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Jennifer E Flythe, Tandrea Hilliard, Graciela Castillo, Kourtney Ikeler, Jazmine Orazi, Emaad Abdel-Rahman, Amy Barton Pai, Matthew B Rivara, Wendy L St Peter, Steven D Weisbord, Caroline Wilkie, Rajnish Mehrotra
BACKGROUND AND OBJECTIVES: Individuals receiving in-center hemodialysis experience a high symptom burden that detrimentally affects their quality of life. There are few evidence-based interventions for symptom relief in this population. To stimulate innovation in symptom management, data on patient symptom prioritization and treatment preferences are needed. We undertook this study to ( 1 ) identify patient-prioritized symptoms for the development of symptom relief therapies and ( 2 ) elicit preferences for treatments among individuals receiving hemodialysis...
March 20, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Katsuji Haneda, Takefumi Oishi, Hiroshi Kimura, Toshiyuki Inazu
A microbioreactor immobilized with a synthase-type mutant enzyme, Endo-M-N175Q (glycosynthase) of endo-β-N-acetylglucosaminidase derived from Mucor hiemalis (Endo-M), was constructed and used for glycoconjugate synthesis. The transglycosylation was performed with a reaction mixture containing an oxazoline derivative of sialo complex-type glycoside (SG), which was prepared from a sialo complex-type glycopeptide SGP derived from hen egg yolk, as a glycosyl donor and N-Fmoc-N-acetylglucosaminyl-l-asparagine [Fmoc-Asn(GlcNAc)-OH] as an acceptor...
March 9, 2018: Bioorganic & Medicinal Chemistry
Neville K Kisalu, Azza H Idris, Connor Weidle, Yevel Flores-Garcia, Barbara J Flynn, Brandon K Sack, Sean Murphy, Arne Scho N, Ernesto Freire, Joseph R Francica, Alex B Miller, Jason Gregory, Sandra March, Hua-Xin Liao, Barton F Haynes, Kevin Wiehe, Ashley M Trama, Kevin O Saunders, Morgan A Gladden, Anthony Monroe, Mattia Bonsignori, Masaru Kanekiyo, Adam K Wheatley, Adrian B McDermott, S Katie Farney, Gwo-Yu Chuang, Baoshan Zhang, Natasha Kc, Sumana Chakravarty, Peter D Kwong, Photini Sinnis, Sangeeta N Bhatia, Stefan H I Kappe, B Kim Lee Sim, Stephen L Hoffman, Fidel Zavala, Marie Pancera, Robert A Seder
Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) from several subjects immunized with an attenuated Pf whole-sporozoite (SPZ) vaccine (Sanaria PfSPZ Vaccine). Passive transfer of one of these antibodies, monoclonal antibody CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection...
March 19, 2018: Nature Medicine
Budimir S Ilić, Ana Kolarević, Gordana Kocić, Andrija Šmelcerović
Apoptotic and/or ROS-induced DNA fragmentation in sperm cells may contribute to the development of male infertility. As the known dietary antioxidant, ascorbic acid prevents ROS production and protects sperm cells from DNA damage. Here, we found that ascorbic acid has the ability to inhibit DNase I, one of the main endonucleases involved in DNA fragmentation during apoptosis. Site Finder and Molecular docking defined the ascorbic acid interactions with the most important residues of DNase I, including H-donor interactions with Asp 168 and Asn 170, and H-acceptor interaction with Asn 170...
March 15, 2018: Biochemical and Biophysical Research Communications
Patricia L Hall, Christina Lam, John J Alexander, Ghazia Asif, Gerard T Berry, Carlos Ferreira, Hudson H Freeze, William A Gahl, Kim K Nickander, Jon D Sharer, Caroline M Watson, Lynne Wolfe, Kimiyo M Raymond
N-glycanase deficiency (NGLY1 deficiency, NGLY1-CDDG), the first autosomal recessive congenital disorder of N-linked deglycosylation (CDDG), is caused by pathogenic variants in NGLY1. The majority of affected individuals have been identified using exome or genome sequencing. To date, no reliable, clinically available biomarkers have been identified. Urine oligosaccharide analysis was included as part of a routine evaluation for possible biomarkers in patients with confirmed NGLY1-CDDG. During the qualitative review of oligosaccharide profiles by an experienced laboratory director an abnormal analyte with a proposed structure of Neu5Ac1Hex1GlcNAc1-Asn was identified in NGLY1-CDDG patient urine samples...
