Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast

We have previously shown that autophagy is required for chronological longevity in the budding yeast Saccharomyces cerevisiae. Here we examine the requirements for autophagy during extension of chronological life span (CLS) by calorie restriction (CR). We find that autophagy is upregulated by two CR interventions that extend CLS: water wash CR and low glucose CR. Autophagy is required for full extension of CLS during water wash CR under all growth conditions tested. In contrast, autophagy was not uniformly required for full extension of CLS during low glucose CR, depending on the atg allele and strain genetic background. Leucine status influenced CLS during CR. Eliminating the leucine requirement in yeast strains or adding supplemental leucine to growth media extended CLS during CR. In addition, we observed that both water wash and low glucose CR promote mitochondrial respiration proficiency during aging of autophagy-deficient yeast. In general, the extension of CLS by water wash or low glucose CR was inversely related to respiration deficiency in autophagy-deficient cells. Also, autophagy is required for full extension of CLS under non-CR conditions in buffered media, suggesting that extension of CLS during CR is not solely due to reduced medium acidity. Thus, our findings show that autophagy is: (1) induced by CR, (2) required for full extension of CLS by CR in most cases (depending on atg allele, strain, and leucine availability) and, (3) promotes mitochondrial respiration proficiency during aging under CR conditions.     

General Validity of Levelt's Propositions Reveals Common Computational Mechanisms for Visual Rivalry

The mechanisms underlying conscious visual perception are often studied with either binocular rivalry or perceptual rivalry stimuli. Despite existing research into both types of rivalry, it remains unclear to what extent their underlying mechanisms involve common computational rules. Computational models of binocular rivalry mechanisms are generally tested against Levelt's four propositions, describing the psychophysical relation between stimulus strength and alternation dynamics in binocular rivalry. Here we use a bistable rotating structure-from-motion sphere, a generally studied form of perceptual rivalry, to demonstrate that Levelt's propositions also apply to the alternation dynamics of perceptual rivalry. Importantly, these findings suggest that bistability in structure-from-motion results from active cross-inhibition between neural populations with computational principles similar to those present in binocular rivalry. Thus, although the neural input to the computational mechanism of rivalry may stem from different cortical neurons and different cognitive levels the computational principles just prior to the production of visual awareness appear to be common to the two types of rivalry.     

Global attributes in visual word recognition: Part 2: The contribution of word length

The influence of perceived word length in the recognition of tachistoscopically presented isolated words in parafoveal vision has been investigated. A direct comparison has been made between responses obtained from work recognition experiments and from length perception experiments on strings derived from those words.Both types of response length distributions resemble each other, in particular with regard to the confusions, clearly showing an underestimation tendency. This indicates that word length operates as a separate cue in the recognition process.Experiments on elongated and shortened words also show that perceived length directly influences word responses.     

Metabolism of nitrogen-13 labelled ammonia in different conditions in dogs,human volunteers and transplant patients

To investigate the rate of metabolism of nitrogen-13 labelled ammonia (¹³NH₃) in different conditions, we have determined the relative amount of unchanged¹³NH₃ in the blood of dogs, volunteers and transplant patients at different times following injection. In dogs, the determinations were made under basal conditions, during adenosine administration and after coronary occlusion. The results show that adenosine administration increases the metabolic rate whereas coronary occlusion does not affect¹³NH₃ metabolism. For both human volunteers and transplant patients the metabolic rate of¹³NH₃ was assessed under basal conditions and during adenosine administration.¹³NH₃ metabolism proceeds faster in transplant patients than in volunteers under both conditions. Adenosine administration causes a faster¹³NH₃ turnover in volunteers but not in transplant patients. Application of individual metabolite correction resulted in a 16% decrease in the calculated blood flow compared to uncorrected values. A smaller difference (5%) was observed between correction with mean metabolite values and individually acquired metabolite values.     

Mitochondrial DNA mutations and apoptosis in mammalian aging

Mutations in mitochondrial DNA (mtDNA) accumulate during aging, but their significance to longevity and age-associated disease has been uncertain. Recently, in support of the hypothesis that mtDNA integrity is important, we have shown that age-associated diseases arise more rapidly in mice where mtDNA mutations and increased levels of apoptosis occur at higher rates than normal due to expression of an error-prone mtDNA polymerase. Further studies in this model may provide deeper insights into the relationship between mitochondria, aging, and susceptibility to age-associated diseases, such as cancer.     

Role of nitric oxide during coronary endothelial dysfunction after myocardial infarction

This study aimed to investigate whether permanent ischaemia influences subacute vasodilatation responses of non-infarcted rat coronary vasculature, and to characterise these coronary changes. Ischaemia led to a significant impairment of the endothelium-dependent vasodilator response, while coronary vasodilatory capacity remained unaltered. In normal coronary circulation, nitric oxide (NO) and prostanoids contributed to vasodilatation, while basal involvement of endothelium-derived hyperpolarising factor was limited. Vasodilatory impairment following myocardial infarction did not originate from alterations in the prostanoid pathway, and only a slightly increased influence of K+ channels was observed. However, NO-mediated vasodilatation was significantly increased after ischaemia, as also confirmed by higher mRNA and protein levels of iNOS and eNOS. Additionally, the amount of superoxide was enhanced following infarction. We conclude that subacute postinfarction remodeling is accompanied by endothelial dysfunction in non-infarcted coronary arteries. Although the NO-mediated response is increased after ischaemia, its final action is restricted due to the presence of superoxide.     

Molecular imaging in oncology: the acceptance of PET/CT and the emergence of MR/PET imaging

In the last decade, PET-only systems have been phased out and replaced with PET-CT systems. This merger of a functional and anatomical imaging modality turned out to be extremely useful in clinical practice. Currently, PET-CT is a major diagnostic tool in oncology. At the dawn of the merger of MRI and PET, another breakthrough in clinical imaging is expected. The combination of these imaging modalities is challenging, but has particular features such as imaging biological processes at the same time in specific body locations.     

Surgical angioplasty and unroofing technique for intramural coronary anomaly

A malign intramural course of the left main coronary artery is a rare anatomical anomaly. Surgical repair is mandatory since the condition is associated with myocardial ischemic syndromes and sudden death. Unroofing the intramural part and reconstructing a neo-ostium is challenging if the neo-ostium is immediately adjacent to the intercoronary commissure as there is a risk of narrowing the newly created ostium. We report a case in which we performed a surgical angioplasty of the left main coronary artery in combination with unroofing of the intramural section and resuspension of the intercoronary commissure.