Mutations in the Arabidopsis Peroxisomal ABC Transporter COMATOSE Allow Differentiation between Multiple Functions In Planta: Insights from an Allelic Series

COMATOSE (CTS), the Arabidopsis homologue of human Adrenoleukodystrophy protein (ALDP), is required for import of substrates for peroxisomal β-oxidation. A new allelic series and a homology model based on the bacterial ABC transporter, Sav1866, provide novel insights into structure-function relations of ABC subfamily D proteins. In contrast to ALDP, where the majority of mutations result in protein absence from the peroxisomal membrane, all CTS mutants produced stable protein. Mutation of conserved residues in the Walker A and B motifs in CTS nucleotide-binding domain (NBD) 1 resulted in a null phenotype but had little effect in NBD2, indicating that the NBDs are functionally distinct in vivo. Two alleles containing mutations in NBD1 outside the Walker motifs (E617K and C631Y) exhibited resistance to auxin precursors 2,4-dichlorophenoxybutyric acid (2,4-DB) and indole butyric acid (IBA) but were wild type in all other tests. The homology model predicted that the transmission interfaces are domain-swapped in CTS, and the differential effects of mutations in the conserved "EAA motif" of coupling helix 2 supported this prediction, consistent with distinct roles for each NBD. Our findings demonstrate that CTS functions can be separated by mutagenesis and the structural model provides a framework for interpretation of phenotypic data

Evaluating Within-Person Change In Implicit Measures Of Alcohol Associations: Increases In Alcohol Associations Predict Increases In Drinking Risk And Vice Versa

Aims: Implicit measures of alcohol associations (i.e. measures designed to assess associations that are fast/reflexive/impulsive) have received substantial research attention. Alcohol associations related to the self (drinking identity), the effects of alcohol (alcohol excite) and appetitive inclinations (alcohol approach) have been found to predict drinking cross-sectionally and over time. A critical next step in this line of research and the goal of this study is to evaluate whether increases in the strength of these associations predict increases in drinking and vice versa. These hypotheses were tested in a sample of first- and second-year US university students: a sample selected because this time period is associated with initiation and escalation of drinking, peak levels of alcohol consumption and severe alcohol-related negative consequences. Short summary: This study's purpose was to evaluate whether increases in the strength of alcohol associations with the self (drinking identity), excitement (alcohol excite) and approach (alcohol approach) as assessed by implicit measures predicted subsequent increases in drinking risk and vice versa using a longitudinal, university student sample. Results were consistent with hypotheses. Methods: A sample of 506 students' (57% women) alcohol associations and alcohol consumption were assessed every 3 months over a 2-year period. Participants' consumption was converted to risk categories based on NIAAA's criteria: non-drinkers, low-risk drinkers and high-risk drinkers. A series of cross-lagged panel models tested whether changes in alcohol associations predicted subsequent change in drinking risk (and vice versa). Results: Across all three measures of alcohol associations, increases in the strength of alcohol associations were associated with subsequent increases in drinking risk and vice versa. Conclusion: Results from this study indicate bi-directional relationships between increases in alcohol associations (drinking identity, alcohol excite and alcohol approach) and subsequent increases in drinking risk. Intervention and prevention efforts may benefit from targeting these associations

Which antidepressants have demonstrated superior efficacy? A review of the evidence

A review of published evidence of superior efficacy of a particular antidepressant in major depressive disorder may assist clinicians in making considered treatment choices. To identify such candidates, an international group of experts met to assess published evidence (identified through searches in Medline and Embase databases and discussions with experts in the field) from randomized, controlled trials and meta-analyses comparing two antidepressants under conditions of fair comparison. Criteria were defined to judge the strength of evidence. Two pivotal studies in moderate-to-severe major depressive disorder that demonstrate superiority on the primary efficacy measure, or alternatively one pivotal study supported by consistent results from meta-analyses, was considered to constitute evidence for definite superiority. Three antidepressants met these criteria: clomipramine, venlafaxine, and escitalopram. Three antidepressants were found to have probable superiority: milnacipran, duloxetine, and mirtazapine. Only escitalopram was found to have definite superiority in the treatment of severe depression; probable superiority was identified for venlafaxine and possible superiority for milnacipran and clomipramine. This review of published data found evidence that only a very few antidepressants are shown to be more effective than other

Modelling Effects of Tariff Liberalisation on India’s Key Export Sectors: Analysis of the EU–India Free Trade Agreement

Trade agreements are increasingly being negotiated between developed and emerging economy partners. An example is the EU–India Free Trade Agreement (FTA) for which negotiations began in 2007. There has been a debate on the potential effects of the proposed FTA and how this can impact on India’s key export sectors. Our study addresses this aspect from a global computable general equilibrium (CGE) modelling perspective. Using the Global Trade Analysis Project (GTAP) framework, we analyse trade and welfare impacts of the proposed FTA between the EU and India. Two scenarios are modelled: first, complete and immediate elimination of tariff on all goods traded and second, selective tariff elimination on textiles, wearing apparel and leather goods—products in which India has a comparative advantage. Results under both scenarios show that India enjoys positive welfare effects though there is a possibility of trade diversion. Under scenario 1, India loses due to a negative terms of trade (ToT) effect. Under scenario 2, with selective sectoral liberalisation, gains are mainly concentrated in the textiles, wearing apparel and leather sectors. There is a positive output effect from change in demand for factors of production, suggesting that the proposed FTA could lead to relocation of labour-intensive production to India

