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Engineering the Fab fragment of the anti-IgE omalizumab to prevent Fab crystallization and permit IgE-Fc complex crystallization
Immunoglobulin E (IgE) plays a central role in the allergic response, in which cross-linking of allergen by Fc ∊ RI-bound IgE triggers mast cell and basophil degranulation and the release of inflammatory mediators. The high-affinity interaction between IgE and Fc ∊ RI is a long-standing target for therapeutic intervention in allergic disease. Omalizumab is a clinically approved anti-IgE monoclonal antibody that binds to free IgE, also with high affinity, preventing its interaction with Fc ∊ RI. All attempts to crystallize the pre-formed complex between the omalizumab Fab and the Fc region of IgE (IgE-Fc), to understa...
Source: Acta Crystallographica Section F - March 1, 2020 Category: Biochemistry Authors: Mitropoulou, A.N. Ceska, T. Heads, J.T. Beavil, A.J. Henry, A.J. McDonnell, J.M. Sutton, B.J. Davies, A.M. Tags: omalizumab allergy Fab immunoglobulin E antibody protein engineering X-ray crystallography research communications Source Type: research

Structural and biophysical characterization of an epitope-specific engineered Fab fragment and complexation with membrane proteins: implications for co-crystallization
This report details the conversion of scFv/EE to an anti-EE Fab format (Fab/EE) followed by its biophysical characterization. The addition of constant chains increased the overall stability and had a negligible impact on the antigen affinity. The 2.0 Å resolution crystal structure of Fab/EE reveals contacts with larger surface areas than those of scFv/EE. Surface plasmon resonance, an enzyme-linked immunosorbent assay, and size-exclusion chromatography were used to assess Fab/EE binding to EE-tagged soluble and membrane test proteins: namely, the β-barrel outer membrane protein intimin and α-helical A2a G protein-coup...
Source: Acta Crystallographica Section D - March 27, 2015 Category: Biochemistry Authors: Johnson, J.L.Entzminger, K.C.Hyun, J.Kalyoncu, S.Heaner, D.P.Morales, I.A.Sheppard, A.Gumbart, J.C.Maynard, J.A.Lieberman, R.L. Tags: Fab fragment crystallization chaperones membrane proteins GPCRs β -barrel research papers Source Type: research

Structural analysis of free and liganded forms of the Fab fragment of a high-affinity anti-cocaine antibody, h2E2
A high-affinity anti-cocaine monoclonal antibody, designated h2E2, is entering phase 1 clinical trials for cocaine abuse therapy. To gain insight into the molecular details of its structure that are important for binding cocaine and cocaine metabolites, the Fab fragment was generated and crystallized with and without ligand. Structures of the unliganded Fab and the Fab fragment bound to benzoylecgonine were determined, and were compared with each other and with other crystallized anti-cocaine antibodies. The affinity of the h2E2 antibody for cocaine is 4   nM, while that of the cocaine metabolite benzoylecgonine is 20 â€...
Source: Acta Crystallographica Section F - November 4, 2019 Category: Biochemistry Authors: Tan, K. Zhou, M. Ahrendt, A.J. Duke, N.E.C. Tabaja, N. Ball, W.J. Kirley, T.L. Norman, A.B. Joachimiak, A. Schiffer, M. Wilton, R. Pokkuluri, P.R. Tags: high-affinity anti-cocaine antibody antigen-binding fragment crystal structure benzoylecgonine complex h2E2 Fab fragment research communications Source Type: research

Structure of the omalizumab Fab
Omalizumab is a humanized anti-IgE antibody that inhibits the binding of IgE to its receptors on mast cells and basophils, thus blocking the IgE-mediated release of inflammatory mediators from these cells. Omalizumab binds to the Fc domains of IgE in proximity to the binding site of the high-affinity IgE receptor Fc∊RI, but the epitope and the mechanisms and conformations governing the recognition remain unknown. In order to elucidate the molecular mechanism of its anti-IgE activity, the aim was to analyse the interaction of omalizumab with human IgE. Therefore, IgE Fc C∊2–4 was recombinantly produced in mammalian HE...
Source: Acta Crystallographica Section F - March 20, 2015 Category: Biochemistry Authors: Jensen, R.K.Plum, M.Tjerrild, L.Jakob, T.Spillner, E.Andersen, G.R. Tags: IgE Fab fragment therapeutic antibody research communications Source Type: research

