Search results for "hate"
showing 10 items of 2099 documents
Design, Synthesis and Biological Evaluation of 7-Chloro-9
2019
Glycogen synthase kinase-3β (GSK-3β) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer’s disease. We herein report on the optimization of a novel class of GSK-3β inhibitors based on the tofacitinib-derived screen hit 3-((3R,4R)-3-((7-chloro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino)-4-methylpiperidin-1-yl)-3-oxopropanenitrile (1). We synthesized a series of 19 novel 7-chloro-9H-pyrimido[4,5-b]indole-based derivatives and studied their structure–activity relationships with focus on the cyanoacetyl piperidine moiety. We unveiled the crucial role of the nitrile group and its importance for the activity of this compound series. A successfu…
Global distributions of diazotrophs abundance and biomass - Depth integrated values computed from a collection of source datasets - Contribution to t…
2013
The MAREDAT atlas covers 11 types of plankton, ranging in size from bacteria to jellyfish. Together, these plankton groups determine the health and productivity of the global ocean and play a vital role in the global carbon cycle. Working within a uniform and consistent spatial and depth grid (map) of the global ocean, the researchers compiled thousands and tens of thousands of data points to identify regions of plankton abundance and scarcity as well as areas of data abundance and scarcity. At many of the grid points, the MAREDAT team accomplished the difficult conversion from abundance (numbers of organisms) to biomass (carbon mass of organisms). The MAREDAT atlas provides an unprecedente…
Global distributions of diazotrophs nitrogen fixation rates - Depth integrated values computed from a collection of source datasets - Contribution to…
2013
The MAREDAT atlas covers 11 types of plankton, ranging in size from bacteria to jellyfish. Together, these plankton groups determine the health and productivity of the global ocean and play a vital role in the global carbon cycle. Working within a uniform and consistent spatial and depth grid (map) of the global ocean, the researchers compiled thousands and tens of thousands of data points to identify regions of plankton abundance and scarcity as well as areas of data abundance and scarcity. At many of the grid points, the MAREDAT team accomplished the difficult conversion from abundance (numbers of organisms) to biomass (carbon mass of organisms). The MAREDAT atlas provides an unprecedente…
Pivotal Advance: Up-regulation of acetylcholine synthesis and paracrine cholinergic signaling in intravascular transplant leukocytes during rejection…
2009
Abstract A new role and source of the old mediator acetylcholine is described, which is produced by graft monocytes and attenuates monocytic ATP-signaling. During acute rejection, large numbers of leukocytes accumulate in the blood vessels of experimental renal allografts. About 70% of them are activated, cytotoxic monocytes that appear to be involved in allograft destruction. ACh exerts anti-inflammatory effects upon monocytes/macrophages and has been proposed to be a key player in neuroimmunological interactions. Its short half-life, however, makes it unlikely that neuronal ACh affects blood leukocytes. Renal transplantation was performed in the allogeneic DA to LEW and in the isogeneic L…
Mechanically-biologically treated municipal solid waste as a support medium for microbial methane oxidation to mitigate landfill greenhouse emissions.
2005
The residual fraction of mechanically-biologically treated municipal solid waste (MBT residual) was studied in the laboratory to evaluate its suitability and environmental compatibility as a support medium in methane (CH(4)) oxidative biocovers for the mitigation of greenhouse gas emissions from landfills. Two MBT residuals with 5 and 12 months total (aerobic) biological stabilisation times were used in the study. MBT residual appeared to be a favourable medium for CH(4) oxidation as indicated by its area-based CH(4) oxidation rates (12.2-82.3 g CH(4) m(-2) d(-1) at 2-25 degrees C; determined in CH(4)-sparged columns). The CH(4) oxidation potential (determined in batch assays) of the MBT re…
Cytosolic Ca2+ and Phosphoinositide Hydrolysis Linked to Constitutively Active α1d-Adrenoceptors in Vascular Smooth Muscle
2003
In the present study, we analyzed changes in intracellular Ca2+ levels and inositol phosphate accumulation related to a population of alpha 1d-adrenoceptors in rat aorta resembling constitutively active receptors. Following intracellular Ca2+ store depletion by noradrenaline in Ca2+-free medium and removal of the agonist, restoration of extracellular Ca2+ induced four signals: a biphasic (transient and sustained) increase in [Ca2+]i, inositol phosphate accumulation, and a contractile response in the aorta. The transient increase in Ca2+, the inositol phosphate accumulation, and the contractile response were not observed in aortae incubated with prazosin or BMY 7378 [8-[2-[4-(2-methoxyphenyl…
Co-transmitter mediated facilitation by sympathetic nerve stimulation of evoked acetylcholine release from the rabbit perfused atria preparation.
1995
Rabbit atria were isolated with the extrinsic right sympathetic and vagus nerves attached and perfused with Tyrode solution. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline and fractionation of the radioactivity on cation exchange columns. Sympathetic nerve stimulation (SNS, 2 Hz, 3 min) carried out together with vagus nerve stimulation (VNS, 2 Hz, 3 min), but each SNS pulse preceding a vagal one by 19 ms, caused a facilitation of acetylcholine overflow of about 60% versus independent controls in the absence of SNS. Antagonists of putative neurotransmitters were tested to find out the prejunctional mediator involved in the facilitation. The …
Closer to nature: an ATP-driven bioinspired catalytic oxidation process
2013
The capability of DNA to acquire enzyme-like properties has led to the emergence of the so-called DNAzyme field; herein, we take a further leap along this nature-inspired road, demonstrating that a template assembled synthetic G-quartet (TASQ) can act as a pre-catalyst for catalytic peroxidase-mimicking oxidation reactions, whatever its nature (guanine or guanosine-based G-quartets), in an ATP-dependent manner, thereby bringing this bioinspired TASQzyme process even closer to nature.
Extracellular cyclic GMP and its derivatives GMP and guanosine protect from oxidative glutamate toxicity.
2013
Cell death in response to oxidative stress plays a role in a variety of neurodegenerative diseases and can be studied in detail in the neuronal cell line HT22, where extracellular glutamate causes glutathione depletion by inhibition of the glutamate/cystine antiporter system xc(-), elevation of reactive oxygen species and eventually programmed cell death caused by cytotoxic calcium influx. Using this paradigm, we screened 54 putative extracellular peptide or small molecule ligands for effects on cell death and identified extracellular cyclic guanosine monophosphate (cGMP) as a protective substance. Extracellular cGMP was protective, whereas the cell-permeable cGMP analog 8-pCPT-cGMP or the …
�ber das Vorkommen der Glucose-6-Phosphat-Dehydrogenase im Blutserum von Psoriasis vulgaris-Kranken
1963
ImBlutserum von 48Psoriasis vulgaris-Kranken konnte, weitgehend in Abhangigkeit von der Ausdehnung und Akuitat der Hauterscheinungen, eineErhohung derGlucose-6-Phosphat-Dehydrogenase nachgewiesen werden. Dieser Befund wird vergleichend mit den Ergebnissen bei Gesunden und anderen Hautkranken diskutiert und als psoriasistypisches, nicht aber psoriasisspezifisches Phanomen gewertet, fur dessen Zustandekommen auf Grund der bisherigen Untersuchungen eine Erklarung nicht gegeben werden kann, wenngleich im Hinblick auf das Vorkommen von Pentosen in pathologisch veranderter Psoriasis-Haut zu diesem, den Pentose-Cyclus einleitenden Enzym eine hypothetische Verbindung gegeben scheint.