Non-transferrin-bound iron and protein glycation in type 2 diabetes

Background and Methods The involvement of iron in the risk for, and complications of, type 2 diabetes has generated substantial interest over the past 15 years, initially sparked by an association with raised serum ferritin, and the observation that people with iron overload diseases frequently develop diabetes. Considerable advances have since been made in understanding the effect glucose has on molecules, cells, and tissues; and the role that oxidative stress plays in the development of the pathologies of long-term diabetes. Poorly liganded iron is potentially both a contributor to, and consequence of, these complications. In vitro experiments with glucose-incubated transferrin by earlier workers have demonstrated loss of function with increasing glycation, leading to the suggestion that the failure of this key iron-binding protein may contribute to diabetic pathology, via the presence of redox active non-transferrin-bound iron (NTBI). In vitro glycated transferrin is examined here by ultrafiltration, to assess loss of function and possible oxidative fragmentation. Mass spectrometry is used to identify a range of amino acid glycation sites on in vitro glycated transferrin for the first time. Finally, several groups have previously measured NTBI in people with diabetes, finding little agreement in results. NTBI is measured here in a cohort of people with type 2 diabetes, using a new adaptation of earlier NTBI assays. NTBI is also assessed in pre-dialysis chronic kidney disease (CKD) stages I to III for the first time. Results and Conclusions Experiments with glycated transferrin in vitro demonstrate oxidative fragmentation, explaining the loss of function reported by earlier groups. In vitro glycated transferrin examined by mass spectrometry reveals a substantial number and range of amino acids subject to glycation. Comparison with in vivo glycated transferrin suggests that many of the in vitro glycation sites are not glycated in vivo, and that there are many oxidized methionine residues which are potential artefacts, or likely to be repaired by methionine sulphoxide reductases in vivo. A study of people with type 2 diabetes finds no direct association between NTBI and protein glycation. Unexpected correlations between NTBI and LDL, and LDL and haemoglobin with increasing protein glycation, are reported for the first time. NTBI is suggested to be iron sourced from haemoglobin or haem, from erythrocyte haemolysis prior to sample collection. In people with pre-dialysis CKD stages I to III no significant difference in NTBI level compared to controls is seen, or correlations with markers of renal function. No link between NTBI and kidney function at this stage of disease is indicated

Therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published scientific studies and guidelines, in a form that is reasonably comprehensible to patients and people without medical training. This final version was approved at the Hemochromatosis International meeting on 12th May 2017 in Los Angeles

Non-transferrin-bound iron and protein glycation in type 2 diabetes

Background and Methods: The involvement of iron in the risk for, and complications of, type 2 diabetes has generated substantial interest over the past 15 years, initially sparked by an association with raised serum ferritin, and the observation that people with iron overload diseases frequently develop diabetes. Considerable advances have since been made in understanding the effect glucose has on molecules, cells, and tissues; and the role that oxidative stress plays in the development of the pathologies of long-term diabetes. Poorly liganded iron is potentially both a contributor to, and consequence of, these complications. In vitro experiments with glucose-incubated transferrin by earlier workers have demonstrated loss of function with increasing glycation, leading to the suggestion that the failure of this key iron-binding protein may contribute to diabetic pathology, via the presence of redox active non-transferrin-bound iron (NTBI). In vitro glycated transferrin is examined here by ultrafiltration, to assess loss of function and possible oxidative fragmentation. Mass spectrometry is used to identify a range of amino acid glycation sites on in vitro glycated transferrin for the first time. Finally, several groups have previously measured NTBI in people with diabetes, finding little agreement in results. NTBI is measured here in a cohort of people with type 2 diabetes, using a new adaptation of earlier NTBI assays. NTBI is also assessed in pre-dialysis chronic kidney disease (CKD) stages I to III for the first time. Results and Conclusions: Experiments with glycated transferrin in vitro demonstrate oxidative fragmentation, explaining the loss of function reported by earlier groups. In vitro glycated transferrin examined by mass spectrometry reveals a substantial number and range of amino acids subject to glycation. Comparison with in vivo glycated transferrin suggests that many of the in vitro glycation sites are not glycated in vivo, and that there are many oxidized methionine residues which are potential artefacts, or likely to be repaired by methionine sulphoxide reductases in vivo. A study of people with type 2 diabetes finds no direct association between NTBI and protein glycation. Unexpected correlations between NTBI and LDL, and LDL and haemoglobin with increasing protein glycation, are reported for the first time. NTBI is suggested to be iron sourced from haemoglobin or haem, from erythrocyte haemolysis prior to sample collection. In people with pre-dialysis CKD stages I to III no significant difference in NTBI level compared to controls is seen, or correlations with markers of renal function. No link between NTBI and kidney function at this stage of disease is indicated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Monitoring invasive mammalian predator populations sharing habitat with the Critically Endangered Puerto Rican parrot Amazona vittata

