Effective ocean management and the conservation of highly migratory species depend on resolving the overlap between animal movements and distributions, and fishing effort. However, this information ...is lacking at a global scale. Here we show, using a big-data approach that combines satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space-use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively), and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of fishing effort in marine areas beyond national jurisdictions (the high seas). Our results demonstrate an urgent need for conservation and management measures at high-seas hotspots of shark space use, and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real-time, dynamic management.
Summary
A hallmark of obesity is chronic low‐grade inflammation, which plays a major role in the process of atherosclerotic cardiovascular disease (ACVD). Gut microbiota is one of the factors ...influencing systemic immune responses, and profound changes have been found in its composition and metabolic function in individuals with obesity. This systematic review assesses the association between the gut microbiota and markers of low‐grade inflammation in humans. We identified 14 studies which were mostly observational and relatively small (n = 10 to 471). The way in which the microbiome is analysed differed extensively between these studies. Lower gut microbial diversity was associated with higher white blood cell counts and high sensitivity C‐reactive protein (hsCRP) levels. The abundance of Bifidobacterium, Faecalibacterium, Ruminococcus and Prevotella were inversely related to different markers of low‐grade inflammation such as hsCRP and interleukin (IL)‐6. In addition, this review speculates on possible mechanisms through which the gut microbiota can affect low‐grade inflammation and thereby ACVD. We discuss the associations between the microbiome and the inflammasome, the innate immune system, bile acids, gut permeability, the endocannabinoid system and TMAO. These data reinforce the importance of human research into the gut microbiota as potential diagnostic and therapeutic strategy to prevent ACVD.
Epigenetic changes in diabetes Keating, ST; El-Osta, A
Clinical genetics,
July 2013, Letnik:
84, Številka:
1
Journal Article
Recenzirano
Diabetes is a multifactorial disease with numerous pathways influencing its progression and recent observations suggest that the complexity of the disease cannot be entirely accounted for by genetic ...predisposition. A compelling argument for an epigenetic component is rapidly emerging. Epigenetic processes at the chromatin template significantly sensitize transcriptional and phenotypic outcomes to environmental signaling information including metabolic state, nutritional requirements and history. Epigenetic mechanisms impact gene expression that could predispose individuals to the diabetic phenotype during intrauterine and early postnatal development, as well as throughout adult life. Furthermore, epigenetic changes could account for the accelerated rates of chronic and persistent microvascular and macrovascular complications associated with diabetes. Epidemiological and experimental animal studies identified poor glycemic control as a major contributor to the development of diabetic complications and highlight the requirement for early intervention. Early exposure to hyperglycemia can drive the development of complications that manifest late in the progression of the disease and persist despite improved glycemic control, indicating a memory of the metabolic insult. Understanding the molecular events that underlie these transcriptional changes will significantly contribute to novel therapeutic interventions to prevent, reverse or retard the deleterious effects of the diabetic milieu.
Abstract
Objectives
Hyperuricemia is a metabolic condition central to gout pathogenesis. Urate exposure primes human monocytes towards a higher capacity to produce and release IL-1β. In this study, ...we assessed the epigenetic processes associated to urate-mediated hyper-responsiveness.
Methods
Freshly isolated human peripheral blood mononuclear cells or enriched monocytes were pre-treated with solubilized urate and stimulated with LPS with or without monosodium urate (MSU) crystals. Cytokine production was determined by ELISA. Histone epigenetic marks were assessed by sequencing immunoprecipitated chromatin. Mice were injected intraarticularly with MSU crystals and palmitate after inhibition of uricase and urate administration in the presence or absence of methylthioadenosine. DNA methylation was assessed by methylation array in whole blood of 76 participants with normouricemia or hyperuricemia.
Results
High concentrations of urate enhanced the inflammatory response in vitro in human cells and in vivo in mice, and broad-spectrum methylation inhibitors reversed this effect. Assessment of histone 3 lysine 4 trimethylation (H3K4me3) and histone 3 lysine 27 acetylation (H3K27ac) revealed differences in urate-primed monocytes compared to controls. Differentially methylated regions (e.g. HLA-G, IFITM3, PRKAB2) were found in people with hyperuricemia compared to normouricemia in genes relevant for inflammatory cytokine signaling.
Conclusion
Urate alters the epigenetic landscape in selected human monocytes or whole blood of people with hyperuricemia compared to normouricemia. Both histone modifications and DNA methylation show differences depending on urate exposure. Subject to replication and validation, epigenetic changes in myeloid cells may be a therapeutic target in gout.
The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as ...an intracellular DNA sensor that mediates the induction of interferon-β (IFN-β). IFI16 directly associated with IFN-β-inducing viral DNA motifs. STING, a critical mediator of IFN-β responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-κB induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-β induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).
We retrospectively reviewed outcomes of 79 patients with periprosthetic hip fractures around cemented tapered polished stem (CTPS) implants treated with osteosynthesis between January 1997 and July ...2011. All patients underwent open reduction and fixation using a broad dynamic compression plate (DCP).
Seventy two (91%) of fractures united. There were seven (9%) non-unions with failure of metal work, three (4%) as a result of infection and four (5%) due to mechanical failure. Significant subsidence (>5mm) of the implant was seen in seven (9%) of cases. Ten (13%) cases developed post-operative infection. Non-anatomic reduction and infection were identified as predictors of poor outcome.
