Региоселективный синтез и свойства ацетильных производных фенолгликозидов

Региоселективный синтез и свойства ацетильных производных фенолгликозидов. Работа посвящена выявлению реакционной способности при кислотном дезацетилировании с использованием HCl / EtOH в CHCl3, которая приводит к дезацетилированию на O-3, O-4 и O-6. Описанный реагент оказался общим и уникальным, и была получена серия 2-О-ацетиларилгликозидов. Вообще, частично ацетилированные арилгликозиды широко встречаются в природе. В частности, можно найти множество примеров 2-O-ацетиларилгликозидов.Regioselective synthesis and properties of acetyl derivatives of phenol glycosides. The thesis is devoted to the detection of reactivity during acid deacetylation using HCl / EtOH in CHCl3, which leads to deacetylation at O-3, O-4 and O-6. The described reagent proved to be general and unique and the series of 2-О-acetyl aryl glycosides were prepared. Generally, partially acetylated aryl glycosides are widely found in nature. Particularly, many examples of 2-O-acetyl aryl glycosides can be found

Oncostatin M-induced and constitutive activation of the JAK2/STAT5/CIS pathway suppresses CCL1, but not CCL7 and CCL8, chemokine expression

The recruitment of leukocytes to injured tissue is crucial for the initiation of inflammatory responses as well as for immune surveillance to fight tumor progression. In this study, we show that oncostatin M, a member of the IL-6-type cytokine family and potent proinflammatory cytokine stimulates the expression of the chemokines CCL1, CCL7, and CCL8 in primary human dermal fibroblasts at a faster kinetic than IL-1beta or TNF-alpha. The production of CCL1 and CCL8 is important for migration of monocytes, while specific Abs against CCL1 additionally inhibit the migration of T lymphocytes. We identify the mitogen-activated protein kinases ERK1/2 and p38 as crucial factors for the enhanced expression of CCL1 and CCL8. Depletion of the ERK1/2 target genes c-Jun or c-Fos strongly decrease CCL1 and CCL8 expression, while p38 MAPK prolongs the half-life of CCL1, CCL7, and CCL8 mRNA through inhibition of tristetraprolin. None of the STAT transcription factors STAT1, STAT3, or STAT5 stimulate transcription of CCL1 or CCL8. However, we identify a negative regulatory function of activated STAT5 for the gene expression of CCL1. Importantly, not STAT5 itself, but its target gene cytokine inducible SH2-domain containing protein is required for the STAT5 inhibitory effect on CCL1 expression. Finally, we show that constitutive activation of STAT5 through a mutated form of JAK2 (JAK2 V617F) occurring in patients with myeloproliferative disorders similarly suppresses CCL1 expression. Taken together, we identify novel important inflammatory target genes of OSM which are independent of STAT signaling per se, but depend on MAPK activation and are partly repressed through STAT5-dependent expression of cytokine inducible SH2-domain containing protein

WORKSHOP ON GUIDELINES FOR MANAGEMENT STRATEGY EVALUATIONS (WKGMSE2)

The purpose of the meeting was to bring up to date the methodologies and technical specifications that should be incorporated in Management Strategy Evaluation (MSE) work in ICES. The workshop was tasked with reviewing recent methodological and practical MSE work conducted in ICES and around the world, as well as the guidelines provided by the 2013 ICES Workshop on Guidelines for Management Strategy Evaluations (WKGMSE). The Terms of Reference indicated that the revision should include all aspects involved in MSE, while paying specific attention to several issues that had been identified through ICES practice. The Terms of Reference also requested WKGMSE 2 to consider how best to disseminate the guidelines to experts within the ICES community and the need for training courses. The workshop addressed all its Terms of Reference. The main results of the workshop are the revised MSE guidelines, as well as recommendations in relation to the ICES criterion for defining a management strategy as precautionary and in relation to the evaluation and advice on rebuilding strategies.publishedVersio

Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis

Background: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85-90%) and primary progressive (PP) MScl (10-15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins. Methodology/Principal Findings: CSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant proteins, such as protein jagged-1 and vitamin D-binding protein. Protein jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding protein was only detected in the RR MScl samples. These two proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types. Conclusions/Significance: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl

Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Multiple sclerosis is a complex neurological disease, with 3c20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFN\u3b3 biology, and NF\u3baB signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS. In a large multi-cohort study, unexplained heritability for multiple sclerosis is detected in low-frequency coding variants that are missed by GWAS analyses, further underscoring the role of immune genes in MS pathology

