Time and Life: Applications of Modern Chronobiology

Chronobiology is that branch of science which objectively quantifies and explores mechanisms of biological time structure. It is an integrating discipline that impacts on all forms of life. When physiological functions are plotted along a time scale, they appear as regularly repetitive wave forms with means, amplitudes, phasing and periods. In nature these rhythms are found to have many frequencies, from a fraction of a second (ultradian) to a year or more (infradian or circannual); and those with periods of about one day (circadian) have been explored extensively. Examples of several circadian rhythms are given for experimental animals and man. Evidence is presented to show that it is particularly important to consider biological rhythmicity when interpreting experimental results or attempting to extrapolate from one species to another. An organism is indeed a different biochemical and morphological entity at different times, and it may be expected to react differently to a stimulus at different circadian phases. By taking advantage of natural rhythms in the susceptability to drugs, it is possible to optimize chemotherapy and radiotherapy for cancer and other diseases

The Effect of a Financial Crisis on Household Finances: A Case Study of Iceland’s Financial Crisis

Iceland experienced a financial crisis in 2008–2009 when its banking system collapsed, the currency lost half its value, most businesses became technically insolvent, house prices fell, and household debt increased due to indexation to foreign currencies or the price level. This paper tells the story of the crisis and maps the losses to households using a dataset from tax returns that includes all taxpayers in the country and contains the value of housing, mortgage debt, disposable income, and net worth. For relative losses in net worth, the results show that families with children, especially those with parents aged between 24 and 45 years, suffered the largest proportional losses in net worth. The losses were also greater in urban areas. The fall in net worth, measured in local currency, correlated with income and education level as well as the number of children and the urban area. Real disposable income fell by one third or more for a large fraction of the population, causing a further increase in the burden of debt, which increased most for the high-income groups before falling due to rising income and mortgage relief. Urban areas, where banks are located, experienced a boom-bust cycle, while the rural areas experienced this cycle to a much lesser extent. We find that net worth took many years to recover but that by 2019, net worth had recovered for all age groups

S-nitrosylation in Neuropathic pain and Autophagy

Dissertation for attaining the PhD degree of Natural Sciences submitted to the Faculty of Biochemistry, Chemistry and Pharmacy of the Johann Wolfgang Goethe University in Frankfurt am MainNeuropathic pain is a maladaptive form of chronic pain caused by a primary injury or lesions in the central or peripheral nervous systems. Recently nitric oxide (NO) has emerged as important pro-nociceptive signaling molecule in pain signaling and processing. Chemical inhibiton or deletion of Nitric oxide synthase (NOS), as well and inhibition of the NOS-coenzyme tetrahydrobiopterin is known to reduce or inhibit neuropathic pain. NO exert its influence through two major pathways: by stimulation of sGC and by direct S-nitrosylation (SNO) of target proteins. This study assessed in the spinal cord the SNO-proteome with two methods, two-dimensional S-nitrosothiol difference gel electrophoresis (2D SNO-DIGE) and SNO-site identification (SNOSID) at baseline and 24 h after sciatic nerve injury with/without pretreatment with the nitric oxide synthase inhibitor L-NAME. At 24h after nerve injury, SNO-DIGE revealed 30 proteins with increased S-nitrosylation and 23 proteins with decreased S-nitrosylation. SNO-sites were identified for 17 out of these 53 proteins. L-NAME pretreatment substantially reduced both constitutive and nerve injury evoked up-S-nitrosylation. For the top candidates S-nitrosylation was confirmed with the biotin switch technique and time course analyses at 1 and 7 days after nerve injury showed that SNO modifications of protein disulfide isomerase (PDI), glutathione synthase (GSS) and peroxiredoxin-6 (Prdx6) had returned to baseline within 7 days whereas S-nitrosylation of mitochondrial aconitase 2 (Aco2) was further increased. The identified SNO modified proteins are primarily involved in mitochondrial function, protein folding and transport, synaptic signaling and redox control. Several targets, including PDI, Heat shock cognate 71 kDa protein, and Serpin B6, indicated that NO might play a role in protein quality control, metabolism, and folding. Subsequently an investigation into the potential role of NO and SNO in proteasomal degradation and autophagy was performed. Autophagy is a basic catabolic mechanism involving the degradation of unnecessary or dysfunctional cellular components through the lysosomal machinery and is an important factor in the recovery of neurons after injury. A cellular model of neuronal nitric oxide synthase (nNOS) over-expressing neuroblastoma cell culture stimulated with rapamycin to induce autophagy was used. The effects of nNOS overexpression on autophagic processes were evaluated by western blotting with antibodies for known markers of autophagy. S-nitrosylation was evaluated using a combination of SNO-DIGE, SNOSID, SNO-SILAC, and SNO-ELISA methods. Increased (+ 144%, p < 0.05) LC3-I / LC3-II ratio in the nNOS over-expressing cells compared to the wild type after stimulation with rapamycin suggested that the autophagic activity may be impaired by the increase of NO and possibly by an increase of direct protein S-nitrosylation. In the nNOS over-expressing cells the total ubiquitination was increased (+100%, p < 0.01) while it was decreased (-30%, p < 0.01)) in the wild type cells after rapamycin stimulation. This indicates that the targeting or degradation processes may be impaired by the increase in S-nitrosylation of the E1, E2 or E3 ubiquitin ligases. The results suggest that S-nitrosylation may regulate protein folding, ubiquitination, and possibly de novo protein generation. In this study several proteins have emerged as major candidates for being targets of S-nitrosylation and consequentially may affect the autophagic processes, namely heat shock cognate 71 kDa protein and pyruvate kinase isozymes M1/M2, calreticulin, ubiquitin-conjugating enzyme E2 D1, and elongation factor 2. The results suggest that NO, in addition to its known regulation of cGMP signaling, may contribute to the fine tuning of protein folding and degradation which are key mechanisms for allowing neurons to recover stability after axonal injury

