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https://www.readbyqxmd.com/read/29679495/insights-into-the-post-translational-modifications-of-archaeal-sis10b-alba-lysine-16-is-methylated-not-acetylated-and-this-does-not-regulate-transcription-or-growth
#1
Jingjing Cao, Qian Wang, Tao Liu, Nan Peng, Li Huang
Nucleic acid-binding proteins of the Sac10b family, also referred to as Alba (for acetylation lowers binding affinity), are highly conserved in Archaea. It was reported that Sso10b, a Sac10b homologue from Sulfolobus solfataricus, was acetylated at the ε-amino group of K16 and the α-amino group of the N-terminal residue. Notably, acetylation of K16 reduced the affinity of Sso10b for DNA and de-repressed transcription in vitro. Here we show that Sis10b, a Sac10b homologue from Sulfolobus islandicus, underwent a range of post-translational modifications (PTMs)...
April 21, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29679204/efficacy-of-curcumin-for-age-associated-cognitive-decline-a-narrative-review-of-preclinical-and-clinical-studies
#2
REVIEW
Marjana Rahman Sarker, Susan F Franks
Processes such as aberrant redox signaling and chronic low-grade systemic inflammation have been reported to modulate age-associated pathologies such as cognitive impairment. Curcumin, the primary therapeutic component of the Indian spice, Turmeric (Curcuma longa), has long been known for its strong anti-inflammatory and antioxidant activity attributable to its unique molecular structure. Recently, an interest in this polyphenol as a cognitive therapeutic for the elderly has emerged. The purpose of this paper is to critically review preclinical and clinical studies that have evaluated the efficacy of curcumin in ameliorating and preventing age-associated cognitive decline and address the translational progress of preclinical to clinical efficacy...
April 21, 2018: GeroScience
https://www.readbyqxmd.com/read/29679025/combining-electrical-stimulation-and-tissue-engineering-to-treat-large-bone-defects-in-a-rat-model
#3
Liudmila Leppik, Han Zhihua, Sahba Mobini, Vishnu Thottakkattumana Parameswaran, Maria Eischen-Loges, Andrei Slavici, Judith Helbing, Lukas Pindur, Karla M C Oliveira, Mit B Bhavsar, Lukasz Hudak, Dirk Henrich, John H Barker
Bone Tissue engineering (BTE) has recently been introduced as an alternative to conventional treatments for large non-healing bone defects. BTE approaches mimic autologous bone grafts, by combining cells, scaffold, and growth factors, and have the added benefit of being able to manipulate these constituents to optimize healing. Electrical stimulation (ES) has long been used to successfully treat non-healing fractures and has recently been shown to stimulate bone cells to migrate, proliferate, align, differentiate, and adhere to bio compatible scaffolds, all cell behaviors that could improve BTE treatment outcomes...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29678925/role-of-the-novel-endoribonuclease-slfn14-and-its-disease-causing-mutations-in-ribosomal-degradation
#4
Sarah J Fletcher, Vera P Pisareva, Abdullah Khan, Andrew Tcherepanov, Neil V Morgan, Andrey V Pisarev
Platelets are anucleate and mostly ribosome-free cells within the bloodstream, derived from megakaryocytes within bone marrow and crucial for cessation of bleeding at sites of injury. Inherited thrombocytopenias are a group of disorders characterized by a low platelet count and are frequently associated with excessive bleeding. SLFN14 is one of the most recently discovered genes linked to inherited thrombocytopenia where several heterozygous missense mutations in SLFN14 were identified to cause defective megakaryocyte maturation and platelet dysfunction...
