Coenzyme Q10 Prevents Insulin Signaling Dysregulation and Inflammation Prior to Development of Insulin Resistance in Male Offspring of a Rat Model of Poor Maternal Nutrition and Accelerated Postnatal Growth.

Low birth weight and rapid postnatal growth increases the risk of developing insulin resistance and type 2 diabetes in later life. However, underlying mechanisms and potential intervention strategies are poorly defined. Here we demonstrate that male Wistar rats exposed to a low-protein diet in utero that had a low birth weight but then underwent postnatal catch-up growth (recuperated offspring) had reductions in the insulin signaling proteins p110-β (13% ± 6% of controls [P < .001]) and insulin receptor substrate-1 (39% ± 10% of controls [P < .05]) in adipose tissue. These changes were not accompanied by any change in expression of the corresponding mRNAs, suggesting posttranscriptional regulation. Recuperated animals displayed evidence of a proinflammatory phenotype of their adipose tissue with increased IL-6 (139% ± 8% [P < .05]) and IL1-β (154% ± 16% [P < .05]) that may contribute to the insulin signaling protein dysregulation. Postweaning dietary supplementation of recuperated animals with coenzyme Q (CoQ10) (1 mg/kg of body weight per day) prevented the programmed reduction in insulin receptor substrate-1 and p110-β and the programmed increased in IL-6. These findings suggest that postweaning CoQ10 supplementation has antiinflammatory properties and can prevent programmed changes in insulin-signaling protein expression. We conclude that CoQ10 supplementation represents an attractive intervention strategy to prevent the development of insulin resistance that results from suboptimal in utero nutrition.This work was supported by The British Heart Foundation [PG/09/037/27387, FS/09/029/27902]; Medical Research Council [MC UU 12012/4] and Diabetes UK [12/0004508]. SEO is a member of the MRC Metabolic Diseases Unit. IPH is supported by the Department of Health’s NIHR Biomedical Research Centres funding scheme at UCLH/UCL.This is the author accepted manuscript. The final version is available from the Endocrine Society via http://dx.doi.org/10.1210/en.2015-142

Participation of Glutamate-354 of the CP43 Polypeptide in the Ligation of Manganese and the Binding of Substrate Water in Photosystem II

In the current X-ray crystallographic structural models of photosystem II, Glu354 of the CP43 polypeptide is the only amino acid ligand of the oxygen-evolving Mn4Ca cluster that is not provided by the D1 polypeptide. To further explore the influence of this structurally unique residue on the properties of the Mn4Ca cluster, the CP43-E354Q mutant of the cyanobacterium Synechocystis sp. PCC 6803 was characterized with a variety of biophysical and spectroscopic methods, including polarography, EPR, X-ray absorption, FTIR, and mass spectrometry. The kinetics of oxygen release in the mutant were essentially unchanged from those in wild type. In addition, the oxygen flash yields exhibited normal period four oscillations having normal S state parameters, although the yields were lower, correlating with the mutant's lower steady-state rate (approximately 20% compared to wild type). Experiments conducted with H218O showed that the fast and slow phases of substrate water exchange in CP43-E354Q thylakoid membranes were accelerated 8.5- and 1.8-fold, respectively, in the S3 state compared to wild type. Purified oxygen-evolving CP43-E354Q PSII core complexes exhibited a slightly altered S1 state Mn-EXAFS spectrum, a slightly altered S2 state multiline EPR signal, a substantially altered S 2-minus-S1 FTIR difference spectrum, and an unusually long lifetime for the S2 state (>10 h) in a substantial fraction of reaction centers. In contrast, the S2 state Mn-EXAFS spectrum was nearly indistinguishable from that of wild type. The S2-minus-S 1 FTIR difference spectrum showed alterations throughout the amide and carboxylate stretching regions. Global labeling with 15N and specific labeling with l-[1-13C]alanine revealed that the mutation perturbs both amide II and carboxylate stretching modes and shifts the symmetric carboxylate stretching modes of the α-COO- group of D1-Ala344 (the C-terminus of the D1 polypeptide) to higher frequencies by 3-4 cm -1 in both the S1 and S2 states. The EPR and FTIR data implied that 76-82% of CP43-E354Q PSII centers can achieve the S 2 state and that most of these can achieve the S3 state, but no evidence for advancement beyond the S3 state was observed in the FTIR data, at least not in a majority of PSII centers. Although the X-ray absorption and EPR data showed that the CP43-E354Q mutation only subtly perturbs the structure and spin state of the Mn4Ca cluster in the S 2 state, the FTIR and H218O exchange data show that the mutation strongly influences other properties of the Mn4Ca cluster, altering the response of numerous carboxylate and amide groups to the increased positive charge that develops on the cluster during the S1 to S2 transition and weakening the binding of both substrate water molecules (or water-derived ligands), especially the one that exchanges rapidly in the S3 state. The FTIR data provide evidence that CP43-Glu354 coordinates to the Mn4Ca cluster in the S1 state as a bridging ligand between two metal ions but provide no compelling evidence that this residue changes its coordination mode during the S1 to S 2 transition. The H218O exchange data provide evidence that CP43-Glu354 interacts with the Mn ion that ligates the substrate water molecule (or water-derived ligand) that is in rapid exchange in the S 3 state

Coenzyme Q10 prevents hepatic fibrosis, inflammation, and oxidative stress in a male rat model of poor maternal nutrition and accelerated postnatal growth.

