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https://www.readbyqxmd.com/read/29330428/structural-insights-into-two-distinct-binding-modules-for-lys63-linked-polyubiquitin-chains-in-rnf168
#1
Tomio S Takahashi, Yoshihiro Hirade, Aya Toma, Yusuke Sato, Atsushi Yamagata, Sakurako Goto-Ito, Akiko Tomita, Shinichiro Nakada, Shuya Fukai
The E3 ubiquitin (Ub) ligase RNF168 plays a critical role in the initiation of the DNA damage response to double-strand breaks (DSBs). The recruitment of RNF168 by ubiquitylated targets involves two distinct regions, Ub-dependent DSB recruitment module (UDM) 1 and UDM2. Here we report the crystal structures of the complex between UDM1 and Lys63-linked diUb (K63-Ub2) and that between the C-terminally truncated UDM2 (UDM2ΔC) and K63-Ub2. In both structures, UDM1 and UDM2ΔC fold as a single α-helix. Their simultaneous bindings to the distal and proximal Ub moieties provide specificity for Lys63-linked Ub chains...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330371/transcriptional-inaccuracy-threshold-attenuates-differences-in-rna-dependent-dna-synthesis-fidelity-between-retroviral-reverse-transcriptases
#2
Alba Sebastián-Martín, Verónica Barrioluengo, Luis Menéndez-Arias
In M13mp2 lacZα forward mutation assays measuring intrinsic fidelity of DNA-dependent DNA synthesis, wild-type human immunodeficiency virus type 1 (HIV-1) RTs of group M/subtype B previously showed >10-fold higher error rates than murine leukaemia virus (MLV) and avian myeloblastosis virus (AMV) RTs. An adapted version of the assay was used to obtain error rates of RNA-dependent DNA synthesis for several RTs, including wild-type HIV-1BH10, HIV-1ESP49, AMV and MLV RTs, and the high-fidelity mutants of HIV-1ESP49 RT K65R and K65R/V75I...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329019/salidroside-influences-the-cellular-cross-talk-of-human-fetal-lung-diploid-fibroblasts-a-proteomic-approach
#3
Wenmin Xing, Wenyan Gao, Huili Su, Sanying Wang, Jing Zhang, Genxiang Mao, Jing Yan
Senescence is a complex multiple factor proces, which is still poorly understood. The purpose of this study was to find the proteome of cultured human fetal lung diploid fibroblasts (2BS) of different population doubling (PD), as well as the altered proteome induced by salidroside (SAL) in 2BS cells. Proteins were identified by two-dimensional electrophoresis (2-DE) combining matrix-assisted laser desorption/ionization-time and flight mass spectrometry (MAL DI-TOF/MS). As a result, we found 16 proteins with two-fold variations in senescent cells or after SAL treatment, some being reduced such as reticulocalbin-1, heat shock protein beta-6, elongation factor 1-delta, F-actin-capping protein subunit alpha-1, and chloride intracellular channel 1...
January 5, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29327589/transition-metal-dichalcogenide-nanosheets-for-visual-monitoring-pcr-rivaling-a-real-time-pcr-instrument
#4
Liu Wang, Zhicheng Huang, Rui Wang, Yibo Liu, Cheng Qian, Jian Wu, Juewen Liu
Monitoring the progress of polymerase chain reactions (PCR) is of critical importance in bioanalytical chemistry and molecular biology. While real-time PCR thermocyclers are ideal for this purpose, its high cost has limited applications in resource-poor areas. Direct visual detection would be a more attractive alternative. To monitor PCR amplification, DNA staining dyes such as SYBR Green I (SG) are often used. Although these dyes give higher fluorescence when binding to double-stranded (ds) DNA products, they also yield strong background fluorescence in the presence of a high concentration of single-stranded (ss) DNA primers...
January 12, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29325712/a-novel-gata-like-zinc-finger-transcription-factor-involving-in-hematopoiesis-of-eriocheir-sinensis
#5
Yannan Li, Zhihao Jia, Qilin Yi, Xiaorui Song, Yu Liu, Yunke Jia, Lingling Wang, Linsheng Song
GATA transcription factor is a family of DNA-binding proteins that can recognize and bind to sequence of (A/T) GATA (A/G). In the present study, a GATA-like protein (named as EsGLP) was characterized from Eriocheir sinensis, including an 834 bp full length open reading frame of EsGLP, encoding a polypeptide of 277 amino acids. The deduced amino acid sequence of EsGLP contained one conserved GATA-type zinc finger of the form Cys-X2-Cys-X17-Cys-X2-Cys, with four cysteine sites. The EsGLP mRNA transcripts were mainly detected in the hematopoietic tissue, hepatopancreas and gonad...