Critically Endangered Puerto Rican parrots Amazona vittata are one of the rarest birds in the world. Several exotic mammal species capable of preying on Puerto Rican parrots cohabit the Caribbean National Forest with the only wild population of these parrots. We used tracking plates, monitoring blocks and trapping to index black rats, small Indian mongooses and feral cats in parrot habitat and in public-use areas in the same habitat type. We had high trap success for black rats at all sites (42% of all sites combined), among the highest reported in the world. Rat response to monitoring (nontoxic bait) blocks was universally high, regardless of ground or tree placement. Mongooses were present at all sites, with a greater proportion of plates tracked within the forest than at public-use sites. Cats were present at all forest sites and one of the public-use sites. Presence of the three species did not appear to be linked to human disturbance. Because only 30–40 Puerto Rican parrots survive in the wild, with as few as three pairs nesting in 2002, we concluded that the abundance and pervasiveness of exotic mammalian predators poses a greater threat to the parrots than has been generally acknowledged. This is evidenced by mammalian predation during recent parrot breeding seasons, including six fledglings taken by mongooses and one nest failure from rats during 2000–2003

Joining the dots:How does an apex predator move through an urbanizing landscape?

Examining the movement of apex predators is difficult in urban environments due to private land ownership; however, understanding their movement is critical given the current and rapidly increasing rate of urbanization globally. Of equal importance is the understanding of what landscape factors allow these movements to occur. We used the powerful owl (Ninox strenua), an urban apex predator in Melbourne, Australia, as a case study to understand their movement ecology in urban environments.Owl movement was recorded using automated GPS logging devices deployed on ten powerful owls, resulting in 10870 GPS locations. In combination with these positions, four environmental covariates, and a priori understanding of owl ecology were used to assign movements to three different states (prey handling/eating, foraging and transitory) based on step length and turning angles between sequential locations in a hidden Markov model.We demonstrate that the environmental covariate combination of time of night, Euclidean distance to riparian vegetation, and NDVI best described movement states. Owl movement states changed across the night. Shorter movements with many turns were made towards the beginning of the night in riparian areas with high NDVI. This behavior is most likely linked to prey handling, suggesting powerful owls are more likely to hunt early in the evenings and as such travel short distances while carrying large prey items. Transitory movements with limited changes in turning angles were the dominant movement state towards the end of the night. As owls leave areas of high NDVI, they quickly travel long distances across cleared land and impervious surfaces to connect to the next habitat patch where they then transition back into shorter step lengths where NDVI is higher.This research highlights the critical importance of riparian vegetation and high NDVI areas in driving powerful owl movement and foraging in urban landscapes. Conservation priority should be placed on retaining and restoring riparian corridors as areas not only for powerful owls and their prey, but also for many other species that utilize similar resources. Keywords: GPS telemetry, Powerful owls, Spatial, Temporal, Movement ecolog

Taking the bait : the influence of attractants and microhabitat on detections of fauna by remote-sensing cameras

Autonomously triggered cameras are a common wildlife survey technique. The use of attractants and surrounding microhabitats is likely to influence detection probabilities and survey outcomes; however, few studies consider these factors. We compared three attractants (peanut butter-based, tuna-based and a control) in a Latin square design through a coastal shrubland with high microhabitat variability at Cape Otway, Victoria, Australia (38°50ʹS, 143°30ʹE). Deployments involved 36 cameras for four days in each of five years. The percentage cover of each vegetation structural type (low [no or sparse cover], moderate [grass] or high [shrubs]) within 20 m of each camera was calculated and reduced to a single variable using PCA. Dynamic occupancy modelling, with lure type and vegetation structure as covariates of detection probability, found that peanut butter attracted the greatest diversity of species (24 of 35 species, 69%) and yielded the greatest number of detections (50% of 319) when compared with tuna oil (66% and 24%, respectively) and the control (43% and 26%, respectively). Peanut butter attracted more Macropodidae (wallabies) and Muridae (rats and mice); however, vegetation structural variables were the greatest influence on Corvidae/Artamidae (raven/currawong) detections with higher detectability in more open areas. Vegetation structure also influenced Muridae detections. This study reinforces the critical choice of appropriate attractants and camera placement when investigating vertebrate groups and highlights the role of microhabitat in the detection of small mammals and birds. We suggest future large-scale camera surveys consider different bait types and microhabitats in their designs, to control for any biases and enable future advice on ‘optimal’ methods

Therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype.

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published scientific studies and guidelines, in a form that is reasonably comprehensible to patients and people without medical training. This final version was approved at the Hemochromatosis International meeting on 12th May 2017 in Los Angeles