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Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT
Abstract: The spore-forming gut bacterium Clostridium difficile is the leading cause of antibiotic-associated diarrhea in hospitalized patients. The major virulence factors are two large glucosylating cytotoxins. Hypervirulent strains (e.g. ribotype 027) with higher morbidity and mortality additionally produce the binary CDT toxin (Clostridium difficile transferase) that ADP-ribosylates actin and induces microtubule-based cell protrusions. Nanobodies are robust single domain antibodies derived from camelid heavy chain antibodies. Here we report the generation of functional nanobodies against the enzymatic CDTa and the heptameric receptor binding subunit CDTb. The nanobodies were obtained from a variable-domain repertoire library isolated from llamas immunized with recombinant CDTa or CDTb. Five CDTa-specific nanobodies blocked CDTa-mediated ADP-ribosylation of actin. Three CDTa-specific and two CDTb-specific nanobodies neutralized the cytotoxicity of CDTa+b. These nanobodies hold promise as new tools for research, diagnosis and therapy of C. difficile associated disease
Vegetative Physiology and Biochemistry
The Eye: Volume 1, Vegetative Physiology and Biochemistry is a compendium of papers that describes the physiology of the eye, particularly its gross anatomy and embryology including its intra-ocular fluids, the intra-ocular pressure, the vitreous body, lens, cornea, and sciera. Several papers review the eyeball, the protective apparatus of the eye, the structure of the tissue in relation to the intra-ocular fluids, and the flow of aqueous humor. Several methods can be used to measure the intra-ocular pressure such as the manometric method and the tonometer. Giles (1959) reports that tonometer measurements in the newborn are within the normal adult range. One paper notes that in man, liquefac...
Principles of Molecular Recognition
The importance of molecular recognition in chemistry and biology is reflected in a recent upsurge in relevant research, promoted in particular by high-profile initiatives in this area in Europe, the USA and Japan. Although molecular recognition is necessarily microscopic in origin, its consequences are de facto macroscopic. Accordingly, a text that starts with intermolecular interactions between simple molecules and builds to a discussion of molecular recognition involving larger scale systems is timely. This book was planned with such a development in mind. The book begins with an elementary but rigorous account of the various types of forces between molecules. Chapter 2 is concerned with t...
Interiorae
A mash-up of day-to-day drama and surreal fantasy.
Human Pathobiochemistry
This textbook uses a case-study approach to present the core principles of biochemistry and molecular biology in the context of human disease to students who will be involved in patient care. The 29 clinical cases have been carefully selected to cover key scientific concepts and some common, and other not so common, diseases. While the principal focus is on topics relating to metabolic disease, further subjects such as connective tissue disorders, neurological disorders, auto-inflammatory disorders, infective diseases, and cancer are also addressed. Each chapter provides a specific patient report that includes the natural history, pertinent clinical laboratory data, physical findings, subsequent diagnosis, and therapy. This is followed by a comprehensive discussion of the normal biochemical processes and reactions pertaining to the case, along with the pathophysiological mechanisms of the disease. Graphical diagrams are provided in each chapter for ease of comprehension.
Rush of Blood
Perfect strangers. A perfect vacation. The perfect murder. . . . “Hugely effective and entertaining [with] many twists and shocks” (TheTimes, London). Three British couples meet around the pool on their Florida holiday and become fast friends. But on Easter Sunday, the last day of their vacation, tragedy strikes: The fourteen-year-old daughter of an American vacationer goes missing, and her body is later found floating in the mangroves. When the shocked couples return home to the United Kingdom, they remain in contact, and over the course of three increasingly fraught dinner parties they come to know one another better. But they don’t always like what they find. Buried beneath these apparently normal exteriors are some unusual kinks and unpleasant vices. Then, a second girl goes missing, in Kent—not far from where the couples live. Could it be that one of these six has a secret far darker than anybody can imagine? Ambitiously plotted and laced with dark humor, Rush of Blood is a “sizzling thriller” by the international bestselling author of the Tom Thorne Novels (The Globe and Mail, Toronto).
Stolen Verses and Other Poems
This collection of poems employs different forms, such as sonnets and free verse in both English and the original Spanish. It includes the poems, John Lennon 1940-1980, Sigmund Freud Under Hypnosis and Fixed Stars in a White Sky.
Sorry
Berlin. Four friends. One extreme idea. One of the most gripping thrillers ever written.
