Observation of the Magneto-Optic Voigt Effect in a Paramagnetic Diamond Membrane

The magneto-optic Voigt effect is observed in a synthetic diamond membrane with a substitutional nitrogen defect concentration in the order of 200 ppm and a nitrogen-vacancy defect sub-ensemble generated through neutron irradiation and annealing. The measured polarisation rotation in the reflected light is observed to be quadratically proportional to the applied magnetic field and to the incident reflection angle. Additionally, it is observed to be modifiable by illuminating the diamond with a 532 nm laser. Spectral analysis of the reflected light under 532 nm illumination shows a slow narrowing of the spectral distribution, indicating a small increase in the overall magnetisation, as opposed to magnetisation degradation caused by heating. Further analysis of the optical power dependence suggest this may be related to a shift in the spin ensembles charge state equilibrium and, by extension, the resulting ensemble magnetisation.Comment: 6 pages, 5 figure

A device for extraction, manipulation and stretching of DNA from single human chromosomes

We describe the structure and operation of a micro/nanofluidic device in which individual metaphase chromosomes can be isolated and processed without being displaced during exchange of reagents. The change in chromosome morphology as a result of introducing protease into the device was observed by time-lapse imaging; pressure-driven flow was then used to shunt the chromosomal DNA package into a nanoslit. A long linear DNA strand (>1.3 Mbp) was seen to stretch out from the DNA package and along the length of the nanoslit. Delivery of DNA in its native metaphase chromosome package as well as the microfluidic environment prevented DNA from shearing and will be important for preparing ultra-long lengths of DNA for nanofluidic analysis

Structural and dynamics studies of a truncated variant of CI repressor from bacteriophage TP901-1

International audienceThe CI repressor from the temperate bacteriophage TP901-1 consists of two folded domains, an N-terminal helix-turn-helix DNA-binding domain (NTD) and a C-terminal oligomerization domain (CTD), which we here suggest to be further divided into CTD1 and CTD2. Full-length CI is a hexameric protein, whereas a truncated version, CI∆58, forms dimers. We identify the dimerization region of CI∆58 as CTD1 and determine its secondary structure to be helical both within the context of CI∆58 and in isolation. To our knowledge this is the first time that a helical dimerization domain has been found in a phage repressor. We also precisely determine the length of the flexible linker connecting the NTD to the CTD. Using electrophoretic mobility shift assays and native mass spectrometry, we show that CI∆58 interacts with the OL operator site as one dimer bound to both half-sites, and with much higher affinity than the isolated NTD domain thus demonstrating cooperativity between the two DNA binding domains. Finally, using small angle X-ray scattering data and state-of-the-art ensemble selection techniques, we delineate the conformational space sampled by CI∆58 in solution, and we discuss the possible role that the dynamics play in CI-repressor function

Polyautoimmunity in patients with cutaneous lupus erythematosus:A nationwide sex- and age-matched cohort study from Denmark

BACKGROUND: Polyautoimmunity is defined as having 2 or more autoimmune diseases. Little is known about polyautoimmunity in patients with cutaneous lupus erythematosus (CLE).OBJECTIVES: To estimate prevalence and 5-year incidence of non-lupus erythematosus (LE) autoimmune diseases in patients with CLE.METHODS: Patients with CLE were identified In the Danish National Patient Registry and each patient was age- and sex-matched with 10 general population controls. Outcome information on non-LE autoimmune diseases was obtained by register-linkage between Danish National Patient Registry and the National Prescription Register. The risk ratio (RR) for prevalent non-LE autoimmune disease at time of CLE diagnosis was calculated in modified Poisson regression; and hazard ratios (HRs) for incident non-LE autoimmune disease were estimated in Cox regression analyses.RESULTS: Overall, 1674 patients with CLE had a higher prevalence of a non-LE autoimmune disease than the comparators (18.5 vs 7.9%; RR 2.4; 95% CI, 2.1 to 2.6). Correspondingly, the cumulative incidence of a non-LE autoimmune disease during 5 years of follow-up was increased for the patients with CLE: HR 3.5 (95% CI, 3.0 to 4.0).LIMITATIONS: Risk of detection and misclassification bias, mainly pertaining to the CLE group.CONCLUSION: Patients with CLE had higher prevalence and 5-year cumulative incidence of a non-LE autoimmune disease than the general population.</p

