Evaluation of Biased and Balanced Salvinorin A Analogs in Preclinical Models of Pain

This work is licensed under a Creative Commons Attribution 4.0 International License.In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential. Salvinorin A (SalA) is a potent and selective KOPr agonist, however, clinical utility is limited by the short duration of action and aversive side effects. Biasing KOPr signaling toward G-protein activation has been highlighted as a key cellular mechanism to reduce the side effects of KOPr agonists. The present study investigated KOPr signaling bias and the acute antinociceptive effects and side effects of two novel analogs of SalA, 16-Bromo SalA and 16-Ethynyl SalA. 16-Bromo SalA showed G-protein signaling bias, whereas 16-Ethynyl SalA displayed balanced signaling properties. In the dose-response tail-withdrawal assay, SalA, 16-Ethynyl SalA and 16-Bromo SalA were more potent than the traditional KOPr agonist U50,488, and 16-Ethynyl SalA was more efficacious. 16-Ethynyl SalA and 16-Bromo SalA both had a longer duration of action in the warm water tail-withdrawal assay, and 16-Ethynyl had greater antinociceptive effect in the hot-plate assay, compared to SalA. In the intraplantar 2% formaldehyde test, 16-Ethynyl SalA and 16-Bromo SalA significantly reduced both nociceptive and inflammatory pain-related behaviors. Moreover, 16-Ethynyl SalA and 16-Bromo SalA had no anxiogenic effects in the marble burying task, and 16-Bromo SalA did not alter behavior in the elevated zero maze. Overall, 16-Ethynyl SalA significantly attenuated acute pain-related behaviors in multiple preclinical models, while the biased KOPr agonist, 16-Bromo SalA, displayed modest antinociceptive effects, and lacked anxiogenic effects.Health Research Council – Explorer grant (16/646)National Institute on Drug Abuse (DA018151)Victoria University of Wellington doctoral scholarshi

O vrstama zmija u gorju Zapadni Taurus, Turska

A total of 85 specimens belonging to 14 snake species collected from the Western Taurus Mountain Range were examined in this study. Along with morphological information about the species, the study contains some topographical observations concerning the localities. The collection of material from a number of new localities helped efforts to complete missing information related to the distribution of species in this region. Moreover, the data obtained were compared with those contained in the relevant literature with the purpose of shedding light on the taxonomical status of the species.Obrađeno je ukupno 85 primjeraka odnosno 14 vrsta zmija prikupljenih u gorju Zapadni Taurus. Rad donosi morfološke osobitosti vrsta te neka topografska opažanja lokaliteta. Prikupljeni materijal pomogao je upotpuniti nedostatke u poznavanju rasprostranjenja vrsta koje žive u ovoj regiji. Prikupljeni podaci uspoređeni su s relevantnom literaturom u svrhu produbljivanja znanja o taksonomiji vrsta

Mediterranean sea turtles: Current knowledge and priorities for conservation and research

This is the final version. Available on open access from Inter Research via the DOI in this recordThe available information regarding the 2 sea turtle species breeding in the Mediterranean (loggerhead turtle Caretta caretta and green turtle Chelonia mydas) is reviewed, including biometrics and morphology, identification of breeding and foraging areas, ecology and behaviour, abundance and trends, population structure and dynamics, anthropogenic threats and conservation measures. Although a large body of knowledge has been generated, research efforts have been inconsistently allocated across geographic areas, species and topics. Significant gaps still exist, ranging from the most fundamental aspects, such as the distribution of major nesting sites and the total number of clutches laid annually in the region, to more specific topics like age at maturity, survival rates and behavioural ecology, especially for certain areas (e.g. south-eastern Mediterranean). These gaps are particularly marked for the green turtle. The recent positive trends of nest counts at some nesting sites may be the result of the cessation of past exploitation and decades of conservation measures on land, both in the form of national regulations and of continued active protection of clutches. Therefore, the current status should be considered as dependent on such ongoing conservation efforts. Mitigation of incidental catch in fisheries, the main anthropogenic threat at sea, is still in its infancy. From the analysis of the present status a comprehensive list of re search and conservation priorities is proposed.C.C. is supported by the project CTM2013-48163 of the Spanish Ministry of Economy and Competitivity. The Cyprus Wildlife Society (CWS) acknowledges the financial support of the Department of Fisheries and Marine Research of the Government to the CWS for the implementation of the Turtle Conservation Project in the period 2010−2016 and for all its assistance to the Society in previous years. J.T. is supported by project Prometeo II (2015-018) of the Generalitat Valenciana and projects MEDSEALITTER-INTERREG and INDICIT of the European Union

Recoilless Resonant Absorption of Monochromatic Neutrino Beam for Measuring Delta m^2_{31} and theta_{13}

