, these results suggest that a major part of cognitive impairment is due to current symptomatology, especially sleep disorder and sub-syndromal depression. Rigorous treatment of these symptoms thus might well improve cognitive deficits and, as a consequence, overall functioning in BD.

Das Internet findet in den letzten Jahren zunehmende Verbreitung – auch unter Arzten. Neben dem Nutzen zur Recherche von medizinischen Daten entdecken zunehmend Arzte und Kliniken dieses Medium zur Prasentation der eigenen Leistungsfahigkeit. Indes ist arztliche Internetprasenz in Deutschland gesetzlich eng reglementiert. Die Arbeit stellt die einschlagigen Rechtsnormen, sowie Konsequenzen bei Verstosen vor. Weiterhin werden Vorschlage zu rechtskonformen arztlichen Internetseiten gegeben.

This study was conducted to quantify the effect of systemic Catalase, a hydrogen peroxide scavenger, on villous microcirculation in the inflamed small intestine of the rat. Intestinal inflammation was induced with s.c. application of Indomethacin. Intravital fluorescence microscopy and FITC-labeled erythrocytes were used to quantify erythrocyte velocity and arteriolar diameter in the main arteriole of the villi in the terminal ileum following i.v. application of Catalase in the inflamed intestine, and the blood flow was calculated. Control groups were formed for Ringer's lactate, Catalase and Indomethacin, respectively. We found that villous blood flow was significantly increased in the in the inflamed intestine. Application of Catalase led to a significant decrease in villous perfusion, but had no effect in the control group. The increase in villous blood flow was accompanied by changes in the diameter of the main arteriole. This effect on arteriolar diameter was reversed by i.v. Catalase. Our results provide evidence that systemic application of Indomethacin leads to vasodilatation of the main arteriole of the villus in the rat ileum and hyperemia in the mucosa. Hyperemia and the vascular diameter of the main arteriole were significantly reduced by H 2 O 2 -scavenger Catalase, suggesting that endogenous H 2 O 2 may be one of the mediators of hyperemia in the mucosa in this animal model of intestinal inflammation.

Changes of blood flow in the intestine occur under various pathological conditions. The mucosa of the intestine is especially sensitive to tissue damage resulting in swelling, loss of tissue integrity, and ulceration. Changes of blood supply to the mucosa may contribute to local tissue damage. Therefore, the quantification of the perfusion of the intestinal mucosa in an animal model may help to elucidate the involved pathophysiological mechanisms. In our study, autologous erythrocytes were labeled with fluorescein-isothiocyanate and used for the evaluation of erythrocyte velocity in the main arteriole of the villi in the distal part of the ileum using intravital microscopy. In addition, the arteriolar diameter was determined, and the arteriolar blood flow was calculated. Under stable cardiovascular and respiratory conditions, blood flow ranged between 6.6 +/- 0.3 and 5.9 +/- 0.3 nl/min (means +/- SEM) during the observation period of 120 min. Our results suggest that this approach is a feasible method to quantify blood flow in the main arteriole of the villi and is therefore a suitable method for further investigating changes of mucosal blood flow in acute and chronic states of bowel disease.

Background and Study Aims: Based on the positive results of endorectal ultrasound we evaluated flexible colonic endosonography for colonic tumors. At present there are no generally accepted indications for this procedure. Moreover, it is unclear whether the results are valid enough to warrant specific therapeutic interventions. Patients and Methods: Over a one-year period we performed flexible colonic endosonography (12 MHz rotating scanner) on 31 patients with colonic tumors. The examination was only performed when therapeutic implications were expected (e.g. endoscopic procedure when there was no sign of malignancy; oncological resection when there were signs of malignancy in ulcerative colitis or familial polyposis). Results: Of 40 tumors examined, 36 were correctly staged by endosonography, compared to postoperative histology as the gold standard (16 of 17 adenomas, 5 of 5 pT1 carcinomas, 8 of 8 pT3 carcinomas). In two cases pT4 carcinomas were wrongly classified endosonographically as uT3 carcinomas, because the infiltration of the visceral peritoneum was technically not recognizable. Overall the accuracy rate of staging was 85 %. Lymph node staging was correct in 36 of 40 patients, amounting to an accuracy rate of 90 %. Conclusion: Because of its high accuracy rate flexible colonic endosonography has a place in the preoperative staging of colonic tumors in selected patients, especially those with ulcerative colitis, familial adenomatous polyposis or macroscopically suspicious adenomas. It helps to clarify the extent (oncological resection, lymphadenectomy) of resection required in conventional surgery and helps to avoid laparoscopic procedures in advanced colonic cancer.

Endorectal ultrasound (EUS) is important for the indication of preoperative radio(chemo)therapy of locally advanced rectal carcinomas. Preoperative radio(chemo)therapy causes an increased echogenity of the ultrasound, which histologically corresponds with increased fibrosis. After preoperative radio(chemo)therapy, the accuracy rate of EUS of tumor infiltration depth (T) and lymph-node status (N) is 75% compared with postoperative histology. With the help of EUS before and after radio(chemo)therapy (n = 28 patients) "downstaging" was noticed endosonographically in 10 patients (3 times in T and 7 times in N staging) and "upstaging" in 3 patients (3 times in T and 1 times in N staging). There was no "understaging" of local tumor infiltration depth after preoperative radio(chemo)therapy.

This study looks closely at how inequality operates in egalitarian groups. It is wellestablished in the literature that some type of unequal power dynamic always occurs in democratic organizations, but there is little information on the structure of those dynamics. By using a multiple case study participant observation approach, it was discovered that democratic groups have a fluid orientation toward equality that moves them across two dimensions of power: structure, the extent to which the power relationships are formalized, and struggle, the extent to which the relationships are contested.

A Rey-Osterrieth Complex Figure Test (ROCFT) equation incorporating copy and recognition was found to be useful in detecting negative response bias in neuropsychological assessments (ROCFT Effort Equation; Lu, P. H., Boone, K. B., Cozolino, L., & Mitchell, C. (2003). Effectiveness of the Rey-Osterrieth Complex Figure Test and the Meyers and Meyers recognition trial in the detection of suspect effort. Clinical Neuropsychologist, 17, 426-440). In the current cross validation of this validity, the credible patient group (n = 146; 124 with equation data) outperformed the noncredible group (n = 157; 115 with equation data) on copy, 3-min recall, total recognition correct and the Effort Equation, but the latter was most effective in classifying subjects. A cut-off of ≤50 maintained specificity of 90% and achieved sensitivity of 80%. Results of the current cross validation provide corroboration that the ROCFT Effort Equation is an effective measure of neurocognitive response bias.

Endorectal ultrasound (EUS) is known to be a reliable method for preoperative staging of rectal tumors. In this study, EUS was used to select patients with rectal cancer suitable for preoperative radiation therapy. By performing EUS before and after radiation, the aim of the study was to evaluate the role of EUS in monitoring the effects of preoperative radiation therapy. In 17 patients with large T3 or T4 rectal tumors, a complete staging by EUS was done before and after radiation therapy. Beside a shrinkage of the tumor, there was a change of echopattern to more hyperechoic gray levels to be observed in the irradiated tumor. The rectal wall lost its normal architecture, and lymph nodes disappeared or changed their echopattern from echopoor to echorich. There was no down-staging of a tumor seen by EUS. Complete preoperative staging was correct in 13 of 17 patients because of endosonographic examination before and after preoperative radiation therapy. New interpretation criteria are given for evaluation of patients with rectal cancer treated by radiation therapy.