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      International primate neuroscience research regulation, public engagement and transparency opportunities

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          Highlights

          • Identifying the international standards for research ethics and regulations concerning non-human primates (NHPs).

          • Introduction of an international animal welfare and use committee (IAWUC).

          • Implementation of standards for animal welfare and care in research facilitates global collaboration efforts.

          • International collaborations can improve the standards of animal welfare and care.

          • Transparency in scientific research with NHPs influences public opinion and aids in public engagement.

          Abstract

          Scientific excellence is a necessity for progress in biomedical research. As research becomes ever more international, establishing international collaborations will be key to advancing our scientific knowledge. Understanding the similarities in standards applied by different nations to animal research, and where the differences might lie, is crucial. Cultural differences and societal values will also contribute to these similarities and differences between countries and continents. Our overview is not comprehensive for all species, but rather focuses on non-human primate (NHP) research, involving New World marmosets and Old World macaques, conducted in countries where NHPs are involved in neuroimaging research. Here, an overview of the ethics and regulations is provided to help assess welfare standards amongst primate research institutions. A comparative examination of these standards was conducted to provide a basis for establishing a common set of standards for animal welfare. These criteria may serve to develop international guidelines, which can be managed by an International Animal Welfare and Use Committee (IAWUC). Internationally, scientists have a moral responsibility to ensure excellent care and welfare of their animals, which in turn, influences the quality of their research. When working with animal models, maintaining a high quality of care (“culture of care”) and welfare is essential. The transparent promotion of this level of care and welfare, along with the results of the research and its impact, may reduce public concerns associated with animal experiments in neuroscience research.

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          Most cited references81

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          Power failure: why small sample size undermines the reliability of neuroscience.

          A study with low statistical power has a reduced chance of detecting a true effect, but it is less well appreciated that low power also reduces the likelihood that a statistically significant result reflects a true effect. Here, we show that the average statistical power of studies in the neurosciences is very low. The consequences of this include overestimates of effect size and low reproducibility of results. There are also ethical dimensions to this problem, as unreliable research is inefficient and wasteful. Improving reproducibility in neuroscience is a key priority and requires attention to well-established but often ignored methodological principles.
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            Genome editing. The new frontier of genome engineering with CRISPR-Cas9.

            The advent of facile genome engineering using the bacterial RNA-guided CRISPR-Cas9 system in animals and plants is transforming biology. We review the history of CRISPR (clustered regularly interspaced palindromic repeat) biology from its initial discovery through the elucidation of the CRISPR-Cas9 enzyme mechanism, which has set the stage for remarkable developments using this technology to modify, regulate, or mark genomic loci in a wide variety of cells and organisms from all three domains of life. These results highlight a new era in which genomic manipulation is no longer a bottleneck to experiments, paving the way toward fundamental discoveries in biology, with applications in all branches of biotechnology, as well as strategies for human therapeutics. Copyright © 2014, American Association for the Advancement of Science.
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              Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.

              Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.
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                Author and article information

                Contributors
                Journal
                Neuroimage
                Neuroimage
                Neuroimage
                Academic Press
                1053-8119
                1095-9572
                01 April 2021
                01 April 2021
                : 229
                : 117700
                Affiliations
                [a ]Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom
                [b ]Centre for Integrative Neurosciences, University of Tübingen, Tübingen, Germany
                [c ]Max Planck Institute for Biological Cybernetics, Tübingen, Germany
                [d ]Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
                [e ]Fuster Laboratory of Cognitive Neuroscience Department of Psychiatry and Biobehavioral Sciences UCLA Los Angeles 90095, CA United States
                [f ]Understanding Animal Research, London, United Kingdom
                [g ]Princeton Neuroscience Institute & Department of Psychology, Princeton University, Princeton, United States
                [h ]Biosciences Institute & Centre for Behaviour and Evolution, Faculty of Medical Sciences, Newcastle University, United Kingdom
                Author notes
                [* ]Corresponding author. anna.mitchell@ 123456psy.ox.ac.uk
                [1]

                Joint first authors

                Article
                S1053-8119(20)31185-X 117700
                10.1016/j.neuroimage.2020.117700
                7994292
                33418072
                373ec2ed-38cc-467c-8736-77fc314be79b
                © 2020 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 September 2020
                : 8 December 2020
                : 19 December 2020
                Categories
                Article

                Neurosciences
                primates,housing standards,neuroimaging,mri,welfare,culture of care,public engagement
                Neurosciences
                primates, housing standards, neuroimaging, mri, welfare, culture of care, public engagement

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