Books in the Experientia Supplementum series

This book provides a comprehensive overview of the genetic basis underlying endocrine diseases. Several endocrine diseases have a genetic background, and contemporary research in the field plays a crucial role in the clinical care of endocrine diseases.

This book focuses on host-pathogen interactions at the metabolic level. It explores the metabolic requirements of the infectious agents, the microbial metabolic pathways that are dedicated to circumvent host immune mechanisms as well as the molecular mechanisms by which pathogens hijack host cell metabolism for their own benefit.

This project will show the context where inflammasomes are being studied and the molecular implications in the medical and clinical contexts. Other important topic of the inflammasomes will be the development of pharmacological inhibitors in order to improve new clinical applications.

This work was compiled to serve as a convenient source that covers a number of techniques (and details of their use) in the rather large field of nanomedicine, with special attention paid to gene delivery.

AMPK has emerged as an important integrator of signals that control energy balance through the regulation of multiple biochemical pathways in eukaryotes. The contributions are written by leading experts in the field and give an extensive overview of the current knowledge of AMPK biology and the role of AMPK in health and disease.

Transfection, which is the infection of a cell with naked viral nucleic acid with the consequent production of complete virus, was first reported in 1956 for the ribonucleic acid of tobacco mosaic virus. Many reports of transfection, and several reviews of the field, have appeared since then. Crucial for the demonstration of transfection is that the viral nucleic acid is not damaged in the process of obtaining it from the virions, or from the infected tissue. To this end, procedures are designed to minimize the possibili­ ties of degradation of the viral nucleic acid by nucleases present in the biolo­ gical source. The most common method for preparing viral nucleic acid is the phenol method in which virus or infected-tissue preparations are extracted with phenol. Much of the protein goes down into the phenol phase, whereas the viral nucleic acid stays up in the aqueous phase. The transfection methods for animal virus nucleic acids are of three major kinds: (a) hypertonic methods; (b) insoluble facilitator methods; and (c) polycation methods. These methods have wide applicability to vertebrate celli animal virus NA systems, but anyone method does not seem to be highly effective for all such systems with the possible exception of the method using the polycation diethylaminoethyl-dextran. The insoluble facilitator method shows astonishing 'cell-specificity'; that is, it is a very effective method for transfecting some kinds of vertebrate cells, but nearly ineffective for some other kinds.

The Fourth International Symposium on Polarization Phenomena in Nuclear Reactions took place from August 25 to 29, 1975, at the Swiss Federal Instituteof Technology in Zurich (ETHZ). Apart from the host institution the Symposium was also supported by the International Union of Pure and Applied Physics, the Swiss National Science Founda­ tion and the Swiss Physical Society. The program of the Symposium was set up with the advice of an International Program Committee with the following members: Prof. I. Ja. Barit, USSR Academy of Sciences, Moscow, USSR Prof. E. Baumgartner, University of Basel, Basel, Switzerland Prof. H. E. Conzett, Lawrence Berkeley Laboratory, Berkeley, USA Dr. W. Gruebler, Laboratorium fUr Kernphysik, ETH Zurich Prof. W. Haeberli, University of Wisconsin, Madison, USA Prof. S. S. Hanna, Stanford University, Stanford, USA Prof. J. McKee, University of Manitoba, Winnipeg, Canada Prof. G. C. Morrison, University of Birmingham, England Dr. G. G. Ohlsen, LASL, Las Alamos, USA Prof. J. Raynal, C. E. N. Saclay, France Dr. M. Simonius, Laboratorium fUr Kernphysik, ETH Zurich The Local Organizing Committee consisted of Dr. R. Balzer Dr. W. Grtiebler Dr. H. Jung Dr. V. Konig Prof. J. Lang Dr. M. Simonius Prof. W. G. Weitkamp (on leave from University of Washington, Seattle) It was generally felt that the Fourth Polarization Symposium should emphasize the importance of polarization measurements in the different fields of nuclear physics and explain the physical content of polariza­ tion phenomena.