March 10, 2018: Molecular Genetics and Metabolism
Sarah M Tete, Åsne Jul-Larsen, Sina Rostami, Turid Helen Felli Lunde, Hanne Søland, Florian Krammer, Rebecca J Cox
The 2009 pandemic H1N1 (A(H1N1)pdm09) virus had a highly divergent hemagglutinin (HA) compared to pre-2009 seasonal H1N1 strains. Most peoples were immunologically naïve to the A(H1N1)pdm09, although hospital workers were exposed early in the pandemic before pandemic vaccines became available. Here, we evaluated how pre-existing antibodies influence the induction of cross-functional HA stalk antibodies following A(H1N1)pdm09 vaccination. Fifty-six healthcare workers vaccinated with AS03 adjuvanted A(H1N1)pdm09 vaccine were chosen by their pre-vaccination priming status (primed HI titers ≥ 40 or unprimed < 40)...
March 13, 2018: Vaccine
Todd A Miano, Ebbing Lautenbach, F Perry Wilson, Wensheng Guo, Yuliya Borovskiy, Sean Hennessy
BACKGROUND AND OBJECTIVES: Despite colistin's longstanding reported association with nephrotoxicity, the attributable risk and timing of toxicity onset are still unknown. Whether substantial toxicity occurs during the initial 72 hours of exposure has important implications for early treatment decisions. The objective of this study was to compare colistin-exposed patients with a matched control group given other broad spectrum antibiotics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study in patients treated for multidrug-resistant Pseudomonas , Klebsiella , or Acinetobacter spp...
March 15, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Nisar Ahmed, Adeel Riaz, Zahra Zubair, Muhammad Saqib, Sehrish Ijaz, Muhammad Shah Nawaz-Ul-Rehman, Ahmed Al-Qahtani, Muhammad Mubin
BACKGROUND: The infection in dogs due to canine parvovirus (CPV), is a highly contagious one with high mortality rate. The present study was undertaken for a detailed genetic analysis of partial VP2 gene i.e., 630 bp isolated from rectal swab samples of infected domestic and stray dogs from all areas of district Faisalabad. Monitoring of viruses is important, as continuous prevalence of viral infection might be associated with emergence of new virulent strains. METHODS: In the present study, 40 rectal swab samples were collected from diarrheic dogs from different areas of district Faisalabad, Pakistan, in 2014-15 and screened for the presence of CPV by immunochromatography...
March 15, 2018: Virology Journal
Baruch B Hertzog, Yael Kaufman, Debabrata Biswas, Miriam Ravins, Poornima Ambalavanan, Reuven Wiener, Veronique Angeli, Swaine L Chen, Emanuel Hanski
Bacteria use quorum sensing (QS) to regulate gene expression. We identified a group A Streptococcus (GAS) strain possessing the QS system sil, which produces functional bacteriocins, through a sequential signaling pathway integrating host and bacterial signals. Host cells infected by GAS release asparagine (ASN), which is sensed by the bacteria to alter its gene expression and rate of proliferation. We show that upon ASN sensing, GAS upregulates expression of the QS autoinducer peptide SilCR. Initial SilCR expression activates the autoinduction cycle for further SilCR production...
March 14, 2018: Cell Host & Microbe
Muhammad Ramzan Manwar Hussain, Zeeshan Iqbal, Wajahat M Qazi, Daniel C Hoessli
The structural and functional diversity of the human proteome is mediated by N - and O- linked glycosylations that define the individual properties of extracellular and membrane-associated proteins. In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N -glycosylation. Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N -glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins...
