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Claudia Abeijon, Julia Dilo, Jacqueline M Tremblay, Agostinho G Viana, Lilian L Bueno, Silvio F G Carvalho, Ricardo T Fujiwara, Charles B Shoemaker, Antonio Campos-Neto
We have recently developed a sensitive and specific urine-based antigen detection ELISA for the diagnosis of visceral leishmaniasis (VL). This assay used rabbit IgG and chicken IgY polyclonal antibodies specific for the Leishmania infantum proteins iron superoxide dismutase 1 (Li-isd1), tryparedoxin1 (Li-txn1), and nuclear transport factor 2 (Li-ntf2). However, polyclonal antibodies have limitations for upscaling and continuous supply. To circumvent these hurdles, we began to develop immortalized monoclonal antibodies...
August 18, 2018: Parasite Immunology
Lian C T Shoute, Afreen Anwar, Scott MacKay, Gaser N Abdelrasoul, Donghai Lin, Zhimin Yan, Anh H Nguyen, Mark T McDermott, Manzoor A Shah, Jian Yang, Jie Chen, Xiujie S Li
Sclerotinia stem rot, caused by the fungal pathogen Sclerotinia sclerotiorum, is a destructive disease of canola and many other broadleaf crops. The primary inoculum responsible for initiating Sclerotinia epidemics is airborne ascospores released from the apothecia of sclerotia. Timely detection of the presence of airborne ascospores can serve as an early-warning system for forecasting and management of the disease. A major challenge is to develop a portable and automated device which can be deployed onsite to detect and quantify the presence of minute quantities of ascospores in the air and serves as a unit in a network of systems for forecasting of the epidemic...
August 17, 2018: Scientific Reports
David Martino, Melanie Neeland, Thanh Dang, Joanna Cobb, Justine Ellis, Alice Barnett, Mimi Tang, Peter Vuillermin, Katrina Allen, Richard Saffery
Food allergy poses a significant clinical and public health burden affecting 2-10% of infants. Using integrated DNA methylation and transcriptomic profiling, we found that polyclonal activation of naive CD4+ T cells through the T cell receptor results in poorer lymphoproliferative responses in children with immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle-related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory genes (IL1R, IL18RAP, CD82) underpins this suboptimal response...
August 17, 2018: Nature Communications
Giuseppe Lofano, Matthew J Gorman, Ashraf S Yousif, Wen-Han Yu, Julie M Fox, Anne-Sophie Dugast, Margaret E Ackerman, Todd J Suscovich, Joshua Weiner, Dan Barouch, Hendrik Streeck, Susan Little, Davey Smith, Douglas Richman, Douglas Lauffenburger, Bruce D Walker, Michael S Diamond, Galit Alter
HIV-specific broadly neutralizing antibodies (bNAbs) confer protection after passive immunization, but the immunological mechanisms that drive their development are poorly understood. Structural features of bNAbs indicate that they originate from extensive germinal center (GC) selection, which relies on persistent GC activity. However, why a fraction of infected individuals are able to successfully drive more effective affinity maturation is unclear. Delivery of antigens in the form of antibody-immune complexes (ICs), which bind to complement receptors (CRs) or Fc receptors (FcRs) on follicular dendritic cells, represents an effective mechanism for antigen delivery to the GC...
August 17, 2018: Science Immunology
Valerie Wiles, Jamie Haddad, Nicole Leibman, Anne C Avery, Kelly L Hughes
A 12-y-old neutered male Portuguese Water dog was presented because of a 1-y history of persistent hyporexia, diarrhea, and recurrent pyelonephritis. Abdominal ultrasound revealed hepatic nodules and diffuse splenomegaly, and radiographs revealed a mediastinal mass. Fine-needle aspirates of the liver, spleen, and mediastinal mass were suspicious for lymphoma. Flow cytometry identified small T cells that co-expressed CD4 and CD8 at all sites, most suspicious for thymoma, but lymphoma could not be ruled out. PCR for antigen receptor rearrangements analysis identified polyclonal amplification of the T-cell receptor genes, more consistent with thymoma than lymphoma...
