Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

An evaluation of the status of living collections for plant, environmental, and microbial research

Citation: McCluskey, K., Parsons, J. P., Quach, K., & Duke, C. S. (2017). An evaluation of the status of living collections for plant, environmental, and microbial research. Journal of Biosciences, 42(2), 321-331. https://doi.org/10.1007/s12038-017-9685-6While living collections are critical for biological research, support for these foundational infrastructure elements is inconsistent, which makes quality control, regulatory compliance, and reproducibility difficult. In recent years, the Ecological Society of America has hosted several National Science Foundation–sponsored workshops to explore and enhance the sustainability of biological research infrastructure. At the same time, the United States Culture Collection Network has brought together managers of living collections to foster collaboration and information exchange within a specific living collections community. To assess the sustainability of collections, a survey was distributed to collection scientists whose responses provide a benchmark for evaluating the resiliency of these collections. Among the key observations were that plant collections have larger staffing requirements and that living microbe collections were the most vulnerable to retirements or other disruptions. Many higher plant and vertebrate collections have institutional support and several have endowments. Other collections depend on competitive grant support in an era of intense competition for these resources. Opportunities for synergy among living collections depend upon complementing the natural strong engagement with the research communities that depend on these collections with enhanced information sharing, communication, and collective action to keep them sustainable for the future. External efforts by funding agencies and publishers could reinforce the advantages of having professional management of research resources across every discipline. © 2017 Indian Academy of Science

FeCr₂S₄ in magnetic fields: possible evidence for a multiferroic ground state.

We report on neutron diffraction, thermal expansion, magnetostriction, dielectric, and specific heat measurements on polycrystalline FeCr2S4 in external magnetic fields. The ferrimagnetic ordering temperatures TC ≈ 170 K and the transition at TOO ≈ 10 K, which has been associated with orbital ordering, are only weakly shifted in magnetic fields up to 9 T. The cubic lattice parameter is found to decrease when entering the state below TOO. The magnetic moments of the Cr- and Fe-ions are reduced from the spin-only values throughout the magnetically ordered regime, but approach the spin-only values for fields >5.5 T. Thermal expansion in magnetic fields and magnetostriction experiments indicate a contraction of the sample below about 60 K. Below TOO this contraction is followed by a moderate expansion of the sample for fields larger than ~4.5 T. The transition at TOO is accompanied by an anomaly in the dielectric constant. The dielectric constant depends on both the strength and orientation of the external magnetic field with respect to the applied electric field for T < TOO. A linear correlation of the magnetic-field-induced change of the dielectric constant and the magnetic-field dependent magnetization is observed. This behaviour is consistent with the existence of a ferroelectric polarization and a multiferroic ground state below 10 K

Using a Clinic-based Screening Tool for Primary Care Providers to Identify Commercially Sexually Exploited Children

Introduction: Commercial Sexual Exploitation of Children (CSEC), which encompasses acts of domestic minor sex trafficking, is a hidden problem in the U.S. that affects an estimated 300,000 children. Significant health impacts to victims include violence, substance abuse, mental illness, sexually transmitted diseases, and unintended pregnancy. However, due to the covert nature of sexual exploitation, the lack of understanding among service providers and law enforcement, and complex psychological factors experienced by victims, identifying CSEC is a tremendous challenge. Primary care providers can play a critical role in identifying CSEC victims within clinical settings to help address this silent epidemic. Objective: The goal of this project was to assess the prevalence of CSEC using a clinic-based screening tool within a community health center serving indigent populations, with a large proportion of the patients being of Asian and Pacific Islander descent. Methods: Medical charts were reviewed of young female patients (n=621) between 13-23 years of age and seeking clinical services in Asian Health Services’ Teen Clinic from 2008 through 2011, during the implementation of a clinic-based CSEC screening tool used by primary care providers. The CSEC screening tool consists of two questions about sexual exploitation. Results: Of the 621 patients in the study, 57.5% were Asian and Pacific Islander. Clinical providers applied the CSEC screening tool on 28.5% (n=177) of female patients in the study. Of the 177 patients who were screened, 7.3% (n=13) responded positive to questions about commercial sexual exploitation. Discussion: Using a clinic-based screening tool with patients who have identified risk factors helps primary care providers identify CSEC victims and link them to available resources. Under-reporting among victims and under-screening among providers remain major considerations in estimating CSEC prevalence. To address under-screening, it is important to raise awareness among primary care providers around the CSEC epidemic and their potential role for intervention, including screening for a history of sexual exploitation among youth patients

