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https://www.readbyqxmd.com/read/29145710/testosterone-replacement-in-transgenic-sickle-cell-mice-controls-priapic-activity-and-upregulates-pde5-expression-and-enos-activity-in-the-penis
#1
B Musicki, S Karakus, W Akakpo, F H Silva, J Liu, H Chen, B R Zirkin, A L Burnett
Sickle cell disease (SCD)-associated priapism is characterized by decreased nitric oxide (NO) signaling and downregulated phosphodiesterase (PDE)5 protein expression and activity in the penis. Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the penis in SCD are not known. Given the critical role of androgens in erection physiology and NO synthase (NOS)/PDE5 expression, we hypothesized that testosterone replacement to eugonadal testosterone levels reduces priapism by reversing impaired endothelial (e)NOS activity and molecular abnormalities involving PDE5...
November 16, 2017: Andrology
https://www.readbyqxmd.com/read/29145636/localization-and-functional-characterization-of-the-p-asn965ser-n965s-abca4-variant-in-mice-reveal-pathogenic-mechanisms-underlying-stargardt-macular-degeneration
#2
Laurie L Molday, Daniel Wahl, Marinko Sarunic, Robert S Molday
ABCA4 is a member of the superfamily of ATP-binding cassette (ABC) proteins that transports N-retinylidene-phosphatidylethanolamine (N-Ret-PE) across outer segment disc membranes thereby facilitating the removal of potentially toxic retinoid compounds from photoreceptor cells. Mutations in the gene encoding ABCA4 are responsible for Stargardt disease (STGD1), an autosomal recessive retinal degenerative disease that causes severe vision loss. To define the molecular basis for STGD1 associated with the p.Asn965Ser (N965S) mutation in the Walker A motif of nucleotide binding domain 1 (NBD1), we generated a p...
November 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29145615/iptmnet-an-integrated-resource-for-protein-post-translational-modification-network-discovery
#3
Hongzhan Huang, Cecilia N Arighi, Karen E Ross, Jia Ren, Gang Li, Sheng-Chih Chen, Qinghua Wang, Julie Cowart, K Vijay-Shanker, Cathy H Wu
Protein post-translational modifications (PTMs) play a pivotal role in numerous biological processes by modulating regulation of protein function. We have developed iPTMnet (http://proteininformationresource.org/iPTMnet) for PTM knowledge discovery, employing an integrative bioinformatics approach-combining text mining, data mining, and ontological representation to capture rich PTM information, including PTM enzyme-substrate-site relationships, PTM-specific protein-protein interactions (PPIs) and PTM conservation across species...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29145596/a-crispr-cas9-based-exploration-into-the-elusive-mechanism-for-lactate-export-in-saccharomyces-cerevisiae
#4
Robert Mans, Else-Jasmijn Hassing, Melanie Wijsman, Annabel Giezekamp, Jack T Pronk, Jean-Marc Daran, Antonius J A van Maris
CRISPR/Cas9-based genome editing allows rapid, simultaneous modification of multiple genetic loci in Saccharomyces cerevisiae. Here, this technique was used in a functional analysis study aimed at identifying the hitherto unknown mechanism of lactate export in this yeast. First, an S. cerevisiae strain was constructed with deletions in 25 genes encoding transport proteins, including the complete aqua(glycero)porin family and all known carboxylic-acid transporters. The 25-deletion strain was then transformed with an expression cassette for Lactobacillus casei lactate dehydrogenase (LcLDH)...
November 14, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/29145561/clinical-significance-of-cd73-in-triple-negative-breast-cancer-multiplex-analysis-of-a-phase-iii-clinical-trial
#5
L Buisseret, S Pommey, B Allard, S Garaud, M Bergeron, I Cousineau, L Ameye, Y Bareche, M Paesmans, J P A Crown, A Di Leo, S Loi, M Piccart-Gebhart, K Willard-Gallo, C Sotiriou, J Stagg
Background: CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Patients and methods: Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis...
