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Tim B van der Houwen, P Martin van Hagen, Wilhemina M C Timmermans, Sophinus J W Bartol, King H Lam, Jasper H Kappen, Menno C van Zelm, Jan A M van Laar
OBJECTIVES: Behçet's disease (BD), an auto-inflammatory vasculitis with oro-genital ulcerations, skin lesions and uveitis, is regarded as T cell mediated. A successful trial with rituximab suggests an additive role for B cells in the pathogenesis. Therefore, we studied B cell abnormalities in BD patients and the effect of TNF-blocking therapy. METHODS: B cells in blood (n = 36) and tissue (n = 6) of BD patients were analysed with flow cytometry and/or immunohistochemistry and compared with healthy controls (n = 22)...
October 15, 2016: Rheumatology
Steven R Wiley, Vanitha S Raman
Adjuvants in vaccine formulations are designed to enhance immune responses against a target antigen or pathogen. The ability of these vaccines to induce activation and differentiation of mature naïve B cells to produce pathogen-specific antibodies (immunoglobulins; Ig) helps guarantee long-lived humoral immunity. This process involves clonal expansion of antigen-specific B cells, genomic rearrangement of Ig heavy (IgH) and light (IgL) loci, somatic hypermutation (SHM), and clonal selection for affinity-matured antibody, resulting in a vast but directed repertoire of B cells expressing highly specific antibody proteins...
2017: Methods in Molecular Biology
Hanen Ouadani, Imen Ben-Mustapha, Meriem Ben-Ali, Beya Larguèche, Tihana Jovanic, Sylvie Garcia, Benoit Arcangioli, Houda Elloumi-Zghal, Dahmani Fathallah, Mongia Hachicha, Hatem Masmoudi, François Rougeon, Mohamed-Ridha Barbouche
Activation induced cytidine deaminase (AID) is an essential enzyme for class switch recombination (CSR) and somatic hypermutation (SHM) during secondary immune response. Mutations in the AICDA gene are responsible for Hyper IgM 2 syndrome where both CSR and SHM or only CSR are affected. Indeed, triggering either of the two mechanisms requires the DNA deamination activity of AID. Besides, different domains of AID may be differentially involved in CSR and SHM through their interaction with specific cofactors...
October 4, 2016: Molecular Immunology
G Kerimoğlu, T Mercantepe, H S Erol, A Turgut, H Kaya, S Çolakoğlu, E Odacı
The pathological effects of exposure to an electromagnetic field (EMF) during adolescence may be greater than those in adulthood. We investigated the effects of exposure to 900 MHz EMF during adolescence on male adult rats. Twenty-four 21-day-old male rats were divided into three equal groups: control (Cont-Gr), sham (Shm-Gr) and EMF-exposed (EMF-Gr). EMF-Gr rats were placed in an EMF exposure cage (Plexiglas cage) for 1 h/day between postnatal days 21 and 59 and exposed to 900 MHz EMF. Shm-Gr rats were placed inside the Plexiglas cage under the same conditions and for the same duration, but were not exposed to EMF...
August 11, 2016: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Ang Cui, Roberto Di Niro, Jason A Vander Heiden, Adrian W Briggs, Kris Adams, Tamara Gilbert, Kevin C O'Connor, Francois Vigneault, Mark J Shlomchik, Steven H Kleinstein
Analyses of somatic hypermutation (SHM) patterns in B cell Ig sequences have important basic science and clinical applications, but they are often confounded by the intrinsic biases of SHM targeting on specific DNA motifs (i.e., hot and cold spots). Modeling these biases has been hindered by the difficulty in identifying mutated Ig sequences in vivo in the absence of selection pressures, which skew the observed mutation patterns. To generate a large number of unselected mutations, we immunized B1-8 H chain transgenic mice with nitrophenyl to stimulate nitrophenyl-specific λ(+) germinal center B cells and sequenced the unexpressed κ L chains using next-generation methods...
October 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Liang Zeng, Jing Lin, Liping Huang, Ming Zhao
Besides the phase and group velocities, the amplitude of guided wave mode is also frequency dependent. This amplitude dispersion also influences the performance of guided wave methods in nondestructive evaluation (NDE) and structural health monitoring (SHM). In this paper, the effects of amplitude dispersion to the spectrum and waveform of a propagating wave-packet are investigated. It is shown that the amplitude dispersion results in distortion in the spectrum of guided wave response, and thus influences the waveform of the wave-packet...
September 30, 2016: Sensors
Salvatore Campione, Francois Marquier, Jean-Paul Hugonin, A Robert Ellis, John F Klem, Michael B Sinclair, Ting S Luk
The development of novel thermal sources that control the emission spectrum and the angular emission pattern is of fundamental importance. In this paper, we investigate the thermal emission properties of semiconductor hyperbolic metamaterials (SHMs). Our structure does not require the use of any periodic corrugation to provide monochromatic and directional emission properties. We show that these properties arise because of epsilon-near-zero conditions in SHMs. The thermal emission is dominated by the epsilon-near-zero effect in the doped quantum wells composing the SHM...