August 17, 2018: Journal of Veterinary Diagnostic Investigation
Mona M Al-Shehri, Manal A El-Gendy, Adel S El-Azab, Mohammed A Hamidaddin, Ibrahim A Darwish
AIM: To support the therapeutic drug monitoring of afatinib (AFT), an ELISA was required. RESULTS: A hapten for AFT was prepared and linked to each of BSA and KLH proteins by diazotization/coupling reaction. A polyclonal antibody recognizing AFT with high affinity (IC50  = 40 ng ml-1 ) was generated and used in the development of a competitive ELISA for quantitation of AFT in plasma samples. The assay limit of detection was 2 ng ml-1 . The assay accuracy and precision were proved...
August 17, 2018: Bioanalysis
Jonathon E Himes, Ria Goswami, Riley J Mangan, Amit Kumar, Thomas L Jeffries, Joshua A Eudailey, Holly Heimsath, Quang N Nguyen, Justin Pollara, Celia LaBranche, Meng Chen, Nathan A Vandergrift, James W Peacock, Faith Schiro, Cecily Midkiff, Guido Ferrari, David C Montefiori, Xavier Alvarez Hernandez, Pyone Pyone Aye, Sallie R Permar
Breast milk HIV-1 transmission is currently the predominant contributor to pediatric HIV infections. Yet, only ~10% of breastfeeding infants born to untreated HIV-infected mothers become infected. This study assessed the protective capacity of natural HIV envelope-specific antibodies isolated from the milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. To mimic placental and milk maternal antibody transfer, infant RMs were i.v. infused and orally treated at the time of challenge with a single weakly neutralizing milk monoclonal antibody (mAb), a tri-mAb cocktail with weakly neutralizing and ADCC functionalities, or an anti-influenza control mAb...
August 16, 2018: Mucosal Immunology
Barbara L Parsons
An accurate understanding of the clonal origins of tumors is critical for designing effective strategies to treat or prevent cancer and for guiding the field of cancer risk assessment. The intent of this review is to summarize evidence of multiclonal tumor origin and, thereby, contest the commonly held assumption of monoclonal tumor origin. This review describes relevant studies of X chromosome inactivation, analyses of tumor heterogeneity using other markers, single cell sequencing, and lineage tracing studies in aggregation chimeras and engineered rodent models...
July 2018: Mutation Research
Imperatore Roberta, Coccia Elena, D'Angelo Livia, Varricchio Ettore, De Girolamo Paolo, Marina Paolucci
In this study, evidence for leptin receptor (LR) and gastric leptin immunoreactivity along the digestive tract of the rainbow trout (Oncorhynchus mykiss), is reported. Besides this, the regulation of gastric leptin and its transcript by fatty acids was analyzed in vitro. LR was detected mainly in the cells of the stomach gastric glands and in the brush border of the epithelium of the anterior, middle and distal intestine. In the stomach LR was co-distributed with leptin. The regulation of gastric leptin and its transcript by fatty acids was analyzed by in vitro incubations...
August 13, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Ryan S Atlasi, Ravinder Malik, Christian I Corrales, Laura Tzeplaeff, Julian P Whitelegge, Neil R Cashman, Gal Bitan
Mutations in Cu/Zn-superoxide dismutase (SOD1) gene are linked to 10-20% of familial amyotrophic lateral sclerosis (fALS) cases. The mutations cause misfolding and self-assembly of SOD1 into toxic oligomers and aggregates, resulting in motor neuron degeneration. The molecular mechanisms underlying SOD1 aggregation and toxicity are unclear. Characterization of misfolded SOD1 is particularly challenging due to its metastable nature. Antibodies against misfolded SOD1 are useful tools for this purpose, provided their specificity and selectivity are well characterized...