Optical Spectra of SNR Candidates in NGC 300

We present moderate-resolution (<5A) long-slit optical spectra of 51 nebular objects in the nearby Sculptor Group galaxy NGC 300 obtained with the 2.3 meter Advanced Technology Telescope at Siding Spring Observatory, Australia. Adopting the criterion of [SII]/Ha>=0.4 to confirm supernova remnants (SNRs) from optical spectra, we find that of 28 objects previously proposed as SNRs from optical observations, 22 meet this criterion with six showing [SII]/Ha of less than 0.4. Of 27 objects suggested as SNRs from radio data, four are associated with the 28 previously proposed SNRs. Of these four, three (included in the 22 above) meet the criterion. In all, 22 of the 51 nebular objects meet the [SII]/Ha criterion as SNRs while the nature of the remaining 29 objects remains undetermined by these observations.Comment: Accepted for publication in Astrophysics & Space Scienc

Artificial coiled coil biomineralisation protein for the synthesis of magnetic nanoparticles

Green synthesis of precise inorganic nanomaterials is a major challenge. Magnetotactic bacteria biomineralise magnetite nanoparticles (MNPs) within membrane vesicles (magnetosomes), which are embedded with dedicated proteins that control nanocrystal formation. Some such proteins are used in vitro to control MNP formation in green synthesis; however, these membrane proteins self-aggregate, making their production and use in vitro challenging and difficult to scale. Here, we provide an alternative solution by displaying active loops from biomineralisation proteins Mms13 and MmsF on stem-loop coiled-coil scaffold proteins (Mms13cc/MmsFcc). These artificial biomineralisation proteins form soluble, stable alpha-helical hairpin monomers, and MmsFcc successfully controls the formation of MNP when added to magnetite synthesis, regulating synthesis comparably to native MmsF. This study demonstrates how displaying active loops from membrane proteins on coiled-coil scaffolds removes membrane protein solubility issues, while retains activity, enabling a generic approach to readily-expressible, versatile, artificial membrane proteins for more accessible study and exploitation

HI in the Outskirts of Nearby Galaxies

The HI in disk galaxies frequently extends beyond the optical image, and can trace the dark matter there. I briefly highlight the history of high spatial resolution HI imaging, the contribution it made to the dark matter problem, and the current tension between several dynamical methods to break the disk-halo degeneracy. I then turn to the flaring problem, which could in principle probe the shape of the dark halo. Instead, however, a lot of attention is now devoted to understanding the role of gas accretion via galactic fountains. The current $\rm \Lambda$ cold dark matter theory has problems on galactic scales, such as the core-cusp problem, which can be addressed with HI observations of dwarf galaxies. For a similar range in rotation velocities, galaxies of type Sd have thin disks, while those of type Im are much thicker. After a few comments on modified Newtonian dynamics and on irregular galaxies, I close with statistics on the HI extent of galaxies.Comment: 38 pages, 17 figures, invited review, book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres

“We don’t separate out these things. Everything is related”: Partnerships with Indigenous Communities to Design, Implement, and Evaluate Multilevel Interventions to Reduce Health Disparities

Multilevel interventions (MLIs) are appropriate to reduce health disparities among Indigenous peoples because of their ability to address these communities’ diverse histories, dynamics, cultures, politics, and environments. Intervention science has highlighted the importance of context-sensitive MLIs in Indigenous communities that can prioritize Indigenous and local knowledge systems and emphasize the collective versus the individual. This paradigm shift away from individual-level focus interventions to community-level focus interventions underscores the need for community engagement and diverse partnerships in MLI design, implementation, and evaluation. In this paper, we discuss three case studies addressing how Indigenous partners collaborated with researchers in each stage of the design, implementation, and evaluation of MLIs to reduce health disparities impacting their communities. We highlight the following: (1) collaborations with multiple, diverse tribal partners to carry out MLIs which require iterative, consistent conversations over time; (2) inclusion of qualitative and Indigenous research methods in MLIs as a way to honor Indigenous and local knowledge systems as well as a way to understand a health disparity phenomenon in a community; and (3) relationship building, maintenance, and mutual respect among MLI partners to reconcile past research abuses, prevent extractive research practices, decolonize research processes, and generate co-created knowledge between Indigenous and academic communities

Supermassive Binaries and Extragalactic Jets

Some quasars show Doppler shifted broad emission line peaks. I give new statistics of the occurrence of these peaks and show that, while the most spectacular cases are in quasars with strong radio jets inclined to the line of sight, they are also almost as common in radio-quiet quasars. Theories of the origin of the peaks are reviewed and it is argued that the displaced peaks are most likely produced by the supermassive binary model. The separations of the peaks in the 3C 390.3-type objects are consistent with orientation-dependent "unified models" of quasar activity. If the supermassive binary model is correct, all members of "the jet set" (astrophysical objects showing jets) could be binaries.Comment: 31 pages, PostScript, missing figure is in ApJ 464, L105 (see http://www.aas.org/ApJ/v464n2/5736/5736.html