The structure of the C-terminal domain of the nucleoprotein from the Bundibugyo strain of the Ebola virus in complex with a pan-specific synthetic Fab
The vast majority of platforms for the detection of viral or bacterial antigens rely on immunoassays, typically ELISA or sandwich ELISA, that are contingent on the availability of suitable monoclonal antibodies (mAbs). This is a major bottleneck, since the generation and production of mAbs is time-consuming and expensive. Synthetic antibody fragments (sFabs) generated by phage-display selection offer an alternative with many advantages over Fabs obtained from natural antibodies using hybridoma technology. Unlike mAbs, sFabs are generated using phage display, allowing selection for binding to specific strains or for pan-spe...
Source: Acta Crystallographica Section D - June 27, 2018 Category: Biochemistry Authors: Radwa ń ska, M.J. Jask ó ł owski, M. Davydova, E. Derewenda, U. Miyake, T. Engel, D.A. Kossiakoff, A.A. Derewenda, Z.S. Tags: Fab structure Ebola virus nucleoprotein antibody – antigen interaction synthetic antibody fragments Ebola virus Bundibugyo strain research papers Source Type: research

Crystal structure of the Fab region of a neutralizing antibody against granulocyte-macrophage colony-stimulating factor
An increased level of granulocyte-macrophage colony-stimulating factor has a potential role in the development of autoimmune diseases, and the neutralization of its activity by monoclonal antibodies is a promising therapy for some diseases. Here, the crystal structure of the Fab region of EV1007, a fully human antibody expressed in Chinese hamster ovary cells that was developed from human peripheral blood mononuclear cells, is described. The structure closely resembles that of MB007, which is the Fab region of the same antibody expressed in Escherichia coli [Blech et al. (2012), Biochem. J. 447, 205 – 215], except at the...
Source: Acta Crystallographica Section F - September 19, 2019 Category: Biochemistry Authors: Angkawidjaja, C. Torashima, T. Tags: monoclonal antibodies Fab region granulocyte-macrophage colony-stimulating factor anti-GM-CSF EV1007 research communications Source Type: research

Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy
Mediastinal large B-cell lymphoma (MLBL) represents 2% of mature B-cell non-Hodgkin lymphoma in patients ≤ 18 years of age. We analyzed data from childhood and adolescent patients with stage III MLBL (n = 42) and non-MLBL DLBCL (n = 69) treated with Group B therapy in the French-American-British/Lymphome Malins de Burkitt (FAB/LMB) 96 study. MLBL patients had a male/female 26/16; median age, 15.7 years (range, 12.5-19.7); and LDH < 2 versus ≥ 2 x the upper limit of normal, 23:19. Six MLBL patients (14%) had < a 20% response to initial COP (cyclophosphamide, vincristine, and prednisone) therapy. Central patholog...
Source: Blood - January 10, 2013 Category: Hematology Authors: Gerrard, M., Waxman, I. M., Sposto, R., Auperin, A., Perkins, S. L., Goldman, S., Harrison, L., Pinkerton, R., McCarthy, K., Raphael, M., Patte, C., Cairo, M. S., on behalf of the French-American-British/Lymphome Malins de Burkitt 96 (FAB/LMB 96) Internat Tags: Free Research Articles, Lymphoid Neoplasia, Editorials, Clinical Trials and Observations Source Type: research

Social Media in Clinical Practice: Chapter 2, Medical Search Engines and Google
When I realized Springer made the individual chapters of my book, Social Media in Clinical Practice, available, I thought it would be useful for future readers to get some insights about each chapter one by one. Here is the short summary of what you can read about, and an excerpt of the second chapter, Using Medical Search Engines with a Special Focus on Google: There are billions of pages on the World Wide Web and search engines help us find the information we are looking for. Having so many pages with a huge amount of information online is the biggest advantage and disadvantage of the Internet at the same time. Inste...
Source: ScienceRoll - September 4, 2013 Category: Geneticists and Genetics Commentators Authors: Dr. Bertalan Meskó Tags: Medical Search Medicine Medicine 2.0 Social Media in Clinical Practice Web 2.0 Source Type: blogs

