298 research outputs found
The Role of TASK-3 Two-Pore Domain Potassium Channels in the Entrainment of Mammalian Circadian Rhythms
No full textIn mammals light is the principal timing cue for alignment of physiology to the external environment. Illumination from the unrelenting 24-hour day-night cycle enters the biological system and is communicated to the master pacemaker, the suprachiasmatic nucleus (SCN) to drive circadian entrainment.
The decoding of light by the retina and the signalling pathways to and from the SCN rely on neural excitation mechanisms, achieved through changes in membrane potential from a resting state stabilised by K2P channels. With TASK-3 being the most abundant K2P channel in the rodent SCN it is feasible this channel has a crucial role in regulating SCN neural transmission for effective circadian entrainment. This study investigates this role through the use of transgenic TASK-3 KO mice.
In the first experimental chapter I demonstrate the presence of TASK-3 mRNA in the SCN and retina of wild type mice. Further, I reveal a circadian pattern in TASK-3 mRNA expression with significant midday nadir which feasibly influences resting membrane potential (RMP) supporting increased neuronal excitation reported at this time.
The following three chapters explore TASK-3 conductance in behavioural output rhythms via locomotor activity studies under light-dark cycles and in constant darkness. This series of experiments highlights how TASK-3 is essential for effective adjustment to changing light and how loss of this channel reduces light-driven and endogenous activity intensity and rhythm amplitude.
With light entering the circadian system exclusively via the eyes, the role of TASK-3 at the level of the retina is of upmost importance to entrainment. This is investigated in chapter 6 using pupillary light reflex as a measure of retinal sensitivity and decoding capacity. Through manipulation of intensity and wavelength specific classes of photoreceptor are studied for their contribution to this non-image forming response. These experiments show TASK-3 ablation significantly attenuates retinal sensitivity to sub-saturating light in a mechanism likely to be melanopsin-independent.
Finally examination of mRNA expression of core clock genes reveals the role of TASK-3 at the level of the SCN. Here, loss of TASK-3 conductance is shown to alter daily rhythms in several key genes thereby linking the properties of this background leakage channel to the molecular clockwork.
Overall these experiments demonstrate some of the roles TASK-3 conductance plays within the SCN and in output rhythms; and the requirement of this channel within the retina for effective retinal decoding across the visible spectrum over a range of light intensities
Quarta pars operum Johannis Gerson prius non impressa
No full text[Hrsg.von Jakob Wimpheling ; mit Hiolzschnitt von Albrecht Dürer]Kolophon auf Bl. T7v: "...prodeunt feliciter ex officina Martini Flacci iunioris Argen., exactissima Mathie Schurer Sletstatini ... iij. kal. Martij. Anno. 1502."Bogensignaturen: aa-bb6, a-z6, A8, B6, C-F8, G-H6, I8. K6, L-M8, N-O6, P8, Q-R6, S-T
Involvement of Nitric Oxide in Microcirculatory Reactions after Ischemia-Reperfusion of the Rat Urinary Bladder
No full textBackground: Nitric oxide ( NO) plays a role in inflammation. Our aim was to investigate the role of NO in the microcirculatory changes after ischemia-reperfusion (I/R) of the bladder using intravital videomicroscopy (IVM). Methods: In rats, 60 min of bladder ischemia followed by 30 min of reperfusion was performed in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME), the NO precursor L-arginine, or saline pre-treatments. Venular red blood cell velocity (RBCV), functional capillary density (FCD), vessel diameters, and leukocyte-endothelial cell interactions in postcapillary venules were determined. Concentrations of nitrite/nitrate in the plasma and myeloperoxidase (MPO) levels in the lungs and the bladder were measured. Results: Elevations of the numbers of rolling and adherent leukocytes, and of plasma nitrite/nitrate levels were found, while FCD and RBCV decreased. L-NAME pretreatment ameliorated the enhanced leukocyte-endothelial cell interactions without influencing the microcirculatory perfusion. In contrast, the L - arginine pretreatment further increased plasma nitrite/nitrate levels and preserved the FCD and RBCV, but did not affect leukocyte-endothelial interactions. None of these treatments influenced MPO activities. Conclusion: Our results suggest that NO plays an enhancing role in the I/R-induced neutrophil-endothelial interactions of the bladder. Supplementation of NO ameliorates the microcirculatory perfusion deficit without influencing the postischemic microcirculatory inflammatory reactions. Copyright (c) 2008 S. Karger AG, Base
ABSOLUTE DIFFERENTIAL CROSS-SECTIONS FOR pi+- p ELASTIC SCATTERING AT 30 <= T (pi) <= 67-MeV
No full textAbsolute π±p differential cross sections have been measured at incident pion energies of 30.0, 45.0, and 66.8 MeV, using active targets of scintillator plastic (CH1.1) to detect recoil protons in coincidence with scattered pions. Statistical uncertainties are typically ±3%; systematic uncertainties are ±2%. The results are consistent with two earlier measurements by this group employing different experimental techniques at 67 MeV and higher incident pion energies. The π-p cross sections are in good agreement with currently accepted phase-shift analyses, but the corresponding π+p predictions are typically 15% higher at large angles than the π+p cross sections reported here
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