Книги з теми "Molecular adaptor"

This article examines the properties of protein-DNA conjugates and their potential for analytic applications. It begins with a discussion of DNA as a rigid construction tool for protein networks, reducing its functionality to the molecular equivalent of a steel bar in 'large-scale' architecture. It then describes DNA functionality in protein-DNA conjugates, like specific recognition of nucleotide sequences or its unique use as an amplification template. It also considers a range of applications for protein-DNA conjugates, including the use of artificial DNA-protein nanostructures as supramolecular building blocks and DNA-antibody conjugates for ultrasensitive antigen detection. Finally, it evaluates DNA-directed immobilization of protein-DNA adaptor molecules for flexible protein arrays. It shows that protein-DNA conjugates can be used as analytical targets for challenging and calibrating the properties of high-resolution atomic force microscopy, as well as analytical reagents for ultrasensitive target detection in immuno-PCR and related techniques.

Chapter 2 begins with a depiction of the evolutionary origins of CRF in living things. CRF appears to date back hundreds of millions of years. It is found in diverse invertebrates, including flies and bees. Invertebrates’ brains look nothing like those of vertebrates except for the diverse information molecules that underlie both brain systems. There is no clear anatomical organ like the HPA axis in invertebrates, yet information molecules, including CRF, are just as important to invertebrate functioning as they are to vertebrates. CRF in invertebrates is linked to basic regulatory functions such as osmotic regulation, food intake, learning, and circadian rhythmicity. There are many examples of regulatory molecules that, over time, become adapted to serve multiple functions. Once a gene for a potent regulatory molecule exists, the potential for the differentiation of function, regulation, and mode of action exist as well.

Animal models of autism are now prolific as human genetic findings in autism provide a compelling rationale for developing bona fide mouse models of subtypes of human autism/mental retardation. Furthermore, these findings provide the opportunity to understand at a molecular, cellular, and circuit level the pathogenesis of a subset of ASDs. This chapter introduces neuroligins and neurexins, their function, their genetic link to autism, genetic mouse models of autism based on neuroligin and neurexin mutation/deletion, and the potential for understanding the pathogenesis and ultimately treatment of ASDs linked to these genes. This chapter is updated and adapted from an earlier published version (Powell & Boucard, 2010).

In the writings of this period, we see Boltzmann responding to criticism by British kinetic theorists and by the German mathematician Ernst Zermelo regarding the equipartition of energy and the H theorem. Boltzmann also acted as a critic of other authors. He ridiculed Joseph Bertrand’s attack on Maxwell’s kinetic-molecular reasoning and, after much pounding on Max Planck’s early radiation theory, he managed to convince Planck to alter his approach to irreversibility. Boltzmann also gave a last critical review of the problem of specific heats. During the same period, he was working on his Gastheorie and this prompted him to discuss Johannes Diderik van der Waals’s theory in the light of the Maxwell–Boltzmann theory, with similar reasoning adapted to the problem of chemical dissociation.

This chapter describes the ways in which the Monte Carlo importance sampling method may be adapted to improve the calculation of ensemble averages, particularly those associated with free energy differences. These approaches include umbrella sampling, non-Boltzmann sampling, the Wang–Landau method, and nested sampling. In addition, a range of special techniques have been developed to accelerate the simulation of flexible molecules, such as polymers. These approaches are illustrated with scientific examples and program code. The chapter also explains the analysis of such simulations using techniques such as weighted histograms, and acceptance ratio calculations. Practical advice on selection of methods, parameters, and the direction in which to make comparisons, are given. Monte Carlo methods for modelling phase equilibria and chemical reactions at equilibrium are described.

This book will enable practitioners to understand the many complex intricacies of immunohistochemistry (IHC) and make best use of this powerful analytical tool. Providing a thorough grounding in the fundamentals of immunohistochemistry, the book includes several chapters on robotics and automation technology, giving key information on the design of machines and tips to maximise workflow efficiencies. The relationship between IHC and molecular pathology is explained clearly, demonstrating the increasing impact on personalized medicine and targeted therapies for cancer patients. The staining protocol is deconstructed, allowing the reader to adapt it for a variety of diagnostic and research applications. Written by experts at the forefront of hospital immunohistochemistry, there is a strong emphasis on practical guidance on a range of techniques as well as troubleshooting of common problems driven by the authors' experiences. Extensively illustrated with high-quality colour images, this is an invaluable resource to all pathology practitioners utilising the technique.

Through evolution, our bodies have synchronized to environmental time, making our molecular clock mechanisms responsive to environmental cues such as light and temperature. In providing shelter from extreme climate conditions, however, modern societies have dramatically modified their environment without fully appreciating the consequences. We present an overview of the influence that lighting and thermal and acoustic conditions in our built environment exert on our sleep. These factors have changed substantially in the last century and biological systems have not had sufficient time to adapt. We also present a challenge for public health professionals: how to provide adequate sleeping conditions in low-income communities. We show how sleep quality is severely affected by socio-economic status, and illustrate how environmental injustice could exacerbate future challenges imposed by various climate change scenarios. We also discuss how technology could address these challenges in the built environment to promote conditions that foster good sleep and good health.

