Ariel - Volume 3 Number 7

Editors Richard J. Bonanno Robin A. Edwards Associate Editors Steven Ager Tom Williams Lay-out Editor Eugenia Miller Contributing Editors Paul Bialas Robert Breckenridge David Jacoby Mike LeWitt Terry Burt Michael Leo Editors Emeritus Delvyn C. Case, Jr. Paul M. Fernhof

Ariel - Volume 3 Number 1

Editors Richard J. Bonanno Robin A. Edwards Associate Editors Steven Ager Stephen Flynn Tom Williams Lay-out Editor Eugenia Miller Contributing Editors Michael J. Blecker Milton Parker James J. Nocon Lynne Porter Editors Emeritus Delvyn C. Case, Jr. Paul M. Fernhof

Ariel - Volume 2 Number 7

Editors Richard J. Bonanno Robin A. Edwards Associate Editors Steven Ager Stephen Flynn Shep Dickman Tom Williams Lay-out Editor Eugenia Miller Contributing Editors Michael J. Blecker W. Cherry Light James J. Nocon Lynne Porter Editors Emeritus Delvyn C. Case, Jr. Paul M. Fernhof

Ariel - Volume 4 Number 2

Editors David A. Jacoby Eugenia Miller Tom Williams Associate Editors Paul Bialas Terry Burt Michael Leo Gail Tenikat Editor Emeritus and Business Manager Richard J. Bonnano Movie Editor Robert Breckenridge Staff Richard Blutstein Mary F. Buechler Steve Glinks Len Grasman Alice M. Johnson J. D. Kanofsky Tom Lehman Dave Mayer Bernie Odd

Understanding Persistent Non-compliance in a Remote, Large-Scale Marine Protected Area

UIDB/04647/2020 UIDP/04647/2020Area coverage of large-scale marine protected areas (MPAs) (LSMPAs, > 100,000 km2) is rapidly increasing globally. Their effectiveness largely depends on successful detection and management of non-compliance. However, for LSMPAs this can be difficult due to their large size, often remote locations and a lack of understanding of the social drivers of non-compliance. Taking a case-study approach, we review current knowledge of illegal fishing within the British Indian Ocean Territory (BIOT) LSMPA. Data stemming from enforcement reports (2010–20), and from fieldwork in fishing communities (2018–19) were combined to explore and characterise drivers of non-compliance. Enforcement data included vessel investigation reports (n = 188), transcripts of arrests (20) and catch seizures (58). Fieldwork data included fisher interviews (95) and focus groups (12), conducted in two communities in Sri Lanka previously associated with non-compliance in BIOT LSMPA. From 2010 to 2020, there were 126 vessels suspected of non-compliance, 76% of which were Sri Lankan. The majority of non-compliant vessels targeted sharks (97%), catching an estimated 14,340 individuals during the study period. Sri Lankan vessels were primarily registered to one district (77%) and 85% operated from just two ports within the fieldwork sites. Social Network Analysis (SNA) showed that 66% of non-compliant vessels were linked by social ties, including sharing crew members, compared with only 34% of compliant vessels. Thematic analysis of qualitative data suggested that perceptions of higher populations of sharks and social ties between vessels may both be important drivers. We discuss our findings within a global context to identify potential solutions for LSMPA management.publishersversionpublishe

How European Union Membership Can Undermine the Rule of Law in Emerging Democracies

The European Union views the spread of economic prosperity and rule of law to countries emerging from dictatorship as among its primary goals when considering countries as candidates for membership. Existing literature often suggests that EU membership confers significant benefits on the accession countries, and these countries are willing to undergo costly and difficult reforms to reap these benefits. Through strict membership conditions, member states force accession countries to commit to democracy. Drawing on theoretical work in the fields of law, politics, and economics, this article reassesses the conventional wisdom. It argues that, under certain conditions, the reforms required of would-be members could have the perverse effect of undermining the establishment of legitimate law in transitional democracies. Using an agent-based model, the article elucidates a theory in which placing laws on the books around which no societal consensus exists can create perverse incentives for citizens and government officials and may lead to an erosion of the rule of law

RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction

Aims Programmed necrosis (necroptosis) represents a newly identified mechanism of cell death combining features of both apoptosis and necrosis. Like apoptosis, necroptosis is tightly regulated by distinct signalling pathways. A key regulatory role in programmed necrosis has been attributed to interactions of the receptor-interacting protein kinases, RIP1 and RIP3. However, the specific functional role of RIP3-dependent signalling and necroptosis in the heart is unknown. The aims of this study were thus to assess the significance of necroptosis and RIP3 in the context of myocardial ischaemia. Methods and results Immunoblots revealed strong expression of RIP3 in murine hearts, indicating potential functional significance of this protein in the myocardium. Consistent with a role in promoting necroptosis, adenoviral overexpression of RIP3 in neonatal rat cardiomyocytes and stimulation with TNF-α induced the formation of a complex of RIP1 and RIP3. Moreover, RIP3 overexpression was sufficient to induce necroptosis of cardiomyocytes. In vivo, cardiac expression of RIP3 was up-regulated upon myocardial infarction (MI). Conversely, mice deficient for RIP3 (RIP3−/−) showed a significantly better ejection fraction (45 ± 3.6 vs. 32 ± 4.4%, P < 0.05) and less hypertrophy in magnetic resonance imaging studies 30 days after experimental infarction due to left anterior descending coronary artery ligation. This was accompanied by a diminished inflammatory response of infarcted hearts and decreased generation of reactive oxygen species. Conclusion Here, we show that RIP3-dependent necroptosis modulates post-ischaemic adverse remodelling in a mouse model of MI. This novel signalling pathway may thus be an attractive target for future therapies that aim to limit the adverse consequences of myocardial ischaemi

Zebrafish retinal ganglion cells asymmetrically encode spectral and temporal information across visual space

In vertebrate vision, the tetrachromatic larval zebrafish permits non-invasive monitoring and manipulating of neural activity across the nervous system in vivo during ongoing behavior. However, despite a perhaps unparalleled understanding of links between zebrafish brain circuits and visual behaviors, comparatively little is known about what their eyes send to the brain via retinal ganglion cells (RGCs). Major gaps in knowledge include any information on spectral coding and information on potentially critical variations in RGC properties across the retinal surface corresponding with asymmetries in the statistics of natural visual space and behavioral demands. Here, we use in vivo two-photon imaging during hyperspectral visual stimulation as well as photolabeling of RGCs to provide a functional and anatomical census of RGCs in larval zebrafish. We find that RGCs’ functional and structural properties differ across the eye and include a notable population of UV-responsive On-sustained RGCs that are only found in the acute zone, likely to support visual prey capture of UV-bright zooplankton. Next, approximately half of RGCs display diverse forms of color opponency, including many that are driven by a pervasive and slow blue-Off system—far in excess of what would be required to satisfy traditional models of color vision. In addition, most information on spectral contrast was intermixed with temporal information. Taken together, our results suggest that zebrafish RGCs send a diverse and highly regionalized time-color code to the brain

DOMINO-AD protocol: donepezil and memantine in moderate to severe Alzheimer's disease - a multicentre RCT.

BACKGROUND: Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil. METHOD: DOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with Standardized Mini-Mental State Examination (SMMSE) scores between 5 and 13 are being recruited. Each is randomized to one of four treatment options: continuation of donepezil with memantine placebo added; switch to memantine with donepezil placebo added; donepezil and memantine together; or donepezil placebo with memantine placebo. 800 participants are being recruited and treatment continues for one year. Primary outcome measures are cognition (SMMSE) and activities of daily living (Bristol Activities of Daily Living Scale). Secondary outcomes are non-cognitive dementia symptoms (Neuropsychiatric Inventory), health related quality of life (EQ-5D and DEMQOL-proxy), carer burden (General Health Questionnaire-12), cost effectiveness (using Client Service Receipt Inventory) and institutionalization. These outcomes are assessed at baseline, 6, 18, 30 and 52 weeks. All participants will be subsequently followed for 3 years by telephone interview to record institutionalization. DISCUSSION: There is considerable debate about the clinical and cost effectiveness of anti-dementia drugs. DOMINO-AD seeks to provide clear evidence on the best treatment strategies for those managing patients at a particularly important clinical transition point. TRIAL REGISTRATION: Current controlled trials ISRCTN49545035.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are