Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks especially double-strand breaks (DSBs) that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells [1]. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cell

Complete genome sequence of Streptococcus thermophilus SMQ-301, a model strain for phage-host interactions

Streptococcus thermophilus is used by the dairy industry to manufacture yogurt and several cheeses. Using PacBio and Illumina platforms, we sequenced the genome of S. thermophilus SMQ-301, the host of several virulent phages. The genome is composed of 1,861,792 bp and contains 2,037 genes, 67 tRNAs, and 18 rRNAs

Genome Sequence of SN1, a Bacteriophage That Infects \u3ci\u3eSphaerotilus natans\u3c/i\u3e and \u3ci\u3ePseudomonas aeruginosa\u3c/i\u3e

Phage SN1 infects Sphaerotilus natans and Pseudomonas aeruginosa strains. Its genome consists of 61,858 bp (64.3% GC) and 89 genes, including 32 with predicted functions. SN1 genome is very similar to Pseudomonas phage M6, which contains hypermodified thymidines. Genome analyses revealed similar base-modifying genes as those found in M6. Phage SN1 was isolated in 1979 from activated sludge samples obtained from a wastewater treatment plant (Lincoln, Nebraska, USA) using S. natans ATCC 13338 as the host (1, 2). An early study showed that the siphophage SN1 has unusual bases in its genome as confirmed by cellulose thin-layer chromatography (1). Its genomic DNA also showed resistance to type II restriction endonucleases (2). Host range studies indicate that phage SN1 can also infect Pseudomonas aeruginosa strains PAO33 and OT684 (2). Here, phage SN1 was amplified with its host S. natans ATCC 13338 in nutrient broth (3 g/L beef extract, 5 g/L peptone) and agitated at 30°C (2). Cell debris were removed by filtration (0.45 mm) and filtrates were stored at 4°C until use. Phage SN1 also infected P. aeruginosa PAO1 (HER1153) in TSB/TSA medium at 30°C using both plaque assays and lysis of liquid cultures. Species identification of the above two host strains was confirmed by 16S sequencing

Genome Sequence of SN1, a Bacteriophage That Infects \u3ci\u3eSphaerotilus natans\u3c/i\u3e and \u3ci\u3ePseudomonas aeruginosa\u3c/i\u3e

Phage SN1 infects Sphaerotilus natans and Pseudomonas aeruginosa strains. Its genome consists of 61,858 bp (64.3% GC) and 89 genes, including 32 with predicted functions. SN1 genome is very similar to Pseudomonas phage M6, which contains hypermodified thymidines. Genome analyses revealed similar base-modifying genes as those found in M6

A novel fiber-optic based 0.014 '' pressure wire: Designs of the OptoWire (TM), development phases, and the O-2 first-in-man results

Objectives To review the technical limitations of available pressure-wires, present the design evolution of a nitinol fiber-optic pressure wire and to summarize the First-in-Man (FIM) O-2 pilot study results. Background Despite increasing use of physiology assessment of coronary lesions, several technical limitations persist. We present technical details, design evolution and early clinical results with a novel 0.014 '' nitinol fiber-optic based pressure-wire. Methods and Results The 0.014' OptoWire (TM) (Opsens Medical, Quebec, Canada) was designed to combine improved handling properties compared to standard pressure-wires and to offer extremely reliable pressure recording and transmission due to fiber-optic properties compared to piezo-electric sensors and electrical wires. In vitro assessment showed that OptoWire (TM) steerability, pushability and torquability properties were closer to regular PCI wires than standard electrical pressure wires. In the First-in-Man O(2)study, 60 patients were recruited at 2 centers in Canada. A total of 103 lesions were assessed with the OptoWire (TM) and OptoMonitor (TM), 75 lesions at baseline and 28 lesions post-PCI (without disconnection). In all crossed lesions (n = 100, 97%), mean Pd/Pa and FFR could be adequately measured. In 11 cases assessed successively with OptoWire (TM) and Aegis (TM) (Abbott Vascular, USA) bland-Altman analysis showed a mean difference of 0.002 +/- 0.052 mmHg (p = .91) for Pd/Pa and 0.01 +/- 0.06 for FFR calculation (p= .45). There was no device-related complication. Upon these initial results, several design changes aimed to improve overall performance including torquability, stiffness, resistance to kink and pressure drift were completed. Conclusion The novel 0.014 '' fiber-optic OptoWire (TM) provides superior wire handling with reduced risk of pressure drift allowing reliable pre- and post-PCI physiology assessment

Left Main Coronary Angioplasty: Assessment of a “Risk Score” to Predict Acute and Long‐Term Outcome

Due to the recent emergence of adjunctive techniques such as cardiopulmonary bypass support, left main angioplasty may become more routinely applied in the near future. In order to choose the best possible therapy, a precise risk assessment will be desirable. Twenty‐two left main angioplasties were thus re

DNA Repair Domain Modeling Can Predict Cell Death and Mutation Frequency for Wide Range Spectrum of Radiation

Exploration missions to Mars and other destinations raise many questions about the health of astronauts. The continuous exposure of astronauts to galactic cosmic rays is one of the main concerns for long-term missions. Cosmic ionizing radiations are composed of different ions of various charges and energies notably, highly charged energy (HZE) particles. The HZE particles have been shown to be more carcinogenic than low-LET radiation, suggesting the severity of chromosomal aberrations induced by HZE particles is one possible explanation. However, most mathematical models predicting cell death and mutation frequency are based on directly fitting various HZE dose response and are in essence empirical approaches. In this work, we assume a simple biological mechanism to model DNA repair and use it to simultaneously explain the low- and high-LET response using the exact same fitting parameters. Our work shows that the geometrical position of DNA repair along tracks of heavy ions are sufficient to explain why high-LET particles can induce more death and mutations. Our model is based on assuming DNA double strand breaks (DSBs) are repaired within repair domain, and that any DSBs located within the same repair domain cluster into one repair unit, facilitating chromosomal rearrangements and increasing the probability of cell death. We introduced this model in 2014 using simplified microdosimetry profiles to predict cell death. In this work, we collaborated with NASA Johnson Space Center to generate more accurate microdosimetry profiles derived by Monte Carlo techniques, taking into account track structure of HZE particles and simulating DSBs in realistic cell geometry. We simulated 224 data points (D, A, Z, E) with the BDSTRACKS model, leading to a large coverage of LET from ~10 to 2,400 keV/m. This model was used to generate theoretical RBE for various particles and energies for both cell death and mutation frequencies. The RBE LET dependence is in agreement with experimental data known in human and murine cells. It suggests that cell shape and its orientation with respect to the HZE particle beam can modify the biological response to radiation. Such discovery will be tested experimentally and, if proven accurate, will be another strong supporting evidence for DNA repair domains and their critical role in interpreting cosmic radiation sensitivity

First complete genome sequence of Staphylococcus xylosus, a meat starter culture and a host to propagate Staphylococcus aureus phages

Staphylococcus xylosus is a bacterial species used in meat fermentation and a commensal microorganism found on animals. We present the first complete circular genome from this species. The genome is composed of 2,757,557 bp, with a GC content of 32.9%, and contains 2,514 genes and 79 structural RNAs

Acute complications of percutaneous transluminal coronary angioplasty for total occlusion

The incidence of major complications after percutaneous coronary angioplasty (PTCA) of a totally occluded artery was assessed retrospectively. A total of 1649 PTCA procedures were analyzed. After exclusion of procedures for acute myocardial infarction or total occlusion that resulted from restenosis, 90 patients wer