Spin-locking in low-frequency reaction yield detected magnetic resonance

The purported effects of weak magnetic fields on various biological systems from animal magnetoreception to human health have generated widespread interest and sparked much controversy in the past decade. To date the only well established mechanism by which the rates and yields of chemical reactions are known to be influenced by magnetic fields is the radical pair mechanism, based on the spin-dependent reactivity of radical pairs. A diagnostic test for the operation of the radical pair mechanism was proposed by Henbest et al. [J. Am. Chem. Soc., 2004, 126, 8102] based on the combined effects of weak static magnetic fields and radiofrequency oscillating fields in a reaction yield detected magnetic resonance experiment. Here we investigate the effects on radical pair reactions of applying relatively strong oscillating fields, both parallel and perpendicular to the static field. We demonstrate the importance of understanding the effect of the strength of the radiofrequency oscillating field; our experiments demonstrate that there is an optimal oscillating field strength above which the observed signal decreases in intensity and eventually inverts. We establish the correlation between the onset of this effect and the hyperfine structure of the radicals involved, and identify the existence of ‘overtone’ type features appearing at multiples of the expected resonance field positio

Bird Cryptochrome 1a Is Excited by Blue Light and Forms Long-Lived Radical- Pairs

Cryptochromes (Cry) have been suggested to form the basis of light-dependent magnetic compass orientation in birds. However, to function as magnetic compass sensors, the cryptochromes of migratory birds must possess a number of key biophysical characteristics. Most importantly, absorption of blue light must produce radical pairs with lifetimes longer than about a microsecond. Cryptochrome 1a (gwCry1a) and the photolyase-homology-region of Cry1 (gwCry1-PHR) from the migratory garden warbler were recombinantly expressed and purified from a baculovirus/Sf9 cell expression system. Transient absorption measurements show that these flavoproteins are indeed excited by light in the blue spectral range leading to the formation of radicals with millisecond lifetimes. These biophysical characteristics suggest that gwCry1a is ideally suited as a primary light-mediated, radical-pair-based magnetic compass recepto

Modulation of Hydrogen Peroxide Production in Cellular Systems by Low Level Magnetic Fields

Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, suggesting that ROS might be involved in the development of these cells. However, recent studies suggest that inducing an excess of ROS in cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumors frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially modulate the development of these cells by controlling their ROS production. Low levels of ROS are also important for the development and survival of normal cells. In this manuscript, we present data on the influence of the suppression of the Earth's magnetic field (low level magnetic fields or LLF) which magnitudes range from 0.2 µT to 2 µT on the modulation of hydrogen peroxide (H2O2) in human fibrosarcoma cancer cell line HT1080, pancreatic AsPC-1 cancer cell line, and bovine pulmonary artery endothelial cells (PAEC) exposed to geomagnetic field (control; 45 µT–60 µT). Reduction of the Earth's magnetic field suppressed H2O2 production in cancer cells and PAEC. The addition of catalase and superoxide dismutase (SOD) mimetic MnTBAP inhibited the magnetic field effect. Modulating ROS production by magnetic fields may open new venues of biomedical research and therapeutic strategies

Determining Material Response for Polyvinyl Butyral (PVB) in Blast Loading Situations

Protecting structures from the effect of blast loads requires the careful design of all building components. In this context, the mechanical properties of Polyvinyl Butyral (PVB) are of interest to designers as the membrane behaviour will affect the performance of laminated glass glazing when loaded by explosion pressure waves. This polymer behaves in a complex manner and is difficult to model over the wide range of strain rates relevant to blast analysis. In this study, data from experimental tests conducted at strain rates from 0.01 s−1 to 400 s−1 were used to develop material models accounting for the rate dependency of the material. Firstly, two models were derived assuming Prony series formulations. A reduced polynomial spring and a spring derived from the model proposed by Hoo Fatt and Ouyang were used. Two fits were produced for each of these models, one for low rate cases, up to 8 s−1, and one for high rate cases, from 20 s−1. Afterwards, a single model representing all rates was produced using a finite deformation viscoelastic model. This assumed two hyperelastic springs in parallel, one of which was in series with a non-linear damper. The results were compared with the experimental results, assessing the quality of the fits in the strain range of interest for blast loading situations. This should provide designers with the information to choose between the available models depending on their design needs

The Short-Lived Signaling State of the Photoactive Yellow Protein Photoreceptor Revealed by Combined Structural Probes

The signaling state of the photoactive yellow protein (PYP) photoreceptor is transiently developed via isomerization of its blue-light-absorbing chromophore. The associated structural rearrangements have large amplitude but, due to its transient nature and chemical exchange reactions that complicate NMR detection, its accurate three-dimensional structure in solution has been elusive. Here we report on direct structural observation of the transient signaling state by combining double electron electron resonance spectroscopy (DEER), NMR, and time-resolved pump-probe X-ray solution scattering (TR-SAXS/WAXS). Measurement of distance distributions for doubly spin-labeled photoreceptor constructs using DEER spectroscopy suggests that the signaling state is well ordered and shows that interspin-label distances change reversibly up to 19 Å upon illumination. The SAXS/WAXS difference signal for the signaling state relative to the ground state indicates the transient formation of an ordered and rearranged conformation, which has an increased radius of gyration, an increased maximum dimension, and a reduced excluded volume. Dynamical annealing calculations using the DEER derived long-range distance restraints in combination with short-range distance information from (1)H-(15)N HSQC perturbation spectroscopy give strong indication for a rearrangement that places part of the N-terminal domain in contact with the exposed chromophore binding cleft while the terminal residues extend away from the core. Time-resolved global structural information from pump-probe TR-SAXS/WAXS data supports this conformation and allows subsequent structural refinement that includes the combined energy terms from DEER, NMR, and SAXS/WAXS together. The resulting ensemble simultaneously satisfies all restraints, and the inclusion of TR-SAXS/WAXS effectively reduces the uncertainty arising from the possible spin-label orientations. The observations are essentially compatible with reduced folding of the I(2)' state (also referred to as the 'pB' state) that is widely reported, but indicates it to be relatively ordered and rearranged. Furthermore, there is direct evidence for the repositioning of the N-terminal region in the I(2)' state, which is structurally modeled by dynamical annealing and refinement calculations

Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole

Aims To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min…&lt;1 h, 1 h…&lt;24 h, ≥ 24 h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD. Methods In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in and results each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs ≥6 min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min…&lt;1 h, 99.6% (253/254) for episodes 1 h…&lt;24 h, 100% (71/71) for episodes ≥24 h, or 97.5% for all episodes (595/ 610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA 2DS 2-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF. Conclusion A 99.7% detection accuracy for AHRE ≥1 h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.</p

Chemical Magnetoreception: Bird Cryptochrome 1a Is Excited by Blue Light and Forms Long-Lived Radical-Pairs

Cryptochromes (Cry) have been suggested to form the basis of light-dependent magnetic compass orientation in birds. However, to function as magnetic compass sensors, the cryptochromes of migratory birds must possess a number of key biophysical characteristics. Most importantly, absorption of blue light must produce radical pairs with lifetimes longer than about a microsecond. Cryptochrome 1a (gwCry1a) and the photolyase-homology-region of Cry1 (gwCry1-PHR) from the migratory garden warbler were recombinantly expressed and purified from a baculovirus/Sf9 cell expression system. Transient absorption measurements show that these flavoproteins are indeed excited by light in the blue spectral range leading to the formation of radicals with millisecond lifetimes. These biophysical characteristics suggest that gwCry1a is ideally suited as a primary light-mediated, radical-pair-based magnetic compass receptor