An exploratory study of engagement in a technology-supported substance abuse intervention

BACKGROUND: The continuing gap between the number of people requiring treatment for substance use disorders and those receiving treatment suggests the need to develop new approaches to service delivery. Meanwhile, the use of technology to provide counseling and support in the substance abuse field is exploding. Despite the increase in the use of technology in treatment, little is known about the impact of technology-supported interventions on access to services for substance use disorders. The E-TREAT intervention brings together the evidence-based practice of Motivational Interviewing and theories of Persuasive Technology to sustain clients' motivation to change substance use behaviors, provide support for change, and facilitate continuity across treatment settings. METHODS: This study used descriptive statistics, tests of statistical significance, and logistic regression to explore the characteristics and perceptions of the first 157 people who agreed to participate in E-TREAT and the predictors of their active engagement in E-TREAT services. In addition, responses to open-ended questions about the participants' experiences with the intervention were analyzed. RESULTS: The data reveal that clients who engaged in E-TREAT were more likely than those who did not engage to be female, have children and report a positive relationship with their recovery coach, and were less likely to have completed treatment for a substance use disorder in the past. A majority of people engaging in E-TREAT reported that it was helpful to talk with others with similar problems and that the program assisted them in developing a sense of community. CONCLUSIONS: The authors conclude that technology-assisted interventions hold promise in expanding access to treatment for substance use disorders especially for women and parents. Further, the characteristics of the relationship with a coach or helper may be critical to engagement in technology-supported interventions. Additional investigation into ways technology may be useful to enhance treatment access for certain subgroups is needed

Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe

Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency ☆

Triosephosphate isomerase (TPI) is a glycolytic enzyme which homodimerizes for full catalytic activity. Mutations of the TPI gene elicit a disease known as TPI Deficiency, a glycolytic enzymopathy noted for its unique severity of neurological symptoms. Evidence suggests that TPI Deficiency pathogenesis may be due to conformational changes of the protein, likely affecting dimerization and protein stability. In this report, we genetically and physically characterize a human disease-associated TPI mutation caused by an I170V substitution. Human TPI I170V elicits behavioral abnormalities in Drosophila. An examination of hTPI I170V enzyme kinetics revealed this substitution reduced catalytic turnover, while assessments of thermal stability demonstrated an increase in enzyme stability. The crystal structure of the homodimeric I170V mutant reveals changes in the geometry of critical residues within the catalytic pocket. Collectively these data reveal new observations of the structural and kinetic determinants of TPI Deficiency pathology, providing new insights into disease pathogenesis

A multi-decade record of high quality fCO2 data in version 3 of the Surface Ocean CO2 Atlas (SOCAT)

The Surface Ocean CO2 Atlas (SOCAT) is a synthesis of quality-controlled fCO2 (fugacity of carbon dioxide) values for the global surface oceans and coastal seas with regular updates. Version 3 of SOCAT has 14.7 million fCO2 values from 3646 data sets covering the years 1957 to 2014. This latest version has an additional 4.6 million fCO2 values relative to version 2 and extends the record from 2011 to 2014. Version 3 also significantly increases the data availability for 2005 to 2013. SOCAT has an average of approximately 1.2 million surface water fCO2 values per year for the years 2006 to 2012. Quality and documentation of the data has improved. A new feature is the data set quality control (QC) flag of E for data from alternative sensors and platforms. The accuracy of surface water fCO2 has been defined for all data set QC flags. Automated range checking has been carried out for all data sets during their upload into SOCAT. The upgrade of the interactive Data Set Viewer (previously known as the Cruise Data Viewer) allows better interrogation of the SOCAT data collection and rapid creation of high-quality figures for scientific presentations. Automated data upload has been launched for version 4 and will enable more frequent SOCAT releases in the future. High-profile scientific applications of SOCAT include quantification of the ocean sink for atmospheric carbon dioxide and its long-term variation, detection of ocean acidification, as well as evaluation of coupled-climate and ocean-only biogeochemical models. Users of SOCAT data products are urged to acknowledge the contribution of data providers, as stated in the SOCAT Fair Data Use Statement. This ESSD (Earth System Science Data) “living data” publication documents the methods and data sets used for the assembly of this new version of the SOCAT data collection and compares these with those used for earlier versions of the data collection (Pfeil et al., 2013; Sabine et al., 2013; Bakker et al., 2014). Individual data set files, included in the synthesis product, can be downloaded here: doi:10.1594/PANGAEA.849770. The gridded products are available here: doi:10.3334/CDIAC/OTG.SOCAT_V3_GRID