April 20, 2018: RNA
https://www.readbyqxmd.com/read/29677376/endothelial-protein-c-targeting-liposomes-show-enhanced-uptake-and-improved-therapeutic-efficacy-in-human-retinal-endothelial-cells
#5
Anthoula Arta, Anne Z Eriksen, Fredrik Melander, Paul Kempen, Michael Larsen, Thomas L Andresen, Andrew J Urquhart
Purpose: To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid-loaded functionalized liposomes that exhibit both enhanced uptake by HRECs and superior biologic activity compared to nontargeting liposomes and free drug. Methods: EPCR expression of HRECs was investigated through flow cytometry and Western blot assays...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29677173/what-does-this-mutation-mean-the-tools-and-pitfalls-of-variant-interpretation-in-lymphoid-malignancies
#6
REVIEW
Guillermin Yann, Lopez Jonathan, Chabane Kaddour, Hayette Sandrine, Bardel Claire, Salles Gilles, Sujobert Pierre, Huet Sarah
High throughput sequencing (HTS) is increasingly important in determining cancer diagnoses, with subsequent prognostic and therapeutic implications. The biology of cancer is becoming increasingly deciphered and it is clear that therapy needs to be individually tailored. Whilst translational research plays an important role in lymphoid malignancies, few guidelines exist to guide biologists and routine laboratories through this constantly evolving field. In this article, we review the challenges of interpreting HTS in lymphoid malignancies and provide a toolkit to interpret single nucleotide variants obtained from HTS...
April 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29675269/translation-of-remote-control-regenerative-technologies-for-bone-repair
#7
Hareklea Markides, Jane S McLaren, Neil D Telling, Noura Alom, E'atelaf A Al-Mutheffer, Richard O C Oreffo, Andrew Zannettino, Brigitte E Scammell, Lisa J White, Alicia J El Haj
The role of biomechanical stimuli, or mechanotransduction, in normal bone homeostasis and repair is understood to facilitate effective osteogenesis of mesenchymal stem cells (MSCs) in vitro. Mechanotransduction has been integrated into a multitude of in vitro bone tissue engineering strategies and provides an effective means of controlling cell behaviour towards therapeutic outcomes. However, the delivery of mechanical stimuli to exogenous MSC populations, post implantation, poses a significant translational hurdle...
2018: NPJ Regenerative Medicine
https://www.readbyqxmd.com/read/29675094/up-regulation-of-eif3e-is-associated-with-the-progression-of-esophageal-squamous-cell-carcinoma-and-poor-prognosis-in-patients
#8
Fengkai Xu, Jie Gu, Lin Wang, Ronghua Liu, Yunfeng Yuan, Hao Wang, Jiahao Jiang, Wei Mao, Chunlai Lu, Di Ge
Introduction : Esophageal cancer is one of the most common malignant tumors in the world. Eukaryotic translation initiation factors 3e (eIF3e) makes a notable difference in the initiation of protein synthesis and tumor progression. However, the role of eIF3e in ESCC has not been revealed yet. This study aims to investigate the bio-functional and prognostic role of eIF3e in human ESCC tissues and cells. Methods : Immunohistochemical staining and Western blot were performed to detect the eIF3e expression in ESCC patients' tissues...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29671116/mpdu1-regulates-ceacam1-and-cell-adhesion-in-vitro-and-in-vivo
#9
Daniel C Bennett, Aurelie Cazet, Jon Charest, Joseph N Contessa
N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins. Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO). The genetics of LLO biosynthesis have been established in yeast and Chinese hamster systems, but human models of LLO biosynthesis are lacking. In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1...
