Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications

Pericytes are mural vascular cells found predominantly on the abluminal wall of capillaries, where they contribute to the maintenance of capillary structural integrity and vascular permeability. Generally quiescent cells in the adult, pericyte activation and proliferation occur during both physiological and pathological vascular and tissue remodeling. A considerable body of research indicates that pericytes possess attributes of a multipotent adult stem cell, as they are capable of self-renewal as well as commitment and differentiation into multiple lineages. However, pericytes also display phenotypic heterogeneity and recent studies indicate that lineage potential differs between pericyte subpopulations. While numerous microenvironmental cues and cell signaling pathways are known to regulate pericyte functions, the roles that metabolic pathways play in pericyte quiescence, self-renewal or differentiation have been given limited consideration to date. This review will summarize existing data regarding pericyte metabolism and will discuss the coupling of signal pathways to shifts in metabolic pathway preferences that ultimately regulate pericyte quiescence, self-renewal and trans-differentiation. The association between dysregulated metabolic processes and development of pericyte pathologies will be highlighted. Despite ongoing debate regarding pericyte classification and their functional capacity for trans-differentiation in vivo, pericytes are increasingly exploited as a cell therapy tool to promote tissue healing and regeneration. Ultimately, the efficacy of therapeutic approaches hinges on the capacity to effectively control/optimize the fate of the implanted pericytes. Thus, we will identify knowledge gaps that need to be addressed to more effectively harness the opportunity for therapeutic manipulation of pericytes to control pathological outcomes in tissue remodeling.York University Librarie

Chemical analysis of volatile components of Juniperus communis L. with the newest methods of GC-MS

Im Rahmen dieser Diplomarbeit wurden Juniperus communis L. Proben mit den neuesten Präparations- und Analysentechniken untersucht. Für die Charakterisierung der Proben wurde ein Vergleich von traditionellen Herstellungstechniken ätherischer Öle, wie Wasserdampfdestillation, mit der modernen Extraktionstechnik, head space solid phase microextraction (HS-SPME), durchgeführt. Um die Analysenzeiten zu verkürzen, wurde HS-SPME mit Fast Gaschromatographie (FastGC) kombiniert. Des Weiteren, wurden die Resultate zweier verschiedener Detektoren, Flammenionisationsdetektor (FID) und Massenspektrometriedetektor (MS), miteinander verglichen.In the context of this master thesis, Juniperus communis L. samples are analysed with recent preparation and analytical techniques. A comparison of traditional essential oil preparation techniques such as hydrodistillation to the modern extraction technique of headspace solid phase microextraction (HS-SPME), for sample characterisation, is made. In order to speed-up the analysis times, HS-SPME technique is coupled with fast gas chromatography (FastGC). Furthermore, the response of two different detectors, flame ionisation detector (FID) and mass spectrometry (MS), are compared

The palaeoecological value of Diporotheca rhizophila ascospores (Diporothecaceae, Ascomycota) found in Holocene sediments from Lake Nussbaumersee, Switzerland

International audienceLake Nussbaumersee, a medium-sized lake SWof Lake Constance (Switzerland) and well known for its Neolithic and Bronze Age pile-dwelling settlements, provides invaluable insights into the possible interpretation of Diporotheca rhizophila ascospores (Diporothecaceae, Ascomycota) in palaeoecological studies. Calcareous gyttja sediments from a 7500 yrs old stratigraphy were analysed palynologically, resulting in statistical correlations of Diporotheca spores with pollen and non-pollen palynomorphs(NPPs). Positive correlation existed with arboreal taxa such as Corylus avellana and Acer, herb taxasuchas Allium, and aquatic taxa such as Anabaena (Cyanobacteria) and Filinia eggs (Rotifera). Negative statistical correlation was shown between Diporotheca and the arboreal taxa Quercus and Betula, Poaceae and Cyperaceae, and the fern Pteridium aquilinum. These results suggest that ecological indicator values for the root parasite D. rhizophila may not only be closely related to the autecology of its common host Solanum, but that D. rhizophila may generally be an indicator of major soil disturbance and extensive soil erosion due to the impact of agricultural activities by prehistorical people, as well as due to livestock trampling of wetlands and lake shore ecosystem

Investigating patterns of local climate governance: How low-carbon municipalities and intentional communities intervene in social practices

The local level has gained prominence in climate policy and governance in recent years as it is increasingly perceived as a privileged arena for policy experimentation and social and institutional innovation. However, the success of local climate governance in industrialized countries has been limited. One reason may be that local communities focus too much on strategies of technology-oriented ecological modernization and individual behavior change and too little on strategies that target unsustainable social practices and their embeddedness in complex socioeconomic patterns. In this paper we assess and compare the strategies of "low-carbon municipalities" (top-down initiatives) and those of "intentional communities" (bottom-up initiatives). We were interested to determine to what extent and in which ways each community type intervenes in social practices to curb carbon emissions and to explore the scope for further and deeper interventions on the local level. Using an analytical framework based on social practice theory we identify characteristic patterns of intervention for each community type. We find that low-carbon municipalities face difficulties in transforming carbon-intensive social practices. While offering some additional low-carbon choices, their ability to reduce carbon-intensive practices is very limited. Their focus on efficiency and individual choice shows little transformative potential. Intentional communities, by contrast, have more institutional and organizational options to intervene in the web of social practices. Finally, we explore to what extent low-carbon municipalities can learn from intentional communities and propose strategies of hybridization for policy innovation to combine the strengths of both models