Molekulare Mechanismen der Oncostatin M-vermittelten Signaltransduktion und deren Bedeutung in der Entzündung sowie der antiviralen Immunabwehr

Die Dissertation beschäftigt sich mit der Oncostatin M-vermittelten Signaltransduktion und dessen Bedeutung für den entzündlichen Verlauf einer Rheumatoiden Arthritis, die immunmodulatorischen Fähigkeiten von Tumoren sowie die antivirale Immunantwort

Turn-of-the-month effect: New evidence from an emerging stock market

Due to copyright restrictions, the access to the full text of this article is only available via subscription.This paper analyzes the turn-of-the-month (ToM) effect in Turkish equity returns. We show that the ToM effect is strongly significant in BIST100 index over 1988–2014, and distinct from other calendar anomalies. In particular, the mean daily index return is 0.46% in the three-day period that covers the last trading day of each month and the first two trading days of the next month, and 0.09% in the remaining days. The ToM effect is more significant following months with (a) significant information flow and (b) above average market performance, and the fraction of index returns generated within the ToM period increases secularly from 39% over 1988–1996 to 49% over 1997–2005 and to 86% over 2006–2014. A similar month-end seasonal does not exist in index trading volume or realized volatility, ruling out standard liquidity or risk-based explanations. Estimating an e-GARCH model with daily index returns, however, we link the ToM effect to a decline in expected volatility in the days leading to month-turns. These findings resonate best with a story where gradual resolution of uncertainty following high information risk periods releases a large pool of “liquid funds” accumulated during such periods into the equity market, creating an abundance of liquidity and pushing equity prices up

Oncostatin M-induced and constitutive activation of the JAK2/STAT5/CIS pathway suppresses CCL1, but not CCL7 and CCL8, chemokine expression

The recruitment of leukocytes to injured tissue is crucial for the initiation of inflammatory responses as well as for immune surveillance to fight tumor progression. In this study, we show that oncostatin M, a member of the IL-6-type cytokine family and potent proinflammatory cytokine stimulates the expression of the chemokines CCL1, CCL7, and CCL8 in primary human dermal fibroblasts at a faster kinetic than IL-1beta or TNF-alpha. The production of CCL1 and CCL8 is important for migration of monocytes, while specific Abs against CCL1 additionally inhibit the migration of T lymphocytes. We identify the mitogen-activated protein kinases ERK1/2 and p38 as crucial factors for the enhanced expression of CCL1 and CCL8. Depletion of the ERK1/2 target genes c-Jun or c-Fos strongly decrease CCL1 and CCL8 expression, while p38 MAPK prolongs the half-life of CCL1, CCL7, and CCL8 mRNA through inhibition of tristetraprolin. None of the STAT transcription factors STAT1, STAT3, or STAT5 stimulate transcription of CCL1 or CCL8. However, we identify a negative regulatory function of activated STAT5 for the gene expression of CCL1. Importantly, not STAT5 itself, but its target gene cytokine inducible SH2-domain containing protein is required for the STAT5 inhibitory effect on CCL1 expression. Finally, we show that constitutive activation of STAT5 through a mutated form of JAK2 (JAK2 V617F) occurring in patients with myeloproliferative disorders similarly suppresses CCL1 expression. Taken together, we identify novel important inflammatory target genes of OSM which are independent of STAT signaling per se, but depend on MAPK activation and are partly repressed through STAT5-dependent expression of cytokine inducible SH2-domain containing protein

Design and optimization of an energy manager for an office building

Nowadays saving energy in the building sector is more important than ever. To achieve a reduction of energy consumption and also CO2 emissions of buildings, energy efficient Building Energy Management Systems (BEMS), respectively called energy managers, are developed in the research projectenerMAT. Therefore, enerMAT creates a novel approach for simulation, optimization, and verification that will aim to design a new generation of energy aware optimized BEMS which will allow an overall cross-trade automatic control of energy flows to maintain user comfort whilst minimizing energy consumption and CO2 emission. The optimization referenced to energy uses a model-based approach with an overall building system model enabling the assessment of the energy performance for different design and operation alternatives of the energy manager in interaction with the building. This system model allows a simulation-based, energy aware, global, dynamic, multi-criterial optimization of the energy manager. In this paper, the idea, the modeling of an office building and its energy manager and different optimization studies and their results are presented