Measurement of Directional Wave Spectra Using Aircraft Laser Altimeters

A remote sensing method to measure directional oceanic surface waves by three laser altimeters on the NOAA LongEZ aircraft is investigated. To examine feasibility and sensitivity of the wavelet analysis method to various waves, aircraft motions, and aircraft flight directions relative to wave propagation directions, idealized surface waves are simulated from various idealized aircraft flights. In addition, the wavelet analysis method is also applied to two cases from field measurements, and the results are compared with traditional wave spectra from buoys. Since the wavelet analysis method relies on the “wave slopes” measured through phase differences between the time series of the laser distances between the aircraft and sea surface at spatially separated locations, the resolved directional wavenumber and wave propagation direction are not affected by aircraft motions if the resolved frequencies of the aircraft motion and the wave are not the same. However, the encounter wave frequency, which is directly resolved using the laser measurement from the moving aircraft, is affected by the Doppler shift due to aircraft motion relative to wave propagations. The wavelet analysis method could fail if the aircraft flies in the direction such that the aircraft speed along the wave propagation direction is the same as the wave phase speed (i.e., the aircraft flies along wave crests or troughs) or if two waves with different wavelengths and phase speed have the same encountered wavelength from the aircraft. In addition, the data noise due to laser measurement uncertainty or natural isotropic surface elevation perturbations can also affect the relative phase difference between the laser distance measurements, which in turn affects the accuracy of the resolved wavenumber and wave propagation direction. The smallest waves measured by the lasers depend on laser sampling rate and horizontal distances between the lasers (for the LongEZ this is 2 m). The resolved wave direction and wavenumber at the peak wave from the two field experiments compared well with on-site buoy observations. Overall, the study demonstrates that three spatially separated laser altimeters on moving platforms can be utilized to resolve two-dimensional wave spectra

Mutant Versions of the S. cerevisiae Transcription Elongation Factor Spt16 Define Regions of Spt16 That Functionally Interact with Histone H3

In eukaryotic cells, the highly conserved FACT (FAcilitates Chromatin Transcription) complex plays important roles in several chromatin-based processes including transcription initiation and elongation. During transcription elongation, the FACT complex interacts directly with nucleosomes to facilitate histone removal upon RNA polymerase II (Pol II) passage and assists in the reconstitution of nucleosomes following Pol II passage. Although the contribution of the FACT complex to the process of transcription elongation has been well established, the mechanisms that govern interactions between FACT and chromatin still remain to be fully elucidated. Using the budding yeast Saccharomyces cerevisiae as a model system, we provide evidence that the middle domain of the FACT subunit Spt16 – the Spt16-M domain – is involved in functional interactions with histone H3. Our results show that the Spt16-M domain plays a role in the prevention of cryptic intragenic transcription during transcription elongation and also suggest that the Spt16-M domain has a function in regulating dissociation of Spt16 from chromatin at the end of the transcription process. We also provide evidence for a role for the extreme carboxy terminus of Spt16 in functional interactions with histone H3. Taken together, our studies point to previously undescribed roles for the Spt16 M-domain and extreme carboxy terminus in regulating interactions between Spt16 and chromatin during the process of transcription elongation

Autonomous Seawater \u3ci\u3ep\u3c/i\u3eCO\u3csub\u3e2\u3c/sub\u3e and pH Time Series From 40 Surface Buoys and the Emergence of Anthropogenic Trends

Ship-based time series, some now approaching over 3 decades long, are critical climate records that have dramatically improved our ability to characterize natural and anthropogenic drivers of ocean carbon dioxide (CO2) uptake and biogeochemical processes. Advancements in autonomous marine carbon sensors and technologies over the last 2 decades have led to the expansion of observations at fixed time series sites, thereby improving the capability of characterizing sub-seasonal variability in the ocean. Here , we present a data product of 40 individual autonomous moored surface ocean pCO2 (partial pressure of CO2) time series established between 2004 and 2013, 17 also include autonomous pH measurements. These time series characterie a wide range of surface ocean carbonate conditions in diffferent oceanic (17 sites), coastal (13 sites), and coral reef (10 sites) regimes. A time of trend emergence (ToE) methodology applied ot the time series that exhibit well-constrained daily to interannual variability and an estimate of decadal variability indicates that the length of sustained observations necessary to detect statistically significant anthropogenic trends varies by marine environment. The ToE estisites, and 9 to 22 years at the coral reef sites. Only two open ocean pCO2 and pH range from 8 to 15 years at the open ocean sites, 16 to 41 years at the coastal sites, and 9 to 22 years at the coral reef sites. Only two open ocean pCO2 time series, Woods Hole Oceanographic Institution Hawaii Ocean Time-series Station (WHOTS) in the subtropical North Pacific and Stratus n the South Pacific gyre, have been deployed longer than the estimated trend detection time and, for these, deseasoned monthly means show estimated anthropogenic trends of 1.9 ± 0.3 and 1.6 ± 0.3 μatm yr-1, respectively. In the future, it is possible that updates to this product will allow for the estimation of anthropogenic trends at more sites; however, the product currently provides a valuable tool in an accessible format for evaluating climatology and natural variability of surface ocean carbonate chemistry in a variety of regions. Data are available at https://doi.org/10.7289/V5DB8043 and https://www.nodc.noaa.gov/ocads/oceans/Moorings/ndp097.html (Sutton et al., 2018)

