Nitromusk and Polycyclic Musk Compounds as Long-Term Inhibitors of Cellular Xenobiotic Defense Systems Mediated by Multidrug Transporters

Synthetic musk compounds, widely used as fragrances in consumer products, have been detected in human tissue and, surprisingly, in aquatic organisms such as fish and mollusks. Although their persistence and potential to bioaccumulate are of concern, the toxicity and environmental risks of these chemicals are generally regarded as low. Here, however, we show that nitromusks and polycyclic musks inhibit the activity of multidrug efflux transporters responsible for multixenobiotic resistance (MXR) in gills of the marine mussel Mytilus californianus. The IC(10) (concentration that inhibits 10%) values for the different classes of musks were in the range of 0.09–0.39 μM, and IC(50) values were 0.74–2.56 μM. The immediate consequence of inhibition of efflux transporters is that normally excluded xenobiotics will now be able to enter the cell. Remarkably, the inhibitory effects of a brief 2-hr exposure to musks were only partially reversed after a 24- to 48-hr recovery period in clean seawater. This unexpected consequence of synthetic musks—a long-term loss of efflux transport activity—will result in continued accumulation of normally excluded toxicants even after direct exposure to the musk has ended. These findings also point to the need to determine whether other environmental chemicals have similar long-term effects on these transporters. The results are relevant to human health because they raise the possibility that exposure to common xenobiotics and pharmaceuticals could cause similar long-term inhibition of these transporters and lead to increased exposure to normally excluded toxicants

Two-Dimensional Pulsed TRIPLE at 95 GHz

The one-dimensional (1D) pulsed TRIPLE resonance experiment, introduced by Mehring et al. (M. Mehring, P. Höfer, and A. Grupp, Ber. Bunseges. Phys. Chem. 91, 1132-1137 (1987)) is a modification of the standard Davies ENDOR experiment where an additional RF π-pulse is applied during the mixing time. While the first RF pulse is set to one of the ENDOR transitions, the frequency of the second RF pulse is scanned to generate the TRIPLE spectrum. The difference between this spectrum and the ENDOR spectrum yields the difference TRIPLE spectrum, which exhibits only ENDOR lines that belong to the same Ms manifold as the one selected by the first RF pulse. We have extended this experiment in two dimensions (2D) by sweeping the frequencies of both RF pulses. This experiment is particularly useful when the spectrum is congested and consists of signals originating from different paramagnetic centers. The connectivities between the peaks in the 2D spectrum enable a straightforward assignment of the signals to their respective centers and Ms manifolds, thus providing the relative signs of hyperfine couplings. Carrying out the experiment at high fields has the additional advantage that nuclei with different nuclear gyromagnetic ratios are well separated. This is particularly true for protons which appear at significantly higher frequencies than other nuclei. The feasibility and effectiveness of the experiment is demonstrated at W-band (94.9 GHz) on a crystal of Cu2+-doped L-histidine. Homonuclear 1H-1H, 14N/35Cl-14N/35Cl and heteronuclear 1H-14N/35Cl 2D TRIPLE spectra were measured and from the various connectivities in the 2D map the 1H, 14N, and 35Cl signals that belong to two different Cu2+ centers were identified and grouped according to their Ms manifolds. © 2000 Academic Press

Comparison of pulse sequences for R1-based electron paramagnetic resonance oxygen imaging

© 2015 Elsevier Inc. All rights reserved. Electron paramagnetic resonance (EPR) spin-lattice relaxation (SLR) oxygen imaging has proven to be an indispensable tool for assessing oxygen partial pressure in live animals. EPR oxygen images show remarkable oxygen accuracy when combined with high precision and spatial resolution. Developing more effective means for obtaining SLR rates is of great practical, biological and medical importance. In this work we compared different pulse EPR imaging protocols and pulse sequences to establish advantages and areas of applicability for each method. Tests were performed using phantoms containing spin probes with oxygen concentrations relevant to in vivo oxymetry. We have found that for small animal size objects the inversion recovery sequence combined with the filtered backprojection reconstruction method delivers the best accuracy and precision. For large animals, in which large radio frequency energy deposition might be critical, free induction decay and three pulse stimulated echo sequences might find better practical usage

Resonators ″loop-slot″ for pulse ESR spectrometers of 3 cm range

Constructions of two-loop ″loop-slot″-type resonators for pulse electron paramagnetic resonance spectrometers of 3 cm range are described. The resonators are characterized by 1 GHz frequency tuning and controlled connection with waveguide line. Microwave power which is necessary for optimum echo attainment at the usage of these resonators is shown to be by 10 db less than in a case of usual rectangular resonator

Effects of a Mindfulness-Based Intervention on Distress, Weight Gain, and Glucose Control for Pregnant Low-Income Women: A Quasi-Experimental Trial Using the ORBIT Model.

