Showing papers by "University of Tübingen published in 2001"

Conduction Model of Metal Oxide Gas Sensors

Abstract: Tin dioxide is a widely used sensitive material for gas sensors. Many research and development groups in academia and industry are contributing to the increase of (basic) knowledge/(applied) know-how. However, from a systematic point of view the knowledge gaining process seems not to be coherent. One reason is the lack of a general applicable model which combines the basic principles with measurable sensor parameters. The approach in the presented work is to provide a frame model that deals with all contributions involved in conduction within a real world sensor. For doing so, one starts with identifying the different building blocks of a sensor. Afterwards their main inputs are analyzed in combination with the gas reaction involved in sensing. At the end, the contributions are summarized together with their interactions. The work presented here is one step towards a general applicable model for real world gas sensors.

Auxin transport inhibitors block PIN1 cycling and vesicle trafficking

Abstract: Polar transport of the phytohormone auxin mediates various processes in plant growth and development, such as apical dominance, tropisms, vascular patterning and axis formation. This view is based largely on the effects of polar auxin transport inhibitors. These compounds disrupt auxin efflux from the cell but their mode of action is unknown. It is thought that polar auxin flux is caused by the asymmetric distribution of efflux carriers acting at the plasma membrane. The polar localization of efflux carrier candidate PIN1 supports this model. Here we show that the seemingly static localization of PIN1 results from rapid actin-dependent cycling between the plasma membrane and endosomal compartments. Auxin transport inhibitors block PIN1 cycling and inhibit trafficking of membrane proteins that are unrelated to auxin transport. Our data suggest that PIN1 cycling is of central importance for auxin transport and that auxin transport inhibitors affect efflux by generally interfering with membrane-trafficking processes. In support of our conclusion, the vesicle-trafficking inhibitor brefeldin A mimics physiological effects of auxin transport inhibitors.

Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies

Abstract: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. In approximately 80% of patients, auto-antibodies to the muscle nicotinic acetylcholine receptor (AChR) are present. These antibodies cause loss of AChR numbers and function, and lead to failure of neuromuscular transmission with muscle weakness. The pathogenic mechanisms acting in the 20% of patients with generalized MG who are seronegative for AChR-antibodies (AChR-Ab) have not been elucidated, but there is evidence that they also have an antibody-mediated disorder, with the antibodies directed towards another, previously unidentified muscle-surface-membrane target. Here we show that 70% of AChR-Ab-seronegative MG patients, but not AChR-Ab-seropositive MG patients, have serum auto-antibodies against the muscle-specific receptor tyrosine kinase, MuSK. MuSK mediates the agrin-induced clustering of AChRs during synapse formation, and is also expressed at the mature neuromuscular junction. The MuSK antibodies were specific for the extracellular domains of MuSK expressed in transfected COS7 cells and strongly inhibited MuSK function in cultured myotubes. Our results indicate the involvement of MuSK antibodies in the pathogenesis of AChR-Ab-seronegative MG, thus defining two immunologically distinct forms of the disease. Measurement of MuSK antibodies will substantially aid diagnosis and clinical management.

Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress

Abstract: Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1–10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported.

Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis.

Abstract: The association of pericytes (PCs) to newly formed blood vessels has been suggested to regulate endothelial cell (EC) proliferation, survival, migration, differentiation, and vascular branching. Here, we addressed these issues using PDGF-B– and PDGF receptor-β (PDGFR-β)–deficient mice as in vivo models of brain angiogenesis in the absence of PCs. Quantitative morphological analysis showed that these mutants have normal microvessel density, length, and number of branch points. However, absence of PCs correlates with endothelial hyperplasia, increased capillary diameter, abnormal EC shape and ultrastructure, changed cellular distribution of certain junctional proteins, and morphological signs of increased transendothelial permeability. Brain endothelial hyperplasia was observed already at embryonic day (E) 11.5 and persisted throughout development. From E 13.5, vascular endothelial growth factor-A (VEGF-A) and other genes responsive to metabolic stress became upregulated, suggesting that the abnormal microvessel architecture has systemic metabolic consequences. VEGF-A upregulation correlated temporally with the occurrence of vascular abnormalities in the placenta and dilation of the heart. Thus, although PC deficiency appears to have direct effects on EC number before E 13.5, the subsequent increased VEGF-A levels may further abrogate microvessel architecture, promote vascular permeability, and contribute to formation of the edematous phenotype observed in late gestation PDGF-B and PDGFR-β knock out embryos.

