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  • Wiley (CrossRef)  (23)
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  • 1
    Language: English
    In: European Journal of Organic Chemistry, July 2008, Vol.2008(19), pp.3314-3327
    Description: The stability of various substituted aryl‐3,3‐dialkyltriazenes, valuable synthetic intermediates, under several reaction conditions has been evaluated. To do so, anthranilonitrile and 2‐amino‐6‐(trifluoromethyl)benzonitrile have been reacted in the presence of different secondary amines to the corresponding 1‐(2‐R‐phenyl)‐3,3‐dialkyltriazenes. These compounds have been submitted to a series of different reaction conditions with special emphasis on strong basic and metal/acid reductive conditions in order to test the stability of the triazene moiety under these circumstances. Generally, triazenes are unstable in metal/acid reducing conditions. A lot of 1‐aryl‐3,3‐dialkyltriazenes are known to undergo deprotonation in α‐position of N‐3 in the presence of strong bases, thus limiting the scope of action of this class of compounds. Among the tested substances, most triazenes were stable in the presence of titanium isopropoxide and/or strong nucleophiles. 1‐(2‐R‐phenyl)‐3,3‐diisopropyltriazenes turned out to be particularly stable under strong basic conditions. 1,2‐addition reactions in the presence of Grignard reagents or lithiated compounds, showed in most cases no side products resulting from a degradation of the triazene function. The same was true for the titanium‐catalyzed Kulinkovich–de Meijere cyclopropanation or for reductive amination. In both cases, no triazene degradation products could be detected. 1‐(2‐R‐phenyl)‐3,3‐diisopropyltriazenes were even stable in the presence of strong Lewis acids like trimethylaluminium. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) 1‐(2‐Substituted phenyl)‐3,3‐diisopropyltriazenes are versatile and valuable synthetic intermediates because they are capable to stand strong bases. Beside they tolerate, in contrast to most triazenes, metal/acid reductive conditions and even the presence of strong Lewis acids like AlMe.
    Keywords: Triazenes ; Synthetic Intermediates ; Heterocycles ; Cyclopropanation ; Reductive Amination
    ISSN: 1434-193X
    E-ISSN: 1099-0690
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  • 2
    In: Annals of the New York Academy of Sciences, May 2013, Vol.12871(1), pp.45-58
    Description: In recent years, vitamin D has been received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries and the identification of extraskeletal effects of vitamin D, suggesting unexpected benefits of vitamin D in health and disease, beyond bone health. The possibility of extraskeletal effects of vitamin D was first noted with the discovery of the vitamin D receptor (VDR) in tissues and cells that are not involved in maintaining mineral homeostasis and bone health, including skin, placenta, pancreas, breast, prostate and colon cancer cells, and activated T cells. However, the biological significance of the expression of the VDR in different tissues is not fully understood, and the role of vitamin D in extraskeletal health has been a matter of debate. This report summarizes recent research on the roles for vitamin D in cancer, immunity and autoimmune diseases, cardiovascular and respiratory health, pregnancy, obesity, erythropoiesis, diabetes, muscle function, and aging.