Xenobiotic Exposure and Migraine-Associated Signaling:A Multimethod Experimental Study Exploring Cellular Assays in Combination with Ex Vivo and In Vivo Mouse Models

BACKGROUND: Mechanisms for how environmental chemicals might influence pain has received little attention. Epidemiological studies suggest that environmental factors such as pollutants might play a role in migraine prevalence. Potential targets for pollutants are the transient receptor potential (TRP) channels ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), which on activation release pain-inducing neuropeptide calcitonin gene-related peptide (CGRP). OBJECTIVE: In this study, we aimed to examine the hypothesis that environmental pollutants via TRP channel signaling and subsequent CGRP release trigger migraine signaling and pain. METHODS: A calcium imaging-based screen of environmental chemicals was used to investigate activation of migraine pain-associated TRP channels TRPA1 and TRPV1. Based on this screen, whole-cell patch clamp and in silico docking were performed for the pesticide pentachlorophenol (PCP) as proof of concept. Subsequently, PCP-mediated release of CGRP and vasodilatory responses of cerebral arteries were investigated. Finally, we tested whether PCP could induce a TRPA1-dependent induction of cutaneous hypersensitivity in vivo in mice as a model of migraine-like pain. RESULTS: A total of 16 out of the 52 screened environmental chemicals activated TRPA1 at 10 or formula presented . None of the investigated compounds activated TRPV1. Using PCP as a model of chemical interaction with TRPA1, in silico molecular modeling suggested that PCP is stabilized in a lipid-binding pocket of TRPA1 in comparison with TRPV1. In vitro, ex vivo, and in vivo experiments showed that PCP induced calcium influx in neurons and resulted in a TRPA1-dependent CGRP release from the brainstem and dilation of cerebral arteries. In a mouse model of migraine-like pain, PCP induced a TRPA1-dependent increased pain response (formula presented ). DISCUSSION: Here we show that multiple environmental pollutants interact with the TRPA1-CGRP migraine pain pathway. The data provide valuable insights into how environmental chemicals can interact with neurobiology and provide a potential mechanism for putative increases in migraine prevalence over the last decades. https://doi.org/10.1289/EHP12413.</p

Constraints on a Local Group X-ray Halo

A simple model for a hot Local Group halo is constructed, using the standard beta-model for the halo density and by choosing model parameters based on all available observations of X-ray emission in other groups of galaxies and on optical data on Local Group morphology. From the predicted X-ray intensities, total Local Group mass, and central cooling time of the halo, we derive very conservative upper limits on the central halo density N_0 and global temperature T of N_0 = 5e-4 cm-3 and kT = 0.5 keV, irrespective of realistic values of the density profile parameters r_c and beta. A typical poor group value of beta = 0.5 requires kT < 0.15 keV and N_0 < 1e-4 cm-3, from which it is concluded that the Local Group is very unlikely to possess a significant X-ray halo. The prospects for further constraining of halo parameters from UV absorption line observations are considered. We explicitly calculate the ability of the halo to distort the cosmic microwave background (CMB) in terms of the resulting CMB temperature variations and multipole anisotropies.Comment: 24 pages, 16 figures. Accepted for publication in the Astrophysical Journa

Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis

<p>Abstract</p> <p>Background</p> <p>Approximately half of all human genes use alternative transcription start sites (TSSs) to control mRNA levels and broaden the transcriptional output in healthy tissues. Aberrant expression patterns promoting carcinogenesis, however, may arise from alternative promoter usage.</p> <p>Results</p> <p>By profiling 108 colorectal samples using exon arrays, we identified nine genes (<it>TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5</it>, and <it>SCIN</it>) showing tumor-specific alternative TSS usage in both adenoma and cancer samples relative to normal mucosa. Analysis of independent exon array data sets corroborated these findings. Additionally, we confirmed the observed patterns for selected mRNAs using quantitative real-time reverse-transcription PCR. Interestingly, for some of the genes, the tumor-specific TSS usage was not restricted to colorectal cancer. A comprehensive survey of the nine genes in lung, bladder, liver, prostate, gastric, and brain cancer revealed significantly altered mRNA isoform ratios for <it>CHEK1, OSBPL1A</it>, and <it>TCF12 </it>in a subset of these cancer types.</p> <p>To identify the mechanism responsible for the shift in alternative TSS usage, we antagonized the Wnt-signaling pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably led to a shift in the preferred TSS for both <it>OSBPL1A </it>and <it>TRAK1</it>. This indicated a regulatory role of the Wnt pathway in selecting TSS, possibly also involving TP53 and SOX9, as their transcription binding sites were enriched in the promoters of the tumor preferred isoforms together with their mRNA levels being increased in tumor samples.</p> <p>Finally, to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry was used to show deregulation of the total protein levels of both TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore, the level of nuclear TCF12 had a significant correlation to progression free survival in a cohort of 248 stage II colorectal cancer samples.</p> <p>Conclusions</p> <p>Alternative TSS usage in colorectal adenoma and cancer samples has been shown for nine genes, and <it>OSBPL1A </it>and <it>TRAK1 </it>were found to be regulated <it>in vitro </it>by Wnt signaling. TCF12 protein expression was upregulated in cancer samples and correlated with progression free survival.</p

