Critical analysis of the governance of the Sainte Luce Locally Managed Marine Area (LMMA), southeast Madagascar

The Marine Protected Area Governance (MPAG) framework is applied to critically assess the governance of the Sainte Luce Locally Managed Marine Area (LMMA), southeast Madagascar. Madagascar experiences rapid population growth, widespread poverty, corruption and political instability, which hinders natural resource governance. Community-based natural resource management (CBNRM) has been repeatedly employed to circumvent the lack of state capacity. This includes the LMMA model, which has rapidly proliferated, represented by MIHARI, Madagascar's LMMA network. The lobster fishing is the primary source of income for households in the impoverished community of Sainte Luce, one of the key landing sites in the regional export industry. However, fishers, industry actors and available data suggest a significant decline of local and regional stocks, likely due to over-exploitation driven by poverty and migration. In 2013, SEED Madagascar a UK NGO, worked to establish community-based fishery management in Sainte Luce, setting up a local management committee, which introduced a periodic no take zone (NTZ). Despite the community's efforts and some significant achievements, the efficacy of management is limited. To date, limited state support and the lack of engagement by actors throughout the value chain have hampered effective governance. The study reinforces the finding that resilient governance relies on a diversity of actors and the incentives they collectively employ. Here and elsewhere, there is a limit to what can be achieved by bottom-up approaches in isolation. Resilient management of marine resources in Madagascar relies on improving the capacity of community, state, NGO and industry actors to collectively govern resources

What does Brexit mean for the UK social care workforce? Perspectives from the recruitment and retention frontline.

The UK's departure from the European Union (Brexit) is likely to result in greater immigration and employment restrictions on European Union/European Economic Area (EU/EEA) nationals within the United Kingdom. EU/EEA citizens constitute a significant proportion of the current social care workforce. Research evaluating the impact of Brexit on social care has highlighted potentially severe future workforce shortfalls, but has not engaged in detail with the experiences of social care personnel involved in day-to-day recruitment and retention activities. This article explores how social care managers evaluate Brexit's prospects for future workforce sustainability, through the prism of their organisation's workforce requirements. This qualitative study incorporated in-depth semi-structured interviews and questionnaire surveys with domiciliary and residential care managers. Data collection focused on an urban conurbation in south-west England, with demographic characteristics likely to make post-Brexit recruitment and retention in social care particularly challenging. A key finding is that, irrespective of whether they employ EU/EEA workers or not, research participants have deep concerns about Brexit's potential impact on the social care labour market. These include apprehensions about future restrictions on hiring EU/EEA nurses, as well as fears about increased competition for care staff and their organisation's future financial viability. This article amplifies the voices of managers as an under-researched group, bringing their perspectives on Brexit to bear on wider debates on social care workforce sustainability

Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.

Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNAAla mouse. Through application of a programmable nuclease therapy approach, using systemically administered, mitochondrially targeted zinc-finger nucleases (mtZFN) delivered by adeno-associated virus, we induced specific elimination of mutant mtDNA across the heart, coupled to a reversion of molecular and biochemical phenotypes. These findings constitute proof of principle that mtDNA heteroplasmy correction using programmable nucleases could provide a therapeutic route for heteroplasmic mitochondrial diseases of diverse genetic origin

NADH Shuttling Couples Cytosolic Reductive Carboxylation of Glutamine with Glycolysis in Cells with Mitochondrial Dysfunction.

The bioenergetics and molecular determinants of the metabolic response to mitochondrial dysfunction are incompletely understood, in part due to a lack of appropriate isogenic cellular models of primary mitochondrial defects. Here, we capitalize on a recently developed cell model with defined levels of m.8993T>G mutation heteroplasmy, mTUNE, to investigate the metabolic underpinnings of mitochondrial dysfunction. We found that impaired utilization of reduced nicotinamide adenine dinucleotide (NADH) by the mitochondrial respiratory chain leads to cytosolic reductive carboxylation of glutamine as a new mechanism for cytosol-confined NADH recycling supported by malate dehydrogenase 1 (MDH1). We also observed that increased glycolysis in cells with mitochondrial dysfunction is associated with increased cell migration in an MDH1-dependent fashion. Our results describe a novel link between glycolysis and mitochondrial dysfunction mediated by reductive carboxylation of glutamine

Use of passive alpha detectors to screen for uranium contamination in a field at Fernald, Ohio

This paper reports the results from a field test of newly developed techniques for inexpensive, in situ screening of soil for alpha contamination. Passive alpha detectors that are commercially available for the detection indoor airborne alpha activity (i.e., {sup 222}Rn) have been modified so they can be applied to the detection of alpha contamination on surfaces or in soils. Results reported here are from an intercomparison involving several different techniques with all measurements being made at the same sites in a field near the formerly used uranium processing facility at Fernald, Ohio, during the summer of 1994. The results for two types of passive alpha detector show that the quality of calibration is improved if soils samples are milled to increase homogeneity within the soil matrices. The correlation between laboratory based radiochemical analyses and quick, field-based screening measurements is acceptable and can be improved if the passive devices are left for longer exposure times in the field. The total cost per measurement for either type of passive alpha detector is probably less than $25 and should provide a cost-effective means for site managers to develop the information needed to find areas with remaining alpha contamination so resources can be allocated efficiently

Linear mitochondrial DNA is rapidly degraded by components of the replication machinery.

