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https://www.readbyqxmd.com/read/29022099/defibrotide-for-the-treatment-of-sinusoidal-obstruction-syndrome-evaluation-of-response-to-therapy-and-patient-outcomes
#1
John Coutsouvelis, Sharon Avery, Michael Dooley, Carl Kirkpatrick, Andrew Spencer
PURPOSE: Defibrotide is an agent used to treat sinusoidal obstruction syndrome (SOS/VOD) in patients undergoing haemopoietic stem cell transplantation. The aim of this study was to evaluate the effectiveness of defibrotide used within institutional guidelines for the treatment of SOS/VOD in patients undergoing haemopoietic stem cell transplantation (HSCT). METHODS: Data for 23 patients was retrospectively reviewed to evaluate the effectiveness of defibrotide and the utility of response criteria to direct therapy as specified within institution guidelines...
October 11, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29020633/erasure-of-tet-oxidized-5-methylcytosine-by-a-srap-nuclease
#2
Soo-Mi Kweon, Bing Zhu, Yibu Chen, L Aravind, Shuang-Yong Xu, Douglas E Feldman
Enzymatic oxidation of 5-methylcytosine (5mC) in DNA by the Tet dioxygenases reprograms genome function in embryogenesis and postnatal development. Tet-oxidized derivatives of 5mC such as 5-hydroxymethylcytosine (5hmC) act as transient intermediates in DNA demethylation or persist as durable marks, yet how these alternative fates are specified at individual CpGs is not understood. Here, we report that the SOS response-associated peptidase (SRAP) domain protein Srap1, the mammalian ortholog of an ancient protein superfamily associated with DNA damage response operons in bacteria, binds to Tet-oxidized forms of 5mC in DNA and catalyzes turnover of these bases to unmodified cytosine by an autopeptidase-coupled nuclease...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/29018116/quinolone-resistance-reversion-by-targeting-the-sos-response
#3
E Recacha, J Machuca, P Díaz de Alba, M Ramos-Güelfo, F Docobo-Pérez, J Rodriguez-Beltrán, J Blázquez, A Pascual, J M Rodríguez-Martínez
Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies...
October 10, 2017: MBio
https://www.readbyqxmd.com/read/28977128/bone-mass-by-quantitative-ultrasound-of-finger-phalanges-in-young-karate-practitioners
#4
Camila Justino de Oliveira Barbeta, Ezequiel Moreira Gonçalves, Keila Donassolo Santos Ribeiro, Roberto Ribeiro, Everton Paulo Roman, Gil Guerra-Júnior
OBJECTIVE: To evaluate bone mass by quantitative ultrasound of the phalanges in young karate practitioners compared to a control group. METHODS: Sample composed of 162 karate practitioners (52 females) and 326 healthy controls (110 females) aged 6 to 16 years old, in Western Paraná (Southern Brazil). Weight, height, BMI, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were evaluated. BMI, AD-SoS and BTT values were converted to Z scores...
September 21, 2017: Revista Paulista de Pediatria: Orgão Oficial da Sociedade de Pediatria de São Paulo
https://www.readbyqxmd.com/read/28947673/phenotypes-of-dnaxe145a-mutant-cells-indicate-that-the-escherichia-coli-clamp-loader-has-a-role-in-the-restart-of-stalled-replication-forks
#5
Ingvild Flåtten, Emily Helgesen, Ida Benedikte Pedersen, Torsten Waldminghaus, Christiane Rothe, Riikka Taipale, Line Johnsen, Kirsten Skarstad
The E. coli dnaXE145A mutation was discovered in connection with a screen for multicopy suppressors of the temperature sensitive Topoisomerase IV mutation parE10 The gene for the clamp loader subunits τ and γ, dnaX, but not the mutant dnaXE145A , was found to suppress parE10 (Ts) when over-expressed. Purified mutant protein was found to be functional in vitro, and few phenotypes were found in vivo apart from problems with partitioning of DNA in rich medium. We show here that a large number of the replication forks that initiate at oriC never reach the terminus in dnaXE145A mutant cells...
