Avigdor Shafferman

Nano-biotechnology for biomedical and diagnostic research

Preface.- 1. Biomolecule/Nanomaterial Hybrid Systems for Nanobiotechnology.- 1.1. Electrical Contacting of Enzymes with Electrodes for the Construction of Amperometric Biosensors and Biofuel Cells.- 1.2. Catalytic Properties of Metalic Nanoparticles (NPs) and their Implementation for Sensing and Nanocircuitry.- 1.3. Bioanalytical Applications of Hybrid Semiconductor-Protein Systems.- 1.4. Biomolecules as Templates for Nanoscale Circuitry.- 1.5. Conclusions and Perspectives.- 2. Superresolution Optical Flunctuation Imaging.- 2.1. Main article.- 2.2. Conclusion.- 3. Application of Nanoparticles for the Detection and Sorting of Pathogenic Bacteria by Flow-Cytometry.- 3.1. Introduction.- 3.2. Results.- 3.3. Conclusion.- 4. Advancing Nanostructured Porous Si-Based Optical Transducers for Label Free Bacteria Detection.- 4.1. Introduction.- 4.2. Materials and Methods.- 4.3. Results and Discussion.- 4.4. Conclusions.- 5. Gold Fibers as a Platform for Biosensing.- 5.1. Introduction.- 5.2. Experimental.- 5.3. Results and Discussion.- 5.4. Electrochemical Evaluation of Gox on Gold Fibers.- 5.5. Summary and Conclusions.- 6. Surface-Enhanced Raman Spectroscopy of Organic Molecules Adsorbed on Metallic Nanoparticles.- 6.1. Introduction.- 6.2. Experimental.- 6.3. Results and Discussion.- 6.4. Summary and Conclusions.- 7. Quantum Dots and Fluorescent Protein FRET-based Biosensors.- 7.1. Introduction.- 7.2. Materials and Methods.- 7.3. Results.- 7.4. Discussion.- 8. Semiconductor Quantum Dots as FRET-Acceptors for Multiplexed Diagnostics and Molecular Ruler Application.- 8.1. Introduction.- 8.2. Short Theoretical and Practical Background.- 8.3. Applications.- 8.4. Conclusions and Outlook.- 9. Assembly and Microscopic Characterization of DNA Origami Structures.- 9.1. Introduction.- 9.2. DNA as a Material for ?Molecular Self-Assembly.- 9.3. Modification of Origami Structures.- 9.4. Characterization of DNA Origami Structures.- 9.5. Conclusion and Outlook.- 10. DNA Nanotechnology.- 10.1. DNA Nanostructures for Amplified Sensing.- 10.2. Ultrasensitive Detection of DNA through Isothermal Replication Processes using DNA Enzymes.- 10.3. Programmed Nanostructures Acting as DNA Machines.- 10.4. Self-Assembly of Functional DNA-Protein Nanostructures.- 10.5. Conclusions and Perspectives.- 11. Role of Carbohydrate (lectin) receptors in the Macrophage Uptake of Dextran-Coated Iron Oxide Nanoparticles.- 11.1. Introduction.- 11.2. Materials and Methods.- 11.3. Results and Discussion.- 11.4. Conclusions.- 12. Toxicity of Gold Nanoparticles on Somatic and Reproductive Cells.- 12.1. Introduction.- 12.2. Effect of Gold Nanoparticles on Somatic Cells.- 12.3. Reproductive Toxicology of Gold Nanoparticles.- 12.4. Conclusion.-13. Ultrasound Activated Nano-Encapsulated Targeted Drug Delivery and Tumour Cell Poration.- 13.1. Introduction.- 13.2. Materials and Methods.- 13.3. Results.- 13.4. Discussion.- 13.5. Future Work.- 14. Ultrasound Mediated Localized Drug Delivery.- 14.1. Introduction.- 14.2. Ultrasound Intensity Level of 1.5 MPa.- 14.3. Ultrasound Intensity Levels Below 1 MPa.- 14.4. Localized SHERPA Activation.- 14.5. Discussion.- 14.6. Conclusions.- 15. Sonochemical Proteinaceous Microspheres for Wound Healing.- 15.1. Introduction.- 15.2. Materials and Methods.- 15.3. Results and Discussion.- 15.4. Conclusions.- 16. Alendronate Liposomes for Antitumor Therapy: Activation of gammadelta T Cells and Inhibition of Tumor Growth.- 16.1. Introduction.- 16.2. Materials and Methods.- 16.3. Results.- 16.4. Discussion.

Novel strategies in the design and production of vaccines.