October 5, 2016: Scientific Reports
Tineke Cantaert, Jean-Nicolas Schickel, Jason M Bannock, Yen-Shing Ng, Christopher Massad, Fabien R Delmotte, Natsuko Yamakawa, Salome Glauzy, Nicolas Chamberlain, Tuure Kinnunen, Laurence Menard, Aubert Lavoie, Jolan E Walter, Luigi D Notarangelo, Julie Bruneau, Waleed Al-Herz, Sara Sebnem Kilic, Hans D Ochs, Charlotte Cunningham-Rundles, Mirjam van der Burg, Taco W Kuijpers, Sven Kracker, Hideo Kaneko, Yujin Sekinaka, Shigeaki Nonoyama, Anne Durandy, Eric Meffre
Patients with mutations in AICDA, which encodes activation-induced cytidine deaminase (AID), display an impaired peripheral B cell tolerance. AID mediates class-switch recombination (CSR) and somatic hypermutation (SHM) in B cells, but the mechanism by which AID prevents the accumulation of autoreactive B cells in blood is unclear. Here, we analyzed B cell tolerance in AID-deficient patients, patients with autosomal dominant AID mutations (AD-AID), asymptomatic AICDA heterozygotes (AID+/-), and patients with uracil N-glycosylase (UNG) deficiency, which impairs CSR but not SHM...
October 4, 2016: Journal of Clinical Investigation
Jing Wang, Gongliu Yang, Jing Li, Xiao Zhou
For real-time solution of inertial navigation system (INS), the high-degree spherical harmonic gravity model (SHM) is not applicable because of its time and space complexity, in which traditional normal gravity model (NGM) has been the dominant technique for gravity compensation. In this paper, a two-dimensional second-order polynomial model is derived from SHM according to the approximate linear characteristic of regional disturbing potential. Firstly, deflections of vertical (DOVs) on dense grids are calculated with SHM in an external computer...
2016: Sensors
Nicolas Quaegebeur, Nidhal Bouslama, Maxime Bilodeau, Robin Guitel, Patrice Masson, Ahmed Maslouhi, Philippe Micheau
Validation of guided-wave based systems for Non-Destructive Evaluation (NDE) and Structural Health Monitoring (SHM) under realistic conditions or environment requires complex setups. For this purpose, numerical or theoretical approaches are useful to save time and cost associated with experiential tests. However, the interaction with realistic geometrical (rivets, thickness changes, stiffeners, extrusions) or damage features (fatigue cracks, fillet cracks, delaminations, disbonds) must be accurately captured in order to be representative...
September 14, 2016: Ultrasonics
Sachini U Siriwardena, Kang Chen, Ashok S Bhagwat
The AID/APOBEC family enzymes convert cytosines in single-stranded DNA to uracils, causing base substitutions and strand breaks. They are induced by cytokines produced during the body's inflammatory response to infections, and they help combat infections through diverse mechanisms. AID is essential for the maturation of antibodies and causes mutations and deletions in antibody genes through somatic hypermutation (SHM) and class-switch recombination (CSR) processes. One member of the APOBEC family, APOBEC1, edits mRNA for a protein involved in lipid transport...
September 1, 2016: Chemical Reviews
Ahmed M Abdelrahman, Hala M El Cheweikh, Dina Ms El-Fayoumi, Riham Shm Allam
PURPOSE: To describe a new ultrasound biomicroscopic (UBM) sign seen in patients who underwent deep sclerectomy (DS) as a surgical procedure for the management of uncontrolled primary open-angle glaucoma (POAG). The presence of this sign in ultrasound biomicroscopy is suggested to be an indicator of successful surgery. We would like to name this sign as the "dolphin head sign." DESIGN: Prospective interventional study. MATERIALS AND METHODS: Twenty-eight eyes of 17 patients with POAG underwent DS with intraoperative mitomycin C (MMC) 0...
May 2016: Journal of Current Glaucoma Practice
Gertjan J Driessen, Hanna IJspeert, Marjolein Wentink, Helger G Yntema, P Martin van Hagen, Arthur van Strien, Giorgia Bucciol, Ozgur Cogulu, Margreet Trip, Willy Nillesen, Els A Peeters, Ingrid Pico-Knijnenburg, Barbara H Barendregt, Marta Rizzi, Jacques J van Dongen, Necil Kutukculer, Mirjam van der Burg
PTEN deficiency in humans is associated with PTEN Hamartoma Tumor Syndromes (PHTS). It causes increased activation of the PI3K/Akt pathway and we here show that the humoral immune response is deregulated resulting in CSR and SHM deficiency. This is clinically apparent in part of the PHTS patients as antibody deficiency. In conclusion, PI3K/Akt signaling is important for the human B-cell response to antigens and deregulated signaling is implicated in the pathophysiology of antibody deficiency.