September 25, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28943390/the-e-coli-s30-lysate-proteome-a-prototype-for-cell-free-protein-production
#6
Daniel Foshag, Erik Henrich, Ekkehard Hiller, Miriam Schäfer, Christian Kerger, Anke Burger-Kentischer, Irene Diaz-Moreno, Sofía M García-Mauriño, Volker Dötsch, Steffen Rupp, Frank Bernhard
Protein production using processed cell lysates is a core technology in synthetic biology and these systems are excellent to produce difficult toxins or membrane proteins. However, the composition of the central lysate of cell-free systems is still a "black box". Escherichia coli lysates are most productive for cell-free expression, yielding several mgs of protein per ml of reaction. Their preparation implies proteome fractionation, resulting in strongly biased and yet unknown lysate compositions. Many metabolic pathways are expected to be truncated or completely removed...
September 21, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28938097/effect-of-sos-induced-levels-of-imuabc-on-spontaneous-and-damage-induced-mutagenesis-in-caulobacter-crescentus
#7
Ingrid R Alves, Marco A Lima-Noronha, Larissa G Silva, Frank S Fernández-Silva, Aline Luiza D Freitas, Marilis V Marques, Rodrigo S Galhardo
imuABC (imuAB dnaE2) genes are responsible for SOS-mutagenesis in Caulobacter crescentus and other bacterial species devoid of umuDC. In this work, we have constructed operator-constitutive mutants of the imuABC operon. We used this genetic tool to investigate the effect of SOS-induced levels of these genes upon both spontaneous and damage-induced mutagenesis. We showed that constitutive expression of imuABC does not increase spontaneous or damage-induced mutagenesis, nor increases cellular resistance to DNA-damaging agents...
September 14, 2017: DNA Repair
https://www.readbyqxmd.com/read/28934502/blocking-the-reca-activity-and-sos-response-in-bacteria-with-a-short-%C3%AE-helical-peptide
#8
Alexander Yakimov, Georgii Pobegalov, Irina Bakhlanova, Mikhail Khodorkovskii, Michael Petukhov, Dmitry Baitin
The RecX protein, a very active natural RecA protein inhibitor, can completely disassemble RecA filaments at nanomolar concentrations that are two to three orders of magnitude lower than that of RecA protein. Based on the structure of RecX protein complex with the presynaptic RecA filament, we designed a short first in class α-helical peptide that both inhibits RecA protein activities in vitro and blocks the bacterial SOS-response in vivo. The peptide was designed using SEQOPT, a novel method for global sequence optimization of protein α-helices...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28930680/systematic-kinase-inhibitor-profiling-identifies-cdk9-as-a-synthetic-lethal-target-in-nut-midline-carcinoma
#9
Johannes Brägelmann, Marcel A Dammert, Felix Dietlein, Johannes M Heuckmann, Axel Choidas, Stefanie Böhm, André Richters, Debjit Basu, Verena Tischler, Carina Lorenz, Peter Habenberger, Zhizhou Fang, Sandra Ortiz-Cuaran, Frauke Leenders, Jan Eickhoff, Uwe Koch, Matthäus Getlik, Martin Termathe, Muhammad Sallouh, Zoltán Greff, Zoltán Varga, Hyatt Balke-Want, Christopher A French, Martin Peifer, H Christian Reinhardt, László Örfi, György Kéri, Sascha Ansén, Lukas C Heukamp, Reinhard Büttner, Daniel Rauh, Bert M Klebl, Roman K Thomas, Martin L Sos
Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and depend on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell-cycle arrest in these cells...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28915012/managing-the-sos-response-for-enhanced-crispr-cas-based-recombineering-in-e-%C3%A2-coli-through-transient-inhibition-of-host-reca-activity
#10
Eirik Adim Moreb, Benjamin Hoover, Adam Yaseen, Nisakorn Valyasevi, Zoe Roecker, Romel Menacho-Melgar, Michael D Lynch
Phage-derived "recombineering" methods are utilized for bacterial genome editing. Recombineering results in a heterogeneous population of modified and unmodified chromosomes, and therefore selection methods, such as CRISPR-Cas9, are required to select for edited clones. Cells can evade CRISPR-Cas-induced cell death through recA-mediated induction of the SOS response. The SOS response increases RecA dependent repair as well as mutation rates through induction of the umuDC error prone polymerase. As a result, CRISPR-Cas selection is more efficient in recA mutants...
