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DNA replication can still spring surprises
Heather L Hendrickson
Genome Biology , 2008, DOI: 10.1186/gb-2008-9-8-317
Abstract: The first EMBO conference on the replication and segregation of chromosomes held recently in Norway brought together researchers from around the world. Many different techniques and organisms are being used to approach one of the oldest problems in biology: how does one organism become two? The breadth of work covered was exceptional; this report describes just a few of the most striking innovations in technology and concepts presented at the meeting, with particular reference to bacterial DNA replication.Antoine van Oijen (Harvard Medical School, Boston, USA) amusingly described the problem of ensemble averaging in DNA replication as an alien race concluding that humans must each have one testicle and one ovary. To avoid this pitfall, his group makes single-molecule observations of the four-protein replisome of the phage T7. The copy of gp5 (the DNA polymerase) acting on the lagging strand can be washed away, allowing observation of the processivity of leading-strand replication in isolation. Measurements of processivity are possible because the passage of the replication fork on the tethered DNA causes long double-stranded (ds) DNA to be transformed into more compact single-stranded (ss) DNA. Restoring the second polymerase and adding the T7 single-strand binding protein makes the looping out of lagging strand DNA itself observable as transient changes in the length of the tethered DNA.The archaea are apparent amalgams of eukaryotic and eubacterial traits. Their replication machinery is homologous to that of eukaryotes despite their eubacteria-like circular chromosomes; most distinctively, archaea can have multiple origins of replication in these circular chromosomes. Stephen Bell (University of Oxford, UK) described his laboratory's investigations into DNA replication in the archaeal genus Sulfolobus. He and his colleagues are characterizing the proteins EscrtIII, which is unique to archaea, and Vps4, which is also found in eukaryotes. These proteins are of inter
SOS assay, a current review.
Daniel Francisco Arencibia Arrebola,Luis Alfredo Rosario Fernández,Juan Francisco Infante Bourzac,Dayisell Lazara Curveco Sánchez
RETEL : Revista de Toxicología en Línea , 2009,
Abstract: In prokarionts it is denominated SOS response, to the system cellular emergency that allows the bacterial survival before the detention of the DNA replicación that has been damaged by genotoxic agents. The SOS response consists on the induction of more than 20 genes that are low the control of the recA/lexA circuit. The recA protein, is the positive regulator of the circuit, it is activated after the interaction with the sign molecule: DNA of simple chain, lexA is the negative regulator, well-known as the transcriptional represor of all the SOS genes in those that the own lexA and recA are included. The present work had as objective to current on the SOS phenomenon topic and SOS response, highlighting their utility like genotoxic assay commonly call (SOS assay), being useful to the researchers that work the genetic toxicology in vitro topic, to determine the genotoxicity and radioprotective of their products. We made allusion the ionizing radiation effect on the DNA, bacterial SOS response, repair for recombination, SOS mutagenesis, other genes involved in the SOS response, bacterial assay based on transcriptionals melt of SOS genes and lastly the antimutagenesis and radioprotective linked to this assay.
Surprises in the RHIC Data  [PDF]
J. H. Thomas
Physics , 2003,
Abstract: The data from RHIC have produced many unanticipated results. I will describe a few of the surprises that occur in the soft spectra while my colleagues at this conference will summarize the hard spectra. One particularly important discovery is that properties of the initial state have an impact on the final state in relativistic heavy ion collisions. Another important discovery is that the collision zone is opaque to the passage of hadrons and perhaps even partons. And finally, the data tell us very precisely where the colliding systems hadronize on the phase diagram for nuclear matter.
Asbestos is still with us: repeat call for a universal ban
Collegium Ramazzini
International Journal of Occupational Medicine and Environmental Health , 2010, DOI: 10.2478/v10001-010-0017-4
Abstract: All forms of asbestos are proven human carcinogens. All forms of asbestos cause malignant mesothelioma, lung, and laryngeal cancers, and may cause ovarian, gastrointestinal and other cancers. No exposure to asbestos is without risk, and there is no safe threshold of exposure to asbestos. Asbestos cancer victims die painful lingering deaths. These deaths are almost entirely preventable. When evidence of the carcinogenicity of asbestos became incontrovertible, the concerned parties, including the Collegium Ramazzini, called for a universal ban on the mining, manufacture and use of asbestos in all countries around the world [1]. Asbestos is now banned in 52 countries [2], and safer products have replaced many materials that once were made with asbestos. Nonetheless, a large number of countries still use, import, and export asbestos and asbestos-containing products. And in many countries that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos continues to be permitted, an exemption that has no basis in medical science but rather reflects the political and economic influence of the asbestos mining and manufacturing industry. To protect the health of all people in the world — industrial workers, construction workers, women and children, now and in future generations — the Collegium Ramazzini calls again today on all countries of the world, as we have repeatedly in the past, to join in the international endeavor to ban all forms of asbestos. An international ban on asbestos is urgently needed.