BACKGROUND: It is well established that low birth weight and accelerated postnatal growth increase the risk of liver dysfunction in later life. However, molecular mechanisms underlying such developmental programming are not well characterized, and potential intervention strategies are poorly defined. OBJECTIVES: We tested the hypotheses that poor maternal nutrition and accelerated postnatal growth would lead to increased hepatic fibrosis (a pathological marker of liver dysfunction) and that postnatal supplementation with the antioxidant coenzyme Q10 (CoQ10) would prevent this programmed phenotype. DESIGN: A rat model of maternal protein restriction was used to generate low-birth-weight offspring that underwent accelerated postnatal growth (termed "recuperated"). These were compared with control rats. Offspring were weaned onto standard feed pellets with or without dietary CoQ10 (1 mg/kg body weight per day) supplementation. At 12 mo, hepatic fibrosis, indexes of inflammation, oxidative stress, and insulin signaling were measured by histology, Western blot, ELISA, and reverse transcriptase-polymerase chain reaction. RESULTS: Hepatic collagen deposition (diameter of deposit) was greater in recuperated offspring (mean ± SEM: 12 ± 2 μm) than in controls (5 ± 0.5 μm) (P < 0.001). This was associated with greater inflammation (interleukin 6: 38% ± 24% increase; P < 0.05; tumor necrosis factor α: 64% ± 24% increase; P < 0.05), lipid peroxidation (4-hydroxynonenal, measured by ELISA: 0.30 ± 0.02 compared with 0.19 ± 0.05 μg/mL per μg protein; P < 0.05), and hyperinsulinemia (P < 0.05). CoQ10 supplementation increased (P < 0.01) hepatic CoQ10 concentrations and ameliorated liver fibrosis (P < 0.001), inflammation (P < 0.001), some measures of oxidative stress (P < 0.001), and hyperinsulinemia (P < 0.01). CONCLUSIONS: Suboptimal in utero nutrition combined with accelerated postnatal catch-up growth caused more hepatic fibrosis in adulthood, which was associated with higher indexes of oxidative stress and inflammation and hyperinsulinemia. CoQ10 supplementation prevented liver fibrosis accompanied by downregulation of oxidative stress, inflammation, and hyperinsulinemia.This work was supported by The British Heart Foundation [PG/09/037/27387, FS/09/029/27902]; and The Medical Research Council [MC_UU_12012/4]. Serum analysis was performed by The Wellcome Trust Supported Cambridge Mouse Laboratory, UK. SEO is a member of the MRC Metabolic Diseases Unit. IPH is supported by the Department of Health’s NIHR Biomedical Research Centers funding scheme at UCLH/UCL.This is the final version of the article. It first appeared from the American Society for Nutrition via http://dx.doi.org/10.3945/ajcn.115.11983

Concurrent Oral 9 - Rheumatoid Arthritis: Aetiopathogenesis [OP59-OP64]: OP59. The Value of Interleukin-17 Serum Level in Rheumatoid Arthritis Immunopathogenesis