October 2, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28914546/defibrotide-an-oligonucleotide-for-sinusoidal-obstruction-syndrome
#11
May T Aziz, Payal P Kakadiya, Samantha M Kush, Kylie Weigel, Denise K Lowe
OBJECTIVE: To review the efficacy and safety of defibrotide as well as its pharmacology, mechanism of action, pharmacokinetics (PK), drug-drug interactions, dosing, cost considerations, and place in therapy. DATA SOURCES: A PubMed search was performed through August 2017 using the terms defibrotide, oligonucleotide, hepatic veno-occlusive disease (VOD), sinusoidal obstruction syndrome (SOS), and hematopoietic cell transplantation (HCT). Other data sources were from references of identified studies, review articles, and conference abstracts plus manufacturer product labeling and website, the Food and Drug Administration website, and clinicaltrials...
September 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28904348/transcriptome-profiling-of-genes-involved-in-induced-systemic-salt-tolerance-conferred-by-bacillus-amyloliquefaciens-fzb42-in-arabidopsis-thaliana
#12
Shaofang Liu, Haiting Hao, Xiang Lu, Xia Zhao, Yun Wang, Yubao Zhang, Zhongkui Xie, Ruoyu Wang
Plant growth-promoting Bacillus amyloliquefaciens FZB42 induces systemic salt tolerance in Arabidopsis and enhances the fresh and dry weight. However, the underlying molecular mechanism that allows plants to respond to FZB42 and exhibit salt tolerance is largely unknown. Therefore, we performed large-scale transcriptome sequencing of Arabidopsis shoot tissues grown under salt stress with or without FZB42 inoculation by using Illumina sequencing to identify the key genes and pathways with important roles during this interaction...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28888611/comparison-of-mammary-lipid-metabolism-in-dairy-cows-and-goats-fed-diets-supplemented-with-starch-plant-oil-or-fish-oil
#13
L Bernard, P G Toral, Y Chilliard
A direct comparison of cow and goat performance and milk fatty acid (FA) responses to diets known to induce milk fat depression in the bovine has suggested interspecies differences in rumen and mammary lipid metabolism. Thus, this study was conducted to infer some potential mechanisms responsible for the differences in mammary lipogenesis due to diet and ruminant species. To meet this objective, 12 cows and 15 goats were fed a basal diet (control), a similar diet supplemented with 2.2% fish oil (FO), or a diet containing 5...
November 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28884290/attempt-at-standardization-of-bone-quantitative-ultrasound-in-japan
#14
REVIEW
Takahiko Otani, Masao Fukunaga, Kosei Yho, Takami Miki, Kaoru Yamazaki, Hideaki Kishimoto, Mami Matsukawa, Nobuyuki Endoh, Hiroyuki Hachiya, Hiroshi Kanai, Saeko Fujiwara, Yoshinori Nagai
Dual X-ray absorptiometry (DXA) is used to diagnose osteoporosis. On the other hand, quantitative ultrasound (QUS) is widely used to assess bone density as part of medical screening as it is relatively inexpensive and easy to perform. Current QUS devices do not share precise ultrasound-related parameters, such as frequency, waveform, beam pattern, transient response, definition of propagation time, definition of degree of attenuation, and precise measurement site, resulting in different measurements across models...
September 7, 2017: Journal of Medical Ultrasonics
https://www.readbyqxmd.com/read/28881168/proteomic-analysis-reveals-that-a-global-response-is-induced-by-subinhibitory-concentrations-of-ampicillin
#15
Lina Xiong, Dongjiang Liao, Xinpeng Lu, He Yan, Lei Shi, Ziyao Mo
In this study, a recipient-donor co-culture system was used to research the effect of subinhibitory concentrations of antibiotics on horizontal transmission in bacteria and the influence of antibiotics on protein expression. We employed two-dimensional gel electrophoresis combined with mass spectrometry to compare the protein expression profiles in systems with or without 0.5 × the minimum inhibitory concentration of ampicillin. RT-PCR was used to assess the transcriptional levels of the differentially expressed genes...