November 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29145549/generational-differences-in-the-5-year-incidence-of-age-related-macular-degeneration
#6
Karen J Cruickshanks, David M Nondahl, Lauren J Johnson, Dayna S Dalton, Mary E Fisher, Guan-Hua Huang, Barbara E Klein, Ronald Klein, Carla R Schubert
Importance: Whether a reported decline in the risk of developing age-related macular degeneration (AMD) continued for people born during the Baby Boom years (1946-1964) or later is unknown. These data are important to plan for ocular health care needs in the 21st century. Objectives: To determine whether the 5-year risk for AMD declined by generation and to identify factors that contributed to improvement in risk. Design, Setting, and Participants: Data came from the longitudinal cohort Beaver Dam Eye Study (March 1, 1988, through September 15, 1990, and March 1, 1993, through June 15, 1995) and the Beaver Dam Offspring Study (June 8, 2005, through August 4, 2008, and July 12, 2010, through March 21, 2013)...
November 16, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29145506/the-prpf-protein-of-shewanella-oneidensis-mr-1-catalyzes-the-isomerization-of-2-methyl-cis-aconitate-during-the-catabolism-of-propionate-via-the-acnd-dependent-2-methylcitric-acid-cycle
#7
Christopher J Rocco, Karl M Wetterhorn, Graeme S Garvey, Ivan Rayment, Jorge C Escalante-Semerena
The 2-methylcitric acid cycle (2-MCC) is a common route of propionate catabolism in microorganisms. In Salmonella enterica, the prpBCDE operon encodes most of the 2-MCC enzymes. In other organisms, e.g., Shewanella oneidensis MR-1, two genes, acnD and prpF replace prpD, which encodes 2-methylcitrate dehydratase. We showed that together, S. oneidensis AcnD and PrpF (SoAcnD, SoPrpF) compensated for the absence of PrpD in a S. enterica prpD strain. We also showed that SoAcnD had 2-methylcitrate dehydratase activity and that PrpF has aconitate isomerase activity...
2017: PloS One
https://www.readbyqxmd.com/read/29145498/antigenicity-of-the-2015-2016-seasonal-h1n1-human-influenza-virus-ha-and-na-proteins
#8
Amelia M Clark, Marta L DeDiego, Christopher S Anderson, Jiong Wang, Hongmei Yang, Aitor Nogales, Luis Martinez-Sobrido, Martin S Zand, Mark Y Sangster, David J Topham
Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015-2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015-2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic...
2017: PloS One
https://www.readbyqxmd.com/read/29145401/anatomically-specific-intratubular-and-interstitial-biominerals-in-the-human-renal-medullo-papillary-complex
#9
Ling Chen, Ryan S Hsi, Feifei Yang, Benjamin A Sherer, Marshall L Stoller, Sunita P Ho
Limited information exists on the anatomically-specific early stage events leading to clinically detectable mineral aggregates in the renal papilla. In this study, quantitative multiscale correlative maps of structural, elemental and biochemical properties of whole medullo-papillary complexes from human kidneys were developed. Correlative maps of properties specific to the uriniferous and vascular tubules using high-resolution X-ray computed tomography, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, and immunolocalization of noncollagenous proteins (NCPs) along with their association with anatomy specific biominerals were obtained...
2017: PloS One
https://www.readbyqxmd.com/read/29145111/a-novel-protein-tyrosine-phosphatase-like-phytase-from-lactobacillus-fermentum-nkn51-cloning-characterization-and-application-in-mineral-release-for-food-technology-applications
#10
Rekha Sharma, Piyush Kumar, Vandana Kaushal, Rahul Das, Naveen Kumar Navani
A novel protein tyrosine phosphatase like phytase (PTPLP), designated as PhyLf from probiotic bacterium Lactobacillus fermentum NKN51 was identified, cloned, expressed and characterized. The recombinant PhyLf showed specific activity of 174.5 U/mg. PhyLf exhibited strict specificity towards phytate and optimum temperature at 60 °C, pH 5.0 and ionic strength of 100 mM. Km and Kcat of PhyLf for phytate were 0.773 mM and 84.31 s(-1), respectively. PhyLf exhibited high resistance against oxidative inactivation...