Facilitating low-carbon living? A comparison of intervention measures in different community-based initiatives

The challenge of facilitating a shift towards sustainable housing, food and mobility has been taken up by diverse community-based initiatives ranging from ‘top-down’ approaches in low-carbon municipalities to ‘bottom-up’ approaches in intentional communities. This paper compares intervention measures of these two types, focusing on their potential of re-configuring daily housing, food and mobility practices. Taking up critics on dominant intervention framings of diffusing low-carbon technical innovations and changing individual behaviour, we draw on social practice theory for the empirical analysis of four case studies. Framing interventions in relation to re-configuring daily practices, the paper reveals differences and weaknesses of current low-carbon measures of community-based initiatives in Germany and Austria. Low-carbon municipalities mainly focus on introducing technologies and offering additional infrastructure and information to promote low-carbon practices. They avoid interfering into residents’ daily lives and do not restrict carbon-intensive practices. In contrast, intentional communities base their interventions on the collective creation of shared visions, decisions and rules and thus provide social and material structures, which foster everyday low-carbon practices and discourage carbon-intensive ones. The paper discusses the relevance of organisational and governance structures for implementing different types of low-carbon measures and points to opportunities for broadening current policy strategies

Prevalence of Bicuspid Aortic Valve in Turner Syndrome Patients Receiving Cardiac MRI and CT: A Meta-Analysis

Turner syndrome (TS) is a rare disorder affecting 25–50 in 100000 female newborns. Bicuspid aortic valve (BAV) is assumed to be the most common congenital heart defect (CHD) in TS. In literature, reported BAV prevalence in TS ranges between 14% and 34%. The specific BAV prevalence in TS is still unknown. The aim of this study was to give a more precise estimation of BAV prevalence in TS by conducting a meta-analysis of TS-studies, which detected BAV by either cardiac magnetic resonance imaging (MRI) or cardiac computed tomography (CT). We searched PubMed, Cochrane Library, and Web of Science databases to collect observational studies including the prevalence of BAV identified by cardiac MRI or cardiac CT in TS patients up to June 4th, 2021. After screening for inclusion, data extraction, and quality assessment by two independent reviewers, the meta-analysis was performed with R 4.1.1 software. Results are shown as proportion and weighted mean difference with 95% confidence intervals (95% CI). In total, 11 studies involving 1177 patients were included. Pooled data showed that the prevalence of BAV in TS patients was 23.7% (95% CI: 21.3% to 26.1%). No high heterogeneity was found between the included studies. The current meta-analysis reveals that BAV can be detected in 23.7% of TS patients receiving cardiac MRI or cardiac CT. Therefore, BAV can be considered as the most common CHD in TS. Compared to TTE, cardiac MRI and cardiac CT might represent superior imaging modalities in BAV assessment of adult TS patients

Investigating patterns of local climate governance: how low-carbon municipalities and intentional communities intervene into social practices

The local level has gained prominence in climate policy and governance in recent years as it is increasingly perceived as privileged arena for policy experimentation and social and institutional innovation. Yet, the success of local climate governance in industrialised countries has been limited so far. One reason may be that local communities focus too much on strategies of technology-oriented ecological modernisation (EM) and individual behaviour change and too little on strategies that target unsustainable social practices and their embeddedness in complex patterns of practices. In this paper we assess and compare the strategies of ‘low-carbon municipalities’ (top-down initiatives) and those of ‘intentional communities’ (bottom-up initiatives). We are interested to find out to what extent and in which ways each community type intervenes in social practices to curb carbon emissions and to explore the scope for further and deeper interventions on the local level. Employing an analytical framework based on social practice theory we identify characteristic patterns of intervention for each community type. We find that low-carbon municipalities face tenacious difficulties in transforming carbon-intensive social practices. While offering some additional low-carbon choices, their ability to reduce carbon-intensive practices is very limited. Their focus on efficiency and individual choice shows little transformative potential. Intentional communities, by contrast, have more institutional and organisational options to intervene into the web of social practices. Finally, we explore to what extent low-carbon municipalities can learn from intentional communities and propose strategies of hybridisation for policy innovation to combine the strengths of both models

Yale Global Tic Severity Scale (YGTSS): Psychometric Quality of the Gold Standard for Tic Assessment Based on the Large-Scale EMTICS Study.