Regulation of plant growth by cytokinin

Abstract: Cytokinins are a class of plant-specific hormones that play a central role during the cell cycle and influence numerous developmental programs. Because of the lack of biosynthetic and signaling mutants, the regulatory roles of cytokinins are not well understood. We genetically engineered cytokinin oxidase expression in transgenic tobacco plants to reduce their endogenous cytokinin content. Cytokinin-deficient plants developed stunted shoots with smaller apical meristems. The plastochrone was prolonged, and leaf cell production was only 3–4% that of wild type, indicating an absolute requirement of cytokinins for leaf growth. In contrast, root meristems of transgenic plants were enlarged and gave rise to faster growing and more branched roots. These results suggest that cytokinins are an important regulatory factor of plant meristem activity and morphogenesis, with opposing roles in shoots and roots.

The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society.

Abstract: This review summarises the results and discussions of an UNESCO-MCBN supported symposium on oxidative stress and its role in the onset and progression of diabetes. There is convincing experimental and clinical evidence that the generation of reactive oxygen species (ROI) is increased in both types of diabetes and that the onset of diabetes is closely associated with oxidative stress. Nevertheless there is controversy about which markers of oxidative stress are most reliable and suitable for clinical practice. There are various mechanisms that contribute to the formation of ROI. It is generally accepted that vascular cells and especially the endothelium become one major source of ROI. An important role of oxidative stress for the development of vascular and neurological complications is suggested by experimental and clinical studies. The precise mechanisms by which oxidative stress may accelerate the development of complications in diabetes are only partly known. There is however evidence for a role of protein kinase C, advanced glycation end products (AGE) and activation of transcription factors such as NF kappa B, but the exact signalling pathways and the interactions with ROI remain a matter of discussion. Additionally, results of very recent studies suggest a role for ROI in the development of insulin resistance. ROI interfere with insulin signalling at various levels and are able to inhibit the translocation of GLUT4 in the plasma membrane. Evidence for a protective effect of antioxidants has been presented in experimental studies, but conclusive evidence from patient studies is missing. Large-scale clinical trials such as the DCCT Study or the UKPDS Study are needed to evaluate the long-term effects of antioxidants in diabetic patients and their potential to reduce the medical and socio-economic burden of diabetes and its complications.

Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-κB

Abstract: Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-kappaBp65. A comparable increase in NF-kappaBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta. These data demonstrate that ligands of RAGE can induce sustained activation of NF-kappaB as a result of increased levels of de novo synthesized NF-kappaBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-kappaB activation observed in hyperglycemia and possibly other chronic diseases.

Spatial awareness is a function of the temporal not the posterior parietal lobe

Abstract: Our current understanding of spatial behaviour and parietal lobe function is largely based on the belief that spatial neglect in humans (a lack of awareness of space on the side of the body contralateral to a brain injury) is typically associated with lesions of the posterior parietal lobe. However, in monkeys, this disorder is observed after lesions of the superior temporal cortex1, a puzzling discrepancy between the species. Here we show that, contrary to the widely accepted view, the superior temporal cortex is the neural substrate of spatial neglect in humans, as it is in monkeys. Unlike the monkey brain, spatial awareness in humans is a function largely confined to the right superior temporal cortex, a location topographically reminiscent of that for language on the left2. Hence, the decisive phylogenetic transition from monkey to human brain seems to be a restriction of a formerly bilateral function to the right side, rather than a shift from the temporal to the parietal lobe. One may speculate that this lateralization of spatial awareness parallels the emergence of an elaborate representation for language on the left side.

Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine

Abstract: Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria.

Dermcidin: a novel human antibiotic peptide secreted by sweat glands.

Abstract: Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47–amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.