We discuss, in the context of precision measurement of Delta m^2_{31} and theta_{13}, physics capabilities enabled by the recoilless resonant absorption of monochromatic antineutrino beam enhanced by the M\"ossbauer effect recently proposed by Raghavan. Under the assumption of small relative systematic error of a few tenth of percent level between measurement at different detector locations, we give analytical and numerical estimates of the sensitivities to Delta m^2_{31} and sin^2 2theta_{13}. The accuracies of determination of them are enormous; The fractional uncertainty in Delta m^2_{31} achievable by 10 point measurement is 0.6% (2.4%) for sin^2 2theta_{13} = 0.05, and the uncertainty of sin^2 2theta_{13} is 0.002 (0.008) both at 1 sigma CL with the optimistic (pessimistic) assumption of systematic error of 0.2% (1%). The former opens a new possibility of determining the neutrino mass hierarchy by comparing the measured value of Delta m^2_{31} with the one by accelerator experiments, while the latter will help resolving the theta_{23} octant degeneracy.Comment: 23 pages, 3 figures, version to appear in New Journal of Physic

Protein Content and Oil Composition of Almond from Moroccan Seedlings: Genetic Diversity, Oil Quality and Geographical Origin

The protein and oil content and the fatty acid profile of the kernels of selected almond genotypes from four different Moroccan regions were determined in order to evaluate the kernel quality of the plant material of these different regions. The ranges of oil content (48.7–64.5 % of kernel DW), oleic (61.8–80.2 % of total oil), linoleic (11.4–27.0 %), palmitic (5.6–7.7 %), stearic (1.3–3.1 %), and palmitoleic (0.4–0.9 %) acid percentages agreed with previous results of other almond genotypes, but the protein content (14.1–35.1 % of kernel DW) showed that some genotypes had higher values than any previously recorded in almond. Some genotypes from mountainous regions showed kernels with very high oil content as well as high and consistent oleic and linoleic ratio, establishing a possible differentiation according to the geographical origin. These differences may allow establishing a geographical denomination for almond products. In terms of genetic diversity, oleic and linoleic acids were confirmed to be the most variable components of almond oil chemical composition among genotypes. Additionally, the genotypes with extreme favorable values, such as high protein content, could be incorporated into an almond breeding program aiming at an increase in kernel quality.Peer ReviewedPrunus amygdalusProtein contentOil contentFatty acidsQualityGenetic resourcesBreedingPublishe

Expression analysis of Clavata1-like and Nodulin21-like genes from Pinus sylvestris during ectomycorrhiza formation

The ecology and physiology of ectomycorrhizal (EcM) symbiosis with conifer trees are well documented. In comparison, however, very little is known about the molecular regulation of these associations. In an earlier study, we identified three EcM-regulated Pinus expressed sequence tags (EST), two of which were identified as homologous to the Medicago truncatula nodulin MtN21. The third EST was a homologue to the receptor-like kinase Clavata1. We have characterized the expression patterns of these genes and of auxin- and mycorrhiza-regulated genes after induction with indole-3-butyric acid in Pinus sylvestris and in a time course experiment during ectomycorrhizal initiation with the co-inoculation of 2,3,5-triiodobenzoic acid, an auxin transport inhibitor. Our results suggest that different P. sylvestris nodulin homologues are associated with diverse processes in the root. The results also suggest a potential role of the Clv1-like gene in lateral root initiation by the ectomycorrhizal fungus

Network analysis of sea turtle movements and connectivity: A tool for conservation prioritization

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available in the Supplementary Material of this article and Zenodo (https://doi.org/10.5281/zenodo.5898578). Details for all animals included in this study are provided in Appendices S1 and S2. Data used to create the spatial networks are listed in the Appendices S3 and S4. The geospatial files for all networks are available on the Migratory Connectivity in the Ocean Project website (https://mico.eco) and Dryad (https://doi.org/10.5061/dryad.j3tx95xg9). Additional data that support the findings of this study are available from the corresponding author upon reasonable request.Aim Understanding the spatial ecology of animal movements is a critical element in conserving long-lived, highly mobile marine species. Analyzing networks developed from movements of six sea turtle species reveals marine connectivity and can help prioritize conservation efforts. Location Global. Methods We collated telemetry data from 1235 individuals and reviewed the literature to determine our dataset's representativeness. We used the telemetry data to develop spatial networks at different scales to examine areas, connections, and their geographic arrangement. We used graph theory metrics to compare networks across regions and species and to identify the role of important areas and connections. Results Relevant literature and citations for data used in this study had very little overlap. Network analysis showed that sampling effort influenced network structure, and the arrangement of areas and connections for most networks was complex. However, important areas and connections identified by graph theory metrics can be different than areas of high data density. For the global network, marine regions in the Mediterranean had high closeness, while links with high betweenness among marine regions in the South Atlantic were critical for maintaining connectivity. Comparisons among species-specific networks showed that functional connectivity was related to movement ecology, resulting in networks composed of different areas and links. Main conclusions Network analysis identified the structure and functional connectivity of the sea turtles in our sample at multiple scales. These network characteristics could help guide the coordination of management strategies for wide-ranging animals throughout their geographic extent. Most networks had complex structures that can contribute to greater robustness but may be more difficult to manage changes when compared to simpler forms. Area-based conservation measures would benefit sea turtle populations when directed toward areas with high closeness dominating network function. Promoting seascape connectivity of links with high betweenness would decrease network vulnerability.International Climate Initiative (IKI)German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU

Are we working towards global research priorities for management and conservation of sea turtles?

In 2010, an international group of 35 sea turtle researchers refined an initial list of more than 200 research questions into 20 metaquestions that were considered key for management and conservation of sea turtles. These were classified under 5 categories: reproductive biology, biogeography, population ecology, threats and conservation strategies. To obtain a picture of how research is being focused towards these key questions, we undertook a systematic review of the peer-reviewed literature (2014 and 2015) attributing papers to the original 20 questions. In total, we reviewed 605 articles in full and from these 355 (59%) were judged to substantively address the 20 key questions, with others focusing on basic science and monitoring. Progress to answering the 20 questions was not uniform, and there were biases regarding focal turtle species, geographic scope and publication outlet. Whilst it offers some meaningful indications as to effort, quantifying peer-reviewed literature output is ob viously not the only, and possibly not the best, metric for understanding progress towards informing key conservation and management goals. Along with the literature review, an international group based on the original project consortium was assigned to critically summarise recent progress towards answering each of the 20 questions. We found that significant research is being expended towards global priorities for management and conservation of sea turtles. Although highly variable, there has been significant progress in all the key questions identified in 2010. Undertaking this critical review has highlighted that it may be timely to undertake one or more new prioritizing exercises. For this to have maximal benefit we make a range of recommendations for its execution. These include a far greater engagement with social sciences, widening the pool of contributors and focussing the questions, perhaps disaggregating ecology and conservatio

‘Does My Haltung Look Big In This?”: The Use of Social Pedagogical Theory for the Development of Ethical and Value Led Practice

The aim of this article is to set out how the use of social pedagogical Haltung can support the exploration of values and how this informs and shapes a practitioner’s direct work. Haltung is a German concept that has no direct English translation but means ‘mind set’, ‘ethos’ or ‘attitude’ (Eichsteller, 2010) and relates to an individual’s value base. Mührel’s (2008, cited in Eichsteller, 2010), sets out that a social pedagogical Haltung is based on the two concepts of empathic understanding and regard. This paper argues that the use of a social pedagogical Haltung gives practitioners a philosophical framework to support the reflection of core values and ethics held on a personal level. It also supports an understanding of how these influence practitioners and students when using ‘self’ in relationship based practice. The understanding of Haltung is important but for social pedagogical practice to be undertaken it also has to be demonstrated by actions. The reflective activity Values Alive in Practice, set out in this article, provides a tool for social workers, practitioners and students to critically explore their own values and practice and make more meaningful connections between their Haltung and their behaviours demonstrated in their everyday work. In the UK, values and standards for social work practice are set out by British Association of Social Work and Social Work England. Arguably, these have, at times, been reduced to a checklist for students and practitioners and can lack more in depth and explicit links to practice. The analysis of practice is more likely to focus on the skills and abilities of practitioners rather than the value base that underpins these. Whilst the understanding and key application of core knowledge and skills is essential for competent social work practice (Forrester et al., 2019), this article argues that it must also be supported and shaped by ethical principles. This article seeks to explore how social workers can be supported to adopt value led approaches to complex work within an outcome focussed culture

Blending human and artificial intelligence to support Autistic children’s social communication skills

This paper examines the educational efficacy of a learning environment in which children diagnosed with Autism Spectrum Conditions (ASC) engage in social interactions with an artificially intelligent (AI) virtual agent and where a human practitioner acts in support of the interactions. A multi-site intervention study in schools across the UK was conducted with 29 children with ASC and learning difficulties, aged 4-14 years old. For reasons related to data completeness and amount of exposure to the AI environment, data for 15 children was included in the analysis. The analysis revealed a significant increase in the proportion of social responses made by ASC children to human practitioners. The number of initiations made to human practitioners and to the virtual agent by the ASC children also increased numerically over the course of the sessions. However, due to large individual differences within the ASC group, this did not reach significance. Although no evidence of transfer to the real-world post-test was shown, anecdotal evidence of classroom transfer was reported. The work presented in this paper offers an important contribution to the growing body of research in the context of AI technology design and use for autism intervention in real school contexts. Specifically, the work highlights key methodological challenges and opportunities in this area by leveraging interdisciplinary insights in a way that (i) bridges between educational interventions and intelligent technology design practices, (ii) considers the design of technology as well as the design of its use (context and procedures) on par with one another, and (iii) includes design contributions from different stakeholders, including children with and without ASC diagnosis, educational practitioners and researchers