Der bei allen Säugetieren vorkommende Gebärmutterhals, als Abschluß der Ge­ bärmutterhöhle gegenüber dem Scheidenraum definiert, zeichnet sich beim Rinde durch einen besonders komplizierten Bau aus. Sein anatomischer und histologischer Aufbau wird anband der Literatur beschrieben und die hormo­ nellen und nervösen Einflüsse, welche seine Funktion steuern, besprochen. Das funktionelle Verhalten der Cervix uteri des Rindes wird während Brunst, Dioestrum, Trächtigkeit und Geburt im einzelnen geschildert. Da über die Invo­ lution der Cervix im Anschluß an die Geburt nur ältere Literaturangaben vorlie­ gen, wurde anband eigener Untersuchungen an 36 Normalgeburten das Verhal­ ten der Cervix im Puerperium beschrieben und auf die Bedeutung des raschen Abschlusses der Gebärmutterhöhle durch den sich bildenden Zervixschleim hin­ gewiesen. Nach einer weiteren Literaturübersicht zur Pathologie der Cervix wird in eigenen Untersuchungen über den Zusammenhang zwischen Zervixverände­ rungen und Konzeptionsstörungen beim Rind berichtet. Von insgesamt 694 wegen Fruchtbarkeitsstörungen untersuchten Rindern und Kühen litten 203 = 29,25% an einer Zervixveränderung. In 108 Fällen war nur die Cervix verändert, während in den restlichen 95 Fällen gleichzeitig eine klinisch nachweisbare Erkrankung der Gebärmutter vorlag. Die Entzündung der Cervix äußert sich in einer vermehrten Hyperämie, Lappenbildung und In­ duration der Portio vaginalis uteri und häufig auch des ersten « Burdiringes». Veränderungen im übrigen Verlauf des Zervikalkanales wurden nur zweimal, im Anschluß an Geburtstraumen, beobachtet.

As a consequence, researchers and project managers in the pharmaceutical industry should have a solid knowledge of the more important methods available to drug discovery, because it is the rapidly and intelligently combined use of these which will determine the success or failure of preclinical projects.

Galanin is a neuropeptide found both in the central and peripheral nervous system. The studies reviewed in this volume give a fairly complete overview of the spectrum of the biological actions and functions of galanin and its receptors and on possible therapeutic applications in a number of pathological conditions.

J. M. Polak and S. R. Bloom For some time Experientia has published, as a unique feature, interdis­ ciplinary multi-author reviews, giving a comprehensive overview of sub­ jects regarded as 'growing edges' of science. The enthusiasm shown by the readers was contagious and thus it was felt necessary to compile a special volume dealing with the novel aspects of regulatory peptides. This book covers some of the growing areas in regulatory peptide research and, although it is based on the original volume of Experientia, it is expanded and updated. The topic of 'regulatory peptides' is relatively young and has grown at an unprecedented pace, from the embryonic conception of 'gut hor­ mones' or 'brain neuropeptides' some 15 years ago to the realisation that these active pep tides are found, almost without exception, in every part of l8 23 the body in all vertebrate and many invertebrate species ¿ Why the term 'regulatory peptides'? It represents a convenient label encompassing both the active peptides present in nerves, which are re­ leased as (putative) neurotransmitters, and those in endocrine cells, which act locally or at a distance as circulating hormones, these being the l8 main components of the so-called diffuse neuroendocrine or APUD 17 system ¿ Morphological studies support this physiological viewpoint.

I: Cadmium in the Environment.- Geochemistry of cadmium.- Evaluation of methods for the speciation of cadmium.- Cadmium in the atmosphere.- Cadmium in fresh and estuarine waters.- The distribution of cadmium in the sea.- Cadmium in sediments.- Removal of cadmium from wastewaters.- II: Bioaccumulation of Cadmium.- Cadmium in sludges used as fertilizer.- Bioaccumulation of cadmium in marine organisms.- Cadmium in freshwater ecosystems.- Cadmium contamination in agriculture and zootechnology.- Pathways and distribution of cadmium in grasslands.- Contamination and effects of cadmium in native plants.- III: Cadmium and Human Health.- Cadmium in foods and the diet.- Cadmium in human population.- Biological indicators of cadmium exposure and toxicity.- Human health effects of exposure to cadmium.- Cadmium, the environment and human health.

Many arthropods use celestial (skylight) and terrestrial (magnetic) compass cues for orientation, and some of them were shown to develop, through experience, oriented behaviours based on a variety of innate, hard-wired orientation mechanisms.

Carbonic anhydrase (CA) is a seemingly ubiquitous enzyme of profound physiological importance, which plays essential roles in respiration, acid-base homeostasis, bone resorption, calcification, photosynthesis, several biosynthetic pathways and a variety of processes involving ion, gas and fluid transfer.