Since the publication of the first edition of Gene Targeting: A Practical Approach in 1993 there have been many advances in gene targeting and this new edition has been thoroughly updated and rewritten to include all the major new techniques. It provides not only tried-and-tested practical protocols but detailed guidance on their use and applications. As with the previous edition Gene Targeting: A Practical Approach 2e concentrates on gene targeting in mouse ES cells, but the techniques described can be easily adapted to applications in tissue culture including those for human cells. The first chapter covers the design of gene targeting vectors for mammalian cells and describes how to distinguish random integrations from homologous recombination. It is followed by a chapter on extending conventional gene targeting manipulations by using site-specific recombination using the Cre-loxP and Flp-FRT systems to produce 'clean' germline mutations and conditionally (in)activating genes. Chapter 3 describes methods for introducing DNA into ES cells for homologous recombination, selection and screening procedures for identifying and recovering targeted cell clones, and a simple method for establishing new ES cell lines. Chapter 4 discusses the pros and cons or aggregation versus blastocyst injection to create chimeras, focusing on the technical aspects of generating aggregation chimeras and then describes some of the uses of chimeras. The next topic covered is gene trap strategies; the structure, components, design, and modification of GT vectors, the various types of GT screens, and the molecular analysis of GT integrations. The final chapter explains the use of classical genetics in gene targeting and phenotype interpretation to create mutations and elucidate gene functions. Gene Targeting: A Practical Approach 2e will therefore be of great value to all researchers studying gene function.

Cystic echinococcosis (CE)\cystic hydatid disease is one of the most widespread and important global helminth zoonoses. The parasite Echinococcus granulosus is maintained in a wide spectrum of intermediate hosts, including sheep, goats, camels, cattle, pigs and equines. A number of wild intermediate hosts occur, including cervids in the northern part of the North American continent and Eurasia, marsupials in Australia and wild herbivores in East and southern Africa. The application of a range of molecular techniques to the characterization of the parasite has confirmed the existence of mostly host-adapted strains and genotypes of the parasite and several new species have been proposed. The ubiquitous domestic dog serves as the most important definitive host for the transmission of the parasite throughout its wide geographical range.A wide range of diagnostic techniques, including necropsy, arecoline purgation, coproantigen ELISA and DNA based tests are available for detecting E. granulosus infection in the definitive host. In intermediate animal hosts, diagnosis at post mortem still remains the most reliable option. In humans, imaging techniques including ultrasound, nuclear magnetic resonance (NMR) or computer aided tomography (CAT-scan provide not only a method of diagnosis but also reveal important clinical information on the location, condition, number and size of the hydatid cysts in man. Of these ultrasound is the most widely used diagnostic technique and is the only imaging technique for screening of populations in rural areas, where the disease is most common. A classification system has been developed which can be used to assess the likely development of a cyst and hence guide the clinician in treatment options for the patient. Treatment relies on surgery and/or percutaneous interventions, especially ‘Puncture, Aspiration, Injection, Re-aspiration’ (PAIR) and/or antiparasitic treatment with albendazole (and alternatively mebendazole).CE is largely a preventable disease. Successful elimination programmes have focused on frequent periodic treatments of dogs with anthelmintics and the control of slaughter of domestic livestock. In many regions elimination or even control remains a problem as the parasite is endemic over vast areas of low income countries where there may be limited resources for control. In some areas, such as former communist administered countries, the parasite is resurgent. New tools are becoming available to control the parasite, including a highly effective vaccine in sheep which prevents the infection in sheep and breaks the transmission cycle. In addition cost effective methods are being developed which may be appropriate in low income countries where financial resources are not available for intensive control programmes that have been successful in high income countries.

The poxviruses are a large family of complex viruses infecting many species of vertebrates as well as arthropods, and members of the three genera Orthopoxvirus, Yatapoxvirus and Parapoxvirus are the cause of sporadic zoonotic infections originating from both wildlife and domestic livestock. Infections of humans are generally associated with localized lesions, regarded as inconvenient rather than life-threatening, although severe illnesses have occurred, particularly in immunologically compromised individuals.The most celebrated of the orthopoxvirus infections is cowpox — a zoonotic infection which has been exploited to the enormous benefit of mankind as it had a pivotal role in the initiation of vaccination strategies that eventually led to the eradication of smallpox. Cowpox occurs only in Eurasia and in recent years it has become evident that infection of cattle is fortuitous and the reservoir of infection is in wild rodents. Monkeypox is another orthopoxvirus causing zoonotic infections in central and west Africa resembling smallpox and is the most serious disease in this category. While monkeypox does not readily spread between people, the potential of the virus to adapt to man is of concern and necessitates sustained surveillance in enzootic areas.The third orthopoxvirus zoonoses of importance is buffalopox in the Indian subcontinent, which is probably a strain of vaccinia that has been maintained in buffalo for at least 30 years following the cessation of vaccination of the human population. Likewise in Brazil, in recent years widespread outbreaks of vaccinia have occurred in milkers and their cattle.Orf virus, the most common of the parapoxviruses to cause zoonotic infection, is largely restricted to those in direct contact with domestic sheep and goats. Generally, infection is associated with a single localized macule affecting the hand which resolves without complications. Infection would appear to be prevalent in all sheep and goat populations and human orf is a relatively common occupational hazard. Sporadic parapoxvirus infections of man also occur following contact with cattle infected with pseudocowpoxvirus, and wildlife, in particular seals.A final serious consideration with the poxvirus zoonoses is the clinical similarity of such infections with smallpox. In view of the potential for smallpox virus to be employed by bio-terrorists there can be an urgency for laboratory confirmation of unexplained zoonotic poxvirus infections. Thus there is a requirement to maintain the capacity for rapid confirmation of poxvirus infections by molecular technique. As representatives of the known poxviruses have all been sequenced, generic and virus specific Polymerase Chain Reactions (PCR) can readily be performed to ensure rapid confirmation of any suspect infection.