3 Advanced Search Techniques for Writing In-Depth Articles
For business people and professionals, writing an in-depth article is a great way to be seen as an authority on your subject. But how do you go about finding new and important information? Instead of the same top ten search results, there is a better way to get more relevant data. When I was a kid and had to do a report for class, I was always amazed how so many of the students came up with the same basic information. Years later, I realized it was because our parents had all bought us the same encyclopedias. The same goes today. Most people will just do a basic Google search and look for links on the first page. Unfortuna...
Source: Success Begins Today - October 11, 2013 Category: Life Coaches Authors: John Richardson Tags: Business SEO Social Media advanced search techniques Source Type: blogs

LITFL Search
The problem with providing education in the hospital environment is the persistent and unwarranted use of Internet Explorer which acts like a cubist Picasso converter to contort the website into a random series of incoherent text boxes Review of the old site highlighted a few functionality issues. One of the most frustrating elements of moving to a scalable mobile responsive design was the dropdown menus. We had far too much information crammed into an unpredictable space which was only intermittently visible…so they have been discarded with the new build. We have decided to run with ‘single menu tabs’ li...
Source: Life in the Fast Lane - November 11, 2013 Category: Emergency Medicine Doctors Authors: Mike Cadogan Tags: Blog News Featured Google Tips and Tricks blogging LITFL LITFL search Source Type: blogs

The Three-Dimensional Job Search
When most nurse job-seekers are in the market for a new nursing position, their job search process can be somewhat one-dimensional. From my perspective, a three-dimensional job search strategy is generally much more effective. And when it comes to career development, it ' s the same thing. One-dimensionsality breeds one-dimensional results -- why not try something more powerful?The One-Dimensional Job SearchIn a one-dimensional job search process, it kind of looks like this: you get up in the morning, make a cup of coffee, eat breakfast, and open your computer. You then peruse job boards like Indeed and Monster looking for...
Source: Digital Doorway - November 6, 2017 Category: Nursing Tags: career career development career management careers healthcare careers job search nurse nurse career nurse careers nurses nursing nursing careers Source Type: blogs

What to use instead of NICE Evidence Search - a first thought
I have been promoting NICE Evidence Search much more systematically this year to " my " first year undergraduates in their first library session.  It is also on the resource lists I ' ve made for each of their courses.  I like the idea that there is one source, where all the results have been evaluated by health information professionals, and I ' ve suggested it ' s a good first place to search for any health topic.  But NICE Evidence Search is closing at the end of March 2022.  So what to use instead?NICE Evidence Search has two lists of sources, one of sites where some of the content is...
Source: Browsing - February 9, 2022 Category: Databases & Libraries Tags: NICE Evidence Search Source Type: blogs

Search the Web, Plant a Tree Every Minute
Google, Yahoo and other search engines make gobs of money from advertisers who pay to have ads pop up when you look for a term. A few more socially minded search engines like Goodsearch and Everyclick donate a few cents to charity when you seek or shop. But one site begun in 2009, Ecosia, donates a whopping 80 percent of its ad revenue to a program that plants trees in the Brazilian rainforest to counter the rapid deforestation there. Ecosia has become popular enough that it recently hit an impressive benchmark: it is now replanting a tree a minute.About 200,000 people are using Ecosia each day, undertaking about half a mi...
Source: Scientific American - Official RSS Feed - November 26, 2013 Category: Science Tags: Energy & Sustainability Source Type: research

The SEARCH for Diabetes in Youth Study: Rationale, Findings, and Future Directions.
Abstract The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, ra...
Source: Diabetes Care - November 25, 2014 Category: Endocrinology Authors: Hamman RF, Bell RA, Dabelea D, D'Agostino RB, Dolan L, Imperatore G, Lawrence JM, Linder B, Marcovina SM, Mayer-Davis EJ, Pihoker C, Rodriguez BL, Saydah S, for the SEARCH for Diabetes in Youth Study Group Tags: Diabetes Care Source Type: research

What to use instead of NICE Evidence Search - some recommendations (sort of)
In an earlier post I searched NICE Evidence Search (closing at the end of March 2022) and then a number of other sources to see which other sources would find the material.I found 27 results (vertigo epley was the search) in NICE Evidence Search.  5 were systematic reviews from DARE, which I decided I was not too worried about, as DARE has not been updated for some timeThen there were results from PubMed, Cochrane, BestBets, CKS, four health organisations, Patient.info, NICE and the Royal Australian College of GPs.SearchingCochraneitself found one more Cochrane review than NICE Evidence Search did.  So, more...
Source: Browsing - March 10, 2022 Category: Databases & Libraries Tags: NICE Evidence Search Source Type: blogs