In the last 25 years, we have witnessed a revolution in the way that ecologists and evolutionary biologists approach their disciplines. This revolution has been fueled by the ability to dissect the genetic and molecular basis of variation that is partly the currency of these disci­ plines. Using modern molecular techniques, we have begun to restruc­ ture the spectrum of questions that can be addressed in studying the mechanisms and consequences of the ecology and evolution of living organisms. The molecular revolution has co me in waves, so to speak, with three particularly important developments. The first concerns the establish­ ment and widespread use of pro tein analysis. Microcomplement fixation and isozyme e1ectrophoresis were the techniques around which much of the genetic work in ecology and evolution were once based. The next wave started with the development of recombinant DNA technology and centered around the use of restriction fragment length polymor­ phisms (RFLPs) and sequencing of DNAs cloned in bacteria. This technology was the first to actually examine and accumulate genetic information at the nucleotide level. The most recent wave of technology that we are currently experiencing is based on our ability to amplify DNA sequences enzymatically via the Polymerase Chain Reaction (PCR). Several techniques re1ated to PCR have been developed and used extensively in ecological and evolutionary studies.

Most organisms and populations have to cope with hostile environments, threatening their existence. Their ability to respond phenotypically and genetically to these challenges and to evolve adaptive mechanisms is, therefore, crucial. The contributions to this book aim at understanding, from a evolutionary perspective, the impact of stress on biological systems. Scientists, applying different approaches spanning from the molecular and the protein level to individuals, populations and ecosystems, explore how organisms adapt to extreme environments, how stress changes genetic structure and affects life histories, how organisms cope with thermal stress through acclimation, and how environmental and genetic stress induce fluctuating asymmetry, shape selection pressure and cause extinction of populations. Finally, it discusses the role of stress in evolutionary change, from stress induced mutations and selection to speciation and evolution at the geological time scale. The book contains reviews and novel scientific results on the subject. It will be of interest to both researchers and graduate students and may serve as a text for graduate courses.

The present book is the ideal complement to the practitioner's manual Techniques in Molecular Systematics and Evolution, recently published by the same editors in the Birkhauser MTBM book series.The first part of this book deals with important applications of evolutionary and systematic analysis at different taxonomic levels.

It is no longer time-consuming analysis of unknown products, but rather selective identifications of individual forms, modifications and processings, and overall analysis of global protein outputs from cells and tissues in health and disease.

Carbonic anhydrase (CA) is a seemingly ubiquitous enzyme of profound physiological importance, which plays essential roles in respiration, acid-base homeostasis, bone resorption, calcification, photosynthesis, several biosynthetic pathways and a variety of processes involving ion, gas and fluid transfer.

Aims to understand, from a evolutionary perspective, the impact of stress on biological systems. This work discusses the role of stress in evolutionary change, from stress induced mutations and selection to speciation and evolution at the geological time scale.

The recognition of the role of NPY in stimulation of food intake has already resulted in discovery of potent and selective NPY receptor Y-5 antagonists which are in clinical development for obesity while NPY Y1 receptors are targeted for cardiovascular indications.

The present book is the ideal complement to the practitioner's manual Techniques in Molecular Systematics and Evolution, recently published by the same editors in the Birkhauser MTBM book series.The first part of this book deals with important applications of evolutionary and systematic analysis at different taxonomic levels.

The highly topical problems of radioprotection will be treated in the following issues of "Experientia" by competent experts in this field. Before printing the papers have been exchanged among the authors to allow them for commenting upon the articles so that a Symposium by Correspondence on Radioprotective Means and Compounds arose. As organizers and editors of this symposium acted A. LOCKER (Vienna) and K. FLEMMING (Freiburg, Br. ). Contents 9 J. D. Chapman and A. P. Reuvers: The Time-Scale of Radioprotection in Mammalian Cells 19 J. Calkins: General Patterns of DNA Repair and their possible Signif­ icance as Necessary Protection from Environmental Radiation Exposure 31 S. Homsey: Protection by Hypoxia and the Effect of Low Oxygen Tensions on Radiosensitivity 45 L. Revesz and B. Littbrand: Radioprotection by Radiosensitizers 53 T. Sugahara, M. Horikawa, M. H. Ikita and N. Nagata: Studies on a Sulfhydryl Radioprotector of Low Toxicity 63 J. M. Yuhas: Systemic Factors Affecting the Radioprotective Effec­ tiveness of Phosphorothioates 71 C. Streffer: Studies on the Mechanism of 5-Hydroxytryptamine in Radioprotection of Mammals 79 K. Flemming: Some Ideas Concerning the Mode of Action of Radio­ protective Agents 87 A. Locker and K. Flemming: Some General Aspects of Radioprotection (A Summary) 9 The Time-Scale of Radioprotection in Mammalian Cells J. D. Chapman* and A. P.

Within each chapter, which is preceded by a list of the sessions featuring the subject, all papers, invited and contributed, whether presented at the Conference or accepted for publication only, have been arranged in some lo gical order.

As a consequence, researchers and project managers in the pharmaceutical industry should have a solid knowledge of the more important methods available to drug discovery, because it is the rapidly and intelligently combined use of these which will determine the success or failure of preclinical projects.