Starvation, Together with the SOS Response, Mediates High Biofilm-Specific Tolerance to the Fluoroquinolone Ofloxacin  [PDF]
Steve P. Bernier,David Lebeaux,Alicia S. DeFrancesco,Amandine Valomon,Guillaume Soubigou,Jean-Yves Coppée,Jean-Marc Ghigo,Christophe Beloin
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003144
Abstract: High levels of antibiotic tolerance are a hallmark of bacterial biofilms. In contrast to well-characterized inherited antibiotic resistance, molecular mechanisms leading to reversible and transient antibiotic tolerance displayed by biofilm bacteria are still poorly understood. The physiological heterogeneity of biofilms influences the formation of transient specialized subpopulations that may be more tolerant to antibiotics. In this study, we used random transposon mutagenesis to identify biofilm-specific tolerant mutants normally exhibited by subpopulations located in specialized niches of heterogeneous biofilms. Using Escherichia coli as a model organism, we demonstrated, through identification of amino acid auxotroph mutants, that starved biofilms exhibited significantly greater tolerance towards fluoroquinolone ofloxacin than their planktonic counterparts. We demonstrated that the biofilm-associated tolerance to ofloxacin was fully dependent on a functional SOS response upon starvation to both amino acids and carbon source and partially dependent on the stringent response upon leucine starvation. However, the biofilm-specific ofloxacin increased tolerance did not involve any of the SOS-induced toxin–antitoxin systems previously associated with formation of highly tolerant persisters. We further demonstrated that ofloxacin tolerance was induced as a function of biofilm age, which was dependent on the SOS response. Our results therefore show that the SOS stress response induced in heterogeneous and nutrient-deprived biofilm microenvironments is a molecular mechanism leading to biofilm-specific high tolerance to the fluoroquinolone ofloxacin.
Predictors of the Degree of Positive Earnings Surprises  [PDF]
Rebecca Abraham, Charles Harrington
Open Journal of Accounting (OJAcct) , 2016, DOI: 10.4236/ojacct.2016.53004
Abstract: This study identifies the predictors of positive earnings surprises at varying levels of earnings surprises under strong and weak business conditions (2014 and 2010, respectively). It measures the impact on surprises of a unique and diverse set of predictors such as analyst coverage and industry type which are security characteristics and sales and cash flow that emanate from financial statements. The study employs technology stocks that were found on the NASDAQ as such stocks have reported high positive earnings surprises from 2013-2015 [1]. The entire population of positive earnings surprises for 8316 NASDAQ stocks in 2010 and 2014 was used. Event studies were used to measure abnormal return and abnormal volume at earnings announcement, while multiple regressions tested the influence of the predictors of positive earnings surprises including number of analysts, sales, cash flow and industry type. Number of analysts significantly predicted positive earnings surprises of <20%, 21% - 30%, 31% - 100% and > 100% regardless of business condition, while sales and industry type showed similar results for weak business conditions. Cash flow explained positive earnings surprises in the 21% - 30% earnings surprises range for weak business conditions, while industry type was significant in the <20% and >100% earnings surprises categories for strong business conditions.
What Has 30 Years of HIV Vaccine Research Taught Us?  [PDF]
José Esparza
Vaccines , 2013, DOI: 10.3390/vaccines1040513
Abstract: When HIV was discovered and established as the cause of AIDS in 1983–1984, many people believed that a vaccine would be rapidly developed. However, 30 years have passed and we are still struggling to develop an elusive vaccine. In trying to achieve that goal, different scientific paradigms have been explored. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. Major lessons learned are: the development of an HIV vaccine is an extremely difficult challenge; the temptation of just following the fashion should be avoided; clinical trials are critical, especially large-scale efficacy trials; HIV vaccine research will require long-term commitment; and sustainable collaborations are needed to accelerate the development of an HIV vaccine. Concrete actions must be implemented with the sense of urgency imposed by the severity of the AIDS epidemic.