August 15, 2018: ACS Chemical Biology
Simon Soudet, David Fajgenbaum, Claire Delattre, Alexandra Forestier, Eric Hachulla, Pierre Yves Hatron, David Launay, Louis Terriou
Patients with HHV-8-negative/idiopathic multicentric Castleman disease (iMCD) experience systemic inflammatory symptoms and polyclonal lymphoproliferation due to an unknown etiology. Schnitzler's syndrome (SS) is characterized by recurrent urticarial rash, monoclonal IgM gammopathy, and other clinical signs of inflammation. To our knowledge, we report the first case of iMCD associated with SS and the fourth case of anakinra inducing a complete response for an iMCD patient. A forty-four year old woman with a history of a recurrent urticarial rash, presented to our hospital complaining of 6 months of night sweats, fever, chronic urticaria, iliac bone pain, and generalized lymphadenopathy...
August 11, 2018: Current Research in Translational Medicine
Taku Hatano, Masashi Takanashi, Hitoshi Tsuchihashi, Shin-Ichi Ueno, Arisa Hayashida, Yutaka Tsukune, Kazuaki Kanai, Yasushi Shimo, Nobutaka Hattori
BACKGROUND: Cutaneous and systemic plasmacytosis are skin disorders characterized by cutaneous polyclonal plasma cell infiltration accompanied by polyclonal hypergammaglobulinemia. Cutaneous plasmacytosis involvement is limited to the skin, mainly on the face and trunk, while systemic plasmacytosis also involves 2 or more organ systems. However, there have been no reports of inflammatory myositis due to plasmacytosis. Here, we report a patient with plasmacytosis who developed myalgia and easy fatigability due to inflammatory myositis...
August 14, 2018: BMC Neurology
Hui-Ling Hsu, Chuan-Chang Chuang, Chung-Chih Liang, Der-Jiang Chiao, Hsueh-Ling Wu, Yu-Ping Wu, Feng-Ping Lin, Rong-Hwa Shyu
BACKGROUND: Yersinia pestis is a contributing agent to the epidemic disease, plague, which killed an estimated 200 million people during historical times. In this study, a rapid, cheap, sensitive, and specific technique, the lateral flow assay (F1 strips), has been successfully developed to detect this pathogen, by using paired monoclonal antibodies (MAbs) against Y. pestis capsule like fraction 1 (F1) protein. Compared with the polyclonal antibody (PAb) based F1 strips, the Mab-based F1 strips have a remarkable increased detection limitation (10 to 100 folds)...
August 14, 2018: BMC Infectious Diseases
Benjamin Sobkowiak, Judith R Glynn, Rein M G J Houben, Kim Mallard, Jody E Phelan, José Afonso Guerra-Assunção, Louis Banda, Themba Mzembe, Miguel Viveiros, Ruth McNerney, Julian Parkhill, Amelia C Crampin, Taane G Clark
BACKGROUND: Mixed, polyclonal Mycobacterium tuberculosis infection occurs in natural populations. Developing an effective method for detecting such cases is important in measuring the success of treatment and reconstruction of transmission between patients. Using whole genome sequence (WGS) data, we assess two methods for detecting mixed infection: (i) a combination of the number of heterozygous sites and the proportion of heterozygous sites to total SNPs, and (ii) Bayesian model-based clustering of allele frequencies from sequencing reads at heterozygous sites...
August 14, 2018: BMC Genomics
Oren Avram, Anna Vaisman-Mentesh, Dror Yehezkel, Haim Ashkenazy, Tal Pupko, Yariv Wine
Reproducible and robust data on antibody repertoires are invaluable for basic and applied immunology. Next-generation sequencing (NGS) of antibody variable regions has emerged as a powerful tool in systems immunology, providing quantitative molecular information on antibody polyclonal composition. However, major computational challenges exist when analyzing antibody sequences, from error handling to hypermutation profiles and clonal expansion analyses. In this work, we developed the ASAP (A webserver for Immunoglobulin-Seq Analysis Pipeline) webserver (https://asap...