January 8, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29323497/multi-funnel-landscape-of-the-fold-switching-protein-rfah-ctd
#6
Nathan A Bernhardt, Ulrich H E Hansmann
Proteins such as the transcription factor RfaH can change biological function by switching between distinct three-dimensional folds. RfaH regulates transcription if the C-terminal domain folds into a double helix bundle, and promotes translation when this domain assumes a β-barrel form. This fold-switch has been also observed for the isolated domain, dubbed by us RfaH-CTD, and is studied here with a variant of the RET approach recently introduced by us. We use the enhanced sampling properties of this technique to map the free energy landscape of RfaH-CTD and to propose a mechanism for the conversion process...
January 11, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29322164/efficacy-of-transdermal-estradiol-and-micronized-progesterone-in-the-prevention-of-depressive-symptoms-in-the-menopause-transition-a-randomized-clinical-trial
#7
Jennifer L Gordon, David R Rubinow, Tory A Eisenlohr-Moul, Kai Xia, Peter J Schmidt, Susan S Girdler
Importance: The menopause transition and early postmenopausal period are associated with a 2- to 4-fold increased risk for clinically significant depressive symptoms. Although a few studies suggest that hormone therapy can effectively manage existing depression during this time, to our knowledge, there have been no studies testing whether hormone therapy can prevent the onset of perimenopausal and early postmenopausal depressive symptoms. Objective: To examine the efficacy of transdermal estradiol plus intermittent micronized progesterone (TE+IMP) in preventing depressive symptom onset among initially euthymic perimenopausal and early postmenopausal women...
January 10, 2018: JAMA Psychiatry
https://www.readbyqxmd.com/read/29321040/automated-image-analysis-detects-aging-in-clinical-grade-mesenchymal-stromal-cell-cultures
#8
S Oja, P Komulainen, A Penttilä, J Nystedt, M Korhonen
BACKGROUND: Senescent cells are undesirable in cell therapy products due to reduced therapeutic activity and risk of aberrant cellular effects, and methods for assessing senescence are needed. Early-passage mesenchymal stromal cells (MSCs) are known to be small and spindle-shaped but become enlarged upon cell aging. Indeed, cell morphology is routinely evaluated during MSC production using subjective methods. We have therefore explored the possibility of utilizing automated imaging-based analysis of cell morphology in clinical cell manufacturing...
January 10, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29320682/translational-entropy-and-dna-duplex-stability
#9
Peter L Privalov, Colyn Crane-Robinson
Investigation of folding/unfolding DNA duplexes of various size and composition by superprecise calorimetry has revised several long-held beliefs concerning the forces responsible for the formation of the double helix. It was established that: 1) the enthalpy and the entropy of duplex unfolding are temperature dependent, increasing with temperature rise and having the same heat capacity increment for CG and AT pairs; 2) the enthalpy of AT melting is greater than that of the CG pair, so the stabilizing effect of the CG pair in comparison with AT results not from its larger enthalpic contribution (as expected from its extra hydrogen bond), but from the larger entropic contribution of the AT pair that results from its ability to fix ordered water in the minor groove and release it upon duplex unfolding; 3) the translation entropy, resulting from the appearance of a new kinetic unit on duplex dissociation, determines the dependence of duplex stability on its length and its concentration (it is an order-of-magnitude smaller than predicted from the statistical mechanics of gases and is fully expressed by the stoichiometric correction term); 4) changes in duplex stability on reshuffling the sequence (the "nearest-neighbor effect") result from the immobilized water molecules fixed by AT pairs in the minor groove; and 5) the evaluated thermodynamic components permit a quantitative expression of DNA duplex stability...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29320589/a-multicenter-double-blinded-randomized-split-face-study-of-the-safety-and-efficacy-of-a-novel-hyaluronic-acid-gel-for-the-correction-of-nasolabial-folds
#10
Michael H Gold, Leslie Stafford Baumann, Clifford P Clark Iii, Joel Schlessinger
BACKGROUND: Injectable hyaluronic acid is frequently used to correct volume loss in nasolabial folds. OBJECTIVE: To compare the safety and efficacy of a novel hyaluronic acid gel to a non-animal stabilized hyaluronic acid (Comparator) gel for the correction of nasolabial folds (NLF). METHODS: Qualified subjects had NLF with a Wrinkle Severity Rating Scale (WSRS) score of 3 or 4 (moderate or severe). NLFs were treated with Test Product on one side of the face and Comparator on the other side of the face (facial side randomly assigned)...