The Yale Global Tic Severity Scale (YGTSS) is a clinician-rated instrument considered as the gold standard for assessing tics in patients with Tourette's Syndrome and other tic disorders. Previous psychometric investigations of the YGTSS exhibit different limitations such as small sample sizes and insufficient methods. To overcome these shortcomings, we used a subsample of the large-scale "European Multicentre Tics in Children Study" (EMTICS) including 706 children and adolescents with a chronic tic disorder and investigated convergent, discriminant and factorial validity, as well as internal consistency of the YGTSS. Our results confirm acceptable convergent and good to very good discriminant validity, respectively, indicated by a sufficiently high correlation of the YGTSS total tic score with the Clinical Global Impression Scale for tics (r <sub>s</sub> = 0.65) and only low to medium correlations with clinical severity ratings of attention deficit/hyperactivity symptoms (r <sub>s</sub> = 0.24), obsessive-compulsive symptoms (r <sub>s</sub> = 27) as well as internalizing symptoms (r <sub>s</sub> = 0.27). Internal consistency was found to be acceptable (Ω = 0.58 for YGTSS total tic score). A confirmatory factor analysis supports the concept of the two factors "motor tics" and "phonic tics," but still demonstrated just a marginal model fit (root mean square error of approximation = 0.09 [0.08; 0.10], comparative fit index = 0.90, and Tucker Lewis index = 0.87). A subsequent analysis of local misspecifications revealed correlated measurement errors, suggesting opportunities for improvement regarding the item wording. In conclusion, our results indicate acceptable psychometric quality of the YGTSS. However, taking the wide use and importance of the YGTSS into account, our results suggest the need for further investigations and improvements of the YGTSS. In addition, our results show limitations of the global severity score as a sum score indicating that the separate use of the total tic score and the impairment rating is more beneficial

Influence of platelet count at diagnosis and during the course of disease on prognosis in MDS patients

Thrombocytopenia at diagnosis and platelet drop within the first 6~months have an adverse effect on prognosis of MDS patients. We therefore were interested in the association and impact on prognosis of morphologic findings of megakaryocytes and platelets with platelet count at diagnosis, bleeding complications, and the drop of platelets during the course of disease. This retrospective analysis was based on 334 MDS patients from the Duesseldorf MDS registry that were followed up for blood counts, bleeding, transfusion dependency, and AML evolution and correlated with morphology of the megakaryocytes and platelets. Thrombocytopenia was found more frequently in higher risk MDS and was associated with hypocellularity of the megakaryocytes in the bone marrow. Signs of bleeding were present at diagnosis in 14% and occurred during the disease in 48% of all MDS patients. Death due to bleeding was ranked third behind infections and AML. A decrement of platelets during the first 6~months was associated with an inferior overall survival of 21 vs. 49~months and with a higher cumulative 2-year AML rate of 22.2% vs. 8.3% (p = 0.001). In a multivariate analysis, besides bone marrow blasts and karyotype, decreasing platelets were also associated with an inferior outcome. Signs of bleeding are present in a relevant number of MDS patients and account for significant morbidity and mortality in MDS. We could demonstrate the prognostic importance of decreasing platelets during the course of disease in all MDS patients, identifying patients at higher risk for death or AML progression

Female Mice Have Higher Angiogenesis in Perigonadal Adipose Tissue Than Males in Response to High-Fat Diet

Background: Impaired capillary growth (angiogenesis) in skeletal muscle and adipose tissue contributes to the development of metabolic disorders in obese males. This association remains unexplored in females, despite mounting evidence that endothelial cells have sex-specific transcriptional profiles. Therefore, herein we assessed whether males and females show distinct angiogenic capacities in response to diet-induced obesity.Methods: Age-matched male and female mice were fed normal chow or high-fat obesogenic diets for 16 weeks. At the end of diet period, systemic glucose disposal was assessed as well as insulin sensitivity of skeletal muscle and visceral adipose tissue. Capillary content and the expression of angiogenic regulators were also evaluated in these tissues.Results: When placed on a high-fat diet, female mice gained less weight than males and showed a metabolic phenotype similar to NC-fed mice, contrasting with the impaired whole-body glucose metabolism observed in high-fat-fed males. However, high-fat-feeding elevated serum lipid levels similarly in male and female mice. Although skeletal muscle of high-fat–fed female mice had higher insulin sensitivity than male counterparts, no sex difference was detected in muscle capillarization. Metabolic functions of perigonadal white adipose tissue (pgWAT) were retained in high-fat-fed females, as evidenced by smaller adipocytes with preserved insulin sensitivity, greater responsiveness to isoproterenol, higher expression of Adiponectin and a lower ratio of Leptin:Adiponectin mRNA. An enhanced browning phenotype was detected in HF-fed female adipocytes with upregulation of Ucp1 expression. PgWAT from high-fat-fed females also showed augmented capillary number and expression of endothelial cell markers, which was associated with elevated mRNA levels of pro-angiogenic mediators, including vascular endothelial growth factor A (Vegfa) and its receptor (Vegfr2), the Notch ligand Jagged-1 (Jag1) and Angiopoietin-2 (Angpt2).Conclusion: Taken together, our findings provide novel evidence that visceral adipose tissue of female mice display greater levels of pro-angiogenic factors and vascularity than males in response to high-fat diet. This phenotype is associated with preserved metabolic homeostasis at both tissue and systemic levels. Our study discloses that a thus-far-unappreciated sex-specific difference in the regulation of adipose angiogenesis may contribute to an individual’s susceptibility to developing adipose dysfunction and obesity-related metabolic disturbances