Functional Genomics Differentiate Inherent and Environmentally Influenced Traits in Dinoflagellate and Diatom Communities

Dinoflagellates and diatoms are among the most prominent microeukaryotic plankton groups, and they have evolved different functional traits reflecting their roles within ecosystems. However, links between their metabolic processes and functional traits within different environmental contexts warrant further study. The functional biodiversity of dinoflagellates and diatoms was accessed with metatranscriptomics using Pfam protein domains as proxies for functional processes. Despite the overall geographic similarity of functional responses, abiotic (i.e., temperature and salinity; ~800 Pfam domains) and biotic (i.e., taxonomic group; ~1500 Pfam domains) factors influencing particular functional responses were identified. Salinity and temperature were identified as the main drivers of community composition. Higher temperatures were associated with an increase of Pfam domains involved in energy metabolism and a decrease of processes associated with translation and the sulfur cycle. Salinity changes were correlated with the biosynthesis of secondary metabolites (e.g., terpenoids and polyketides) and signal transduction processes, indicating an overall strong effect on the biota. The abundance of dinoflagellates was positively correlated with nitrogen metabolism, vesicular transport and signal transduction, highlighting their link to biotic interactions (more so than diatoms) and suggesting the central role of species interactions in the evolution of dinoflagellates. Diatoms were associated with metabolites (e.g., isoprenoids and carotenoids), as well as lysine degradation, which highlights their ecological role as important primary producers and indicates the physiological importance of these metabolic pathways for diatoms in their natural environment. These approaches and gathered information will support ecological questions concerning the marine ecosystem state and metabolic interactions in the marine environment

Cytokine Effects on Gap Junction Communication and Connexin Expression in Human Bladder Smooth Muscle Cells and Suburothelial Myofibroblasts

BACKGROUND: The last decade identified cytokines as one group of major local cell signaling molecules related to bladder dysfunction like interstitial cystitis (IC) and overactive bladder syndrome (OAB). Gap junctional intercellular communication (GJIC) is essential for the coordination of normal bladder function and has been found to be altered in bladder dysfunction. Connexin (Cx) 43 and Cx45 are the most important gap junction proteins in bladder smooth muscle cells (hBSMC) and suburothelial myofibroblasts (hsMF). Modulation of connexin expression by cytokines has been demonstrated in various tissues. Therefore, we investigate the effect of interleukin (IL) 4, IL6, IL10, tumor necrosis factor-alpha (TNFα) and transforming growth factor-beta1 (TGFβ1) on GJIC, and Cx43 and Cx45 expression in cultured human bladder smooth muscle cells (hBSMC) and human suburothelial myofibroblasts (hsMF). METHODOLOGY/PRINCIPAL FINDINGS: HBSMC and hsMF cultures were set up from bladder tissue of patients undergoing cystectomy. In cytokine stimulated cultured hBSMC and hsMF GJIC was analyzed via Fluorescence Recovery after Photo-bleaching (FRAP). Cx43 and Cx45 expression was assessed by quantitative PCR and confocal immunofluorescence. Membrane protein fraction of Cx43 and Cx45 was quantified by Dot Blot. Upregulation of cell-cell-communication was found after IL6 stimulation in both cell types. In hBSMC IL4 and TGFβ1 decreased both, GJIC and Cx43 protein expression, while TNFα did not alter communication in FRAP-experiments but increased Cx43 expression. GJ plaques size correlated with coupling efficacy measured, while Cx45 expression did not correlate with modulation of GJIC. CONCLUSIONS/SIGNIFICANCE: Our finding of specific cytokine effects on GJIC support the notion that cytokines play a pivotal role for pathophysiology of OAB and IC. Interestingly, the effects were independent from the classical definition of pro- and antiinflammatory cytokines. We conclude, that connexin regulation involves genomic and/or post-translational events, and that GJIC in hBSMC and hsMF depend of Cx43 rather than on Cx45

Comparative Metabarcoding and Metatranscriptomic Analysis of Microeukaryotes Within Coastal Surface Waters of West Greenland and Northwest Iceland

