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SOS response

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https://www.readbyqxmd.com/read/29440291/small-molecule-mediated-activation-of-ras-elicits-biphasic-modulation-of-phospho-erk-levels-that-are-regulated-through-negative-feedback-on-sos1
#1
Jennifer E Howes, Denis T Akan, Michael C Burns, Olivia W Rossanese, Alex G Waterson, Stephen W Fesik
Oncogenic mutation of RAS results in aberrant cellular signaling and is responsible for more than 30% of all human tumors. Therefore, pharmacological modulation of RAS has attracted great interest as a therapeutic strategy. Our laboratory has recently discovered small molecules that activate Son of Sevenless (SOS)-catalyzed nucleotide exchange on RAS and inhibit downstream signaling. Here we describe how pharmacologically targeting SOS1 induced biphasic modulation of RAS-GTP and ERK phosphorylation levels, which we observed in a variety of cell lines expressing different RAS mutant isoforms...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29432559/glutamate-receptor-homolog3-4-is-involved-in-regulation-of-seed-germination-under-salt-stress-in-arabidopsis
#2
Yao Cheng, Xiuxiu Zhang, Tianyang Sun, Qiuying Tian, Wen-Hao Zhang
Seed germination is sensitive to salt stress, and abscisic acid (ABA) and Ca2+ are involved in the regulation of seed germination under salt stress. Ca2+ influx mediated by glutamate receptors (GLRs) plays important roles in many physiological processes in plants. Here, we investigated the correlation of GLRs, Ca2+ and ABA during seed germination in response to salt stress by using Arabidopsis thaliana wild-type and T-DNA insertion knockout mutants of glutamate receptors homolog3.4. We demonstrated that atglr3...
February 7, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29410519/rationale-and-design-of-an-inhibitor-of-reca-protein-as-an-inhibitor-of-acinetobacter-baumannii
#3
Vishvanath Tiwari, Monalisa Tiwari, Deepika Biswas
Acinetobacter baumannii is one of the ESKAPE pathogen, which causes pneumonia, urinary tract infections, and is linked to high degree of morbidity and mortality. One-way antibiotic and disinfectant resistance is acquired by the activation of RecA-mediated DNA repair (SOS-response) that maintain ROS-dependent DNA damage caused by these anti-bacterial molecules. To increase the efficacy of different anti-microbial, there is a need to design an inhibitor against RecA of A. baumannii. We have performed homology modeling to generate the structure of RecA, followed by model refinement and validation...
February 6, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29390081/construct-validity-of-the-societal-outreach-scale-sos
#4
David S Fike, Jason Denton, Matt Walk, Jennifer Kish, Ira Gorman
BACKGROUND: The American Physical Therapy Association (APTA) has been working toward a vision of increasing professional focus on societal level health. However, performance of social responsibility and related behaviors by physical therapists remains relatively poorly integrated into practice. Promoting a focus on societal outreach is necessary for all healthcare professionals to impact the health of their communities. OBJECTIVE: The objective was to document the validity of the 14-item Societal Outreach Scale (SOS) for use with practicing physical therapists...
January 30, 2018: Physical Therapy
https://www.readbyqxmd.com/read/29378890/the-conserved-dna-binding-protein-whia-influences-chromosome-segregation-in-bacillus-subtilis
#5
Laura C Bohorquez, Katarina Surdova, Martijs J Jonker, Leendert W Hamoen
The DNA binding protein WhiA is conserved in Gram-positive bacteria, and is also present in the genetically simple, cell wall-lacking, mycoplasmas. The protein shows homology to eukaryotic homing endonucleases but lacks nuclease activity. WhiA was first characterized in streptomycetes, where it regulates expression of key differentiation genes, including the cell division gene ftsZ essential for sporulation. For Bacillus subtilis it was shown that WhiA is essential when certain cell division genes are deleted...