BackgroundStress can lead to excessive weight gain. Mindfulness-based stress reduction that incorporates mindful eating shows promise for reducing stress, overeating, and improving glucose control. No interventions have tested mindfulness training with a focus on healthy eating and weight gain during pregnancy, a period of common excessive weight gain. Here, we test the effectiveness of such an intervention, the Mindful Moms Training (MMT), on perceived stress, eating behaviors, and gestational weight gain in a high-risk sample of low income women with overweight/obesity.MethodWe conducted a quasi-experimental study assigning 115 pregnant women to MMT for 8 weeks and comparing them to 105 sociodemographically and weight equivalent pregnant women receiving treatment as usual. Our main outcomes included weight gain (primary outcome), perceived stress, and depression.ResultsWomen in MMT showed significant reductions in perceived stress (β = - 0.16) and depressive symptoms (β = - 0.21) compared to the treatment as usual (TAU) control group. Consistent with national norms, the majority of women (68%) gained excessive weight according to Institute of Medicine weight-gain categories, regardless of group. Slightly more women in the MMT group gained below the recommendation. Among secondary outcomes, women in MMT reported increased physical activity (β = 0.26) and had lower glucose post-oral glucose tolerance test (β = - 0.23), being 66% less likely to have impaired glucose tolerance, compared to the TAU group.ConclusionA short-term intervention led to significant improvements in stress, and showed promise for preventing glucose intolerance. However, the majority of women gained excessive weight. A longer more intensive intervention may be needed for this high-risk population. Clinical Trials.gov #NCT01307683

Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals

Investigation of the Stationary and Transient A1·− Radical in Trp → Phe Mutants of Photosystem I

Photosystem I (PS I) contains two symmetric branches of electron transfer cofactors. In both the A- and B-branches, the phylloquinone in the A1 site is π-stacked with a tryptophan residue and is H-bonded to the backbone nitrogen of a leucine residue. In this work, we use optical and electron paramagnetic resonance (EPR) spectroscopies to investigate cyanobacterial PS I complexes, where these tryptophan residues are changed to phenylalanine. The time-resolved optical data show that backward electron transfer from the terminal electron acceptors to P700·+ is affected in the A- and B-branch mutants, both at ambient and cryogenic temperatures. These results suggest that the quinones in both branches take part in electron transport at all temperatures. The electron-nuclear double resonance (ENDOR) spectra of the spin-correlated radical pair P700·+A1·− and the photoaccumulated radical anion A1·−, recorded at cryogenic temperature, allowed the identification of characteristic resonances belonging to protons of the methyl group, some of the ring protons and the proton hydrogen-bonded to phylloquinone in the wild type and both mutants. Significant changes in PS I isolated from the A-branch mutant are detected, while PS I isolated from the B-branch mutant shows the spectral characteristics of wild-type PS I. A possible short-lived B-branch radical pair cannot be detected by EPR due to the available time resolution; therefore, only the A-branch quinone is observed under conditions typically employed for EPR and ENDOR spectroscopies

Spectrometer manager: A versatile control software for pulse EPR spectrometers

A versatile control software for pulse EPR spectrometers is introduced. Common and task-specific problems are discussed and their solutions are described. The software provides the full spectrum of possibilities needed to perform arbitrary multidimensional pulse experiments. It allows for an easy interfacing of commonly used hardware components and enables straightforward modifications of the spectrometer. Good performance, configurability, and a number of unique features turn this software into an excellent tool for the operation of modern EPR spectrometers and upgrading old ones. © 2005 Wiley Periodicals, Inc

The association between socio-demographic characteristics and adherence to breast and colorectal cancer screening: Analysis of large sub populations

<p>Abstract</p> <p>Background</p> <p>Populations having lower socioeconomic status, as well as ethnic minorities, have demonstrated lower utilization of preventive screening, including tests for early detection of breast and colorectal cancer.</p> <p>The objective</p> <p>To explore socio-demographic disparities in adherence to screening recommendations for early detection of cancer.</p> <p>Methods</p> <p>The study was conducted by Maccabi Healthcare Services, an Israeli HMO (health plan) providing healthcare services to 1.9 million members. Utilization of breast cancer (BC) and colorectal cancer (CC) screening were analyzed by socio-economic ranks (SERs), ethnicity (Arab vs non-Arab), immigration status and ownership of voluntarily supplemental health insurance (VSHI).</p> <p>Results</p> <p>Data on 157,928 and 303,330 adults, eligible for BC and CC screening, respectively, were analyzed. Those having lower SER, Arabs, immigrants from Former Soviet Union countries and non-owners of VSHI performed fewer cancer screening examinations compared with those having higher SER, non-Arabs, veterans and owners of VSHI (p < 0.001). Logistic regression model for BC Screening revealed a positive association with age and ownership of VSHI and a negative association with being an Arab and having a lower SER. The model for CC screening revealed a positive association with age and ownership of VSHI and a negative association with being an Arab, having a lower SER and being an immigrant. The model estimated for BC and CC screening among females revealed a positive association with age and ownership of VSHI and a negative association with being an Arab, having a lower SER and being an immigrant.</p> <p>Conclusion</p> <p>Patients from low socio-economic backgrounds, Arabs, immigrants and those who do not own supplemental insurance do fewer tests for early detection of cancer. These sub-populations should be considered priority populations for targeted intervention programs and improved resource allocation.</p