Sensitivity of Ru(bpy)_2dppz^(2+) Luminescence to DNA Defects

The luminescent characteristics of Ru(bpy)_2dppz^(2+) (dppz = dipyrido[3,2-a:2′,3′-c]phenazine), a DNA light switch, were investigated in the presence of oligonucleotides containing single base mismatches or an abasic site. In water, the ruthenium luminescence is quenched, but, bound to well matched duplex DNA, the Ru complex luminesces. Here we show that with DNAs containing a defect, rac-, Δ-, and Λ-Ru(bpy)_2dppz^(2+) exhibit significant luminescent enhancements above that with well matched DNA. In the presence of a single base mismatch, large luminescent enhancements are evident for the Δ-Ru isomer; the Λ-isomer shows particularly high luminescence bound to an oligonucleotide containing an abasic site. Similar increases are not evident with two common DNA-binding organic fluorophores, ethidium bromide and TO-PRO-3. Titrations with hairpin oligonucleotides containing a variable mismatch site show correlation between the level of luminescent enhancement and the thermodynamic destabilization associated with the mismatch. This correlation is reminiscent of that found earlier for a bulky rhodium complex that binds mismatched DNA sites through metalloinsertion, where the complex binds the DNA from the minor groove side, ejecting the mismatched bases into the major groove. Differential quenching studies with minor and major groove quenchers and time-resolved emission studies support this metalloinsertion mode for the dppz complex at the defect site. Certainly these data underscore the utility of Ru(bpy)_2dppz^(2+) as a sensitive luminescent reporter of DNA and its defects

Spin-orbit torque induced dipole skyrmion motion at room temperature

We demonstrate deterministic control of dipole-field-stabilized skyrmions by means of spin-orbit torques arising from heavy transition-metal seed layers. Experiments are performed on amorphous Fe/Gd multilayers that are patterned into wires and exhibit stripe domains and dipole skyrmions at room temperature. We show that while the domain walls and skyrmions are achiral on average due to lack of Dzyaloshinskii-Moriya interactions, the N\'eel-like closure domain walls at each surface are chiral and can couple to spin-orbit torques. The current-induced domain evolutions are reported for different magnetic phases, including disordered stripe domains, coexisting stripes and dipole skyrmions and a closed packed dipole skyrmion lattice. The magnetic textures exhibit motion under current excitations with a current density ~10^8 A/m2. By comparing the motion resulting from magnetic spin textures in Fe/Gd films with different heavy transition-metal interfaces, we confirm spin currents can be used to manipulate achiral dipole skyrmions via spin-orbit torques.Comment: 23 pages, 8 figure

Optimizing pentose utilization in yeast: the need for novel tools and approaches

Hexose and pentose cofermentation is regarded as one of the chief obstacles impeding economical conversion of lignocellulosic biomass to biofuels. Over time, successful application of traditional metabolic engineering strategy has produced yeast strains capable of utilizing the pentose sugars (especially xylose and arabinose) as sole carbon sources, yet major difficulties still remain for engineering simultaneous, exogenous sugar metabolism. Beyond catabolic pathways, the focus must shift towards non-traditional aspects of cellular engineering such as host molecular transport capability, catabolite sensing and stress response mechanisms. This review highlights the need for an approach termed 'panmetabolic engineering', a new paradigm for integrating new carbon sources into host metabolic pathways. This approach will concurrently optimize the interdependent processes of transport and metabolism using novel combinatorial techniques and global cellular engineering. As a result, panmetabolic engineering is a whole pathway approach emphasizing better pathways, reduced glucose-induced repression and increased product tolerance. In this paper, recent publications are reviewed in light of this approach and their potential to expand metabolic engineering tools. Collectively, traditional approaches and panmetabolic engineering enable the reprogramming of extant biological complexity and incorporation of exogenous carbon catabolism

Engineered xylose transporters with reduced glucose inhibition

Provided herein are compositions and methods useful for reducing glucose inhibition in transporting xylose, arabinose and other monosaccharides, into a yeast cell.Board of Regents, University of Texas Syste