April 18, 2018: Glycoconjugate Journal
https://www.readbyqxmd.com/read/29670586/a-new-age-structured-multiscale-model-of-the-hepatitis-c-virus-life-cycle-during-infection-and-therapy-with-direct-acting-antiviral-agents
#10
Barbara de M Quintela, Jessica M Conway, James M Hyman, Jeremie Guedj, Rodrigo W Dos Santos, Marcelo Lobosco, Alan S Perelson
The dynamics of hepatitis C virus (HCV) RNA during translation and replication within infected cells were added to a previous age-structured multiscale mathematical model of HCV infection and treatment. The model allows the study of the dynamics of HCV RNA inside infected cells as well as the release of virus from infected cells and the dynamics of subsequent new cell infections. The model was used to fit in vitro data and estimate parameters characterizing HCV replication. This is the first model to our knowledge to consider both positive and negative strands of HCV RNA with an age-structured multiscale modeling approach...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29670172/acetylcholine-and-necroptosis-are-players-in-follicular-development-in-primates
#11
Yongrui Du, Konstantin Bagnjuk, Maralee S Lawson, Jing Xu, Artur Mayerhofer
Acetylcholine (ACh) in the ovary and its actions were linked to survival of human granulosa cells in vitro and improved fertility of rats in vivo. These effects were observed upon experimental blockage of the ACh-degrading enzyme (ACH esterase; ACHE), by Huperzine A. We now studied actions of Huperzine A in a three-dimensional culture of macaque follicles. Because a form of programmed necrotic cell death, necroptosis, was previously identified in human granulosa cells in vitro, we also studied actions of necrostatin-1 (necroptosis inhibitor)...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29668724/the-somatostatin-receptor-2-antagonist-64cu-nodaga-jr11-outperforms-64cu-dota-tate-in-a-mouse-xenograft-model
#12
Svetlana N Rylova, Christian Stoykow, Luigi Del Pozzo, Keelara Abiraj, Maria Luisa Tamma, Yvonne Kiefer, Melpomeni Fani, Helmut R Maecke
Copper-64 is an attractive radionuclide for PET imaging and is frequently used in clinical applications. The aim of this study was to perform a side-by-side comparison of the in vitro and in vivo performance of 64Cu-NODAGA-JR11 (NODAGA = 1,4,7-triazacyclononane,1-glutaric acid,4,7-acetic acid, JR11 = p-Cl-Phe-cyclo(D-Cys-Aph(Hor)-D-Aph(cbm)-Lys-Thr-Cys)D-Tyr-NH2), a somatostatin receptor 2 antagonist, with the clinically used sst2 agonist 64Cu-DOTA-TATE ((TATE = D-Phe-cyclo(Cys-Tyr-D-Trp-Lys-Thr-Cys)Thr). In vitro studies demonstrated Kd values of 5...
2018: PloS One
https://www.readbyqxmd.com/read/29668079/co-culture-of-adipose-derived-stem-cells-and-chondrocytes-on-three-dimensionally-printed-bioscaffolds-for-craniofacial-cartilage-engineering
#13
Robert J Morrison, Hassan B Nasser, Khaled N Kashlan, David A Zopf, Derek J Milner, Colleen L Flanangan, Matthew B Wheeler, Glenn E Green, Scott J Hollister
OBJECTIVES/HYPOTHESIS: Reconstruction of craniofacial cartilagenous defects are among the most challenging surgical procedures in facial plastic surgery. Bioengineered craniofacial cartilage holds immense potential to surpass current reconstructive options, but limitations to clinical translation exist. We endeavored to determine the viability of utilizing adipose-derived stem cell-chondrocyte co-culture and three-dimensional (3D) printing to produce 3D bioscaffolds for cartilage tissue engineering...
April 18, 2018: Laryngoscope
https://www.readbyqxmd.com/read/29667553/car-t-cell-therapy-a-new-era-in-cancer-immunotherapy
#14
Miliotou N Androulla, Papadopoulou C Lefkothea
BACKGROUND: Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient's immune system. METHODS: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient's autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient...
April 17, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29666835/aptamers-and-apple-pies-a-mini-review-of-psma-aptamers-and-lessons-from-donald-s-coffey
#15
REVIEW
Shawn E Lupold
This mini-review article is part of a special issue dedicated to Donald S. Coffey, a pioneer translational research scientist, exemplary mentor, and leader in urologic and urologic oncology research. This article first briefly reflects on life and scientific lessons from Don Coffey. It then reviews the development of two prostate cancer targeting RNA aptamers, xPSM-A9 and xPSM-A10, through in vitro selection for aptamers that bind to the extracellular domain of the Prostate Specific Membrane Antigen (PSMA)...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29666238/rapid-acquisition-and-model-based-analysis-of-cell-free-transcription-translation-reactions-from-nonmodel-bacteria
#16
Simon J Moore, James T MacDonald, Sarah Wienecke, Alka Ishwarbhai, Argyro Tsipa, Rochelle Aw, Nicolas Kylilis, David J Bell, David W McClymont, Kirsten Jensen, Karen M Polizzi, Rebekka Biedendieck, Paul S Freemont
Native cell-free transcription-translation systems offer a rapid route to characterize the regulatory elements (promoters, transcription factors) for gene expression from nonmodel microbial hosts, which can be difficult to assess through traditional in vivo approaches. One such host, Bacillus megaterium , is a giant Gram-positive bacterium with potential biotechnology applications, although many of its regulatory elements remain uncharacterized. Here, we have developed a rapid automated platform for measuring and modeling in vitro cell-free reactions and have applied this to B...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666154/prediction-and-quantification-of-hepatic-transporter-mediated-uptake-of-pitavastatin-utilizing-a-combination-of-the-relative-activity-factor-approach-and-mechanistic-modeling
#17
Pallabi Mitra, Samantha Weinheimer, Meeghan Michalewicz, Mitchell E Taub
Quantification of the fraction transported (ft) by a particular transporter will facilitate more robust estimations of transporter interactions. Using pitavastatin as a model uptake transporter substrate, we investigated the utility of the relative activity factor (RAF) approach and mechanistic modeling, to estimate ft in hepatocytes. Transporters evaluated were OATP1B1, OATP1B3, and NTCP. Transporter expressing HEK293 cells and human hepatocytes were used for determining RAF values, which were then incorporated into the mechanistic model to simulate hepatocyte uptake of pitavastatin over time...