This is the largest series of a very specific group of periprosthetic fractures treated with osteosynthesis. Open reduction internal fixation with a broad dynamic compression plate for patients with periprosthetic hip fractures around the tip of cemented tapered polished stems is a suitable treatment provided there is no bone loss and the fracture can be precisely, anatomically, reduced and adequately fixed.
Abstract The aim of this study was to identify risk factors for failure of exchange nailing for femoral diaphyseal fracture non-unions. The study cohort comprised 40 patients with femoral diaphyseal ...non-unions treated by exchange nailing, of which six were open injuries. The median time to exchange nailing from primary fixation was 8.4 months. The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Multiple causes for non-union were found in 16 (40%) cases, with infection present in 12 (30.0%) patients. Further surgical procedures were required in nine (22.5%) cases, one of whom (2.5%) required the use of another fixation modality to achieve union. Union was ultimately achieved with exchange nailing in 34/37 (91.9%) patients. The median time to union after the exchange nailing was 9.4 months. Cigarette smoking and infection were risk factors for failure of exchange nailing. Multivariate analysis found infection to be the strongest predictor of exchange failure ( p < 0.05). Exchange nailing is an effective treatment for aseptic femoral diaphyseal fracture non-union. However, 50% of patients undergoing exchange nailing in the presence of infection required at least one further procedure. It is important to counsel patients of this so that they can plan for it and do not consider that the first exchange operation has failed.
The aim of this study was to identify risk factors for the failure of exchange nailing in nonunion of tibial diaphyseal fractures.
A cohort of 102 tibial diaphyseal nonunions in 101 patients with a ...mean age of 36.9 years (15 to 74) were treated between January 1992 and December 2012 by exchange nailing. Of which 33 (32%) were initially open injuries. The median time from primary fixation to exchange nailing was 6.5 months (interquartile range (IQR) 4.3 to 9.8 months). The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Univariate analysis and multiple regression were used to identify risk factors for failure to achieve union.
Multiple causes for the primary nonunion were found for 28 (27%) tibiae, with infection present in 32 (31%). Six patients were lost to follow-up. Further surgical procedures were required in 35 (36%) nonunions. Other fixation modalities were required in five fractures. A single nail exchange procedure achieved union in 60/96 (63%) of all nonunions. Only 11 out of 31 infected nonunions (35.4%) healed after one exchange nail procedure. Up to five repeated exchange nailings, with or without bone grafting, ultimately achieved union in 89 (93%) fractures. The median time to union after exchange nailing was 8.7 months (IQR 5.7 to 14.0 months). Univariate analysis confirmed that an oligotrophic/atrophic pattern of nonunion (p = 0.002), a bone gap of 5 mm or more (p = 0.04) and infection (p < 0.001), were predictive for failure of exchange nailing Multiple regression analysis found that infection was the strongest predictor of failure (p < 0.001).
Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. However, in the presence of severe infection with a highly resistant organism, or extensive sclerosis of the bone, other fixation modalities, such as Ilizarov treatment, should be considered.
Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion.
This study quantifies future changes in tropospheric ozone (O3) using
a simple parameterisation of source–receptor relationships based on
simulations from a range of models participating in the Task ...Force on
Hemispheric Transport of Air Pollutants (TF-HTAP) experiments. Surface and
tropospheric O3 changes are calculated globally and across 16 regions
from perturbations in precursor emissions (NOx, CO, volatile organic compounds – VOCs)
and methane (CH4) abundance only, neglecting any impact from climate
change. A source attribution is provided for each source region along with an
estimate of uncertainty based on the spread of the results from the models.
Tests against model simulations using the Hadley Centre Global Environment
Model version 2 – Earth system configuration (HadGEM2-ES) confirm that the approaches
used within the parameterisation perform well for most regions. The
O3 response to changes in CH4 abundance is slightly larger in
the TF-HTAP Phase 2 than in the TF-HTAP Phase 1 assessment (2010) and provides
further evidence that controlling CH4 is important for limiting
future O3 concentrations. Different treatments of chemistry and
meteorology in models remain one of the largest uncertainties in calculating
the O3 response to perturbations in CH4 abundance and
precursor emissions, particularly over the Middle East and south Asia
regions. Emission changes for the future Evaluating the CLimate and Air Quality
ImPacts of Short-livEd Pollutants (ECLIPSE) scenarios and a subset of
preliminary Shared Socioeconomic Pathways (SSPs) indicate that surface
O3 concentrations will increase regionally by 1 to 8 ppbv in 2050.
Source attribution analysis highlights the growing importance of CH4
in the future under current legislation. A change in the global tropospheric
O3 radiative forcing of +0.07 W m−2 from 2010 to 2050 is
predicted using the ECLIPSE scenarios and SSPs, based solely on changes in
CH4 abundance and tropospheric O3 precursor emissions and
neglecting any influence of climate change. Current legislation is shown to
be inadequate in limiting the future degradation of surface ozone air quality
and enhancement of near-term climate warming. More stringent future emission
controls provide a large reduction in both surface O3 concentrations
and O3 radiative forcing. The parameterisation provides a simple tool
to highlight the different impacts and associated uncertainties of local and
hemispheric emission control strategies on both surface air quality and the
near-term climate forcing by tropospheric O3.
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