Inducible SOS Response System of DNA Repair and Mutagenesis in Escherichia coli
Celina Janion
International Journal of Biological Sciences , 2008,
Abstract: Chromosomal DNA is exposed to continuous damage and repair. Cells contain a number of proteins and specific DNA repair systems that help maintain its correct structure. The SOS response was the first DNA repair system described in Escherichia coli induced upon treatment of bacteria with DNA damaging agents arrest DNA replication and cell division. Induction of the SOS response involves more than forty independent SOS genes, most of which encode proteins engaged in protection, repair, replication, mutagenesis and metabolism of DNA. Under normal growth conditions the SOS genes are expressed at a basal level, which increases distinctly upon induction of the SOS response. The SOS-response has been found in many bacterial species (e.g., Salmonella typhimurium, Caulobacter crescentus, Mycobacterium tuberculosis), but not in eukaryotic cells. However, species from all kingdoms contain some SOS-like proteins taking part in DNA repair that exhibit amino acid homology and enzymatic activities related to those found in E. coli. but are not organized in an SOS system. This paper presents a brief up-to-date review describing the discovery of the SOS system, the physiology of SOS induction, methods for its determination, and the role of some SOS-induced genes.
Ribonuclease E Modulation of the Bacterial SOS Response  [PDF]
Robert Manasherob, Christine Miller, Kwang-sun Kim, Stanley N. Cohen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038426
Abstract: Plants, animals, bacteria, and Archaea all have evolved mechanisms to cope with environmental or cellular stress. Bacterial cells respond to the stress of DNA damage by activation of the SOS response, the canonical RecA/LexA-dependent signal transduction pathway that transcriptionally derepresses a multiplicity of genes–leading to transient arrest of cell division and initiation of DNA repair. Here we report the previously unsuspected role of E. coli endoribonuclease RNase E in regulation of the SOS response. We show that RNase E deletion or inactivation of temperature-sensitive RNase E protein precludes normal initiation of SOS. The ability of RNase E to regulate SOS is dynamic, as down regulation of RNase E following DNA damage by mitomycin C resulted in SOS termination and restoration of RNase E function leads to resumption of a previously aborted response. Overexpression of the RraA protein, which binds to the C-terminal region of RNase E and modulates the actions of degradosomes, recapitulated the effects of RNase E deficiency. Possible mechanisms for RNase E effects on SOS are discussed.
Bacteria under SOS evolve anticancer phenotypes
Shatha F Dallo, Tao Weitao
Infectious Agents and Cancer , 2010, DOI: 10.1186/1750-9378-5-3
Abstract: Bacteria growing with cancer cells in the presence of the replication inhibitors undergo the SOS response and evolve advantageous phenotypes for the bacteria to invade the cancer cells in order to evade the drug attack. This hypothesis predicts that bacteria produce the proteins that mediate bacterial capture and invasion of cancer cells--the advantageous phenotypes. Generation of the phenotypes may be facilitated during the SOS response induced by anticancer drugs.Experimental design: 1) Examine attachment and invasion of bacterium Pseudomonas aeruginosa and the SOS mutant control to cancer cells in the presence of the anticancer drugs that inhibit DNA replication enzymes and trigger the SOS response. 2) Reveal the bacterial proteins that exhibit changes in expression. 3) Identify the genes encoding cancer adhesion and invasion. 4) Construct the mutants for the genes, clone and express these genes. 5) Examine the bacterial capture and invasion of cancer cells in contrast to non-cancer control.Expected results: 1) The bacterial proteins will be differentially induced during bacteria-cancer interaction under the SOS response to the anticancer drugs. 2) Knocking out the bacterial cancer-adhesion-invasion genes will disrupt the adhesion-invasion phenotypes of the bacteria. 3) Expressing these genes will direct the bacterial capture and invasion of cancer cells.Bacteria can evolve anticancer phenotypes targeting metastatic cells. If this hypothesis is true, the outcomes will contribute to development of a novel bacterial anti-metastasis regimen.Attempts with live bacteria to control cancer progression were tried over a century ago [1,2]. Although undesired infections raised a concern, creative hypotheses and progress have sparkled. As reviewed by Chakrabarty [3], antitumor treatment with Clostridium novyi was proposed, based on propensity of the anaerobe to grow in anaerobic core of the tumors and to deprive tumors of oxygen and essential nutrients. Salmonella, a facult
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