Optimum satellite remote sensing of the marine carbonate system using empirical algorithms in the global ocean, the Greater Caribbean, the Amazon Plume and the Bay of Bengal

Improving our ability to monitor ocean carbonate chemistry has become a priority as the ocean continues to absorb carbon dioxide from the atmosphere. This long-term uptake is reducing the ocean pH; a process commonly known as ocean acidification. The use of satellite Earth Observation has not yet been thoroughly explored as an option for routinely observing surface ocean carbonate chemistry, although its potential has been highlighted. We demonstrate the suitability of using empirical algorithms to calculate total alkalinity (AT) and total dissolved inorganic carbon (CT), assessing the relative performance of satellite, interpolated in situ, and climatology datasets in reproducing the wider spatial patterns of these two variables. Both AT and CT in situ data are reproducible, both regionally and globally, using salinity and temperature datasets, with satellite observed salinity from Aquarius and SMOS providing performance comparable to other datasets for the majority of case studies. Global root mean squared difference (RMSD) between in situ validation data and satellite estimates is 17 μmol kg−1 with bias  < 5 μmol kg−1 for AT and 30 μmol kg−1 with bias  < 10 μmol kg−1 for CT. This analysis demonstrates that satellite sensors provide a credible solution for monitoring surface synoptic scale AT and CT. It also enables the first demonstration of observation-based synoptic scale AT and CT temporal mixing in the Amazon plume for 2010–2016, complete with a robust estimation of their uncertainty

TRAF6 Autoubiquitination-Independent Activation of the NFκB and MAPK Pathways in Response to IL-1 and RANKL

The adapter protein TRAF6 is critical for mediating signal transduction from members of the IL-1R/TLR and TNFR superfamilies. The TRAF6 RING finger domain functions as an ubiquitin E3 ligase capable of generating non-degradative K63-linked ubiquitin chains. It is believed that these chains serve as docking sites for formation of signaling complexes, and that K63-linked autoubiquitination of TRAF6 is essential for formation and activation of a complex involving the kinase TAK1 and its adapters, TAB1 and TAB2. In order to assess independently the E3 ligase and ubiquitin substrate functions of TRAF6, we generated, respectively, RING domain and complete lysine-deficient TRAF6 mutants. We found that while the TRAF6 RING domain is required for activation of TAK1, it is dispensable for interaction between TRAF6 and the TAK1-TAB1-TAB2 complex. Likewise, lysine-deficient TRAF6 was found to interact with the TAK1-TAB1-TAB2 complex, but surprisingly was also found to be fully competent to activate TAK1, as well as NFκB and AP-1 reporters. Furthermore, lysine-deficient TRAF6 rescued IL-1-mediated NFκB and MAPK activation, as well as IL-6 elaboration in retrovirally-rescued TRAF6-deficient fibroblasts. Lysine-deficient TRAF6 also rescued RANKL-mediated NFκB and MAPK activation, and osteoclastogenesis in retrovirally-rescued TRAF6-deficient bone marrow macrophages. While incapable of being ubiquitinated itself, we demonstrate that lysine-deficient TRAF6 remains competent to induce ubiquitination of IKKγ/NEMO. Further, this NEMO modification contributes to TRAF6-mediated activation of NFκB. Collectively, our results suggest that while TRAF6 autoubiquitination may serve as a marker of activation, it is unlikely to underpin RING finger-dependent TRAF6 function

An update to the Surface Ocean CO₂ Atlas (SOCAT version 2)

The Surface Ocean CO₂ Atlas (SOCAT), an activity of the international marine carbon research community, provides access to synthesis and gridded fCO₂ (fugacity of carbon dioxide) products for the surface oceans. Version 2 of SOCAT is an update of the previous release (version 1) with more data (increased from 6.3 million to 10.1 million surface water fCO₂ values) and extended data coverage (from 1968–2007 to 1968–2011). The quality control criteria, while identical in both versions, have been applied more strictly in version 2 than in version 1. The SOCAT website (http://www.socat.info/) has links to quality control comments, metadata, individual data set files, and synthesis and gridded data products. Interactive online tools allow visitors to explore the richness of the data. Applications of SOCAT include process studies, quantification of the ocean carbon sink and its spatial, seasonal, year-to-year and longerterm variation, as well as initialisation or validation of ocean carbon models and coupled climate-carbon models