August 13, 2016: Journal of Allergy and Clinical Immunology
Ali H Ellebedy, Katherine J L Jackson, Haydn T Kissick, Helder I Nakaya, Carl W Davis, Krishna M Roskin, Anita K McElroy, Christine M Oshansky, Rivka Elbein, Shine Thomas, George M Lyon, Christina F Spiropoulou, Aneesh K Mehta, Paul G Thomas, Scott D Boyd, Rafi Ahmed
Antigen-specific B cells bifurcate into antibody-secreting cells (ASCs) and memory B cells (MBCs) after infection or vaccination. ASCs (plasmablasts) have been extensively studied in humans, but less is known about B cells that become activated but do not differentiate into plasmablasts. Here we have defined the phenotype and transcriptional program of a subset of antigen-specific B cells, which we have called 'activated B cells' (ABCs), that were distinct from ASCs and were committed to the MBC lineage. We detected ABCs in humans after infection with Ebola virus or influenza virus and also after vaccination...
October 2016: Nature Immunology
Thaddeus M Davenport, Jason Gorman, M Gordon Joyce, Tongqing Zhou, Cinque Soto, Miklos Guttman, Stephanie Moquin, Yongping Yang, Baoshan Zhang, Nicole A Doria-Rose, Shiu-Lok Hu, John R Mascola, Peter D Kwong, Kelly K Lee
Antibody somatic hypermutation (SHM) and affinity maturation enhance antigen recognition by modifying antibody paratope structure to improve its complementarity with the target epitope. SHM-induced changes in paratope dynamics may also contribute to antibody maturation, but direct evidence of this is limited. Here, we examine two classes of HIV-1 broadly neutralizing antibodies (bNAbs) for SHM-induced changes in structure and dynamics, and delineate the effects of these changes on interactions with the HIV-1 envelope glycoprotein (Env)...
July 20, 2016: Structure
Gyeongrak Choi, Jong Won Lee, Ju Young Cha, Young-Ju Kim, Yeon-Sun Choi, Mark J Schulz, Chang Kwon Moon, Kwon Tack Lim, Sung Yong Kim, Inpil Kang
We present a nanocomposite strain sensor (NCSS) to develop a novel structural health monitoring (SHM) sensor that can be easily installed in a composite structure. An NCSS made of a multi-walled carbon nanotubes (MWCNT)/epoxy composite was installed on a target structure with facile processing. We attempted to evaluate the NCSS sensing characteristics and benchmark compared to those of a conventional foil strain gauge. The response of the NCSS was fairly good and the result was nearly identical to the strain gauge...
2016: Sensors
Wilhelmina M C Timmermans, Jan A M van Laar, Tim B van der Houwen, Lieke S J Kamphuis, Sophinus J W Bartol, King H Lam, Rob J Ouwendijk, Miles P Sparrow, Peter R Gibson, P Martin van Hagen, Menno C van Zelm
BACKGROUND: B-cell depletion can improve a variety of chronic inflammatory diseases, but does not appear beneficial for patients with Crohn's disease. OBJECTIVE: To elucidate the involvement of B cells in Crohn's disease, we here performed an 'in depth' analysis of intestinal and blood B-cells in this chronic inflammatory disease. METHODS: Patients with Crohn's disease were recruited to study B-cell infiltrates in intestinal biopsies (n = 5), serum immunoglobulin levels and the phenotype and molecular characteristics of blood B-cell subsets (n = 21)...
2016: PloS One
Edward J Steele
For 30 years two general mechanisms have competed to explain somatic hypermutation of immunoglobulin (Ig) genes. The first, the DNA-based model, is focused only on DNA substrates. The modern form is the Neuberger "DNA Deamination Model" based on activation-induced cytidine deaminase (AID) and short-patch error-prone DNA repair by DNA Polymerase-η operating around AID C-to-U lesions. The other is an RNA-based mechanism or the "Reverse Transcriptase Model" of SHM which produces strand-biased mutations at A:T and G:C base pairs...
September 2016: DNA Repair
Annouschka M Weijsenfeld, Colette Smit, Sophie Cohen, Ferdinand W N M Wit, Michelle Mutschelknauss, Linda C van der Knaap, Laura M van Zonneveld, Bert J Zomer, Nike Nauta, Joke C Patist, Marien H J Kuipers-Jansen, Esther P Smit, Charlotte Blokhuis, Dasja Pajkrt
BACKGROUND: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure...
October 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Cassandra A Simonich, Katherine L Williams, Hans P Verkerke, James A Williams, Ruth Nduati, Kelly K Lee, Julie Overbaugh
HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at ∼1 year post-infection, including one with cross-clade breadth...
June 30, 2016: Cell
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