Brain-computer communication: unlocking the locked in.

Abstract: With the increasing efficiency of life-support systems and better intensive care, more patients survive severe injuries of the brain and spinal cord. Many of these patients experience locked-in syndrome: The active mind is locked in a paralyzed body. Consequently, communication is extremely restricted or impossible. A muscle-independent communication channel overcomes this problem and is realized through a brain-computer interface, a direct connection between brain and computer. The number of technically elaborated brain-computer interfaces is in contrast with the number of systems used in the daily life of locked-in patients. It is hypothesized that a profound knowledge and consideration of psychological principles are necessary to make brain-computer interfaces feasible for locked-in patients.

A defined range of guard cell calcium oscillation parameters encodes stomatal movements

Abstract: Oscillations in cytosolic calcium concentration ([Ca2+]cyt) are central regulators of signal transduction cascades, although the roles of individual [Ca2+]cyt oscillation parameters in regulating downstream physiological responses remain largely unknown. In plants, guard cells integrate environmental and endogenous signals to regulate the aperture of stomatal pores and [Ca2+]cyt oscillations are a fundamental component of stomatal closure. Here we systematically vary [Ca2+]cyt oscillation parameters in Arabidopsis guard cells using a 'calcium clamp' and show that [Ca2+]cyt controls stomatal closure by two mechanisms. Short-term 'calcium-reactive' closure occurred rapidly when [Ca2+]cyt was elevated, whereas the degree of long-term steady-state closure was 'calcium programmed' by [Ca2+]cyt oscillations within a defined range of frequency, transient number, duration and amplitude. Furthermore, in guard cells of the gca2 mutant, [Ca2+]cyt oscillations induced by abscisic acid and extracellular calcium had increased frequencies and reduced transient duration, and steady-state stomatal closure was abolished. Experimentally imposing [Ca2+]cyt oscillations with parameters that elicited closure in the wild type restored long-term closure in gca2 stomata. These data show that a defined window of guard cell [Ca2+]cyt oscillation parameters programs changes in steady-state stomatal aperture.

Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces.

Abstract: Staphylococcus aureus is responsible for a large percentage of infections associated with implanted biomedical devices. The molecular basis of primary adhesion to artificial surfaces is not yet understood. Here, we demonstrate that teichoic acids, highly charged cell wall polymers, play a key role in the first step of biofilm formation. An S. aureus mutant bearing a stronger negative surface charge due to the lack of D-alanine esters in its teichoic acids can no longer colonize polystyrene or glass. The mutation abrogates primary adhesion to plastic while production of the glucosamine-based polymer involved in later steps of biofilm formation is not affected. Our data suggest that repulsive electrostatic forces can lead to reduced staphylococcal biofilm formation, which could have considerable impact on the design of novel implanted materials.

Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D

Abstract: Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss, vestibular dysfunction and visual impairment due to early onset retinitis pigmentosa (RP). So far, six loci (USH1A-USH1F) have been mapped, but only two USH1 genes have been identified: MYO7A for USH1B and the gene encoding harmonin for USH1C. We identified a Cuban pedigree linked to the locus for Usher syndrome type 1D (MIM 601067) within the q2 region of chromosome 10). Affected individuals present with congenital deafness and a highly variable degree of retinal degeneration. Using a positional candidate approach, we identified a new member of the cadherin gene superfamily, CDH23. It encodes a protein of 3,354 amino acids with a single transmembrane domain and 27 cadherin repeats. In the Cuban family, we detected two different mutations: a severe course of the retinal disease was observed in individuals homozygous for what is probably a truncating splice-site mutation (c.4488G-->C), whereas mild RP is present in individuals carrying the homozygous missense mutation R1746Q. A variable expression of the retinal phenotype was seen in patients with a combination of both mutations. In addition, we identified two mutations, Delta M1281 and IVS51+5G-->A, in a German USH1 patient. Our data show that different mutations in CDH23 result in USH1D with a variable retinal phenotype. In an accompanying paper, it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse.