January 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29317815/double-stranded-phosphodiester-cytosine-guanine-oligodeoxynucleotide-complexed-with-calcium-phosphate-as-a-potent-vaccine-adjuvant-for-activating-cellular-and-th1-type-humoral-immunities
#11
Nobutaka Hanagata, Xianglan Li, Min-Hua Chen, Jie Li, Shinya Hattori
Conventional class B cytosine-guanine (CpG) (CpG-B) oligodeoxynucleotide (ODNs) consisting of a single-stranded (ss) phosphorothioate (PT) backbone (ss CpG-B-PT) is converted from a proinflammatory cytokine inducer to a type-I interferon (IFN) inducer when complexed with cationic materials. In this study, we designed ss CpG-B and double-stranded (ds) CpG-B ODNs with a phosphodiester (PD) backbone (ss CpG-B-PD and ds CpG-B-PD, respectively) that became type-I IFN inducers upon complexation with Lipofectamine 2000 (Lipo), a cationic liposome...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29317666/single-very-low-rituximab-doses-in-healthy-volunteers-a-pilot-and-a-randomized-trial-implications-for-dosing-and-biosimilarity-testing
#12
Christian Schoergenhofer, Michael Schwameis, Christa Firbas, Johann Bartko, Ulla Derhaschnig, Robert M Mader, Raute Sunder Plaßmann, Petra Jilma-Stohlawetz, Kalpna Desai, Priya Misra, Ulrich Jäger, Bernd Jilma
There are no  dose-finding trials available for rituximab that could guide dosing in non-malignant diseases. We hypothesized that currently used doses (≥375 mg/m2) exceed several hundred-fold the half-maximal effective dose, which is most sensitive for detecting putative differences between biosimilars and important for dose finding. In an open label, exploratory trial healthy volunteers received single infusions of rituximab at doses of 0.1, 0.3 or 1.0 mg/m2. Subsequently, in a double-blind, randomized trial healthy volunteers received single infusions of two rituximab products at doses of 0...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317118/safety-and-immunogenicity-of-single-dose-live-oral-cholera-vaccine-strain-cvd-103-hgr-in-healthy-adults-age-18-45
#13
James M McCarty, Michael D Lock, Kristin M Hunt, Jakub K Simon, Marc Gurwith
The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, re-developed as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera diarrhea in volunteer challenge studies. We performed a phase 3, placebo controlled, double blind, multi-center study to further assess the safety, immunogenicity, and lot-to-lot consistency of PXVX0200. Adult volunteers 18-45 years of age were randomized 8:1 to receive a single dose of 1 × 109 CFU of PXVX0200 from three production lots or saline placebo...
January 6, 2018: Vaccine
https://www.readbyqxmd.com/read/29316926/rna-guided-single-double-gene-repressions-in-corynebacterium-glutamicum-using-an-efficient-crispr-interference-and-its-application-to-industrial-strain
#14
Jaehyun Park, Hyojung Shin, Sun-Mi Lee, Youngsoon Um, Han Min Woo
BACKGROUND: The construction of microbial cell factories requires cost-effective and rapid strain development through metabolic engineering. Recently, RNA-guided CRISPR technologies have been developed for metabolic engineering of industrially-relevant host. RESULTS: To demonstrate the application of the CRISPR interference (CRISPRi), we developed two-plasmid CRISPRi vectors and applied the CRISPRi in Corynebacterium glutamicum to repress single target genes and double target genes simultaneously...
January 9, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29315819/genetic-and-small-molecule-inhibition-of-arylamine-n-acetyltransferase-1-reduces-anchorage-independent-growth-in-human-breast-cancer-cell-line-mda-mb-231
#15
Marcus W Stepp, Mark A Doll, Samantha M Carlisle, J Christopher States, David W Hein
Arylamine N-acetyltransferase 1 (NAT1) expression is reported to affect proliferation, invasiveness, and growth of cancer cells. MDA-MB-231 breast cancer cells were engineered such that NAT1 expression was elevated or suppressed, or treated with a small molecule inhibitor of NAT1. The MDA-MB-231 human breast cancer cell lines were engineered with a scrambled shRNA, a NAT1 specific shRNA or a NAT1 overexpression cassette stably integrated into a single flippase recognition target (FRT) site facilitating incorporation of these different genetic elements into the same genomic location...