April 17, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29665948/preclinical-tools-for-the-evaluation-of-tuberculosis-treatment-regimens-for-children
#18
E W Tucker, K E Dooley
Tuberculosis (TB) treatment regimens have been extrapolated from adults to children. However, pediatric disease merits different treatment strategies to avoid under- or over-treatment. While animal models have been pivotal in identifying effective regimens for adult disease, pediatric TB is heterogeneous and cannot be represented by a single preclinical model. Infants and young children most commonly have disseminated disease or tuberculous meningitis (TBM), school-aged children have paucibacillary disease, and adolescents have adult-like cavitary lung disease...
May 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29665687/identification-of-fast-acting-2-6-disubstituted-imidazopyridines-that-are-efficacious-in-the-in-vivo-humanized-plasmodium-falciparum-nodscidil2r%C3%AE-null-mouse-model-of-malaria
#19
Aloysius T Nchinda, Claire Le Manach, Tanya Paquet, Diego Gonzalez Cabrera, Kathryn J Wicht, Christel Brunschwig, Mathew Njoroge, Efrem Abay, Dale Taylor, Nina Lawrence, Sergio Wittlin, Maria-Belen Jimenez-Diaz, Maria Santos Martínez-Martínez, Santiago Ferrer, Iñigo Angulo-Barturen, Maria Jose Lafuente-Monasterio, James Duffy, Jeremy N Burrows, Leslie J Street, Kelly Chibale
Optimization of a chemical series originating from whole-cell phenotypic screening against the human malaria parasite, Plasmodium falciparum, led to the identification of two promising 2,6-disubstituted imidazopyridine compounds, 43 and 74. These compounds exhibited potent activity against asexual blood stage parasites that, together with their in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) properties, translated to in vivo efficacy with clearance of parasites in the PfSCID mouse model for malaria within 48 h of treatment...
April 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29665328/effects-of-exposure-to-acetaminophen-and-ibuprofen-on-fetal-germ-cell-development-in-both-sexes-in-rodent-and-human-using-multiple-experimental-systems
#20
Pablo Hurtado-Gonzalez, Richard A Anderson, Joni Macdonald, Sander van den Driesche, Karen Kilcoyne, Anne Jørgensen, Chris McKinnell, Sheila Macpherson, Richard M Sharpe, Rod T Mitchell
BACKGROUND: Analgesic exposure during pregnancy may affect aspects of fetal gonadal development that are targeted by endocrine disruptors. OBJECTIVES: We investigated whether therapeutically relevant doses of acetaminophen and ibuprofen affect germ cell (GC) development in human fetal testes/ovaries using in vitro and xenograft approaches. METHODS: Gonocyte (TFAP2C+ ) number was reduced relative to controls in first-trimester human fetal testes exposed in vitro to acetaminophen (-28%) or ibuprofen (-22%) and also in ovaries exposed to acetaminophen (-43%) or ibuprofen (-49%)...
April 16, 2018: Environmental Health Perspectives
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