    Keywords: Vitamin D ; Cancer ; Immunity ; Pregnancy ; Obesity ; Diabetes ; Pulmonary Disease ; Muscle ; Aging ; Cognitive Function
    ISSN: 0077-8923
    E-ISSN: 1749-6632
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  • 3
    In: Cellular Microbiology, July 2014, Vol.16(7), pp.977-992
    Description: The environmental bacterium causes a severe pneumonia termed egionnaires' disease. employs a conserved mechanism to replicate within a specific vacuole in macrophages or protozoa such as the social soil amoeba . athogen–host interactions depend on the / type secretion system (), which translocates approximately 300 different effector proteins into host cells. Here we analyse the effects of on migration and chemotaxis of amoebae, macrophages or polymorphonuclear neutrophils (). Using under‐agarose assays, inhibited in a dose‐ and ‐dependent manner the migration of towards folate as well as starvation‐induced aggregation of the social amoebae. Similarly, impaired migration of murine 264.7 macrophages towards the cytokines 5 and α, or of primary human towards the peptide respectively. lacking the ‐translocated activator of the small eukaryotic , 1976/1, hyper‐inhibited the migration of , macrophages or . The phenotype was reverted by plasmid‐encoded 1 to an extent observed for mutant bacteria lacking a functional /.Similarly, 1 promoted random migration of ‐infected macrophages and 549 epithelial cells in a ‐dependent manner, or upon ‘microbial microinjection’ into cells by a strain lacking endogenous effectors. Single‐cell tracking and real‐time analysis of ‐infected phagocytes revealed that the velocity and directionality of the cells were decreased, and cell motility as well as microtubule dynamics was impaired. Taken together, these findings indicate that the   activator 1 and consequent microtubule polymerization are implicated in /‐dependent inhibition of phagocyte migration. The amoebae‐resistant opportunistic pathogen determines host cell interactions through the Icm/Dot type IV secretion system, which translocates ∼ 300 different “effector” proteins into cells. was found to inhibit chemotactic and random migration of amoebae, macrophages and neutrophils in an Icm/Dot‐dependent manner. lacking the Icm/Dot‐translocated Ran GTPase activator LegG1 hyper‐inhibited phagocyte migration, and reliant on Ran, LegG1 promoted cell migration. Thus, LegG1‐dependent Ran activation and consequent microtubule polymerization antagonize Icm/Dot‐dependent inhibition of cell migration.
    Keywords: Folic Acid – Analysis;
    ISSN: 1462-5814
    E-ISSN: 1462-5822
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  • 4
    In: Clinical Respiratory Journal, January 2018, Vol.12(1), pp.68-75
    Description: Byline: Sylvia Lehmann, Steffen Leonhardt, Chuong Ngo, Lukas Bergmann, Simone Schrading, Konrad Heimann, Norbert Wagner, Klaus Tenbrock Keywords: cystic fibrosis; EIT; gravity; infiltration; lung; overinflation Abstract Introduction Electrical Impedance Tomography (EIT) is a tomographic, radiation-free technique based on the injection of a harmless alternating current. Objective As electrical impedance strictly correlates with the variation of air content, EIT delivers highly dynamic information about global and regional ventilation. We want to demonstrate the potential of EIT individualizing ventilation by positioning. Methods Gravity-dependent EIT findings were analyzed retrospectively in a critically ill mechanically ventilated pediatric patient with cystic fibrosis and coincident lung diseases. To further evaluate gravity-dependent changes in ventilation, six adult healthy and spontaneously breathing volunteers were investigated during simultaneous detection of EIT, breathing patterns, tidal volume (VT) and breathing frequency (BF). Results EIT findings in healthy lungs in five positions showed gravity-dependent effects of ventilation with overall ventilation of predominantly the right lung (except during left-side positioning) and with the ventral lung in supine, prone and upright position. These EIT-derived observations are in line with pathophysiological mechanisms and earlier EIT studies. Unexpectedly, the patient with cystic fibrosis and lobectomy of the right upper and middle lobe one year earlier, showed improvement of global and regional ventilation in the right position despite reduced lung volume and overinflation of this side. This resulted in individualized positioning and improvement of ventilation. Conclusions Although therapeutic recommendations are available for gravitational influences of lung ventilation, they can be contradictory depending on the underlying lung disease. EIT has the potential to guide therapists in the positioning of patients according to their individual condition and disease, especially in case of multiple lung injury. Article Note: Dr. med. S. Lehmann has obtained permission from all co-authors for the submission of the manuscript. Authorship and contributorship Dr. S. Lehmann: Designed and performed study, collected and analyzed data and wrote the paper. Prof. Dr.-Ing. Dr. med. Steffen Leonhardt: Co-designed the study and reviewed the paper. Chuong Ngo: Analyzed data and reviewed the paper. Lukas Bergmann: Analyzed data and reviewed the paper. Dr. med. Simone Schrading: Performed radiologic data correlation and reviewed the paper. Dr. med. Konrad Heimann: Reviewed the paper. Prof. Dr. Norbert Wagner: Reviewed the paper. PD Dr. Klaus Tenbrock: Co-designed the study and reviewed the paper. Ethics All volunteers provided written informed consent for this study and publication of the results. Conflict of interest S. Leonhardt discloses previous financial support for unrestricted research into EIT-based perfusion imaging from DrAaAaAeAnger Medical Gmb LAaAaAeA beck, Germany; he has also previously received honoraria for lecturi and consulting. There is no conflict of interest with this specific project. All other authors confirm no conflict of interest.