January 29, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29370801/expression-of-cocoa-genes-in-saccharomyces-cerevisiae-improves-cocoa-butter-production
#6
Yongjun Wei, David Bergenholm, Michael Gossing, Verena Siewers, Jens Nielsen
BACKGROUND: Cocoa butter (CB) extracted from cocoa beans (Theobroma cacao) is the main raw material for chocolate production, but CB supply is insufficient due to the increased chocolate demand and limited CB production. CB is mainly composed of three different kinds of triacylglycerols (TAGs), 1,3-dipalmitoyl-2-oleoyl-glycerol (POP, C16:0-C18:1-C16:0), 1-palmitoyl-3-stearoyl-2-oleoyl-glycerol (POS, C16:0-C18:1-C18:0) and 1,3-distearoyl-2-oleoyl-glycerol (SOS, C18:0-C18:1-C18:0). In general, Saccharomyces cerevisiae produces TAGs as storage lipids, which consist of C16 and C18 fatty acids...
January 25, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29351274/dna-polymerase-iv-primarily-operates-outside-of-dna-replication-forks-in-escherichia-coli
#7
Sarah S Henrikus, Elizabeth A Wood, John P McDonald, Michael M Cox, Roger Woodgate, Myron F Goodman, Antoine M van Oijen, Andrew Robinson
In Escherichia coli, damage to the chromosomal DNA induces the SOS response, setting in motion a series of different DNA repair and damage tolerance pathways. DNA polymerase IV (pol IV) is one of three specialised DNA polymerases called into action during the SOS response to help cells tolerate certain types of DNA damage. The canonical view in the field is that pol IV primarily acts at replisomes that have stalled on the damaged DNA template. However, the results of several studies indicate that pol IV also acts on other substrates, including single-stranded DNA gaps left behind replisomes that re-initiate replication downstream of a lesion, stalled transcription complexes and recombination intermediates...
January 19, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29329085/an-integrated-approach-to-assess-the-impacts-of-zinc-pyrithione-at-different-levels-of-biological-organization-in-marine-mussels
#8
Lorna J Dallas, Andrew Turner, Tim P Bean, Brett P Lyons, Awadhesh N Jha
The mechanisms of sublethal toxicity of the antifouling biocide, zinc pyrithione (ZnPT), have not been well-studied. This investigation demonstrates that 14-d sublethal exposure to ZnPT (0.2 or 2 μM, alongside inorganic Zn and sea water controls) is genotoxic to mussel haemocytes but suggests that this is not caused by oxidative DNA damage as no significant induction of oxidised purines was detected by Fpg-modified comet assay. More ecologically relevant endpoints, including decreased clearance rate (CR), cessation of attachment and decreased tolerance of stress on stress (SoS), also showed significant response to ZnPT exposure...
December 27, 2017: Chemosphere
https://www.readbyqxmd.com/read/29317513/cyclic-amp-regulates-bacterial-persistence-through-repression-of-the-oxidative-stress-response-and-sos-dependent-dna-repair-in-uropathogenic-escherichia-coli
#9
Roberto C Molina-Quiroz, Cecilia Silva-Valenzuela, Jennifer Brewster, Eduardo Castro-Nallar, Stuart B Levy, Andrew Camilli
Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli, as measured by survival after exposure to a β-lactam antibiotic...
January 9, 2018: MBio
https://www.readbyqxmd.com/read/29309024/impact-of-m%C3%A3-ni%C3%A3-re-s-disease-on-significant-others-health-and-lives
#10
Vinaya Manchaiah, Ilmari Pyykkő, Hilla Levo, Erna Kentala
BACKGROUND: Ménière's disease (MD) is a chronic and, in part, intermittent illness that poses multiple challenges for both the physical and psychological well-being of patients, as well as on those around them. The patients face psychosocial consequences, which include disruptions to life goals, employment, income, relationships, leisure activities, and daily living activities that also influence their family members and friends. However, there is a limited understanding of the impact of MD on significant others (SOs)...