Recombinant Antigens and Presentation Vectors: Synthetic Vaccines for Infectious and Autoimmune Diseases M. Sela Host Range Restricted, Nonreplicating Vaccinia Virus Vectors as Vaccine Candidates B. Moss, et al. Hybrid Hepatitis B Virus Core Antigen as a Vaccine Carrier Moiety II: Expression in Avirueltn Salmonell spp. for Mucosal Immunization F. Schodel, et al. Synthetic Recombinant Vaccine Induces Antiinfluenza Longterm Immunity and Crossstrain Protection R. Arnon, R. Levy Alphaviurs-based Expression Systems C.M. Rice Alphavirus Hybrid Virion Vaccines A. Shafferman, et al. DNA Vaccines for Bacteria and Viruses J.B. Ulmer, et al. Bacterial Vaccines: Novel Approaches: New Vaccines against Bacterial Toxins R. Rappuoli, et al. Parameters for the Rational Design of Genetic Toxoid Vaccines W.N. Burnette Protective Immunity Induced by Bacillus anthracis Toxin Mutant Strains C. Pezard, et al. Bacterial Outer Membrane Protein Vaccines: The Meningococall Example J.T. Poolman Strategies for HIV Vaccine: Changing Paradigms for an HIV Vaccine A.M. Schultz Complexed HIV Envelope as a Target for an AIDS Vaccine J.M. Gershoni, et al. HIVPeplotion Vaccine: A Novel Approach to Vaccination against AIDS by Transepithelial Transport of Viral Peptides and Antigens to Langerhans Cells for Induction of Cytolytic T Cells by HLA Class I and CD1 Molecules for Long Term Protection Y. Becker Adjuvants and Delivery Systems: The Role of Adjuvants and Delivery Systems in Modulation of Immune Response to Vaccines R.K. Gupta, et al. Unique Immunomodulating Properties of Dimethyl Dioctadecyl Ammonium Bromide (DDA) in Experimental Virus Vaccines D. Katz, etal. Production Processes and Clinical Evaluation: Challenges in the Development of Combination Vaccines R.W. Ellis Polysaccharide Conjugate Vaccines for the Prevention of Grampositive Bacterial Infections R. Naso, A. Fattom Production of Influenza Virus in Cell Cultures for Vaccine Preparation O.W. Merten, et al. Analysis of Bordetella pertussis Suspensions by ELISA and Flow Cytometry W. Jiskoot, et al. Clinical Trials of Shigella Vaccines in Israel D. Cohen, et al. Vaccine Development: General Consideration: Hypothesis: How Licensed Vaccines Confer Protective Immunity J.B. Robbins, et al. Therapeutic Vaccines: A Pandoric Prospect R.E. Spier Index.

Acetylcholinesterase Catalysis - Protein Engineering Studies

Sequence conservation analysis relates the cholinesterases to a superfamily of polypeptides (Myers et al., 1988; Krejci et al., 1991), including enzymes such as microsomal carboxyesterase, cholesterol esterase, lysophospholipase, Geotrichum lipase and Drosophila esterase-6, as well as several noncatalytic polypeptides. AChE is the best characterized enzyme in this superfamily. Kinetic studies have indicated that the active site of AChE consists of two subsites: an anionic subsite to which the trimethylammonium group of acetylcholine binds and an esteratic subsite which interacts with the ester-bond region and mediates catalysis. Evidence also exists for an allosteric regulation of AChE activity by ligand binding to an anionic site(s) physically remote from the active site (Changeux, 1966).

Molecular Organization of Recombinant Human Acetylcholinesterase

Acetylcholinesterase (abbreviated AChE) occurs in multiple molecular forms in different tissues of vertebrates and invertebrates (reviewed in Massoulie and Bon, 1982; (Silman and Futerman, 1987; Chatonnet and Lockridge, 1989). This heterogeneity is generated through tissue-specific associations of various catalytic and structural subunits. Characterized catalytic subunits are divided into two major types, the T-type and the H-type, both derived from a single gene by alternative splicing Schumacher et al., 1988; Sikarov et al., 1988). Structural subunits include the collagen-like structure (Krejci et al., 1991) that allows attachment to the basal lamina and the 20kD lipid-linked hydrophobic subunit (Inestrosa et al., 1987) which is associated with the mammalian brain enzyme.

Structural and Functional Correlates of Human Acetylcholinesterase Mutants for Evaluating Alzheimer’s Disease Treatments

Inhibitors of AChE constitute presently the only successful approach to symptomatic treatment of senile dementia of the Alzheimer’s type, with three such agents (tacrine, E2020 and rivastigmine) in clinical use1. The intensive effort to develop more therapeutically efficatious inhibitors is currently aided by the remarkable progress, made during the last decade, in elucidating the structural and functional properties of the enzyme through x-ray crystallography 2,3 and site directed mutagenesis 4–8. Investigation of the specific roles for most of the residues in this active-center gorge allowed for identification of several functional subsites including the catalytic triad (S203(200)**, H447(440) , E334(327)); the acyl pocket (F295(288) and F297(290)) and the ‘hydrophobic subsite’. The latter accommodates the alcoholic portion of the covalent adduct (tetrahedral intermediate) and may include residues W86 (84) , Y133 (130) , Y337(330) and F338(331), which operate through nonpolar and/or stacking interactions, depending on the substrate. Stabilization of the charged moieties of substrates and other ligands at the active-centre is mediated by cation -π interactions with the residue at position 86 rather than through true ionic interactions2,6,8