0000000000406778

AUTHOR

Christine Ziegler

Der Zellzyklus: Lebenszyklus einer Zelle

„Omnis cellula e cellula“, die Feststellung von Rudolf Virchow aus dem Jahr 1858, dass eine Zelle immer nur aus einer Zelle hervorgehen kann, weist bereits auf den Prozess des Zellzyklus hin. Dieser beschreibt eine Abfolge von Vorgangen, die zur Teilung und Verdopplung von Zellen fuhrt und in unterschiedliche Phasen eingeteilt werden kann, die von miteinander interagierenden Proteinen, den Cyclinen und cyclinabhangigen Kinasen, kontrolliert werden. Dabei ist zwingend, dass die Replikation der DNA konservativ erfolgt, d. h. Struktur und Sequenz wahrend der DNA‐Duplikation, die der Zellteilung vorausgeht, unverandert bleiben. Zur Uberwachung dienen sog. Checkpoints; Proteine wie p53 und Rb si…

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The Effect of Bialaphos on Ammonium-Assimilation and Photosynthesis I. Effect on the Enzymes of Ammonium-Assimilation

Abstract In this investigation, the effect of bialaphos (phosphinothricyl-alanyl-alanine) on the enzymes involved in NH4 +-assimilation - glutamine synthetase, glutamine-2-oxoglutarate aminotransferase, glutamate dehydrogenase - is examined and compared to the effect of phosphinothricin (glufosinate) on the same enzymes. Bialaphos was given to whole plants (in vivo) and to leaf homogenate (in vitro). The investigation showed that bialaphos has an inhibiting effect on glutamine synthetase in vivo, but not in vitro. In contrast to this, phosphinothricin inhibits glutamine synthetase in vitro as well as in vivo. It was found that bialaphos, similar to phosphinothricin, does not inhibit glutami…

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Selected Age-Related Disorders

Aged human individuals are frequently affected by various age-related impairments and disorders at once (multimorbidity) making it difficult to investigate and understand the link between aging as key risk factor and single syndromes. In some chapters of this book links have been identified between molecular mechanisms of aging and the pathogenesis of human disorders in the elderly. Here, the focus is put on Alzheimers disease (AD) and cancer. While cancer in many cases can successfully be treated and sometimes even cured by pharmacology and/or surgery, AD is still an incurable deadly disease. Like almost no other disorder the onset of AD is strictly associated with higher age and experienc…

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Ausgewählte altersbedingte Erkrankungen

Alte Menschen sind haufig von mehreren altersbedingten Beeintrachtigungen und Erkrankungen gleichzeitig betroffen (Multimorbiditat), was die Untersuchung und das Verstandnis der Verknupfung zwischen der Alterung als dem entscheidenden Risikofaktor und einzelnen Syndromen schwierig macht. In einigen Kapiteln dieses Buchs wurden schon Verbindungen zwischen den molekularen Mechanismen der Alterung und der Pathogenese altersassoziierter Krankheiten aufgezeigt. Hier nun liegt der Fokus auf der Alzheimer‐Krankheit (AD, Alzheimer’s disease) und Krebs. Wahrend Krebs mittlerweile in vielen Fallen pharmakologisch und/oder chirurgisch erfolgreich behandelt und manchmal sogar geheilt werden kann, ist A…

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Cell Cycle: The Life Cycle of a Cell

“Where a cell arises, there must be a previous cell”. This early statement of Rudolf Virchow already points to the process that is called cell cycle. It describes a series of events leading to cell division and duplication and can be sectioned into phases that are controlled by a collection of proteins interacting with each other, the cyclines and the cycline-dependent kinases. It is mandatory that DNA replication is conservative meaning that its structure and sequence remain unaltered while the DNA is duplicated before the cell actually divides. Checkpoints are responsible for the supervision, proteins such as p53 and RB being the key protagonists in cell cycle control. Upon DNA damage rec…

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Beyond Amyloid - Widening the View on Alzheimer's Disease