January 2018: Journal of the American Academy of Audiology
https://www.readbyqxmd.com/read/29284707/structural-alterations-of-met-trigger-response-to-met-kinase-inhibition-in-lung-adenocarcinoma-patients
#11
Dennis Plenker, Miriam Bertrand, Adrianus Johannes de Langen, Richard Riedel, Carina Lorenz, Andreas H Scheel, Judith Nadja Müller, Johannes Brägelmann, Juliane Daßler-Plenker, Carsten Kobe, Thorsten Persigehl, Alexander Kluge, Thomas Wurdinger, Pepijn Schellen, Gunther Hartmann, Tobias Zacherle, Roopika Menon, Erik Thunnissen, Reinhard Büttner, Frank Griesinger, Juergen Wolf, Lukas Heukamp, Johannes M Heuckmann, Martin L Sos
PURPOSE: We sought to investigate the clinical response to MET inhibition in patients diagnosed with structural MET alterations and to characterize their functional relevance in cellular models. EXPERIMENTAL DESIGN: Patients were selected for treatment with crizotinib upon results of hybrid capture-based next generation sequencing. To confirm the clinical observations we analyzed cellular models that express these MET kinase alterations. RESULTS: Three individual patients were identified to harbor alterations within the MET receptor...
December 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29281056/phytomelatonin-a-universal-abiotic-stress-regulator
#12
Yanping Wang, Russel J Reiter, Zhulong Chan
Melatonin, a derivative of tryptophan, was detected in plant species in 1995. Melatonin has proven to be a diverse regulator during plant growth, development and stress responses. Recently, great progress has been made toward the detailed functions of melatonin in plant response to abiotic stress. Melatonin priming improved plant tolerance to cold, heat, salt and drought stresses through regulation of genes involved in DREB/CBF, HSF, SOS, and ABA pathways, respectively. As a free radicals scavenger, melatonin also directly detoxifies reactive oxygen species, thus alleviating membrane oxidation...
December 21, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29275629/inhibitors-of-lexa-autoproteolysis-and-the-bacterial-sos-response-discovered-by-an-academic-industry-partnership
#13
Charlie Y Mo, Matthew J Culyba, Trevor Selwood, Jeffrey M Kubiak, Zachary M Hostetler, Anthony J Jurewicz, Paul M Keller, Andrew J Pope, Amy Quinn, Jessica Schneck, Katherine L Widdowson, Rahul M Kohli
The RecA/LexA axis of the bacterial DNA damage (SOS) response is a promising, yet nontraditional, drug target. The SOS response is initiated upon genotoxic stress, when RecA, a DNA damage sensor, induces LexA, the SOS repressor, to undergo autoproteolysis, thereby derepressing downstream genes that can mediate DNA repair and accelerate mutagenesis. As genetic inhibition of the SOS response sensitizes bacteria to DNA damaging antibiotics and decreases acquired resistance, inhibitors of the RecA/LexA axis could potentiate our current antibiotic arsenal...
January 8, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29238335/treatment-with-cefotaxime-affects-expression-of-conjugation-associated-proteins-and-conjugation-transfer-frequency-of-an-inci1-plasmid-in-escherichia-coli
#14
Thea S B Møller, Gang Liu, Anders Boysen, Line E Thomsen, Freja L Lüthje, Sisse Mortensen, Jakob Møller-Jensen, John E Olsen
Horizontal gene transfer (HGT) is the major mechanism responsible for spread of antibiotic resistance. Antibiotic treatment has been suggested to promote HGT, either by directly affecting the conjugation process itself or by selecting for conjugations subsequent to DNA transfer. However, recent research suggests that the effect of antibiotic treatment on plasmid conjugation frequencies, and hence the spread of resistance plasmids, may have been overestimated. We addressed the question by quantifying transfer proteins and conjugation frequencies of a blaCTX-M-1 encoding IncI1 resistance plasmid in Escherichia coli MG1655 in the presence and absence of therapeutically relevant concentrations of cefotaxime (CTX)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29233778/phenotypic-indications-of-ftsz-inhibition-in-hok-sok-induced-bacterial-growth-changes-and-stress-response
#15
ChinweU Chukwudi, Liam Good
The hok/sok locus has been shown to enhance the growth of bacteria in adverse growth conditions such as high temperature, low starting-culture densities and antibiotic treatment. This is in addition to their well-established plasmid-stabilization effect via post-segregational killing of plasmid-free daughter cells. It delays the onset of growth by prolonging the lag phase of bacterial culture, and increases the rate of exponential growth when growth eventually begins. This enables the cells adapt to the prevailing growth conditions and enhance their survival in stressful conditions...