Climate change alters environmental conditions that are expected to have a profound effect on the biodiversity, community composition, and metabolic processes of microeukaryotic plankton in Arctic and Subarctic coastal waters. The molecular biodiversity [large subunit (LSU) rRNA gene] of three plankton size-fractions (micro-, nano-, and picoplankton) from coastal waters of ice-influenced west Greenland was compared with fractions from ice-free northwest Iceland within their summer environmental context. Putative metabolic functions were determined by differentially expressed mRNA (metatranscriptomics) of the microplankton. Temperature and salinity variations were more closely correlated than inorganic macronutrients with metabolic functions and community composition. Temperature explained much of the community variance, approximately 20% among micro- and nanoplankton, whereas other environmental factors accounted for rather low fractional variance (<7%). Species of smaller cell-size were more evenly distributed (Pielou’s evenness index J) across regions, with a higher diversity and total abundance, and thereby indicating high plasticity. The metatranscriptomic profiles in these respective microeukaryotic communities revealed that diatoms were more plastic in their gene expression than dinoflagellates, but dinoflagellates had a more diverse, albeit homogeneously expressed, gene pool. This could be interpreted as expression of alternative lifestyle strategies, whereby the functionally more conservative diatoms fill their niches primarily through variable resource use, whereas dinoflagellates apparently differentiate their niches through more diverse lifestyles. Patterns of microeukaryotic diversity are thus primarily associated with differences in metabolic function and activity of diatom- versus dinoflagellate-dominated communities in Arctic and Subarctic waters during summer

New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC

Palmitate Induced IL-6 and MCP-1 Expression in Human Bladder Smooth Muscle Cells Provides a Link between Diabetes and Urinary Tract Infections

Therefore we studied the effects of the free fatty acid palmitate and bacterial lipopolysaccharide (LPS) on interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) expression and secretion in cultured human bladder smooth muscle cells (hBSMC).Biopsies were taken from patients undergoing cystectomy due to bladder cancer. Palmitate or LPS stimulated hBSMC were analysed for the production and secretion of the IL-6, gp80, gp80soluble, gp130, MCP-1, pSTAT3, SOCS3, NF-κB and SHP2 by quantitative PCR, ELISA, Western blotting, and confocal immunofluorescence. In signal transduction inhibition experiments we evaluated the involvement of NF-κB and MEK1 in IL-6 and MCP-1 regulation. Palmitate upregulates IL-6 mRNA expression and secretion via NF-κB dependent pathways in a concentration- and time-dependent manner. MCP-1 was moderately upregulated by palmitate but was strongly upregulated by LPS involving NF-κB and MEK1 dependent pathways. Soluble IL-6 receptor (gp80soluble) was downregulated by palmitate and LPS, while membrane-bound gp80 was moderately upregulated. LPS increased SOCS3 and SHP2, whereas palmitate only induced SOCS3. Secondary finding: most of the IL-6 is secreted.Bacterial infection (LPS) or metabolic alterations (palmitate) have distinct effects on IL-6 expression in hBSMC, (i) short term LPS induced autocrine JAK/STAT signaling and (ii) long-term endocrine regulation of IL-6 by palmitate. Induction of IL-6 in human bladder smooth muscle cells by fatty acids may represent a pathogenetic factor underlying the higher frequency and persistence of urinary tract infections in patients with metabolic diseases

Introducing DASC-PM: A Data Science Process Model

Data-driven disciplines like data mining and knowledge management already provide process-based frameworks for data analysis projects, such as the well-known cross-industry standard process for data mining (CRISP-DM) or knowledge discovery in databases (KDD). Although the domain of data science addresses a much broader problem space, i.e., also considers economic, social, and ecological impacts of data-driven projects, a corresponding domain-specific process model is still missing. Consequently, based on a total of four identified meta requirements and 17 corresponding requirements that were collected from experts of theory and practice, this contribution proposes the empirically grounded data science process model (DASC-PM)—a framework that maps a data science project as a four-step process model and contextualizes it among scientific procedures, various areas of application, IT infrastructures, and impacts. To illustrate the phase-oriented specification capabilities of the DASCPM, we exemplarily present competence and role profiles for the analysis phase of a data science project