September 7, 2017: Bioengineered
https://www.readbyqxmd.com/read/28874380/the-global-regulatory-protein-crp-controls-multifactorial-fluoroquinolone-susceptibility-in-salmonella-enterica-serovar-typhimurium
#16
Stefani C Kary, Joshua R K Yoneda, Stephen C Olshefsky, Laura A Stewart, Steven B West, Andrew D S Cameron
Fluoroquinolone antibiotics are prescribed for the treatment of Salmonella enterica infections, but resistance to this family of antibiotics is growing. Here we report that loss of the global regulatory protein, CRP, or its allosteric effector, cAMP, reduces susceptibility to fluoroquinolones. A Δcrp mutation was synergistic with the primary fluoroquinolone resistance allele gyrA83, thus can contribute to clinically-relevant resistance. Decreased susceptibility to fluoroquinolones could be partly explained by decreased expression of the outer membrane porin genes ompA and ompF with a concomitant increase in the expression of the ciprofloxacin-resistance efflux pump gene acrB in Δcrp cells...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28861047/gene-expression-in-class-2-integrons-is-sos-independent-and-involves-two-pc-promoters
#17
Thomas Jové, Sandra Da Re, Aurore Tabesse, Amy Gassama-Sow, Marie-Cécile Ploy
Integrons are powerful bacterial genetic elements that permit the expression and dissemination of antibiotic-resistance gene cassettes. They contain a promoter Pc that allows the expression of gene cassettes captured through site-specific recombination catalyzed by IntI, the integron-encoded integrase. Class 1 and 2 integrons are found in both clinical and environmental settings. The regulation of intI and of Pc promoters has been extensively studied in class 1 integrons and the regulatory role of the SOS response on intI expression has been shown...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28855912/salt-sensitive-signaling-networks-in-the-mediation-of-k-na-homeostasis-gene-expression-in-glycyrrhiza-uralensis-roots
#18
Tao Lang, Shurong Deng, Nan Zhao, Chen Deng, Yinan Zhang, Yanli Zhang, Huilong Zhang, Gang Sa, Jun Yao, Caiwu Wu, Yanhong Wu, Qun Deng, Shanzhi Lin, Jianxin Xia, Shaoliang Chen
We investigated the effects of salt-sensitive signaling molecules on ionic fluxes and gene expression related to K(+)/Na(+) homeostasis in a perennial herb, Glycyrrhiza uralensis, during short-term NaCl stress (100 mM, 24 h). Salt treatment caused more pronounced Na(+) accumulation in root cells than in leaf cells. Na(+) ions were mostly compartmentalized in vacuoles. Roots exposed to NaCl showed increased levels of extracellular ATP (eATP), cytosolic Ca(2+), H2O2, and NO. Steady-state flux recordings revealed that these salt-sensitive signaling molecules enhanced NaCl-responsive Na(+) efflux, due to the activated Na(+)/H(+) antiport system in the plasma membrane (PM)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28826208/a-small-molecule-inducible-synthetic-circuit-for-control-of-the-sos-gene-network-without-dna-damage
#19
Jeffrey M Kubiak, Matthew J Culyba, Monica Yun Liu, Charlie Y Mo, Mark Goulian, Rahul M Kohli
The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network...
September 1, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28817750/the-surgeon-on-service-model-for-timely-economically-viable-inpatient-care-of-tracheostomy-patients-in-academic-pediatric-otolaryngology
#20
Jennifer M Lavin, James W Schroeder, Dana M Thompson
Importance: The traditional practice model for pediatric otolaryngologists at high-volume academic centers is to simultaneously balance outpatient care responsibilities with those of the inpatient service, emergency department, and ambulatory care clinics. This model leads to challenges with care coordination, timeliness of nonemergency operative care, and consistent participation in care and consultation at the attending surgeon level. The "surgeon on service" (SOS) model-where faculty members rotate to manage the inpatient service in lieu of outpatient responsibilities-has been described as one method to address this conundrum...
August 17, 2017: JAMA Otolaryngology—Head & Neck Surgery
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