Marine protected areas: Science, policy and management

Marine protected areas (MPAs) generate powerful interactions between social, economic and environmental interests, manifest at a circumscribed and often local scale. Consequently the designation and management of an individual MPA typically plays out in microcosm the general challenge of sustainable development in the marine environment. Some universally relevant questions relating to four commonly held defining attributes of MPAs are articulated. However, while many of the questions are universal, in practice the answers vary greatly. Consequently there are few MPAs which would not provide an informative case study elucidating the dynamics at the intersection between science, policy and management in the marine realm. The papers in this collection exemplify a range of key issues across this spectrum of disciplines. In practice most contentious issues relate to the balance within MPAs between environmental and socio-economic considerations, not least relating to fishing. In this respect greater attention in MPA management plans, to the economic benefits of MPAs for local communities is encouraged. However we also recognise that glib assertions that a secure sustainable balance between conservation and exploitation can be established in practice, typically with few resources in a largely unseen and often data-poor environment, may sometimes be politically expedient but scientifically questionable. Yet it is ultimately the work of all those involved directly with MPAs to collectively achieve the task of transforming the rhetoric of marine conservation policy into a successful reality on the ground and we commend the authors of this collection for their efforts to achieve that goal

Self-generated magnetic flux in YBa2_2Cu3_3O7−x_{7-x} grain boundaries

Grain boundaries in YBa$_2$Cu$_3$O$_{7-x}$ superconducting films are considered as Josephson junctions with a critical current density $j_c(x)$ alternating along the junction. A self-generated magnetic flux is treated both analytically and numerically for an almost periodic distribution of $j_c(x)$. We obtained a magnetic flux-pattern similar to the one which was recently observed experimentally.Comment: 7 pages, 3 figure

Graft immaturity and safety concerns in transplanted human kidney organoids

For chronic kidney disease, regeneration of lost nephrons with human kidney organoids derived from induced pluripotent stem (iPS) cells is proposed to be an attractive potential therapeutic option. It remains unclear, however, whether organoids transplanted into kidneys in vivo would be safe or functional. Here, we purified kidney organoids and transplanted them beneath the kidney capsules of immunodeficient mice to test their safety and maturity. Kidney organoid grafts survived for months after transplantation and became vascularized from host mouse endothelial cells. Nephron-like structures in grafts appeared more mature than kidney organoids in vitro, but remained immature compared with the neighboring mouse kidney tissue. Ultrastructural analysis revealed filtration barrier-like structures, capillary lumens, and tubules with brush border in the transplanted kidney organoids, which were more mature than those of the kidney organoids in vitro but not as organized as adult mammalian kidneys. Immaturity was a common feature of three separate differentiation protocols by immunofluorescence analysis and single cell RNA sequencing. Stroma of transplanted kidney organoid grafts were filled with vimentin-positive mesenchymal cells, and chondrogenesis, cystogenesis, and stromal expansion were observed in the long term. Transcription profiles showed that long-term maintenance after kidney organoid transplantation induced transcriptomic reprogramming with prominent suppression of cell-cycle-related genes and upregulation of extracellular matrix organization. Our data suggest that kidney organoids derived from iPS cells may be transplantable but strategies to improve nephron differentiation and purity are required before they can be applied in humans as a therapeutic option.11Ysciescopuskc

Impacts of a novel shellfishing gear on macrobenthos in a marine protected area: pump-scoop dredging in Poole Harbour, UK

Understanding the impact of bottom-fishing gears at various scales and intensities on habitats and species is necessary to inform management. In Poole Harbour, UK, a multiple use marine protected area, fishermen utilise a unique “pump-scoop” dredge to harvest the introduced Manila clam Ruditapes philippinarum. Managers need to balance the socio-economic benefits of the fishery with ecological concerns across the region, which has required a revision of by-laws that include both spatial and temporal measures. Within an operational fishery, we used a Before-After-Control-Impact sampling design to assess the impacts of pump-scoop dredging on benthic physical characteristics and community structure in an area where there was no dredging, an area newly opened to dredging and an area subject to high levels of historic dredging. A sampling grid was used in each area to best capture any fishing effort in the newly opened area. Core samples were taken to a depth of 30 cm within intertidal mudflats. A significant loss of fine sediments was observed in the site subject to high intensity dredging and a significant change in community structure also occurred in both dredged sites throughout the study period. In the newly opened site this was characterised by a relative increase in species richness, including increased abundance of annelid worms, notably Hediste diversicolor and Aphelochaeta marioni and a decline in the abundance of the bivalve mollusc Abra tenuis. These changes, albeit relatively small, are attributed to physical disturbance as a direct result of pump-scoop dredging, although no difference in the classification of the biotope of the site was observed. This is of particular interest to managers monitoring site condition within areas under the new bylaws as the Manila clam is spreading to other protected estuaries in the region

