DNA double strand break repair: a radiation perspective

SIGNIFICANCE:
Ionizing radiation (IR) can induce a wide range of unique deoxyribonucleic acid (DNA) lesions due to the spatiotemporal correlation of the ionization produced. Of these, DNA double strand breaks (DSBs) play a key role. Complex mechanisms and sophisticated pathways are available within cells to restore the integrity and sequence of the damaged DNA molecules.
RECENT ADVANCES:
Here we review the main aspects of the DNA DSB repair mechanisms with emphasis on the molecular pathways, radiation-induced lesions, and their significance for cellular processes.
CRITICAL ISSUES:
Although the main characteristics and proteins involved in the two DNA DSB repair processes present in eukaryotic cells (homologous recombination and nonhomologous end-joining) are reasonably well established, there are still uncertainties regarding the primary sensing event and their dependency on the complexity, location, and time of the damage. Interactions and overlaps between the different pathways play a critical role in defining the repair efficiency and determining the cellular functional behavior due to unrepaired/miss-repaired DNA lesions. The repair pathways involved in repairing lesions induced by soluble factors released from directly irradiated cells may also differ from the established response mechanisms.
FUTURE DIRECTIONS:
An improved understanding of the molecular pathways involved in sensing and repairing damaged DNA molecules and the role of DSBs is crucial for the development of novel classes of drugs to treat human diseases and to exploit characteristics of IR and alterations in tumor cells for successful radiotherapy applications.

Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin:a randomized, double-blind, placebo-controlled trial

To evaluate the dose-response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes.

Facile Synthesis and Visualization of Janus Double-Brush Copolymers

Well-defined double-brush copolymers with each graft site carrying a polystyrene (PSt) graft and a polylactide (PLA) graft were synthesized by simultaneous reversible addition fragmentation chain transfer (RAFT) and ring-opening polymerization (ROP) processes, followed by ring-opening metathesis polymerization (ROMP) "grafting through" of the resulting diblock macromonomer (MM). Their Janus-type 1 morphologies were detected by transmission electron microscopy (TEM) imaging after thermal annealing to facilitate the intramolecular self-assembly of PSt and PLA grafts. This finding provides critical evidence to verify double-brush copolymers as Janus nanomaterials.

Time-dependent R-matrix theory applied to two-photon double ionization of He

We introduce a time-dependent R-matrix theory generalized to describe double-ionization processes. The method is used to investigate two-photon double ionization of He by intense XUV laser radiation. We combine a detailed B-spline-based wave-function description in an extended inner region with a single-electron outer region containing channels representing both single ionization and double ionization. A comparison of wave-function densities for different box sizes demonstrates that the flow between the two regions is described with excellent accuracy. The obtained two-photon double-ionization cross sections are in excellent agreement with other cross sections available. Compared to calculations fully contained within a finite inner region, the present calculations can be propagated over the time it takes the slowest electron to reach the boundary.

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial

Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.

Monte Carlo studies of quantum and classical annealing on a double well

We present results for a variety of Monte Carlo annealing approaches, both classical and quantum, benchmarked against one another for the textbook optimization exercise of a simple one-dimensional double well. In classical (thermal) annealing, the dependence upon the move chosen in a Metropolis scheme is studied and correlated with the spectrum of the associated Markov transition matrix. In quantum annealing, the path integral Monte Carlo approach is found to yield nontrivial sampling difficulties associated with the tunneling between the two wells. The choice of fictitious quantum kinetic energy is also addressed. We find that a "relativistic" kinetic energy form, leading to a higher probability of long real-space jumps, can be considerably more effective than the standard nonrelativistic one.

The effect of helium accretion efficiency on rates of Type Ia supernovae: Double detonations in accreting binaries

he double-detonation explosion scenario of Type Ia supernovae (SNe Ia) has gained increased support from the SN Ia community as a viable progenitor model, making it a promising candidate alongside the well-known single degenerate and double degenerate scenarios. We present delay times of double-detonation SNe, in which a sub-Chandrasekhar mass carbon–oxygen white dwarf (WD) accretes non-dynamically from a helium-rich companion. One of the main uncertainties in quantifying SN rates from double detonations is the (assumed) retention efficiency of He-rich matter. Therefore, we implement a new prescription for the treatment of accretion/accumulation of He-rich matter on WDs. In addition, we test how the results change depending on which criteria are assumed to lead to a detonation in the helium shell. In comparing the results to our standard case (Ruiter et al.), we find that regardless of the adopted He accretion prescription, the SN rates are reduced by only ∼25 per cent if low-mass He shells (≲0.05 M⊙) are sufficient to trigger the detonations. If more massive (0.1 M⊙) shells are needed, the rates decrease by 85 per cent and the delay time distribution is significantly changed in the new accretion model – only SNe with prompt (<500 Myr) delay times are produced. Since theoretical arguments favour low-mass He shells for normal double-detonation SNe, we conclude that the rates from double detonations are likely to be high, and should not critically depend on the adopted prescription for accretion of He.

Enantioselective Assembly of a Ruthenium(II) Polypyridyl Complex into a Double Helix

Evolution can increase the complexity of matter by self-organization into helical architectures, the best example being the DNA double helix. One common aspect, apparently shared by most of these architectures, is the presence of covalent bonds within the helix backbone. Here, we report the unprecedented crystal structures of a metal complex that self-organizes into a continuous double helical structure, assembled by non-covalent building blocks. Built up solely by weak stacking interactions, this alternating tread stairs-like double helical assembly mimics the DNA double helix structure. Starting from a racemic mixture in aqueous solution, the ruthenium(II) polypyridyl complex forms two polymorphic structures of a left-handed double helical assembly of only the Λ-enantiomer. The stacking of the helices is different in both polymorphs: a crossed woodpile structure versus a parallel columnar stacking.

Origin of double dinitrogen release feature during fast switching between lean and rich cycles for NOx storage reduction catalysts

The performance of NOx storage and reduction over 1.5 wt% Pt/20 wt% KNO3/K2Ti8O17 and 1.5 wt% Pt/K2Ti8O17 catalysts has been investigated using combined fast transient kinetic switching and isotopically labelled (NO)-N-15 at 350 degrees C. The evolution of product N-2 has revealed two significant peaks during 60 s lean/1.3 s rich switches. It also found that the presence of CO2 in the feed affects the release of N-2 in the second peak. Regardless of the presence/absence of water in the feed, only one peak of N-2 was observed in the absence of CO2. Gas-phase NH3 was not observed in any of the experiments. However, in the presence of CO2 the results obtained from in situ DRIFTS-MS analysis showed that isocyanate species are formed and stored during the rich cycles, probably from the reaction between NOx and CO, in which CO was formed via the reverse water-gas shift reaction. 

Synthesis of the C(7)-C(22)-Sector of (+)-Acutiphycin Via O-Directed Double Free Radical Alkyne Hydrostannation with Ph3SnH/Et3B, Double I-Sn Exchange and Double Stille Coupling

Abstract Image

Herein a new double O-directed free radical hydrostannation reaction is reported on the structurally complex dialkyldiyne 11. Through our use of a conformation-restraining acetal to help prevent stereocenter-compromising 1,5-H-atom abstraction reactions by vinyl radical intermediates, the two vinylstannanes of 10 were concurrently constructed with high stereocontrol using Ph3SnH/Et3B/O2. Distannane 10 was thereafter elaborated into the bis-vinyl iodide 9 via O-silylation and double I–Sn exchange; double Stille coupling of 9, O-desilylation, and oxidation thereafter furnished 8.