Sublethal Irradiation Promotes Migration and Invasiveness of Glioma Cells: Implications for Radiotherapy of Human Glioblastoma

Abstract: Human malignant gliomas are highly lethal neoplasms. Involved-field radiotherapy is the most important therapeutic measure. Most relapses originate from the close vicinity of the irradiated target field. Here, we report that sublethal doses of irradiation enhance the migration and invasiveness of human malignant glioma cells. This hitherto unknown biological effect of irradiation is p53 independent, involves enhanced αvβ3 integrin expression, an altered profile of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9) expression and activity, altered membrane type 1 MMP and tissue inhibitor of metalloproteinases-2 expression, and an altered BCL-2/BAX rheostat favoring resistance to apoptosis. BCL-2 gene transfer and irradiation cooperate to enhance migration and invasiveness in a synergistic manner. Sublethal irradiation of rat 9L glioma cells results in the formation of a greater number of tumor satellites in the rat brain in vivo concomitant with enhanced MMP-2 and reduced tissue inhibitor of metalloproteinases-2 expression. Collectively, these data suggest that the current concepts of involved-field radiotherapy for malignant glioma need to be reconsidered and that the pharmacological inhibition of migration and invasion during radiotherapy may represent a new therapeutic approach to improve the therapeutic efficacy of radiotherapy for malignant glioma.

Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization

Abstract: Functional magnetic resonance imaging (fMRI) was employed to determine areas of activation in the cerebellar cortex in 46 human subjects during a series of motor tasks. To reduce the variance due to differences in individual anatomy, a specific transformational procedure for the cerebellum was introduced. The activation areas for movements of lips, tongue, hands, and feet were determined and found to be sharply confined to lobules and sublobules and their sagittal zones in the rostral and caudal spino-cerebellar cortex. There was a clear symmetry mirroring at the midline. The activation mapped as two distinct homunculoid representations. One, a more extended representation, was located upside down in the superior cerebellum, and a second one, doubled and smaller, in the inferior cerebellum. The two representations were remarkably similar to those proposed by Snider and Eldred [1951] five decades ago. In the upper representation, an intralimb somatotopy for the right elbow, wrist, and fingers was revealed. The maps seem to confirm earlier electrophysiological findings of sagittal zones in animals. They differ, however, from micromapping reports on fractured somatotopic maps in the cerebellar cortex of mammals. We assume that the representations that we observed are not solely the result of spatial integration of hemodynamic events underlying the fMRI method and may reflect integration of afferent peripheral and central information in the cerebellar cortex.

Are emotions contagious? Evoked emotions while viewing emotionally expressive faces: quality, quantity, time course and gender differences.

Abstract: In human interactions, frequently one individual becomes 'infected' with emotions displayed by his or her partner. We tested the predictions by Hatfield et al. (1992) (Primitive emotional contagion. Review of Personal and Social Psychology 14, 151-177) that the automatic, mostly unconscious component of this process, called 'primitive emotional contagion', is repeatable and fast, that stronger facial expressions of the sender evoke stronger emotions in the viewer and that women are more susceptible to emotional contagion than men. We presented photos from the Pictures of Facial Affect (Ekman and Friesen, 1976). (Pictures of Facial Affect. Consulting Psychologists Press, Palo Alto) on a PC varying the affective content (happy and sad), the expressive strength and the duration of presentation. After each photo, subjects rated the strength of experienced happiness, sadness, anger, disgust, surprise, fear and pleasure. Feelings of happiness or sadness were significantly, specifically and repeatedly evoked in the viewer - even with presentations lasting only 500 ms. Stronger expressions evoked more emotion. The gender of the viewer had weak effects. We hypothesize that this fast and repeatable reaction is likely to have a 'prewired' neural basis. We propose that the induction of emotional processes within a subject by the perception of emotionally expressive faces is a powerful instrument in the detection of emotional states in others and as the basis for one's own reactions. Detailed knowledge of emotional reactions to faces is also valuable as a basis for psychiatric studies of disorders in affect and/or communication and in studies using functional imaging (fMRI or PET) where faces are increasingly used as stimuli.

Reorganization of motor and somatosensory cortex in upper extremity amputees with phantom limb pain.