    Keywords: Cystic Fibrosis ; Eit ; Gravity ; Infiltration ; Lung ; Overinflation
    ISSN: 1752-6981
    E-ISSN: 1752-699X
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  • 5
    In: CNS Neuroscience & Therapeutics, November 2016, Vol.22(11), pp.894-905
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/cns.12564/abstract Byline: Karen Spruyt, Jian-sheng Lin, Osman S. Ipsiroglu, Nadia Beyzaei, Mai Berger, Alexandra L. Wagner, Sophia Dhalla, Jennifer Garden, Sylvia Stockler Keywords: Attention deficit hyperactivity disorder; Iron deficiency; Periodic limb movements in sleep; Polysomnography; Sleep problem Summary Background Willis-Ekbom disease/restless legs syndrome (WED/RLS) seems to be a frequent cause of intractable chronic insomnia (ICI) but is under-recognized in children/adolescents with neurodevelopmental conditions (NDCs), as many patients do not have the ability to express the underlying "urge-to-move". In light of this, we aim to develop a protocol for behavioral observations supporting the diagnosis of WED/RLS. Methods We investigated 26 pediatric patients (age 1-16 years, median 8) with NDCs, ICI and evidence of familial WED/RLS employing (1) "emplotted narratives" for description of the various "urge-to-move" presentations and (2) self-description and "behavioral observations" during a "suggested clinical immobilization test" (SCIT). Results Parental narratives reflected typical WED/RLS-related "urge-to-move" symptoms during day-, bed-, and nighttime in all patients. Fifteen out of 26 patients could describe the "urge-to-move" during the SCIT. Ten out of 26 patients, unable to describe their symptoms due to cognitive disabilities, showed patterns of "relieving-movements" upon observation. Sensory processing abnormalities were reported in all patients, with tactile sensitivities (26/26) (including shifted pain threshold) as the most common sensory domain. Conclusion "Emplotted narratives" and structured "behavioral observations" support recognition of familial WED/RLS associated movement patterns and provide a useful tool for the diagnosis of WED/RLS in children with NDCs in a clinical office setting.
    Keywords: Attention Deficit Hyperactivity Disorder ; Iron Deficiency ; Periodic Limb Movements In Sleep ; Polysomnography ; Sleep Problem
    ISSN: 1755-5930
    E-ISSN: 1755-5949
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  • 6
    In: Aging Cell, April 2012, Vol.11(2), pp.366-369
    Description: Replicative senescence has fundamental implications on cell morphology, proliferation, and differentiation potential. Here, we describe a simple method to track long‐term culture based on continuous DNA‐methylation changes at six specific CpG sites. This epigenetic senescence signature can be used as biomarker for various cell types to predict the state of cellular senescence with regard to the number of passages, population doublings, or days of culture.
    Keywords: Cellular Senescence ; Epigenetic ; Dna‐Methylation ; Mesenchymal Stem Cells ; Fibroblast
    ISSN: 1474-9718
    E-ISSN: 1474-9726
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  • 7
    In: Ecology and Evolution, November 2017, Vol.7(22), pp.9319-9332
    Description: High biodiversity is known to increase many ecosystem functions, but studies investigating biodiversity effects have more rarely looked at multi‐trophic interactions. We studied a tri‐trophic system composed of (brown knapweed), its flower head‐infesting tephritid fruit flies and their hymenopteran parasitoids, in a grassland biodiversity experiment. We aimed to disentangle the importance of direct effects of plant diversity (through changes in apparency and resource availability) from indirect effects (mediated by host plant quality and performance). To do this, we compared insect communities in transplants, whose growth was influenced by the surrounding plant communities (and where direct and indirect effects can occur), with potted plants, which do not compete with the surrounding plant community (and where only direct effects are possible). Tephritid infestation rate and insect load, mainly of the dominant species , decreased with increasing plant species and functional group richness. These effects were not seen in the potted plants and are therefore likely to be mediated by changes in host plant performance and quality. Parasitism rates, mainly of the abundant chalcid wasps and , increased with plant species or functional group richness in both transplants and potted plants, suggesting that direct effects of plant diversity are most important. The differential effects in transplants and potted plants emphasize the importance of plant‐mediated direct and indirect effects for trophic interactions at the community level. The findings also show how plant–plant interactions critically affect results obtained using transplants. More generally, our results indicate that plant biodiversity affects the abundance of higher trophic levels through a variety of different mechanisms. Previous studies on multi‐trophic interactions have shown that plant diversity effects can cascade up the food chain, but rarely differentiated between direct and indirect effects. Comparing tephritid and parasitoid responses to community plant diversity in potted and transplanted , we separated direct plant community effects from indirect effects mediated by host plant performance in the different communities. Tephritidae, mainly the dominant , negatively responded to increasing plant diversity, and these effects were not seen in the potted plants and are therefore likely to be mediated by changes in host plant performance and quality. Parasitism rates, mainly of the abundant chalcid wasps and , increased with plant diversity in both transplants and potted plants, suggesting that direct effects of plant diversity are most important. More generally, our results indicate that plant biodiversity affects the abundance of higher trophic levels through a variety of different mechanisms.