2018: Frontiers in Oncology
Kanij Rukshana Sumi, Soo Cheol Kim, Jewel Howlader, Won Kyo Lee, Kap Seong Choi, Hoy-Taek Kim, Jong-In Park, Ill-Sup Nou, Kang Hee Kho
In this study, an 1888-bp carbonic anhydrase XII (CA XII) sequence was cloned from the brain of the pufferfish, Takifugu rubripes . The cloned sequence contained a coding region of 1470-bp, which was predicted to translate into a protein of 490 amino acid residues. The predicted protein showed between 68-56% identity with the large yellow croaker ( Larimichthys crocea ), tilapia ( Oreochromis niloticus ), and Asian arowana ( Scleropages formosus ) CA XII proteins. It also exhibited 36% and 53% identity with human CA II and CA XII, respectively...
March 13, 2018: International Journal of Molecular Sciences
Anja Schiffmann, Gerald Gimpl
The oxytocin receptor, a class A G protein coupled receptor (GPCR), is essentially involved in the physiology of reproduction. Two parameters are crucially important to support high-affinity agonist binding of the receptor: Mg2+ and cholesterol, both acting as positive modulators. Using displacement assays with a high-affinity fluorescent antagonist (OTAN-A647), we now show that sodium functions as a negative allosteric modulator of the oxytocin receptor. In membranes from HEK293 cells stably expressing the oxytocin receptor, oxytocin binding occurred with about 15-fold lower affinity when sodium chloride was increased from 0 to 300 mM, whereas antagonist binding remained largely unchanged...
March 7, 2018: Biochimica et Biophysica Acta
Laura C Plantinga, Raymond J Lynch, Rachel E Patzer, Stephen O Pastan, C Barrett Bowling
BACKGROUND AND OBJECTIVES: Serious fall injuries in the setting of ESKD may be associated with poor access to kidney transplant. We explored the burden of serious fall injuries among patients on dialysis and patients on the deceased donor waitlist and the associations of these fall injuries with waitlisting and transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our analytic cohorts for the outcomes of ( 1 ) waitlisting and ( 2 ) transplantation included United States adults ages 18-80 years old who ( 1 ) initiated dialysis ( n =183,047) and ( 2 ) were waitlisted for the first time ( n =37,752) in 2010-2013...
March 6, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Young Dong Yoo, Su Ran Mun, Chang Hoon Ji, Ki Woon Sung, Keum Young Kang, Ah Jung Heo, Su Hyun Lee, Jee Young An, Joonsung Hwang, Xiang-Qun Xie, Aaron Ciechanover, Bo Yeon Kim, Yong Tae Kwon
The conjugation of amino acids to the protein N termini is universally observed in eukaryotes and prokaryotes, yet its functions remain poorly understood. In eukaryotes, the amino acid l-arginine (l-Arg) is conjugated to N-terminal Asp (Nt-Asp), Glu, Gln, Asn, and Cys, directly or associated with posttranslational modifications. Following Nt-arginylation, the Nt-Arg is recognized by UBR boxes of N-recognins such as UBR1, UBR2, UBR4/p600, and UBR5/EDD, leading to substrate ubiquitination and proteasomal degradation via the N-end rule pathway...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Georgia C Boles, Randy L Hightower, Rebecca A Coates, Christopher P McNary, Giel Berden, Jos Oomens, Peter B Armentrout
Complexes of aspartic acid (Asp) cationized with Zn2+: Zn(Asp H)+, Zn(Asp H)+(ACN) where ACN = acetonitrile, and Zn(Asp H)+(Asp), as well as with Cd2+, CdCl+(Asp), were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light generated from a free electron laser. A series of low-energy conformers for each complex was found using quantum chemical calculations in order to identify the structures formed experimentally. The main binding motif observed for the heavy metal complex, CdCl+(Asp)[N,CO,COs], is a charge solvated, tridentate structure where the metal center binds to the backbone amino group and carbonyl oxygens of the backbone and side-chain carboxylic acids...
