Backmasking in the yeast genome: encoding overlapping information for protein-coding and RNA degradation

Backmasking is a recording technique used to hide a sound or message in a music track in reverse, meaning that it is only audible when the record is played backwards. Analogously, the compact yeast genome encodes for diverse sources of information such as overlapping coding and non-coding transcripts, and protein-binding sites on the two complementary DNA strands. Examples are the consensus binding site sequences of the RNA-binding proteins Nrd1 and Nab3 that target non-coding transcripts for degradation. Here, by examining the overlap of stable (SUTs, stable unannotated transcripts) and unstable (CUTs, cryptic unstable transcripts) transcripts with protein-coding genes, we show that the predicted Nrd1 and Nab3-binding site sequences occur at differing frequencies. They are always depleted in the sense direction of protein-coding genes, thus avoiding degradation of the transcript. However in the antisense direction, predicted binding sites occur at high frequencies in genes with overlapping unstable ncRNAs (CUTs), so limiting the availability of non-functional transcripts. In contrast they are depleted in genes with overlapping stable ncRNAs (SUTs), presumably to avoid degrading the non-coding transcript. The protein-coding genes maintain similar amino-acid contents, but they display distinct codon usages so that Nrd1 and Nab3-binding sites can arise at differing frequencies in antisense depending on the overlapping transcript type. Our study demonstrates how yeast has evolved to encode multiple layers of information—protein-coding genes in one strand and the relative chance of degrading antisense RNA in the other strand—in the same regions of a compact genome

Creating European guidelines for Chiropractic Incident Reporting and Learning Systems (CIRLS): relevance and structure

<p>Abstract</p> <p>Background</p> <p>In 2009, the heads of the Executive Council of the European Chiropractors' Union (ECU) and the European Academy of Chiropractic (EAC) involved in the European Committee for Standardization (CEN) process for the chiropractic profession, set out to establish European guidelines for the reporting of adverse reactions to chiropractic treatment. There were a number of reasons for this: first, to improve the overall quality of patient care by aiming to reduce the application of potentially harmful interventions and to facilitate the treatment of patients within the context of achieving maximum benefit with a minimum risk of harm; second, to inform the training objectives for the Graduate Education and Continuing Professional Development programmes of all 19 ECU member nations, regarding knowledge and skills to be acquired for maximising patient safety; and third, to develop a guideline on patient safety incident reporting as it is likely to be part of future CEN standards for ECU member nations.</p> <p>Objective</p> <p>To introduce patient safety incident reporting within the context of chiropractic practice in Europe and to help individual countries and their national professional associations to develop or improve reporting and learning systems.</p> <p>Discussion</p> <p>Providing health care of any kind, including the provision of chiropractic treatment, can be a complex and, at times, a risky activity. Safety in healthcare cannot be guaranteed, it can only be improved. One of the most important aspects of any learning and reporting system lies in the appropriate use of the data and information it gathers. Reporting should not just be seen as a vehicle for obtaining information on patient safety issues, but also be utilised as a tool to facilitate learning, advance quality improvement and to ultimately minimise the rate of the occurrence of errors linked to patient care.</p> <p>Conclusions</p> <p>Before a reporting and learning system can be established it has to be clear what the objectives of the system are, what resources will be required and whether the implementing organisation has the capacity to operate the system to its full advantage. Responding to adverse event reports requires the availability of experts to analyse the incidents and to provide feedback in a timely fashion. A comprehensive strategy for national implementation must be in place including, but not limited to, presentations at national meetings, the provision of written information to all practitioners and the running of workshops, so that all stakeholders fully understand the purposes of adverse event reporting. Unless this is achieved, any system runs the risk of failure, or at the very least, limited usefulness.</p

Properties and expression of Na+/K+-ATPase α-subunit isoforms in the brain of the swamp eel, Monopterus albus, which has unusually high brain ammonia tolerance

10.1371/journal.pone.0084298PLoS ONE812-POLN

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

The effect of increasing power when grooving using phacoemulsification

Rhett S Thomson,1,2 Brian A Bird,3 Lance A Stutz,4 Joshua B Heczko,1 Ashlie A Bernhisel,1 William R Barlow,1 Brian Zaugg,1 Randall J Olson,1 Jeff H Pettey1 1Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA; 2University of Utah School of Medicine, Salt Lake City, UT 84132, USA; 3University of Nevada Reno School of Medicine, Reno, NV 89557, USA; 4University of Texas Southwestern Medical School, Dallas, TX 75390, USA Purpose: To determine optimal power settings on the Centurion Vision System during the grooving step in cataract surgery.Methods: Intact porcine lenses hardened by formalin and placed in a chamber designed to simulate the anterior chamber of the eye were used to test longitudinal power at 40%, 70%, and 100% and torsional power at 0%. Flow rate was set at 40 mL/min. Vacuum was set at 400 mmHg, intraocular pressure was set at 50 mmHg, and a balanced phacoemulsification tip with a 20 degree tip and a 30 degree bevel was used. Efficiency (time to groove the lens in half) was determined.Results: Increasing longitudinal power from 40% to 70% increased efficiency by 28% (P&lt;0.05), and by 32% (P&lt;0.05) when increasing longitudinal power from 40% to 100%. There was no statistically significant increase in efficiency from 70% to 100%.Conclusion: For the tested variables, a longitudinal power of 70% was determined to be most efficient during the grooving step of cataract surgery for equivalent 3&ndash;4+ nuclei. Further increases in power demonstrated no statistically significant improvement in efficiency. Keywords: settings, longitudinal power, efficiency, porcine lens mode

Optimization of the Oertli CataRhex 3&reg; phacoemulsification machine

Lance A Stutz,1 Joshua B Heczko,2 Brian A Bird,3 Rhett S Thomson,2,4 Ashlie A Bernhisel,2 William R Barlow,2 Brian Zaugg,2 Randall J Olson,2 Jeff H Pettey2 1University of Texas Southwestern Medical School, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; 2Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA; 3University of Nevada Reno, School of Medicine, Reno, NV 89557, USA; 4University of Utah, School of Medicine, Salt Lake City, UT 84132, USA Purpose: The aim of this study was to determine optimal bottle height, vacuum, aspiration rate, and power settings of the Oertli CataRhex 3&reg; phacoemulsification machine. Methods: Porcine lens nuclei were hardened with formalin and cut into 2.0 mm cubes. Lens cubes were emulsified using the easyTip&reg; 2.2&nbsp;mm at 30&deg;. Fragment removal time (efficiency) and fragment bounces off the tip (chatter) were measured. Settings tested included bottle height of 60, 80, 100 and 120&nbsp;cm; aspiration rate of 40, 45, and 50&nbsp;mL/min; vacuum of 400, 500, and 600 mmHg; and power of 50, 60, 70, 80, 90, and 100%. Results: Efficiency and chatter increased in a linear fashion with increasing vacuum to 600 mmHg (P=0.017, P=0.046, respectively). The most efficient aspiration rate was 50&nbsp;mL/min, although this finding lacked statistical significance (P=0.66). Increasing power increased efficiency up to 80% without increasing chatter (P=0.042, P=0.71, respectively). Compared to all other power settings, chatter was increased at 100% (P=0.014). Conclusion: The most efficient machine settings were vacuum at 600&nbsp;mmHg, aspiration rate at 50&nbsp;mL/min, and power at 80%. Keywords: cataract, blindness, underserved countries, vacuum, aspiration rate, powe