January 9, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29315699/topical-administration-of-regorafenib-eye-drops-phase-i-dose-escalation-study-in-healthy-volunteers
#16
Torsten Zimmermann, Joachim Höchel, Michael Becka, Michael K Boettger, Beate Rohde, Barbara Schug, Kathleen S Kunert, Frank Donath
AIM: Regorafenib is a multi-kinase inhibitor under investigation for use in neovascular age-related macular degeneration. In this Phase I study, regorafenib eye drops were administered to healthy volunteers to provide information on safety, tolerability and systemic exposure. METHODS: This was a single-centre, randomized, double-masked, parallel-group, dose-escalation, placebo-controlled study. Subjects received regorafenib eye drops (30 mg ml-1 , 25 μL) as a 0...
January 9, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29313242/cost-of-illness-for-five-major-foodborne-illnesses-and-sequelae-in-sweden
#17
Kristian Sundström
OBJECTIVES: The main objective of this study was to derive cost estimates of five major foodborne illnesses (campylobacteriosis, salmonellosis, enterohemorrhagic Escherichia coli (EHEC), yersiniosis and shigellosis) in Sweden. These estimates provide a necessary contribution to perform future cost-benefit analyses aimed at reducing the burden of foodborne disease. A secondary aim was to obtain estimates of the true number of cases that occur in the community, thus providing necessary ground for calculating costs...
January 8, 2018: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/29306001/nanoparticulate-vaccine-inhibits-tumor-growth-via-improved-t-cell-recruitment-into-melanoma-and-huher2-breast-cancer
#18
Eva Zupančič, Caterina Curato, Jung-Seok Kim, Eilam Yeini, Ziv Porat, Ana S Viana, Anat Globerson-Levin, Tova Waks, Zelig Eshhar, João N Moreira, Ronit Satchi-Fainaro, Lea Eisenbach, Steffen Jung, Helena F Florindo
Nanoparticulate vaccines are promising tools to overcome cancer immune evasion. However, a deeper understanding on nanoparticle-immune cell interactions and treatments regime are required for optimal efficacy. We provide a comprehensive study of treatment schedules and mode of antigen-association to nanovaccines on the modulation of T cell immunity in vivo, under steady-state and tumor-bearing mice. The coordinated delivery of antigen and two adjuvants (Monophosphoryl lipid A, oligodeoxynucleotide cytosine-phosphate-guanine motifs (CpG)) by nanoparticles was crucial for dendritic cell activation...
January 3, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29303587/voltage-induced-modulation-of-ionic-concentrations-and-ion-current-rectification-in-mesopores-with-highly-charged-pore-walls
#19
Chih-Yuan Lin, Li-Hsien Yeh, Zuzanna S Siwy
It is believed that ion current rectification (ICR), a property which assures preferential ionic transport in one direction, can only be observed in nanopores when the pore size is comparable to the thickness of the electric double layer (EDL). Rectifying nanopores became the basis of biological sensors and components of ionic circuits. Here we report that appreciable ICR can also occur in highly charged conical, polymer mesopores whose tip diameters are as large as 400 nm thus over 100-fold larger than the EDL thickness...
January 5, 2018: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/29301920/risk-factors-for-recurrent-venous-thromboembolism-after-unprovoked-pulmonary-embolism-the-padis-pe-randomised-trial
#20
Cécile Tromeur, Olivier Sanchez, Emilie Presles, Gilles Pernod, Laurent Bertoletti, Patrick Jego, Elisabeth Duhamel, Karine Provost, Florence Parent, Philippe Robin, Lucile Deloire, Florent Leven, Fanny Mingant, Luc Bressollette, Pierre-Yves Le Roux, Pierre-Yves Salaun, Michel Nonent, Brigitte Pan-Petesch, Benjamin Planquette, Philippe Girard, Karine Lacut, Solen Melac, Patrick Mismetti, Silvy Laporte, Guy Meyer, Dominique Mottier, Christophe Leroyer, Francis Couturaud
We aimed to identify risk factors for recurrent venous thromboembolism (VTE) after unprovoked pulmonary embolism.Analyses were based on the double-blind randomised PADIS-PE trial, which included 371 patients with a first unprovoked pulmonary embolism initially treated during 6 months who were randomised to receive an additional 18 months of warfarin or placebo and followed up for 2 years after study treatment discontinuation. All patients had ventilation/perfusion lung scan at inclusion (i.e. at 6 months of anticoagulation)...
January 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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