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Bart Funnekotter

Bio: Bart Funnekotter is an academic researcher. The author has an hindex of 2, co-authored 2 publications receiving 2601 citations.

Papers
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07 Jun 2005-Eureka

1,705 citations

OtherDOI
07 Jun 2005-Eureka

899 citations


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Journal ArticleDOI
TL;DR: A "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction, and the delicate balance between the positive and negative effects of Ca( 2+) and the signaling events that perturb this balance is highlighted.
Abstract: The mitochondrion is at the core of cellular energy metabolism, being the site of most ATP generation. Calcium is a key regulator of mitochondrial function and acts at several levels within the organelle to stimulate ATP synthesis. However, the dysregulation of mitochondrial Ca(2+) homeostasis is now recognized to play a key role in several pathologies. For example, mitochondrial matrix Ca(2+) overload can lead to enhanced generation of reactive oxygen species, triggering of the permeability transition pore, and cytochrome c release, leading to apoptosis. Despite progress regarding the independent roles of both Ca(2+) and mitochondrial dysfunction in disease, the molecular mechanisms by which Ca(2+) can elicit mitochondrial dysfunction remain elusive. This review highlights the delicate balance between the positive and negative effects of Ca(2+) and the signaling events that perturb this balance. Overall, a "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction.

2,265 citations

Journal ArticleDOI
TL;DR: The fate of the modified components, the energetic costs to the cell of replacing such components, as well as strategies to minimize transfer of oxidatively damaged components to the next generation are considered.
Abstract: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced in many places in living cells and at an increased rate during biotic or abiotic stress. ROS and RNS participate in signal transduction, but also modify cellular components and cause dam- age. We first look at the most common ROS and their properties. We then consider the ways in which the cell can regulate their pro- duction and removal. We critically assess current knowledge about modifications of polyunsaturated fatty acids (PUFAs), DNA, carbo- hydrates, and proteins and illustrate this knowledge with case stories wherever possible. Some oxidative breakdown products, e.g., from PUFA, can cause secondary damage. Other oxidation products are secondary signaling molecules. We consider the fate of the modi- fied components, the energetic costs to the cell of replacing such components, as well as strategies to minimize transfer of oxidatively damaged components to the next generation.

1,643 citations

Journal ArticleDOI
TL;DR: The results of the literature study performed here reveal that there is indeed clear empirical evidence for a positive correlation between corporate social and financial performance as mentioned in this paper. But, the answer to the question has apparently not been found yet, at least that is what many researchers state.
Abstract: One of the older questions in the debate about Corporate Social Responsibility (CSR) is whether it is worthwhile for organizations to pay attention to societal demands. This debate was emotionally, normatively, and ideologically loaded. Up to the present, this question has been an important trigger for empirical research in CSR. However, the answer to the question has apparently not been found yet, at least that is what many researchers state. This apparent ambivalence in CSR consequences invites a literature study that can clarify the debate and allow for the drawing of conclusions. The results of the literature study performed here reveal that there is indeed clear empirical evidence for a positive correlation between corporate social and financial performance. Voices that state the opposite refer to out-dated material. Since the beginnings of the CSR debate, societies have changed. We can therefore clearly state that, for the present Western society, “Good Ethics is Good Business.”

971 citations

Journal ArticleDOI
TL;DR: This review summarizes the basic concepts underlying pressure-volume analysis of ventricular and myocardial systolic and diastolic properties, deviations from ideal conditions typically encountered in real-life applications, how these relationships are appropriately analyzed, including statistical analyses, and the most common problems encountered by investigators and the appropriate remedies.
Abstract: Assessment of left ventricular systolic and diastolic pump properties is fundamental to advancing the understanding of cardiovascular pathophysiology and therapeutics, especially for heart failure. The use of end-systolic and end-diastolic pressure-volume relationships derived from measurements of instantaneous left ventricular pressure-volume loops emerged in the 1970s as a comprehensive approach for this purpose. As invasive and noninvasive techniques for measuring ventricular volume improved over the past decades, these relations have become commonly used by basic, translational, and clinical researchers. This review summarizes 1) the basic concepts underlying pressure-volume analysis of ventricular and myocardial systolic and diastolic properties, 2) deviations from ideal conditions typically encountered in real-life applications, 3) how these relationships are appropriately analyzed, including statistical analyses, and 4) the most common problems encountered by investigators and the appropriate remedies. The goal is to provide practical information and simple guidelines for accurate application and interpretation of pressure-volume data as they pertain to characterization of ventricular and myocardial properties in health and disease.

695 citations

Journal ArticleDOI
TL;DR: A modified GMYC model is developed that allows for a variable transition from coalescent to speciation among lineages and provides a method of species discovery and biodiversity assessment using single-locus data from mixed or environmental samples while building a globally available taxonomic database for future identifications.
Abstract: High-throughput DNA sequencing has the potential to accelerate species discovery if it is able to recognize evolutionary entities from sequence data that are comparable to species. The general mixed Yule-coalescent (GMYC) model estimates the species boundary from DNA surveys by identifying independently evolving lineages as a transition from coalescent to speciation branching patterns on a phylogenetic tree. Applied here to 12 families from 4 orders of insects in Madagascar, we used the model to delineate 370 putative species from mitochondrial DNA sequence variation among 1614 individuals. These were compared with data from the nuclear genome and morphological identification and found to be highly congruent (98% and 94%). We developed a modified GMYC that allows for a variable transition from coalescent to speciation among lineages. This revised model increased the congruence with morphology (97%), suggesting that a variable threshold better reflects the clustering of sequence data into biological species. Local endemism was pronounced in all 5 insect groups. Most species (60-91%) and haplotypes (88-99%) were found at only 1 of the 5 study sites (40-1000 km apart). This pronounced endemism resulted in a 37% increase in species numbers using diagnostic nucleotides in a population aggregation analysis. Sample sizes between 7 and 10 individuals represented a threshold above which there was minimal increase in genetic diversity, broadly agreeing with coalescent theory and other empirical studies. Our results from >1.4 Mb of empirical data suggest that the GMYC model captures species boundaries comparable to those from traditional methods without the need for prior hypotheses of population coherence. This provides a method of species discovery and biodiversity assessment using single-locus data from mixed or environmental samples while building a globally available taxonomic database for future identifications. (Biodiversity; coalescent; DNA barcoding; DNA taxonomy; endemism; GMYC; Madagascar; turnover.)

652 citations