The RNA chaperone Hfq is essential for the virulence of Salmonella typhimurium

The RNA chaperone, Hfq, plays a diverse role in bacterial physiology beyond its original role as a host factor required for replication of Qβ RNA bacteriophage. In this study, we show that Hfq is involved in the expression and secretion of virulence factors in the facultative intracellular pathogen, Salmonella typhimurium. A Salmonella hfq deletion strain is highly attenuated in mice after both oral and intraperitoneal infection, and shows a severe defect in invasion of epithelial cells and a growth defect in both epithelial cells and macrophages in vitro. Surprisingly, we find that these phenotypes are largely independent of the previously reported requirement of Hfq for expression of the stationary phase sigma factor, RpoS. Our results implicate Hfq as a key regulator of multiple aspects of virulence including regulation of motility and outer membrane protein (OmpD) expression in addition to invasion and intracellular growth. These pleiotropic effects are suggested to involve a network of regulatory small non-coding RNAs, placing Hfq at the centre of post-transcriptional regulation of virulence gene expression in Salmonella. In addition, the hfq mutation appears to cause a chronic activation of the RpoE-mediated envelope stress response which is likely due to a misregulation of membrane protein expression

A history of invasion: COI phylogeny of Manila clam Ruditapes philippinarum in Europe

The Manila clam Ruditapes philippinarum – synonym Venerupis philippinarum (Adams and Reeve, 1850) is now one of the top 5 most commercially valuable bivalve species worldwide. Originally from the Indo-Pacific region, it has been introduced in many countries for fisheries and aquaculture, including estuarine environments along Atlantic and Mediterranean European coasts. Yet despite its commercial value and widespread distribution, the precise origins of stocks remain speculative and the genetic diversity of introduced populations is poorly known. Thus, the aim of this work was to collect mtDNA COI (Cytochrome oxidase I) gene sequences from 5 European countries with Manila clam stocks and compare them with native Asian populations to evaluate their genetic diversity and identify possible routes of invasion. The COI gene sequencing supported a strong founder effect in the European populations with 3 main haplotypes occurring at high frequencies, derived from Japan. However, high haplotype diversity was also observed due to the occurrence of 10 rare haplotypes. This supports hypotheses (i) there have been additional, previous unrecorded, introductions as previously hypothesized by analysis of 16S rDNA, and (ii) there has been a limited loss of genetic diversity in introduced populations, as previously suggested by microsatellite data. This is the first genetic comparison of Manila clam populations introduced in to Europe with native clams. Genetic data herein presented are fundamentally important for the traceability of clam products and stock management programmes and will also inform discussion on the potential resilience of exploited Manila clam populations

Socioeconomic deprivation is associated with reduced response and lower treatment persistence with TNF inhibitors in rheumatoid arthritis

Objective To investigate the association between socioeconomic deprivation and outcomes following TNF inhibitor (TNFi) treatment. Methods Individuals commencing their first TNFi in the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) and Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS) cohort were included. Socioeconomic deprivation was proxied using the Index of Multiple Deprivation and categorized as 20% most deprived, middle 40% or 40% least deprived. DAS28-derived outcomes at 6 months (BSRBR-RA) and 3 months (BRAGGSS) were compared using regression models with the least deprived as referent. Risks of all-cause and cause-specific drug discontinuation were compared using Cox models in the BSRBR-RA. Additional analyses adjusted for lifestyle factors (e.g. smoking, BMI) as potential mediators. Results 16 085 individuals in the BSRBR-RA were included (mean age 56 years, 76% female), of whom 18%, 41% and 41% were in the most, middle and least deprived groups, respectively. Of 3459 included in BRAGGSS (mean age 57, 77% female), proportions were 22%, 36% and 41%, respectively. The most deprived group had 0.3-unit higher 6-month DAS28 (95% CI 0.22, 0.37) and were less likely to achieve low disease activity (odds ratio [OR] 0.76; 95% CI 0.68, 0.84) in unadjusted models. Results were similar for 3-month DAS28 (β = 0.23; 95% CI 0.11, 0.36) and low disease activity (OR 0.77; 95% CI 0.63, 0.94). The most deprived were more likely to discontinue treatment (hazard ratio 1.18; 95% CI 1.12, 1.25), driven by ineffectiveness rather than adverse events. Adjusted estimates were generally attenuated. Conclusion Socioeconomic deprivation is associated with reduced response to TNFi. Improvements in determinants of health other than lifestyle factors are needed to address socioeconomic inequities

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease