SVOP Is a Nucleotide Binding Protein

Background: Synaptic Vesicle Protein 2 (SV2) and SV2-related protein (SVOP) are transporter-like proteins that localize to neurotransmitter-containing vesicles. Both proteins share structural similarity with the major facilitator (MF) family of small molecule transporters. We recently reported that SV2 binds nucleotides, a feature that has also been reported for another MF family member, the human glucose transporter 1 (Glut1). In the case of Glut1, nucleotide binding affects transport activity. In this study, we determined if SVOP also binds nucleotides and assessed its nucleotide binding properties. Methodology/Principal Findings: We performed in vitro photoaffinity labeling experiments with the photoreactive ATP analogue, 8-azido-ATP[c] biotin and purified recombinant SVOP-FLAG fusion protein. We found that SVOP is a nucleotide-binding protein, although both its substrate specificity and binding site differ from that of SV2. Within the nucleotides tested, ATP, GTP and NAD show same level of inhibition on SVOP-FLAG labeling. Dose dependent studies indicated that SVOP demonstrates the highest affinity for NAD, in contrast to SV2, which binds both NAD and ATP with equal affinity. Mapping of the binding site revealed a single region spanning transmembrane domains 9–12, which contrasts to the two binding sites in the large cytoplasmic domains in SV2A. Conclusions/Significance: SVOP is the third MF family member to be found to bind nucleotides. Given that the binding sites are unique in SVOP, SV2 and Glut1, this feature appears to have arisen separately

Parallel molecular routes to cold adaptation in eight genera of New Zealand stick insects.

The acquisition of physiological strategies to tolerate novel thermal conditions allows organisms to exploit new environments. As a result, thermal tolerance is a key determinant of the global distribution of biodiversity, yet the constraints on its evolution are not well understood. Here we investigate parallel evolution of cold tolerance in New Zealand stick insects, an endemic radiation containing three montane-occurring species. Using a phylogeny constructed from 274 orthologous genes, we show that stick insects have independently colonized montane environments at least twice. We compare supercooling point and survival of internal ice formation among ten species from eight genera, and identify both freeze tolerance and freeze avoidance in separate montane lineages. Freeze tolerance is also verified in both lowland and montane populations of a single, geographically widespread, species. Transcriptome sequencing following cold shock identifies a set of structural cuticular genes that are both differentially regulated and under positive sequence selection in each species. However, while cuticular proteins in general are associated with cold shock across the phylogeny, the specific genes at play differ among species. Thus, while processes related to cuticular structure are consistently associated with adaptation for cold, this may not be the consequence of shared ancestral genetic constraints

Drivers and Socioeconomic Impacts of Tourism Participation in Protected Areas

Nature-based tourism has the potential to enhance global biodiversity conservation by providing alternative livelihood strategies for local people, which may alleviate poverty in and around protected areas. Despite the popularity of the concept of nature-based tourism as an integrated conservation and development tool, empirical research on its actual socioeconomic benefits, on the distributional pattern of these benefits, and on its direct driving factors is lacking, because relevant long-term data are rarely available. In a multi-year study in Wolong Nature Reserve, China, we followed a representative sample of 220 local households from 1999 to 2007 to investigate the diverse benefits that these households received from recent development of nature-based tourism in the area. Within eight years, the number of households directly participating in tourism activities increased from nine to sixty. In addition, about two-thirds of the other households received indirect financial benefits from tourism. We constructed an empirical household economic model to identify the factors that led to household-level participation in tourism. The results reveal the effects of local households' livelihood assets (i.e., financial, human, natural, physical, and social capitals) on the likelihood to participate directly in tourism. In general, households with greater financial (e.g., income), physical (e.g., access to key tourism sites), human (e.g., education), and social (e.g., kinship with local government officials) capitals and less natural capital (e.g., cropland) were more likely to participate in tourism activities. We found that residents in households participating in tourism tended to perceive more non-financial benefits in addition to more negative environmental impacts of tourism compared with households not participating in tourism. These findings suggest that socioeconomic impact analysis and change monitoring should be included in nature-based tourism management systems for long-term sustainability of protected areas

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways

<p>Abstract</p> <p>Background</p> <p>Synthetic peptides containing the RGD sequence inhibit integrin-related functions in different cell systems. Here, we investigated the effects of synthetic Arg-Gly-Asp-Ser (RGDS) peptide on key inflammatory responses to intratracheal (<it>i.t.</it>) lipopolysaccharide (LPS) treatment and on the integrin signaled mitogen-activated protein (MAP) kinase pathway during the development of acute lung injury.</p> <p>Methods</p> <p>Saline or LPS (1.5 mg/kg) was administered <it>i.t. </it>with or without a single dose of RGDS (1, 2.5, or 5 mg/kg, i.p.), anti-α_vor anti-β₃mAb (5 mg/kg, i.p.). Mice were sacrificed 4 or 24 h post-LPS.</p> <p>Results</p> <p>A pretreatment with RGDS inhibited LPS-induced increases in neutrophil and macrophage numbers, total protein levels and TNF-α and MIP-2 levels, and matrix metalloproteinase-9 activity in bronchoalveolar lavage (BAL) fluid at 4 or 24 h post-LPS treatment. RGDS inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue. Importantly, the inhibition of the inflammatory responses and the kinase pathways were still evident when this peptide was administered 2 h after LPS treatment. Similarly, a blocking antibody against integrin α_vsignificantly inhibited LPS-induced inflammatory cell migration into the lung, protein accumulation and proinflammatory mediator production in BAL fluid, at 4 or 24 h post-LPS. Anti-β₃also inhibited all LPS-induced inflammatory responses, except the accumulation of BAL protein at 24 h post-LPS.</p> <p>Conclusion</p> <p>These results suggest that RGDS with high specificity for α_vintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.</p

Impact of a workplace 'sit less, move more' program on efficiency-related outcomes of office employees.