Оценка экономической эффективности инновационного проекта в IT-сфере

Цель работы - разработка комплекса мероприятий по совершенствованию проектной деятельности в IT-сфере (на примере IT-проекта "UMKA"). В процессе исследования проводились изучения теоретических основ проектной деятельности компании, особенности реализации инновационных проектов в IT-сфере, анализировались модели, методы и показатели оценки эффективности IT-проекта, выявлялись особенности оценки эффективности проектов в IT-сфере. В практической части проводилась оценка эффективности IT-проекта "UMKA", разработанная и реализуемая ООО "I-link".The work purpose - development of complex of measures on improvement of project activities in the IT sphere (on the example of an IT project "UMKA"). In the process of research was conducted to study the theoretical basics of project activities of the company, peculiarities of realization of innovative projects in the IT field, we have analyzed the models, methods and indicators to measure the effectiveness of an IT project and identified the features of estimation of efficiency of projects in the IT sphere. In the practical part of the evaluation of the effectiveness of IT-project "UMKA", developed and implemented by "I-link"

Glatiramer Acetate Treatment in Multiple Sclerosis-Associated Fatigue—Beneficial Effects on Self-Assessment Scales But Not on Molecular Markers

Although fatigue is a common symptom in multiple sclerosis (MS), its pathomechanisms are incompletely understood. Glatiramer acetate (GA), an immunomodulatory agent approved for treatment of relapsing-remitting MS (RRMS), possesses unique mechanisms of action and has been shown to exhibit beneficial effects on MS fatigue. The objective of this study was to correlate clinical, neuropsychological, and immunological parameters in RRMS patients with fatigue before and during treatment with GA. In a prospective, open-label, multicenter trial, 30 patients with RRMS and fatigue were treated with GA for 12 months. Inclusion criterion was the presence of fatigue as one of the most frequent and disabling symptoms. Before and during treatment, fatigue was assessed using the Fatigue Severity Scale (FSS), the MS-FSS, and the Modified Fatigue Impact Scale (MFIS). In addition, fatigue and quality of life were assessed using the Visual Analog Scales (VAS). Laboratory assessments included screening of 188 parameters using real-time PCR microarrays followed by further analysis of several cytokines, chemokines, and neurotrophic factors. Fatigue self-assessments were completed in 25 patients. After 12 months of treatment with GA, 13 of these patients improved in all three scales (with the most prominent effects on the MFIS), whereas 5 patients had deteriorated. The remaining 7 patients exhibited inconsistent effects within the three scales. Fatigue and overall quality of life had improved, as assessed via VAS. Laboratory assessments revealed heterogeneous mRNA levels of cytokines, chemokines, and neurotrophic factors. In conclusion, we were not able to correlate clinical and molecular effects of GA in patients with RRMS and fatigue

Metatranscriptome Profiling Indicates Size-Dependent Differentiation in Plastic and Conserved Community Traits and Functional Diversification in Dinoflagellate Communities

Communities of microscopic dinoflagellates are omnipresent in aquatic ecosystems. Consequently, their traits drive community processes with profound effects on global biogeochemistry. Species traits are, however, not necessarily static but respond to environmental changes in order to maintain fitness and may differ with cell size that scales physiological rates. Comprehending such trait characteristics is necessary for a mechanistic understanding of plankton community dynamics and resulting biogeochemical impacts. Here, we used information theory to analyze metatranscriptomes of micro- and nano-dinoflagellate communities in three ecosystems. Measures of gene expression variations were set as a proxy to determine conserved and plastic community traits and the environmental influence on trait changes. Using metabarcoding, we further investigated if communities with a more similar taxon composition also express more similar traits. Our results indicate that plastic community traits mainly arise from membrane vesicle associated processes in all the environments we investigated. A specific environmental influence on trait plasticity was observed to arise from nitrogen availability in both size classes. Species interactions also appeared to be responsible for trait plasticity in the smaller-sized dinoflagellates. Additionally, the smaller-sized dinoflagellate communities are characterized by the expression of a large pool of habitat specific genes despite being taxonomically more similar across the habitats, in contrast to the microplanktonic assemblages that adapted to their environments by changing species composition. Our data highlight the functional diversification on the gene level as a signature of smaller sized dinoflagellates, nitrogen availability and species interactions as drivers of trait plasticity, and traits most likely linked to fitness and community performance