March 4, 2018: Journal of Physical Chemistry. B
Rasmus K Jensen, Rasmus Pihl, Trine A F Gadeberg, Jan K Jensen, Kasper R Andersen, Steffen Thiel, Nick S Laursen, Gregers Rom Andersen
The complement system is a complex, carefully regulated proteolytic cascade for which suppression of aberrant activation is of increasing clinical relevance and inhibition of the complement alternative pathway is a subject of intense research. Here, we describe the nanobody hC3Nb1 that binds to multiple functional states of C3 with sub-nanomolar affinity. The nanobody causes a complete shutdown of alternative pathway activity in human and murine serum when present in concentrations comparable to C3, and hC3Nb1 is shown to prevent both proconvertase assembly as well as binding of the C3 substrate to C3 convertases...
March 1, 2018: Journal of Biological Chemistry
Kutty Selva Nandakumar
Rheumatoid arthritis (RA) is a polygenic and multifactorial syndrome. Many complex immunological and genetic interactions are involved in the final outcome of the clinical disease. Autoantibodies (rheumatoid factors, anti-citrullinated peptide/protein antibodies) are present in RA patients' sera for a long time before the onset of clinical disease. Prior to arthritis onset, in the autoantibody response, epitope spreading, avidity maturation, and changes towards a pro-inflammatory Fc glycosylation phenotype occurs...
February 28, 2018: International Journal of Molecular Sciences
Solveig Hofvind, Tone Hovda, Åsne S Holen, Christoph I Lee, Judy Albertsen, Hilde Bjørndal, Siri H B Brandal, Randi Gullien, Jon Lømo, Daehoon Park, Linda Romundstad, Pål Suhrke, Einar Vigeland, Per Skaane
Purpose To compare the performance of digital breast tomosynthesis (DBT) and two-dimensional synthetic mammography (SM) with that of digital mammography (DM) in a population-based mammographic screening program. Materials and Methods In this prospective cohort study, data from 37 185 women screened with DBT and SM and from 61 742 women screened with DM as part of a population-based screening program in 2014 and 2015 were included. Early performance measures, including recall rate due to abnormal mammographic findings, rate of screen-detected breast cancer, positive predictive value of recall, positive predictive value of needle biopsy, histopathologic type, tumor size, tumor grade, lymph node involvement, hormonal status, Ki-67 level, and human epidermal growth factor receptor 2 status were compared in women who underwent DBT and SM screening and in those who underwent DM screening by using χ2 tests, two-sample unpaired t tests, and tests of proportions...
March 1, 2018: Radiology
Lara Console, Mariafrancesca Scalise, Annamaria Tonazzi, Nicola Giangregorio, Cesare Indiveri
Exosomes are extracellular vesicles involved in cell-to-cell communication. Previous large scale proteomics revealed that they contain SLC proteins. However, no data on the function of exosomal SLCs is available, so far. An SLC localized in exosomes was here characterized for the first time: the carnitine transporter OCTN2 (SLC22A5). The protein was detected by Western Blot analysis in HEK293 exosomes. To investigate the functional properties of the exosomal OCTN2, the proteins extracted from vesicles were reconstituted into proteolipsomes and the transport function was measured as uptake of3 H-carnitine...
February 28, 2018: Scientific Reports
Naoko Yamada, Nahoko Kato-Kogoe, Koji Yamanegi, Hiroshi Nishiura, Yuki Fujihara, Shigeo Fukunishi, Haruki Okamura, Nobuyuki Terada, Keiji Nakasho
BACKGROUND/AIM: Hypoxia down-regulates the expression of cell surface major histocompatibility class I-related chain molecule A (MICA) without increasing its shedding. Recently, the inhibition of N-linked glycosylation was also shown to reduce the cell-surface expression of MICA. We investigated the participation of asparagine (Asn)-linked glycosylation in hypoxia-induced down-regulation of cell-surface MICA using osteosarcoma cells. MATERIALS AND METHODS: The cell-surface expression and Asn-N-glycosylation of MICA were estimated by flow cytometry, and western blot analyses, respectively...
March 2018: Anticancer Research
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