    Keywords: Chalcid Wasps ; Grassland ; Jena Experiment ; Tephritidae ; Tri‐Trophic System
    ISSN: 2045-7758
    E-ISSN: 2045-7758
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  • 8
    In: Hippocampus, July 2014, Vol.24(7), pp.840-852
    Description: The hippocampus is a brain area characterized by its high plasticity, observed at all levels of organization: molecular, synaptic, and cellular, the latter referring to the capacity of neural precursors within the hippocampus to give rise to new neurons throughout life. Recent findings suggest that promoter methylation is a plastic process subjected to regulation, and this plasticity seems to be particularly important for hippocampal neurogenesis. We have detected the enzyme GNMT (a liver metabolic enzyme) in the hippocampus. GNMT regulates intracellular levels of SAMe, which is a universal methyl donor implied in almost all methylation reactions and, thus, of prime importance for DNA methylation. In addition, we show that deficiency of this enzyme in mice (Gnmt−/−) results in high SAMe levels within the hippocampus, reduced neurogenic capacity, and spatial learning and memory impairment. In vitro, SAMe inhibited neural precursor cell division in a concentration‐dependent manner, but only when proliferation signals were triggered by bFGF. Indeed, SAMe inhibited the bFGF‐stimulated MAP kinase signaling cascade, resulting in decreased cyclin E expression. These results suggest that alterations in the concentration of SAMe impair neurogenesis and contribute to cognitive decline. © 2014 Wiley Periodicals, Inc.
    Keywords: Neurogenesis ; Neural Progenitor Cells ; Memory ; Learning ; Glycine N‐Methyltransferase ; S‐Adenosylmethionine
    ISSN: 1050-9631
    E-ISSN: 1098-1063
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  • 9
    Language: English
    In: Annals of Neurology, April 2005, Vol.57(4), pp.557-560
    Description: Methylation is an important aspect of many fundamental biological processes including creatine biosynthesis. We studied five patients with an inborn error of cobalamin metabolism to characterize the relation between homocysteine and creatine metabolism. Plasma guanidinoacetate concentrations were increased, 14.9 ± 4.8μmol/L ( 〈 0.0001), whereas plasma creatine concentrations were in the low reference range, 43.8 ± 20.7μmol/L ( = not significant). Individuals with combined methylmalonic aciduria and homocystinuria have a functional impairment of the creatine synthetic pathway probably secondary to a relative depletion of labile methyl groups. The neurotoxic effects of guanidinoacetate may be partly responsible for the observed neurological phenotype. Ann Neurol 2005;57:557–560
    Keywords: Neurology & Neuropathology;
    ISSN: 0364-5134
    E-ISSN: 1531-8249
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  • 10
    In: Aquatic Conservation: Marine and Freshwater Ecosystems, September 2016, Vol.26, pp.45-60
    Description: Copyright © 2016 John Wiley & Sons, Ltd.
    Keywords: Marine Areas Beqyond National Jurisdiction Abnj ; High Seas ; International Seabed Area ; Marine Protected Areas Mpas ; Regional Governance ; New Legally‐Binding Instrument Under The United Nations Law Of The Sea Unclos ; Biological Diversity Conservation
    ISSN: 1052-7613
    E-ISSN: 1099-0755
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