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

ObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis.MethodsGWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes.ResultsMIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility

Genome-wide analysis of transposon and retroviral insertions reveals preferential integrations in regions of DNA flexibility

DNA transposons and retroviruses are important transgenic tools for genome engineering. An important consideration affecting the choice of transgenic vector is their insertion site preferences. Previous large-scale analyses of Ds transposon integration sites in plants were done on the basis of reporter gene expression or germline transmission, making it difficult to discern vertebrate integration preferences. Here, we compare over 1300 Ds transposon integration sites in zebrafish, with Tol2 transposon and retroviral integration sites. Genome-wide analysis shows that Ds integration sites in the presence or absence of marker selection are remarkably similar and distributed throughout the genome. No strict motif was found, but a preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift and Slide) was observed. Remarkably, this feature is also found in transposon and retroviral integrations in maize and mouse cells. Our findings show that structural features influence integration of heterologous DNA in genomes, and have implications for targeted genome engineering

Mechanical properties in crumple-formed paper derived materials subjected to compression

The crumpling of precursor materials to form dense three dimensional geometries offers an attractive route towards the utilisation of minor-value waste materials. Crumple-forming results in a mesostructured system in which mechanical properties of the material are governed by complex cross-scale deformation mechanisms. Here we investigate the physical and mechanical properties of dense compacted structures fabricated by the confined uniaxial compression of a cellulose tissue to yield crumpled mesostructuring. A total of 25 specimens of various densities were tested under compression. Crumple formed specimens exhibited densities in the range 0.8–1.3 g cm−3, and showed high strength to weight characteristics, achieving ultimate compressive strength values of up to 200 MPa under both quasi-static and high strain rate loading conditions and deformation energy that compares well to engineering materials of similar density. The materials fabricated in this work and their mechanical attributes demonstrate the potential of crumple-forming approaches in the fabrication of novel energy-absorbing materials from low-cost precursors such as recycled paper. Stiffness and toughness of the materials exhibit density dependence suggesting this forming technique further allows controllable impact energy dissipation rates in dynamic applications

Flight Tests of a Remaining Flying Time Prediction System for Small Electric Aircraft in the Presence of Faults

This paper addresses the problem of building trust in the online prediction of a battery powered aircraft's remaining flying time. A series of flight tests is described that make use of a small electric powered unmanned aerial vehicle (eUAV) to verify the performance of the remaining flying time prediction algorithm. The estimate of remaining flying time is used to activate an alarm when the predicted remaining time is two minutes. This notifies the pilot to transition to the landing phase of the flight. A second alarm is activated when the battery charge falls below a specified limit threshold. This threshold is the point at which the battery energy reserve would no longer safely support two repeated aborted landing attempts. During the test series, the motor system is operated with the same predefined timed airspeed profile for each test. To test the robustness of the prediction, half of the tests were performed with, and half were performed without, a simulated powertrain fault. The pilot remotely engages a resistor bank at a specified time during the test flight to simulate a partial powertrain fault. The flying time prediction system is agnostic of the pilot's activation of the fault and must adapt to the vehicle's state. The time at which the limit threshold on battery charge is reached is then used to measure the accuracy of the remaining flying time predictions. Accuracy requirements for the alarms are considered and the results discussed

Verification of Prognostic Algorithms to Predict Remaining Flying Time for Electric Unmanned Vehicles

This paper addresses the problem of building trust in the online prediction of a eUAVs remaining available flying time powered by lithium-ion polymer batteries. A series of ground tests are described that make use of an electric unmanned aerial vehicle (eUAV) to verify the performance of remaining flying time predictions. The algorithm verification procedure described is implemented on a fully functional vehicle that is restrained to a platform for repeated run-to-functional-failure (charge depletion) experiments. The vehicle under test is commanded to follow a predefined propeller RPM profile in order to create battery demand profiles similar to those expected during flight. The eUAV is repeatedly operated until the charge stored in powertrain batteries falls below a specified limit threshold. The time at which the limit threshold on battery charge is crossed is then used to measure the accuracy of the remaining flying time prediction. In our earlier work battery aging was not included. In this work we take into account aging of the batteries where the parameters were updated to make predictions. Accuracy requirements are considered for an alarm that warns operators when remaining flying time is estimated to fall below the specified limit threshold