Link travel time estimation in urban areas by detectors and probe vehicles fusion

International audienceThis paper presents an approach to estimate link travel time in urban areas. This approach consists of a data fusion from underground loop detectors and probe vehicles equipped with global positioning system (GPS). This method is expected to be more accurate, reliable and robust than using either of these data sources alone. In this approach, an algorithm is developed. This algorithm is based on the unscented Kalman filter using vehicle counts and flows from loop detectors located at the end of every link, and travel time from probe vehicles. From these counts the average travel time is calculated using the "cumulative plot" method. Furthermore, in order to incorporate the GPS data, a map-matching method is used to associate a travel time to the appropriate link

Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders

Alcohol use disorders (AUDs) cause serious problems in society and few effective treatments are available. Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study the neurobiological basis of human behavior with a conserved, fully tractable genome, and a short generation time for fast generation of data at a fraction of the cost of other organisms. C. elegans demonstrate movement toward, and concentration-dependent self-exposure to various psychoactive drugs. The discovery of opioid receptors in C. elegans provided the impetus to test the hypothesis that C. elegans may be used as a medications screen to identify new AUD treatments. We tested the effects of naltrexone, an opioid antagonist and effective treatment for AUDs, on EtOH preference in C. elegans. Six-well agar test plates were prepared with EtOH placed in a target zone on one side and water in the opposite target zone of each well. Worms were treated with naltrexone before EtOH preference testing and then placed in the center of each well. Wild-type worms exhibited a concentration-dependent preference for 50, 70 and 95% EtOH. Naltrexone blocked acute EtOH preference, but had no effect on attraction to food or benzaldehyde in wild-type worms. Npr-17 opioid receptor knockout mutants did not display a preference for EtOH. In contrast, npr-17 opioid receptor rescue mutants exhibited significant EtOH preference behavior, which was attenuated by naltrexone. Chronic EtOH exposure induced treatment resistance and compulsive-like behavior. These data indicate that C. elegans can serve as a model system to identify compounds to treat AUDs

Energy-efficient generation of skyrmion phases in Co/Ni/Pt-based multilayers using Joule heating

We have studied the effects of electrical current pulses on skyrmion formation in a series of Co/Ni/Pt-based multilayers. Transmission X-ray microscopy reveals that by applying electrical current pulses of duration and current density on the order of $\tau$=50 $\mu$s and j=1.7x10$^1$$^0$ A/m$^2$, respectively, in an applied magnetic field of $\mu$$_0$Hz=50 mT, stripe-to-skyrmion transformations are attained. The skyrmions remain stable across a wide range of magnetic fields, including zero field. The skyrmions then remain stable across a wide range of magnetic fields, including zero field. We primarily attribute the transformation to current-induced Joule heating on the order of ~125 K. Reducing the magnetic moment and perpendicular anisotropy using thin rare-earth spacers dramatically reduces the pulse duration, current density, and magnetic field necessary to 25 $\mu$s, 2.4x10$^9$ A/m$^2$, and 27 mT, respectively. These findings show that energetic inputs allow for the formation of skyrmion phases in a broad class of materials and that material properties can be tuned to yield more energy-efficient access to skyrmion phases.Comment: 32 pages, 7 figures, 9 supplemental figure

Statin use and adverse effects among adults \u3e 75 years of age: Insights from the Patient and Provider Assessment of Lipid Management (PALM) registry

Background: Current statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline. Methods and results: We compared statin use and dosing between adults \u3e75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline-recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were \u3e75 years old. For primary prevention, use of any statin or high-dose statin did not vary by age group: any statin, 62.6% in those \u3e75 years old versus 63.1% in those ≤75 years old (P=0.83); high-dose statin, 10.2% versus 12.3% in the same groups (P=0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [P=0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66-1.01 [P=0.06]), but were much less likely to receive a high-intensity statin (23.5% versus 36.2% [PP=0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P=0.003) or myalgias (27.3% versus 33.3%; Conclusions: Overall use of statins was similar for primary prevention in those aged \u3e75 years versus younger patients, yet older patients were less likely to receive high-intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adult