Emerging gene therapy approaches that aim to eliminate pathogenic mutations of mitochondrial DNA (mtDNA) rely on efficient degradation of linearized mtDNA, but the enzymatic machinery performing this task is presently unknown. Here, we show that, in cellular models of restriction endonuclease-induced mtDNA double-strand breaks, linear mtDNA is eliminated within hours by exonucleolytic activities. Inactivation of the mitochondrial 5'-3'exonuclease MGME1, elimination of the 3'-5'exonuclease activity of the mitochondrial DNA polymerase POLG by introducing the p.D274A mutation, or knockdown of the mitochondrial DNA helicase TWNK leads to severe impediment of mtDNA degradation. We do not observe similar effects when inactivating other known mitochondrial nucleases (EXOG, APEX2, ENDOG, FEN1, DNA2, MRE11, or RBBP8). Our data suggest that rapid degradation of linearized mtDNA is performed by the same machinery that is responsible for mtDNA replication, thus proposing novel roles for the participating enzymes POLG, TWNK, and MGME1

The EU as a Good Global Actor

This paper outlines an exploratory workshop at City Law School, City, University of London funded by HEIF/ ‘EUTIP’ Marie Skłodowska-Curie Innovative Training Network (ITN) on understanding of the EU as a Good Global Actor.1 The EU has as its mission to be a good global governance actor yet is continuously challenged in the world. As a global actor, the EU is both a weak and strong actor in a divergent range of global governance areas. It is not comparable to study the EU as a global trade actor for example to its efforts in human rights, data, cyber or the environment. EU international relations constitutes arguably a booming field of law where the EU appears often to be a victim of its own success. The range of the subjects and objects of EU law continues to expand and the EU is arguably increasingly a victim of its own success, increasingly taking decisions with impacts on third countries or parties, subjecting more entities to sanctions regimes, being bound to consult more entities and have more third countries, parties and entities such as lobbyists interested in the directions of EU law. The assessment of the EU as a global actor includes broad checks on normative action ex ante and ex post facto- yet it is no less harsh. Ex ante metrics of EU global action include court-centred ones such as an opinion from the CJEU on legality of an international agreement, often precluded in most constitutional systems on account of its conflict with pacta sunt servanda. The contours of the principle of the autonomy of EU law have the capacity to put more stringent parameters on EU institutionalised evolutions as to international engagement. How can we assess the EU as a global actor given these realities? The aim of the event was to explore informally the nexus between trade and security, trade and economics and trade and human rights as a future research agenda with input from a variety of scholars It reflected upon four major themes: 1) The EU’s Contribution to the Democratisation of Global Governance 2) Deeper Trade Agreements and New Normative Foundations 3) The EU as a Global Actor in Trade and Fundamental Rights 4) EU’s Trade in the Era of Global Data Flows

Energetic costs of cellular and therapeutic control of stochastic mitochondrial DNA populations.

The dynamics of the cellular proportion of mutant mtDNA molecules is crucial for mitochondrial diseases. Cellular populations of mitochondria are under homeostatic control, but the details of the control mechanisms involved remain elusive. Here, we use stochastic modelling to derive general results for the impact of cellular control on mtDNA populations, the cost to the cell of different mtDNA states, and the optimisation of therapeutic control of mtDNA populations. This formalism yields a wealth of biological results, including that an increasing mtDNA variance can increase the energetic cost of maintaining a tissue, that intermediate levels of heteroplasmy can be more detrimental than homoplasmy even for a dysfunctional mutant, that heteroplasmy distribution (not mean alone) is crucial for the success of gene therapies, and that long-term rather than short intense gene therapies are more likely to beneficially impact mtDNA populations

‘Stepping away from the computer and into the sweats': The construction and negotiation of exercise identities in a Norwegian public company

While research has found that a developed exercise identity enables individuals to view exercise participation as self- reinforcing, the social barriers to such exercise identity development and participation have not been fully addressed. The subsequent aim of this study was to explore some of the social complexities at play in terms of how company employees construct and manage their exercise identities within a work place setting. A case-study method was used to address the research issue over a nine-month period. The case to be studied included a sample of 72 employees from a Norwegian public company who participated in an on-going work-based exercise programme called ‘Exercise for all’. The principal means of data collection comprised participant observation, individual interviews and exercise logbooks. The data were subject to inductive analysis. The primary barriers to exercise participation included high levels of social comparison in a competitive working context, particularly in relation to ‘competent colleagues’, and feelings of guilt associated with partaking in ‘recreational’ activities during work hours. Strategies engaged with to overcome and negotiate such obstacles included justifying participation through a health-related discourse, and constructing a more distinct ‘worker-exerciser’ identity