BACKGROUND: Few studies have examined the impact of 'sit less, move more' interventions on workplace performance. This study assessed the short and mid-term impacts of and patterns of change within, a 19-week workplace web-based intervention (Walk@WorkSpain; W@WS; 2010-11) on employees´ presenteeism, mental well-being and lost work performance. METHODS: A site randomised control trial recruited employees at six Spanish university campuses (n = 264; 42 ± 10 years; 171 female), assigned by worksite and campus to an Intervention (IG; used W@WS; n = 129; 87 female) or an active Comparison group (A-CG; pedometer, paper diary and self-reported sitting time; n = 135; 84 female). A linear mixed model assessed changes between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for the IG versus A-CG on (i) % of lost work productivity (Work Limitations Questionnaire; WLQ); (ii) three scales for presenteeism (WLQ) assessing difficulty meeting scheduling demands (Time), performing cognitive and inter-personal tasks (Mental-Interpersonal) and decrements in meeting the quantity, quality and timeliness of completed work (Output); and (iii) mental well-being (Warwick-Edinburgh Mental Well-being Scale). T-tests assessed differences between groups for changes on the main outcomes. In the IG, a multivariate logistic regression model identified patterns of response according to baseline socio-demographic variables, physical activity and sitting time. RESULTS: There was a significant 2 (group) × 2 (program time points) interaction for the Time (F [3]=8.69, p = 0.005), Mental-Interpersonal (F [3]=10.01, p = 0.0185), Output scales for presenteeism (F [3]=8.56, p = 0.0357), and for % of lost work performance (F [3]=10.31, p = 0.0161). Presenteeism and lost performance rose significantly in both groups across all study time points; after baseline performance was consistently better in the IG than in the A-CG. Better performance was linked to employees being more active (Time, p = 0.041) and younger (Mental-interpersonal, p = 0.057; Output, p = 0.017). Higher total sitting time during nonworking days (Mental-interpersonal, p = 0.019) and lower sitting time during workdays (WLQ Index, p = 0.013) also improved performance. CONCLUSION: Versus an active comparison condition, a 'sit less, move more` workplace intervention effectively reduced an array of markers of lost workday productivity. TRIAL REGISTRATION: NCT02960750 ; Date of registration: 07/11/2016

Comparison of foot orthoses made by podiatrists, pedorthists and orthotists regarding plantar pressure reduction in The Netherlands

BACKGROUND: There is a need for evidence of clinical effectiveness of foot orthosis therapy. This study evaluated the effect of foot orthoses made by ten podiatrists, ten pedorthists and eleven orthotists on plantar pressure and walking convenience for three patients with metatarsalgia. Aims were to assess differences and variability between and within the disciplines. The relationship between the importance of pressure reduction and the effect on peak pressure was also evaluated. METHODS: Each therapist examined all three patients and was asked to rate the 'importance of pressure reduction' through a visual analogue scale. The orthoses were evaluated twice in two sessions while the patient walked on a treadmill. Plantar pressures were recorded with an in-sole measuring system. Patients scored walking convenience per orthosis. The effects of the orthoses on peak pressure reduction were calculated for the whole plantar surface of the forefoot and six regions: big toe and metatarsal one to five. RESULTS: Within each discipline there was an extensive variation in construction of the orthoses and achieved peak pressure reductions. Pedorthists and orthotists achieved greater maximal peak pressure reductions calculated over the whole forefoot than podiatrists: 960, 1020 and 750 kPa, respectively (p < .001). This was also true for the effect in the regions with the highest baseline peak pressures and walking convenience rated by patients A and B. There was a weak relationship between the 'importance of pressure reduction' and the achieved pressure reduction for orthotists, but no relationship for podiatrists and pedorthotists. CONCLUSION: The large variation for various aspects of foot orthoses therapy raises questions about a consistent use of concepts for pressures management within the professional groups

Dimensional and hierarchical models of depression using the Beck Depression Inventory-II in an Arab college student sample

Abstract Background An understanding of depressive symptomatology from the perspective of confirmatory factor analysis (CFA) could facilitate valid and interpretable comparisons across cultures. The objectives of the study were: (i) using the responses of a sample of Arab college students to the Beck Depression Inventory (BDI-II) in CFA, to compare the "goodness of fit" indices of the original dimensional three-and two-factor first-order models, and their modifications, with the corresponding hierarchical models (i.e., higher - order and bifactor models); (ii) to assess the psychometric characteristics of the BDI-II, including convergent/discriminant validity with the Hopkins Symptom Checklist (HSCL-25). Method Participants (N = 624) were Kuwaiti national college students, who completed the questionnaires in class. CFA was done by AMOS, version 16. Eleven models were compared using eight "fit" indices. Results In CFA, all the models met most "fit" criteria. While the higher-order model did not provide improved fit over the dimensional first - order factor models, the bifactor model (BFM) had the best fit indices (CMNI/DF = 1.73; GFI = 0.96; RMSEA = 0.034). All regression weights of the dimensional models were significantly different from zero (P Conclusion The broadly adequate fit of the various models indicates that they have some merit and implies that the relationship between the domains of depression probably contains hierarchical and dimensional elements. The bifactor model is emerging as the best way to account for the clinical heterogeneity of depression. The psychometric characteristics of the BDI-II lend support to our CFA results.</p