For 25 years, the amyloid cascade hypothesis, based on the finding that mutations in the amyloid precursor protein are closely linked to familial forms of Alzheimer's disease (AD), dominated the research on this disease. Recent failures of clinical anti-amyloidogenic trials, however, substantially support the reasoning (i) that the pathomechanisms that trigger familial AD, namely the generation, aggregation, and deposition of amyloid beta, cannot necessarily be extrapolated to sporadic cases and (ii) that amyloid beta represents a prominent histopathological feature in AD but not its exclusive causative factor. In autumn 2016, the Volkswagen Foundation hosted the Herrenhausen Symposium ‘Bey…

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Aging and Cell Aging: An Introduction

Since more than 100 years people are constantly growing older and a further significant increase in life time is expected in the decades to come. A person born today has a high statistical chance to reach the age of 100, to become a centenarian. Since aging is the primary risk factor for many human disorders it is mandatory to understand the aging process and how it affects onset and course of disorders of the elderly. Scientifically the medium life span is discriminated from the maximum life span. While the latter is rather constant at approximately 120 years the medium life span is increasing. But not only the whole organism, also each single cell out of the billions making up our body ha…

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When two turn into one: evolution of membrane transporters from half modules

Abstract The recently increasing number of atomic structures for active transporters has not only revealed strong conservation in the architecture of sequence-unrelated transporter families, but also identified a unifying element called the ‘inverted repeat topology,’ which is found in nearly all transporter folds to date. Indeed, most membrane transporters consist of two or more domains with similar structure, so-called repeats. It is tempting to speculate that transporters have evolved by duplication of one repeat followed by gene fusion and modification events. An intriguing question is, whether recent genes encoding such a ‘half-transporter’ still exist as independent folding units. Alt…

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Theories and Mechanisms of Aging

The more one learns about single processes and genes known to be involved in aging, the more it becomes evident that these are connected and there is no unifying theory of aging. The individual theories put individual factors and processes in focus and for each theory there are direct links to life span or to age-related disorders. In the following chapter, the key theories of aging focusing on telomeres, DNA damage, oxidative stress as well as possible roles of nutrition, the interplay between genes and environment (epigenetics) and cellular protein homeostasis are presented. In animal models the life span can be altered by targeting specific genes, proteins and signalling pathways. After …

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Theorien und Mechanismen des Alterns

Je mehr man uber die einzelnen Gene und Prozesse weis, die bei der Alterung eine Rolle spielen, desto evidenter wird, dass diese miteinander in Zusammenhang stehen und es die eine Alternstheorie nicht gibt. Jede einzelne Theorie ruckt einzelne Faktoren und Prozesse in den Mittelpunkt und bei jeder existieren direkte Verbindungen zur Lebensdauer oder zu altersassoziierten Krankheiten. Im folgenden Kapitel werden die wichtigsten Alternstheorien, die sich auf Telomere, DNA‐Schaden, oxidativen Stress, die mogliche Rolle der Ernahrung, das Zusammenspiel von Genen und Umwelt (Epigenetik) und die zellulare Proteinhomoostase konzentrieren, vorgestellt. In Tiermodellen kann die Lebensspanne zudem du…

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The Effect of Bialaphos on Ammonium-Assimilation and Photosynthesis II. Effect on Photosynthesis and Photorespiration

Abstract The application of bialaphos (phosphinothricyl-alanyl-alanine) effects a quick photosynthesis inhibition under atmospheric conditions (400 ppm CO2, 21% O2). However, under conditions (1000 ppm CO2, 2% O2) under which photorespiration cannot occur there is no photosynthesis inhibition. In the previous investigation it could be shown that bialaphos splits in plants into phosphinothricin and alanine. The inhibition of glutamine synthetase through freed phosphinothricin results in an NH4 +-accumulation and a decrease in glutamine. With the addition of glutamine, photosynthesis inhibition by bialaphos can be reduced. An NH4 +-accumulation takes place under atmospheric conditions as well…

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