2018: Frontiers in Immunology
Morie A Gertz
Plasma hyperviscosity is a rare complication of both monoclonal and polyclonal disorders associated with elevation of immunoglobulins. Asymptomatic patients with an elevation in the serum viscosity do not require plasma exchange, and the majority will have other indications for therapeutic intervention. For patients with hemorrhagic or central nervous system manifestations, plasma exchange is the therapy of choice and is relatively safe. Viscosity measurements are not required to initiate therapy, if the index of suspicion is high and the clinical presentation is typical...
August 13, 2018: Blood
Sang-Im Yun, Byung-Hak Song, Jordan C Frank, Justin G Julander, Aaron L Olsen, Irina A Polejaeva, Christopher J Davies, Kenneth L White, Young-Min Lee
Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To investigate the importance of viral and host genetic variations in determining ZIKV infection outcomes, we created three full-length infectious cDNA clones as bacterial artificial chromosomes for each of three spatiotemporally distinct and genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015). Using the three molecularly cloned ZIKVs, together with 13 ZIKV region-specific polyclonal antibodies covering nearly the entire viral protein-coding region, we made three conceptual advances: (i) We created a comprehensive genome-wide portrait of ZIKV gene products and their related species, with several previously undescribed gene products identified in the case of all three molecularly cloned ZIKVs...
August 11, 2018: Viruses
Tomoko Miyata-Takata, Shih-Sung Chuang, Katsuyoshi Takata, Tomohiro Toji, Yoshinobu Maeda, Yasuharu Sato, Tadashi Yoshino
AIMS: Although the neoplastic cells of extranodal NK/T-cell lymphoma (ENKTL) usually do not express T-cell antigens, T-cell receptor (TCR) gene might be rearranged and TCR protein expressed. Downstream TCR pathway is important for the development of peripheral T-cell lymphoma (PTCL), but the expression of TCR pathway components has not been elucidated in ENKTL. METHODS AND RESULTS: We used formalin-fixed paraffin-embedded tissues from 91 ENKTL samples to immunohistochemically characterise the expression of TCR pathway components...
August 13, 2018: Histopathology
Jean Popovici, Lindsey Pierce-Friedrich, Saorin Kim, Sophalai Bin, Vorleak Run, Dysoley Lek, Hee Kim Hor Daryl, Lawrence Lee Soon-U, Matthew V Cannon, David Serre, Didier Menard
Background: Plasmodium vivax resistance to chloroquine has been reported worldwide, although the WHO clinical drug efficacy studies protocol does not allow to classify patient outcomes. Methods: We enrolled 40 vivax malaria patients in northeastern Cambodia, where >17% treatment failures were previously reported. Patients were treated with chloroquine (30mg/kg) and followed for two months, with frequent clinical examination and capillary blood sample collection for microscopy, molecular parasite detection and genotyping, and drug concentration measurements...
August 9, 2018: Journal of Infectious Diseases
Tanja Diana, Andreas Daiber, Matthias Oelze, Susanne Neumann, Paul D Olivo, Michael Kanitz, Paul Stamm, George J Kahaly
Context: We hypothesized that TSH-receptor (TSHR) stimulating antibodies (TSAb) are involved in oxidative stress mechanisms in patients with Graves' disease (GD). Methods: NADPH oxidase (NOX2), oxidative parameters and oxidative burst were measured in serum, urine, and whole blood from GD patients and controls. Superoxide production was investigated in human embryonic kidney (HEK)-293 cells stably overexpressing the TSHR. Lipid peroxidation was determined by immunodot-blot analysis for protein-bound 4-hydroxy-2-nonenal (4-HNE) in human primary thyrocytes and HEK-293-TSHR cells...
August 6, 2018: Journal of Clinical Endocrinology and Metabolism
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