December 9, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29232146/switchable-photoacoustic-intensity-of-methylene-blue-via-sodium-dodecyl-sulfate-micellization
#16
Junxin Wang, Ching-Yu Lin, Colman Moore, Anamik Jhunjhunwala, Jesse V Jokerst
The interaction between methylene blue (MB) and sodium dodecyl sulfate (SDS) has been widely studied spectroscopically, but details about their interactions are limited. Here, we combined photoacoustic (PA) imaging with nanoparticle tracking analysis (NTA) and spectroscopy to further elucidate this interaction. PA imaging of 0.05 mM MB showed a 492-fold increase in intensity upon addition of 3.47 mM SDS. Higher concentrations above SDS's critical micelle concentration (CMC) at 8.67 mM decreased the PA intensity by 54-fold...
December 12, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29221461/seeking-a-second-medical-opinion-composition-reasons-and-perceived-outcomes-in-israel
#17
Liora Shmueli, Nadav Davidovitch, Joseph S Pliskin, Ran D Balicer, Igal Hekselman, Geva Greenfield
BACKGROUND: Seeking a second-opinion (SO) is a common clinical practice that can optimize treatment and reduce unnecessary procedures and risks. We aim to characterize the composition of the population of SO seekers, their reasons for seeking a SO and choosing a specific physician, and their perceived outcomes following the SO. METHODS: A cross-sectional national telephone survey, using a representative sample of the general Israeli population (n = 848, response rate = 62%)...
December 8, 2017: Israel Journal of Health Policy Research
https://www.readbyqxmd.com/read/29215045/auditory-closed-loop-stimulation-of-eeg-slow-oscillations-strengthens-sleep-and-signs-of-its-immune-supportive-function
#18
Luciana Besedovsky, Hong-Viet V Ngo, Stoyan Dimitrov, Christoph Gassenmaier, Rainer Lehmann, Jan Born
Sleep is essential for health. Slow wave sleep (SWS), the deepest sleep stage hallmarked by electroencephalographic slow oscillations (SOs), appears of particular relevance here. SWS is associated with a unique endocrine milieu comprising minimum cortisol and high aldosterone, growth hormone (GH), and prolactin levels, thereby presumably fostering efficient adaptive immune responses. Yet, whether SWS causes these changes is unclear. Here we enhance SOs in men by auditory closed-loop stimulation, i.e., by delivering tones in synchrony with endogenous SOs...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29193518/antimicrobial-activity-of-the-indolicidin-derived-novel-synthetic-peptide-in-58
#19
A S Vasilchenko, A V Vasilchenko, T M Pashkova, M P Smirnova, N I Kolodkin, I V Manukhov, G B Zavilgelsky, E A Sizova, O L Kartashova, A S Simbirtsev, E A Rogozhin, G K Duskaev, M V Sycheva
Natural peptides with antimicrobial activity are extremely diverse, and peptide synthesis technologies make it possible to significantly improve their properties for specific tasks. Here, we investigate the biological properties of the natural peptide indolicidin and the indolicidin-derived novel synthetic peptide In-58. In-58 was generated by replacing all tryptophan residues on phenylalanine in D-configuration; the α-amino group in the main chain also was modified by unsaturated fatty acid. Compared with indolicidin, In-58 is more bactericidal, more resistant to proteinase K, and less toxic to mammalian cells...
December 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29183163/antimutagenic-activity-of-flavonoids-from-sozuku
#20
Yoshiharu Okuno, Shinsuke Marumoto, Mitsuo Miyazawa
Pinocembrin (1) and cardamonin (2) from Sozuku showed a suppressive effect on umu gene expression of SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen furylfuramide. Compounds 1 and 2 suppressed 52% and 36% of SOS-inducing activity at a concentration of 0.20 μmol/mL. The ID50 value of 1 was 0.18 μmol/mL. These compounds showed the suppression of 2-amino-3,4-dimethylimidazo-[4,5-f]quinolone (MeIQ) and UV irradiation-induced SOS response. Pinostrobin (3) and 5,7-dimethoxyflavanone (4), methyl ethers of 1, showed similar activity to 1 against MeIQ-induced SOS response, but that of furylfuramide and UV irradiation were decreased...
November 28, 2017: Natural Product Research
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