This book constitutes the proceedings of the 11th International Conference on Computational Methods in Systems Biology, CMSB 2013, held in Klosterneuburg, Austria, in September 2013. The 15 regular papers included in this volume were carefully reviewed and selected from 27 submissions. They deal with computational models for all levels, from molecular and cellular, to organs and entire organisms.
This book covers allocation of metals in cells, metal transporter, storage and metalloregulatory proteins, cellular responses to metal ion stress, transcription of genes involved in metal ion homeostasis, uptake of essential metals, metal efflux and other detoxification mechanisms. The book also discusses metal bioreporters for the nanomolar range of concentration and tools to address the metallome. In addition, coverage details specific metals.
Bacteria in various habitats are subject to continuously changing environmental conditions, such as nutrient deprivation, heat and cold stress, UV radiation, oxidative stress, dessication, acid stress, nitrosative stress, cell envelope stress, heavy metal exposure, osmotic stress, and others. In order to survive, they have to respond to these conditions by adapting their physiology through sometimes drastic changes in gene expression. In addition they may adapt by changing their morphology, forming biofilms, fruiting bodies or spores, filaments, Viable But Not Culturable (VBNC) cells or moving away from stress compounds via chemotaxis. Changes in gene expression constitute the main component of the bacterial response to stress and environmental changes, and involve a myriad of different mechanisms, including (alternative) sigma factors, bi- or tri-component regulatory systems, small non-coding RNA’s, chaperones, CHRIS-Cas systems, DNA repair, toxin-antitoxin systems, the stringent response, efflux pumps, alarmones, and modulation of the cell envelope or membranes, to name a few. Many regulatory elements are conserved in different bacteria; however there are endless variations on the theme and novel elements of gene regulation in bacteria inhabiting particular environments are constantly being discovered. Especially in (pathogenic) bacteria colonizing the human body a plethora of bacterial responses to innate stresses such as pH, reactive nitrogen and oxygen species and antibiotic stress are being described. An attempt is made to not only cover model systems but give a broad overview of the stress-responsive regulatory systems in a variety of bacteria, including medically important bacteria, where elucidation of certain aspects of these systems could lead to treatment strategies of the pathogens. Many of the regulatory systems being uncovered are specific, but there is also considerable “cross-talk” between different circuits. Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria is a comprehensive two-volume work bringing together both review and original research articles on key topics in stress and environmental control of gene expression in bacteria. Volume One contains key overview chapters, as well as content on one/two/three component regulatory systems and stress responses, sigma factors and stress responses, small non-coding RNAs and stress responses, toxin-antitoxin systems and stress responses, stringent response to stress, responses to UV irradiation, SOS and double stranded systems repair systems and stress, adaptation to both oxidative and osmotic stress, and desiccation tolerance and drought stress. Volume Two covers heat shock responses, chaperonins and stress, cold shock responses, adaptation to acid stress, nitrosative stress, and envelope stress, as well as iron homeostasis, metal resistance, quorum sensing, chemotaxis and biofilm formation, and viable but not culturable (VBNC) cells. Covering the full breadth of current stress and environmental control of gene expression studies and expanding it towards future advances in the field, these two volumes are a one-stop reference for (non) medical molecular geneticists interested in gene regulation under stress.
RNAs form complexes with proteins and other RNAs. The RNA‐infrastructure represents the spatiotemporal interaction of these proteins and RNAs in a cell‐wide network. RNA Infrastructure and Networks brings together these ideas to illustrate the scope of RNA‐based biology, and how connecting RNA mechanisms is a powerful tool to investigate regulatory pathways. This book is but a taste of the wide range of RNA‐based mechanisms that connect in the RNA infrastructure.
Cerebral gliomas account for 45% of all primary central nervous system (CNS) tumors. The median survival after the initial diagnosis of glioblastoma (GBM) is only 15 months, and less than 10% of patients survive three years post-diagnosis. Surgical treatment followed by adjuvant therapies such as radiotherapy and chemotherapy represents the classical strategy in glioma management. The revised WHO 2016 classification now distinguishes the oligodendrogliomas with 1p19q codeletion and IDH mutation from the astrocytomas with or without IDH mutations, thereby creating homogenous and pathologically distinct subgroups. While the status of gene expression and mutations define components of GBM subtypes, it was also found that response to therapies was different for each subtype, suggesting that personalized treatment based on genomic alterations could lead to a more favorable outcome for this disease.