Abstract: Phantom limb pain (PLP) in amputees is associated with reorganizational changes in the somatosensory system To investigate the relationship between somatosensory and motor reorganization and phantom limb pain, we used focal transcranial magnetic stimulation (TMS) of the motor cortex and neuroelectric source imaging of the somatosensory cortex (SI) in patients with and without phantom limb pain For transcranial magnetic stimulation, recordings were made bilaterally from the biceps brachii, zygomaticus, and depressor labii inferioris muscles Neuroelectric source imaging of the EEG was obtained after somatosensory stimulation of the skin overlying face and hand Patients with phantom limb pain had larger motor-evoked potentials from the biceps brachii, and the map of outputs was larger for muscles on the amputated side compared with the intact side The optimal scalp positions for stimulation of the zygomaticus and depressor labii inferioris muscles were displaced significantly more medially (toward the missing hand representation) in patients with phantom limb pain only Neuroelectric source imaging revealed a similar medial displacement of the dipole center for face stimulation in patients with phantom limb pain There was a high correlation between the magnitude of the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortex and phantom limb pain These results show enhanced plasticity in both the motor and somatosensory domains in amputees with phantom limb pain

Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein

Abstract: Outer hair cells (OHCs) of the mammalian cochlea actively change their cell length in response to changes in membrane potential. This electromotility, thought to be the basis of cochlear amplification, is mediated by a voltage-sensitive motor molecule recently identified as the membrane protein prestin. Here, we show that voltage sensitivity is conferred to prestin by the intracellular anions chloride and bicarbonate. Removal of these anions abolished fast voltage-dependent motility, as well as the characteristic nonlinear charge movement ("gating currents") driving the underlying structural rearrangements of the protein. The results support a model in which anions act as extrinsic voltage sensors, which bind to the prestin molecule and thus trigger the conformational changes required for motility of OHCs.

Phantom movements and pain. An fMRI study in upper limb amputees.

Abstract: Using functional MRI, we investigated 14 upper limb amputees and seven healthy controls during the execution of hand and lip movements and imagined movements of the phantom limb or left hand. Only patients with phantom limb pain showed a shift of the lip representation into the deafferented primary motor and somatosensory hand areas during lip movements. Displacement of the lip representation in the primary motor and somatosensory cortex was positively correlated to the amount of phantom limb pain. Thalamic activation was only present during executed movements in the healthy controls. The cerebellum showed no evidence of reorganizational changes. In amputees, movement of the intact hand showed a level of activation similar to movement of the right dominant hand in the healthy controls. During imagination of moving the phantom hand, all patients showed significantly higher activation in the contralateral primary motor and somatosensory cortices compared with imagination of hand movements in the controls. In the patients with phantom limb pain but not the pain-free amputees, imagined movement of the phantom hand activated the neighbouring face area. These data suggest selective coactivation of the cortical hand and mouth areas in patients with phantom limb pain. This reorganizational change may be the neural correlate of phantom limb pain.

Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis

Abstract: Recently, we and others have shown that genetic and environmental changes that increase the load of yeast cells with reactive oxygen species (ROS) lead to a shortening of the life span of yeast mother cells. Deletions of yeast genes coding for the superoxide dismutases or the catalases, as well as changes in atmospheric oxygen concentration, considerably shortened the life span. The presence of the physiological antioxidant glutathione, on the other hand, increased the life span of yeast cells. Taken together, these results pointed to a role for oxygen in the yeast ageing process. Here, we show by staining with dihydrorhodamine that old yeast mother cells isolated by elutriation, but not young cells, contain ROS that are localized in the mitochondria. A relatively large proportion of the old mother cells shows phenotypic markers of yeast apoptosis, i.e. TUNEL (TdT-mediated dUTP nick end labelling) and annexin V staining. Although it has been shown previously that apoptosis in yeast can be induced by a cdc48 allele, by expressing pro-apoptotic human cDNAs or by stressing the cells with hydrogen peroxide, we are now showing a physiological role for apoptosis in unstressed but aged wild-type yeast mother cells.