November 4, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/29145108/acute-calcific-tendinitis-of-the-longus-colli-muscle-masquerading-as-a-retropharyngeal-abscess-a-case-report-and-review-of-the-literature
#11
Uthman Alamoudi, Ahmed A Al-Sayed, Yasser AlSallumi, Matthew H Rigby, S Mark Taylor, Robert D Hart, Jonathan R B Trites
INTRODUCTION: Acute calcific longus colli tendinitis, also known as retropharyngeal or acute calcific prevertebral tendinitis, is a reactive self-limiting inflammatory response to acute or subacute deposition of amorphous calcium hydroxyapatite crystals in the tendons of the longus colli muscle, anterior to the C1-C2 disk space. CASE PRESENTATION: A 53-year-old man presented with a complaint of neck pain and odynophagia over a few days. Blood test findings showed mild leukocytosis and elevated C-reactive protein level...
November 11, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29145028/the-complete-mitochondrial-genome-of-the-alvinocaridid-shrimp-shinkaicaris-leurokolos-decapoda-caridea-insight-into-the-mitochondrial-genetic-basis-of-deep-sea-hydrothermal-vent-adaptation-in-the-shrimp
#12
Shao'e Sun, Ming Hui, Minxiao Wang, Zhongli Sha
Deep-sea hydrothermal vent is one of the most extreme environments on Earth with low oxygen and high levels of toxins. Decapod species from the family Alvinocarididae have colonized and successfully adapted to this extremely harsh environment. Mitochondria plays a vital role in oxygen usage and energy metabolism, thus it may be under selection in the adaptive evolution of the hydrothermal vent shrimps. In this study, the mitochondrial genome (mitogenome) of alvinocaridid shrimp Shinkaicaris leurokolos (Kikuchi & Hashimoto, 2000) was determined through Illumina sequencing...
November 10, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/29145025/coupling-of-on-column-trypsin-digestion-peptide-mapping-and-principal-component-analysis-for-stability-and-biosimilarity-assessment-of-recombinant-human-growth-hormone
#13
Sara M Shatat, Basma M Eltanany, Abeer A Mohamed, Medhat A Al-Ghobashy, Faten A Fathalla, Samah S Abbas
Peptide mapping (PM) is a vital technique in biopharmaceutical industry. The fingerprint obtained helps to qualitatively confirm host stability as well as verify primary structure, purity and integrity of the target protein. Yet, in-solution digestion followed by tandem mass spectrometry is not suitable as a routine quality control test. It is time consuming and requires sophisticated, expensive instruments and highly skilled operators. In an attempt to enhance the fuctionality of PM and extract multi-dimentional data about various critical quality attributes and comparability of biosimilars, coupling of PM generated using immobilized trypsin followed by HPLC-UV to principal component analysis (PCA) is proposed...
November 11, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29144985/a-phase-1-2-study-of-rigosertib-in-patients-with-myelodysplastic-syndromes-mds-and-mds-progressed-to-acute-myeloid-leukemia
#14
Shyamala C Navada, Steven M Fruchtman, Rosalie Odchimar-Reissig, Erin P Demakos, Michael E Petrone, Patrick S Zbyszewski, James F Holland, Lewis R Silverman
This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m(2)/day in 14-day cycles...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29144728/simultaneous-analysis-of-a-non-lipidated-protein-and-its-lipidated-counterpart-enabling-quantitative-investigation-of-protein-lipidation-s-impact-on-cellular-regulation
#15
Agnesa Shala-Lawrence, Melanie Jane Blanden, Svetlana M Krylova, Soumyashree A Gangopadhyay, Stanislav S Beloborodov, James L Hougland, Sergey N Krylov
Here we introduce Protein-Lipidation Quantitation (PLQ) - the first method for quantitative analysis of both a substrate and a product of protein lipidation in a biologically relevant context. Such analysis is required to study roles of protein lipidation in cellular regulation. In PLQ, the substrate is fused with a fluorescent protein to facilitate quantitative detection of both the non-lipidated substrate and the lipidated product. When expressed in cells with endogenous lipidation activity, the substrate is intracellularly lipidated...