Effectiveness of accelerated perioperative care and rehabilitation intervention compared to current intervention after hip and knee arthroplasty. A before-after trial of 247 patients with a 3-month follow-up

<p>Abstract</p> <p>Background</p> <p>In Denmark, approximately 12,000 hip and knee arthroplasties were performed in 2006, and the hospital costs were close to US$ 110,000,000. In a randomized clinical trial, we have recently demonstrated the efficacy of accelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty compared to current intervention under ideal circumstances. We do not, however, know whether these results could be reached under usual circumstances of healthcare practice. We therefore investigated whether length of stay after implementation of accelerated perioperative care and rehabilitation after hip and knee arthroplasty could be reduced in a normal healthcare setting, and how the achieved results matched those observed during the randomized clinical trial.</p> <p>Methods</p> <p>An effectiveness study as a before-after trial was undertaken in which all elective primary total hip and total knee arthroplasty patients were divided into a before-implementation group receiving the current perioperative procedure, and an after-implementation group receiving the new accelerated perioperative care and rehabilitation procedures as provided by a new multi-disciplinary organization. We used the Breakthrough Series Collaborative Model for implementation. The primary outcome measure was in hospital length of stay (LOS), and the secondary outcome measure was adverse effects within 3 months postoperatively.</p> <p>Results</p> <p>We included a total of 247 patients. Mean LOS was significantly (<it>P </it>< 0.001) reduced by 4.4 (95% CI 3.8–5.0) days after implementation of the accelerated intervention, from 8.8 (SD 3.0) days before implementation to 4.3 (SD 1.8) days after implementation. No significant differences in adverse effects were observed. LOS in this effectiveness study was significantly lower than LOS reported in the efficacy study.</p> <p>Conclusion</p> <p>Accelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty was successfully and effectively implemented. Results obtained during usual hospital circumstances matched the results achieved under ideal circumstances in this group of patients.</p

Severity of self-reported diseases and symptoms in Denmark

OBJECTIVE: To estimate and rank the relative severity of self-reported diseases and symptoms in Denmark. METHOD: The 1994 Danish Health and Morbidity Survey collected data from 5,472 Danes older than 16 years of age. Interviews (response frequency: 79%) gave information on diseases and symptoms; a self-administered SF-36 questionnaire (response frequency: 64%) provided information on health-related quality of life. The severity of diseases and symptoms was represented by the health-related quality of life scores that individuals suffering from particular diseases and symptoms obtained on the single dimensions of the SF-36 and on a combined sum of all dimensions. We applied logistic regression to control for the influence of sex, age and socio-economic status on the SF-36 score. We also analysed the interaction between socio-economic status and diseases on the SF-36 score. RESULTS: Females, more frequently than males, reported on all symptoms and all disease groups except injuries. People with relatively low levels of education reported most diseases, especially musculoskeletal and cardiovascular diseases, more frequently than people with higher education. Age-adjusted mean SF-36 scores for all dimensions combined showed that the symptoms of melancholy/depression and breathing difficulties, psychiatric disorders and respiratory diseases scored lowest (i.e. were most often associated with worse health). Females had lower SF-36 combined scores (worse health) than males on all symptoms. We found interaction between socio-economic status and respiratory diseases and musculoskeletal diseases on the SF-36 score. SF-36 scores also indicated significantly worse health among Danes with low education and income levels compared to those with higher education and income. CONCLUSION: In 1994 the Danes most frequently reported musculoskeletal symptoms and diseases. Psychiatric disorders and respiratory diseases were identified as the most severe reported diseases. Due to the interaction between socio-economic status and some diseases, severity estimates should be interpreted with caution or stratified by socio-economic groups