Circadian Rhythmic Localization of tPA and PAI-1 in the SCN 2.2 Cell Culture May Provide Evidence for Determining the Mechanism of Gating Photic Phase Shifts

Mammalian circadian rhythms are controlled by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the brain. The SCN exhibits endogenous rhythms in neuronal activity and entrains to external stimuli, particularly light. Interestingly, phase shifts in response to light only occur at night and the mechanisms gating phase shifting are not well characterized. Our lab demonstrated that the extracellular protease, tissue-type plasminogen activator (tPA) and its inhibitor, plasminogen activator inhibitor (PAI-1), help gate phase shifting. Total tPA and PAI-1 expression are rhythmic in mouse SCN. These proteins mediate different functions depending on their exact subcellular localization. Therefore, knowing where they are located within the SCN will clarify their actions with respect to SCN clock phase regulation. The immortalized rat SCN2.2 cell culture exhibits rhythms in protein expression in vitro that mirror those found in vivo and can be separated into cellular, extracellular matrix, and media fractions. Here, we investigate tPA and PAI-1 expression using western blotting in the cellular fraction of the SCN2.2 line over a 36-hr timecourse. Preliminary results suggest a rhythm of PAI-1 levels inside the cell with peak expression in the early subjective night. Future studies are aimed toward elucidating the subcellular localization and temporal expression patterns of these proteins in the SCN

International earth science information network for global change decision making

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77259/1/AIAA-1991-154-296.pd

Steps Toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. XV. Long-Term Optical Monitoring of NGC 5548

We present the results of three years of ground-based observations of the Seyfert 1 galaxy NGC 5548, which combined with previously reported data, yield optical continuum and broad-line H-beta light curves for a total of eight years. The light curves consist of over 800 points, with a typical spacing of a few days between observations. During this eight-year period, the nuclear continuum has varied by more than a factor of seven, and the H-beta emission line has varied by a factor of nearly six. The H-beta emission line responds to continuum variations with a time delay or lag of 10-20 days, the precise value varying somewhat from year to year. We find some indications that the lag varies with continuum flux in the sense that the lag is larger when the source is brighter.Comment: 29 pages, 6 figures. Accepted for publication in ApJ (1999 Jan 10

A scoring system to predict renal outcome in IgA nephropathy: a nationwide 10-year prospective cohort study

Background. Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis, and a substantial number of patients succumb to end-stage renal disease (ESRD). However, prediction of the renal outcome in individual patients remains difficult. We have already published a scoring system using the data in a prospective cohort of IgAN patients followed up from 1995 to 2002

Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Increased activation of the renin-angiotensin system (RAS) may be important in promoting coronary heart disease (CHD) and renal dysfunction, but limited data are available on associations between angiotensin type 1 receptor (<it>AGT1R</it>) and angiotensinogen (<it>AGT</it>) genotypes in type 2 diabetes.</p> <p>Methods</p> <p>Study participants were diabetics from the Health Professionals Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). We analyzed single nucleotide polymorphisms (SNPs) associated with cardiovascular pathophysiology (including <it>AGT1R </it>T573C, <it>AGT1R </it>A1166C, and <it>AGT </it>M235T) and presence of renal dysfunction (eGFR<60 ml/min/1.73 m²) or history of CHD.</p> <p>Results</p> <p>The <it>AGT1R </it>1166 C-allele was associated with eGFR<60 ml/min/1.73 m²(multivariable OR 1.63 [1.01, 2.65]) in the HPFS men (n = 733) and in the combined dataset (n = 1566) (OR 1.42 [1.02, 1.98]). The <it>AGT1R </it>1166 C-allele was also associated with CHD in men (OR 1.57 [1.10, 2.24]). In NHS women (n = 833), <it>AGT </it>235T-allele was associated with CHD (OR 1.72 [1.20, 2.47]). Removal of hypertension from the fully adjusted models did not influence results, suggesting that the associations may not be mediated by hypertension. There were significant interactions between sex and <it>AGT1R </it>1166 C-allele (p = 0.008) and <it>AGT </it>M235T (p = 0.03) in models for CHD. No significant associations were seen between <it>AGT1R </it>T573 C-allele and renal dysfunction or CHD.</p> <p>Conclusion</p> <p>Polymorphisms in <it>AGT1R </it>and <it>AGT </it>genes are associated with renal dysfunction and CHD in type 2 diabetes and further support the important role of the RAS in these complications. Sex may modify associations between <it>AGT1R </it>1166 C-allele and <it>AGT </it>235T and CHD in type 2 diabetes.</p

Movement of environmental threats modifies the relevance of the defensive eye-blink in a spatially-tuned manner.

Subcortical reflexive motor responses are under continuous cortical control to produce the most effective behaviour. For example, the excitability of brainstem circuitry subserving the defensive hand-blink reflex (HBR), a response elicited by intense somatosensory stimuli to the wrist, depends on a number of properties of the eliciting stimulus. These include face-hand proximity, which has allowed the description of an HBR response field around the face (commonly referred to as a defensive peripersonal space, DPPS), as well as stimulus movement and probability of stimulus occurrence. However, the effect of stimulus-independent movements of objects in the environment has not been explored. Here we used virtual reality to test whether and how the HBR-derived DPPS is affected by the presence and movement of threatening objects in the environment. In two experiments conducted on 40 healthy volunteers, we observed that threatening arrows flying towards the participant result in DPPS expansion, an effect directionally-tuned towards the source of the arrows. These results indicate that the excitability of brainstem circuitry subserving the HBR is continuously adjusted, taking into account the movement of environmental objects. Such adjustments fit in a framework where the relevance of defensive actions is continually evaluated, to maximise their survival value