November 16, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29144552/simultaneous-determination-of-tilianin-and-its-metabolites-in-mice-using-ultra-high-performance-liquid-chromatography-with-tandem-mass-spectrometry-and-its-application-to-a-pharmacokinetic-study
#16
Liping Wang, Qingwei Chen, Lijun Zhu, Xuejun Zeng, Qiang Li, Ming Hu, Xinchun Wang, Zhongqiu Liu
Tilianin is an active flavonoid glycoside found in many medical plants. Data are lacking regarding its pharmacokinetics and disposition in vivo. The objective of this study was to develop a sensitive, reliable, and validated ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantify tilianin and its main metabolites and to determine its pharmacokinetics in wild-type and breast cancer resistance protein knockout (Bcrp1-/-) FVB mice. Chromatographic separation was accomplished on a C18 column by utilizing acetonitrile and 0...
November 16, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29144540/biosynthetic-energy-cost-of-potentially-highly-expressed-proteins-vary-with-niche-in-selected-actinobacteria
#17
Indrani Sarkar, Louis S Tisa, Maher Gtari, Arnab Sen
Amino acid and protein biosynthesis requires a number of high energy phosphate bonds and includes a dual energy cost for the synthesis of chemical intermediates during the fueling reactions and the conversion of precursor molecules to final products. One popular hypothesis is that the proteins encoded by putative highly expressed genes (hence called PHXPs) generally utilize low energy consuming amino acids to reduce the biosynthetic cost of the essential proteins. In our study, we found that this idea was not supported in the case of actinobacteria...
November 16, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29144454/dynamics-of-p-type-atpase-transport-revealed-by-single-molecule-fret
#18
Mateusz Dyla, Daniel S Terry, Magnus Kjaergaard, Thomas L-M Sørensen, Jacob Lauwring Andersen, Jens Peter Andersen, Charlotte Rohde Knudsen, Roger B Altman, Poul Nissen, Scott C Blanchard
Phosphorylation-type (P-type) ATPases are ubiquitous primary transporters that pump cations across cell membranes through the formation and breakdown of a phosphoenzyme intermediate. Structural investigations suggest that the transport mechanism is defined by conformational changes in the cytoplasmic domains of the protein that are allosterically coupled to transmembrane helices so as to expose ion binding sites to alternate sides of the membrane. Here, we have used single-molecule fluorescence resonance energy transfer to directly observe conformational changes associated with the functional transitions in the Listeria monocytogenes Ca(2+)-ATPase (LMCA1), an orthologue of eukaryotic Ca(2+)-ATPases...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144452/ubiquitination-and-degradation-of-gbps-by-a-shigella-effector-to-suppress-host-defence
#19
Peng Li, Wei Jiang, Qin Yu, Wang Liu, Ping Zhou, Jun Li, Junjie Xu, Bo Xu, Fengchao Wang, Feng Shao
Interferon-inducible guanylate-binding proteins (GBPs) mediate cell-autonomous antimicrobial defences. Shigella flexneri, a Gram-negative cytoplasmic free-living bacterium that causes bacillary dysentery, encodes a repertoire of highly similar type III secretion system effectors called invasion plasmid antigen Hs (IpaHs). IpaHs represent a large family of bacterial ubiquitin-ligases, but their function is poorly understood. Here we show that S. flexneri infection induces rapid proteasomal degradation of human guanylate binding protein-1 (hGBP1)...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144403/the-non-homologous-end-joining-protein-paxx-acts-to-restrict-hsv-1-infection
#20
Ben J Trigg, Katharina B Lauer, Paula Fernandes Dos Santos, Heather Coleman, Gabriel Balmus, Daniel S Mansur, Brian J Ferguson
Herpes simplex virus 1 (HSV-1) has extensive interactions with the host DNA damage response (DDR) machinery that can be either detrimental or beneficial to the virus. Proteins in the homologous recombination pathway are known to be required for efficient replication of the viral genome, while different members of the classical non-homologous end-joining (c-NHEJ) pathway have opposing effects on HSV-1 infection. Here, we have investigated the role of the recently-discovered c-NHEJ component, PAXX (Paralogue of XRCC4 and XLF), which we found to be excluded from the nucleus during HSV-1 infection...
November 16, 2017: Viruses
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