Response to the letter to the editor: Venous oxygen saturation is reduced and variable in central retinal vein occlusion

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Retinal Vessel Oxygen Saturation during 100% Oxygen Breathing in Healthy Individuals.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.To detect how systemic hyperoxia affects oxygen saturation in retinal arterioles and venules in healthy individuals.Retinal vessel oxygen saturation was measured in 30 healthy individuals with a spectrophotometric retinal oximeter (Oxymap T1). Oximetry was performed during breathing of room air, 100% oxygen (10 minutes, 6L/min) and then again room air (10 minutes recovery).Mean oxygen saturation rises modestly in retinal arterioles during 100% oxygen breathing (94.5%±3.8 vs. 92.0%±3.7% at baseline, p<0.0001) and dramatically in retinal venules (76.2%±8.0% vs. 51.3%±5.6%, p<0.0001). The arteriovenous difference decreased during 100% oxygen breathing (18.3%±9.0% vs. 40.7%±5.7%, p<0.0001). The mean diameter of arterioles decreased during 100% oxygen breathing compared to baseline (9.7±1.4 pixels vs. 10.3±1.3 pixels, p<0.0001) and the same applies to the mean venular diameter (11.4±1.2 pixels vs. 13.3±1.5 pixels, p<0.0001).Breathing 100% oxygen increases oxygen saturation in retinal arterioles and more so in venules and constricts them compared to baseline levels. The dramatic increase in oxygen saturation in venules reflects oxygen flow from the choroid and the unusual vascular anatomy and oxygen physiology of the eye.Icelandic Centre for Research 100429021 Landspitali-University Hospital Research Fund A-2013-023 Icelandic Fund for Prevention of Blindnes

The effect of a financial crisis on household finances: a case study of Iceland’s financial crisis

Iceland experienced a financial crisis in 2008–2009 when its banking system collapsed, the currency lost half its value, most businesses became technically insolvent, house prices fell, and household debt increased due to indexation to foreign currencies or the price level. This paper tells the story of the crisis and maps the losses to households using a dataset from tax returns that includes all taxpayers in the country and contains the value of housing, mortgage debt, disposable income, and net worth. For relative losses in net worth, the results show that families with children, especially those with parents aged between 24 and 45 years, suffered the largest proportional losses in net worth. The losses were also greater in urban areas. The fall in net worth, measured in local currency, correlated with income and education level as well as the number of children and the urban area. Real disposable income fell by one third or more for a large fraction of the population, causing a further increase in the burden of debt, which increased most for the high-income groups before falling due to rising income and mortgage relief. Urban areas, where banks are located, experienced a boom-bust cycle, while the rural areas experienced this cycle to a much lesser extent. We find that net worth took many years to recover but that by 2019, net worth had recovered for all age groups