Background: Interleukin (IL)-17 is the main Th-1 cytokine, produced by activated T-lymphocytes. The potential IL-17 value in rheumatoid arthritis (RA) pathogenesis consists of its independent inflammatory response induction and mediated stimulation of proinflammatory factors synthesis resulting in joint destruction. The aim of study was to determine the role of IL-17 in immuno-inflammatory/autoimmune reactions development and to reveal IL-17 serum level associations with clinical and immunological characteristics of RA. Methods: 50 patients with early RA (disease duration >, Russia), anti-CCP antibodies (Axies-Shield Diagnostic, UK) were revealed using ELISA immunoassay. Results: On the base of IL-17 serum level patients were divided in two groups: group1 (n = 28) were patients with normal IL-17 serum level and group2 (n = 22) were those with high IL-17 serum level. In the group2, the rate of patients' pain assessment by visual analogue scale (67.3 ± 7.2 vs 32.8 ± 4.6; P < 0.001), tender (16.7 ± 2.0 vs 8.4 ± 1.1; P < 0.01) and swollen (12.3 ± 2.3 vs 3.9 ± 0.8; P < 0.01) joint count, DAS28 (5.0 ± 0.4 vs 2.8 ± 0.2 P < 0.01) were significantly higher compare to group1. It was found that in group2 the higher T-lymphocyte amount (CD3) was due to CD4 higher quantity, at the same time CD8 amount was significantly lower (22.2 ± 1.5% vs 28.4 ± 1.7%, P < 0.05) compare to group1. This caused the immunoregulative index increasing and indicated in the lost of autoimmune process regulation, including B-lymphocytes (CD19) activation. The CD154 expression was significantly lower in the group2 (3.4 ± 0.4% vs 10.8 ± 2.8%, P < 0.05) compare to group1. The difference in autoimmune reaction indices wasn't significant between groups except antibody-producing B-lymphocytes (13.7 ± 1.5% vs 8.5 ± 1.0%, P < 0.05) and IgM RF serum level (2.9 ± 0.3 U/ml vs 1.6 ± 0.5 U/ml, P < 0.05), which were significantly higher in group1. The IL-17 level had a positive correlative connections with DAS28 (r = 0.7; P < 0.05), circulative immune complex level (r = 0.38; P < 0.05), anti-CCP antibodies (r = 0.4; P < 0.05), IgM RF (r = 0.41; P < 0.05), CD4 (r = 0.38; P < 0.05) and negative correlative connection with CD8 (r = -0.39; P < 0.05). Conclusions: The importance of IL-17 value in immuno-inflammatory and autoimmune reactions development through T-lymphocytes activation in RA pathogenesis was confirmed. Thus the influence on T-depended immuno-inflammatory reaction products synthesis could be a new therapeutic target of RA patients' management. Disclosure statement: All authors have declared no conflicts of interes

Seafood in Food Security: a call for bridging the terrestrial-aquatic divide

The contribution of seafood to global food security is being increasingly highlighted in policy. However, the extent to which such claims are supported in the current food security literature is unclear. This review assesses the extent to which seafood is represented in the recent food security literature, both individually and from a food systems perspective, in combination with terrestrially-based production systems. The results demonstrate that seafood remains under-researched compared to the role of terrestrial animal and plant production in food security. Furthermore, seafood and terrestrial production remain siloed, with very few papers addressing the combined contribution or relations between terrestrial and aquatic systems. We conclude that far more attention is needed to the specific and relative role of seafood in global food security and call for the integration of seafood in a wider interdisciplinary approach to global food system research

Seafood in Food Security: A Call for Bridging the Terrestrial-Aquatic Divide

The contribution of seafood to global food security is being increasingly highlighted in policy. However, the extent to which such claims are supported in the current food security literature is unclear. This review assesses the extent to which seafood is represented in the recent food security literature, both individually and from a food systems perspective, in combination with terrestrially-based production systems. The results demonstrate that seafood remains under-researched compared to the role of terrestrial animal and plant production in food security. Furthermore, seafood and terrestrial production remain siloed, with very few papers addressing the combined contribution or relations between terrestrial and aquatic systems. We conclude that far more attention is needed to the specific and relative role of seafood in global food security and call for the integration of seafood in a wider interdisciplinary approach to global food system research

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Application of a Convolutional Neural Network for the Detection of Sea Ice Leads

Despite accounting for a small fraction of the surface area in the Arctic, long and narrow sea ice fractures, known as “leads”, play a critical role in the energy flux between the ocean and atmosphere. As the volume of sea ice in the Arctic has declined over the past few decades, it is increasingly important to monitor the corresponding changes in sea ice leads. A novel approach has been developed using artificial intelligence (AI) to detect sea ice leads using satellite thermal infrared window data from the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Visible Infrared Imaging Radiometer Suite (VIIRS). In this new approach, a particular type of convolutional neural network, a U-Net, replaces a series of conventional image processing tests from our legacy algorithm. Results show the new approach has a high detection accuracy with F1 Scores on the order of 0.7. Compared to the legacy algorithm, the new algorithm shows improvement, with more true positives, fewer false positives, fewer false negatives, and better agreement between satellite instruments

Application of a Convolutional Neural Network for the Detection of Sea Ice Leads

Despite accounting for a small fraction of the surface area in the Arctic, long and narrow sea ice fractures, known as “leads”, play a critical role in the energy flux between the ocean and atmosphere. As the volume of sea ice in the Arctic has declined over the past few decades, it is increasingly important to monitor the corresponding changes in sea ice leads. A novel approach has been developed using artificial intelligence (AI) to detect sea ice leads using satellite thermal infrared window data from the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Visible Infrared Imaging Radiometer Suite (VIIRS). In this new approach, a particular type of convolutional neural network, a U-Net, replaces a series of conventional image processing tests from our legacy algorithm. Results show the new approach has a high detection accuracy with F1 Scores on the order of 0.7. Compared to the legacy algorithm, the new algorithm shows improvement, with more true positives, fewer false positives, fewer false negatives, and better agreement between satellite instruments