Lasso peptides form a growing family of fascinating ribosomally-synthesized and post-translationally modified peptides produced by bacteria. They contain 15 to 24 residues and share a unique interlocked topology that involves an N-terminal 7 to 9-residue macrolactam ring where the C-terminal tail is threaded and irreversibly trapped. The ring results from the condensation of the N-terminal amino group with a side-chain carboxylate of a glutamate at position 8 or 9, or an aspartate at position 7, 8 or 9. The trapping of the tail involves bulky amino acids located in the tail below and above the ring and/or disulfide bridges connecting the ring and the tail. Lasso peptides are subdivided into three subtypes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges. The lasso topology results in highly compact structures that give to lasso peptides an extraordinary stability towards both protease degradation and denaturing conditions. Lasso peptides are generally receptor antagonists, enzyme inhibitors and/or antibacterial or antiviral (anti-HIV) agents. The lasso scaffold and the associated biological activities shown by lasso peptides on different key targets make them promising molecules with high therapeutic potential. Their application in drug design has been exemplified by the development of an integrin antagonist based on a lasso peptide scaffold. The biosynthesis machinery of lasso peptides is therefore of high biotechnological interest, especially since such highly compact and stable structures have to date revealed inaccessible by peptide synthesis. Lasso peptides are produced from a linear precursor LasA, which undergoes a maturation process involving several steps, in particular cleavage of the leader peptide and cyclization. The post-translational modifications are ensured by a dedicated enzymatic machinery, which is composed of an ATP-dependent cysteine protease (LasB) and a lactam synthetase (LasC) that form an enzymatic complex called lasso synthetase. Microcin J25, produced by Escherichia coli AY25, is the archetype of lasso peptides and the most extensively studied. To date only around forty lasso peptides have been isolated, but genome mining approaches have revealed that they are widely distributed among Proteobacteria and Actinobacteria, particularly in Streptomyces, making available a rich resource of novel lasso peptides and enzyme machineries towards lasso topologies.
Provides background information and detailed protocols for developing a mouse colony and using the animals in transgenic and gene-targeting experiments. The protocols list the animals, equipment, and reagents required and step-by-step procedures. Topics include in vitro culture of preimplantation embryos, surgical procedures, the production of chimeras, and the analysis of genome alterations. The third edition adds protocols for cloning mice, modifying embryonic stem cells, intracytoplasmic sperm injection, and cryopreservation of embryos.
The Perfect Slime presents the latest state of knowledge and all aspects of the Extracellular Polymeric Substances, (EPS) matrix – from the ecological and health to the antifouling perspectives. The book brings together all the current material in order to expand our understanding of the functions, properties and characteristics of the matrix as well as the possibilities to strengthen or weaken it. The EPS matrix represents the immediate environment in which biofilm organisms live. From their point of view, this matrix has paramount advantages. It allows them to stay together for extended periods and form synergistic microconsortia, it retains extracellular enzymes and turns the matrix into an external digestion system and it is a universal recycling yard, it protects them against desiccation, it allows for intense communication and represents a huge genetic archive. They can remodel their matrix, break free and eventually, they can use it as a nutrient source. The EPS matrix can be considered as one of the emergent properties of biofilms and are a major reason for the success of this form of life. Nevertheless, they have been termed the “black matter of biofilms” for good reasons. First of all: the isolation methods define the results. In most cases, only water soluble EPS components are investigated; insoluble ones such as cellulose or amyloids are much less included. In particular in environmental biofilms with many species, it is difficult to impossible isolate, separate the various EPS molecules they are encased in and to define which species produced which EPS. The regulation and the factors which trigger or inhibit EPS production are still very poorly understood. Furthermore: bacteria are not the only microorganisms to produce EPS. Archaea, Fungi and algae can also form EPS. This book investigates the questions, What is their composition, function, dynamics and regulation? What do they all have in common?
Achievements and progress in genome mapping and the genomics of microbes supersede by far those for higher plants and animals, in part due to their enormous economic implication but also smaller genome size. In the post-genomic era, whole genome sequences of animal-associated microbes are providing clues to depicting the genetic basis of the complex host-pathogen relationships and the evolution of parasitism; and to improving methods of controlling pathogens. This volume focuses on a globally important group of intracellular prokaryotic pathogens which affect livestock animals. These include Brucella, Mycobacterium, Anaplasma and Ehrlichia, as well as the protozoan pathogens Cryptosporidium and Theileria, for which genome sequence data is available. Insights from comparative genomics of the microbes described provide clues to the adaptation involved in host-microbe interactions, as well as resources potentially useful for application in future research and product development.
An examination of the research and translational application to prevent and treat biofilm-associated diseases In the decade since the first edition of Microbial Biofilms was published, the interest in this field has expanded, spurring breakthrough research that has advanced the treatment of biofilm-associated diseases. This second edition takes the reader on an exciting, extensive review of bacterial and fungal biofilms, ranging from basic molecular interactions to innovative therapies, with particular emphasis on the division of labor in biofilms, new approaches to combat the threat of microbial biofilms, and how biofilms evade the host defense. Chapters written by established investigators cover recent findings, and contributions from investigators new to the field provide unique and fresh insights. Specifically, Microbial Biofilms provides state-of-the-art research in the field of bacterial and fungal biofilms detailed descriptions of the in vitro and in vivo models available to evaluate microbial biofilms future areas of research and their translational and clinical applications Microbial Biofilms is a useful reference for researchers and clinicians. It will also provide insight in the dynamic field of microbial biofilms for graduate and postgraduate students.
