Chelator-facilitated removal of iron from transferrin: Relevance to combined chelation therapy

Current iron chelation therapy consists primarily of DFO (desferrioxamine), which has to be administered via intravenous infusion, together with deferiprone and deferasirox, which are orally-active chelators. These chelators, although effective at decreasing the iron load, are associated with a number of side effects. Grady suggested that the combined administration of a smaller bidentate chelator and a larger hexadentate chelator, such as DFO, would result in greater iron removal than either chelator alone [Grady, Bardoukas and Giardina (1998) Blood 92, 16b]. This in turn could lead to a decrease in the chelator dose required. To test this hypothesis, the rate of iron transfer from a range of bidentate HPO (hydroxypyridin-4-one) chelators to DFO was monitored. Spectroscopic methods were utilized to monitor the decrease in the concentration of the Fe–HPO complex. Having established that the shuttling of iron from the bidentate chelator to DFO does occur under clinically relevant concentrations of chelator, studies were undertaken to evaluate whether this mechanism of transfer would apply to iron removal from transferrin. Again, the simultaneous presence of both a bidentate chelator and DFO was found to enhance the rate of iron chelation from transferrin at clinically relevant chelator levels. Deferiprone was found to be particularly effective at ‘shuttling’ iron from transferrin to DFO, probably as a result of its small size and relative low affinity for iron compared with other analogous HPO chelators

Lithium Prescribing during Pregnancy: A UK Primary Care Database Study

Women taking lithium must decide whether to continue the medication if they conceive or plan to conceive. Little is known about the extent of prescribing of lithium during pregnancy

Assessment of the dysexecutive syndrome in schizophrenia

Background. Cognitive neuropsychological theories hypothesize a role for frontal lobe executive deficits in the aetiology of schizophrenic symptoms. The study examined the performance of a schizophrenic group on the Behavioural Assessment of the Dysexecutive Syndrome (BADS), a test battery which assesses the 'everyday' difficulties associated with the dysexecutive syndrome. Performance of the schizophrenics was contrasted with that of brain injured and healthy volunteer groups. Methods. Matched groups of 31 schizophrenic patients, 35 patients-with brain injuries and 26 healthy volunteers were administered the BADS. Patients were also given tests of general intelligence and memory. Patients and their relatives/carers also completed a questionnaire rating day-to-day failures of executive functioning. Results. Schizophrenic and brain-injured patients showed impairment on the BADS, compared to healthy controls. There were no significant differences between the two patient groups. Significant impairment was found in a subgroup of 16 schizophrenics who showed otherwise intact general intellectual functioning, suggesting the existence of a specific executive deficit. Among the schizophrenic patient group there was evidence of a dissociation between executive and memory impairments. A significant correlation existed between performance on the BADS and relatives ratings of executive problems for the brain injured group, but not for the schizophrenic group. Conclusions. The BADS is a useful tool for identifying executive deficits in people with a diagnosis of schizophrenia, especially those who are otherwise generally intellectually intact. This is particularly important in the context of rehabilitation and community transition programmes.published_or_final_versio

Metabolic Biomarkers for Monitoring in Situ Anaerobic Hydrocarbon Degradation

During the past 15 years researchers have made great strides in understanding the metabolism of hydrocarbons by anaerobic bacteria. Organisms capable of utilizing benzene, toluene, ethylbenzene, xylenes, alkanes, and polycyclic aromatic hydrocarbons have been isolated and described. In addition, the mechanisms of degradation for these compounds have been elucidated. This basic research has led to the development of methods for detecting in situ biodegradation of petroleum-related pollutants in anoxic groundwater. Knowledge of the metabolic pathways used by anaerobic bacteria to break down hydrocarbons has allowed us to identify unique intermediate compounds that can be used as biomarkers for in situ activity. One of these unique intermediates is 2-methylbenzylsuccinate, the product of fumarate addition to o-xylene by the enzyme responsible for toluene utilization. We have carried out laboratory studies to show that this compound can be used as a reliable indicator of anaerobic toluene degradation. Field studies confirmed that the biomarker is detectable in field samples and its distribution corresponds to areas where active biodegradation is predicted. For naphthalene, three biomarkers were identified [2-naphthoic acid (2-NA), tetrahydro-2-NA, and hexahydro-2-NA] that can be used in the field to identify areas of active in situ degradation

Will the real Bemisia tabaci please stand up?

Since Panayiotis Gennadius first identified the whitefly, Aleyrodes tabaci in 1889, there have been numerous revisions of the taxonomy of what has since become one of the world’s most damaging insect pests. Most of the taxonomic revisions have been based on synonymising different species under the name Bemisia tabaci. It is now considered that there is sufficient biological, behavioural and molecular genetic data to support its being a cryptic species complex composed of at least 34 morphologically indistinguishable species. The first step in revising the taxonomy of this complex involves matching the A. tabaci collected in 1889 to one of the members of the species complex using molecular genetic data. To do this we extracted and then amplified a 496 bp fragment from the 39 end of the mitochondrial DNA cytochrome oxidase one (mtCOI) gene belonging to a single whitefly taken from Gennadius’ original 1889 collection. The sequence identity of this 123 year-old specimen enabled unambiguous assignment to a single haplotype known from 13 Mediterranean locations across Greece and Tunisia. This enabled us to unambiguously assign the Gennadius A. tabaci to the member of the B. tabaci cryptic species complex known as Mediterranean or as it is commonly, but erroneously referred to, as the ‘Q-biotype’. Mediterranean is therefore the real B. tabaci. This study demonstrates the importance of matching museum syntypes with known species to assist in the delimitation of cryptic species based on the organism’s biology and molecular genetic data. This study is the first step towards the reclassification of B. tabaci which is central to an improved understanding how best to manage this globally important agricultural and horticultural insect pest complex

Misinterpreting carbon accumulation rates in records from near-surface peat

Peatlands are globally important stores of carbon (C) that contain a record of how their rates of C accumulation have changed over time. Recently, near-surface peat has been used to assess the effect of current land use practices on C accumulation rates in peatlands. However, the notion that accumulation rates in recently formed peat can be compared to those from older, deeper, peat is mistaken – continued decomposition means that the majority of newly added material will not become part of the long-term C store. Palaeoecologists have known for some time that high apparent C accumulation rates in recently formed peat are an artefact and take steps to account for it. Here we show, using a model, how the artefact arises. We also demonstrate that increased C accumulation rates in near-surface peat cannot be used to infer that a peatland as a whole is accumulating more C – in fact the reverse can be true because deep peat can be modified by events hundreds of years after it was formed. Our findings highlight that care is needed when evaluating recent C addition to peatlands especially because these interpretations could be wrongly used to inform land use policy and decisions

Shape-based peak identification for ChIP-Seq

We present a new algorithm for the identification of bound regions from ChIP-seq experiments. Our method for identifying statistically significant peaks from read coverage is inspired by the notion of persistence in topological data analysis and provides a non-parametric approach that is robust to noise in experiments. Specifically, our method reduces the peak calling problem to the study of tree-based statistics derived from the data. We demonstrate the accuracy of our method on existing datasets, and we show that it can discover previously missed regions and can more clearly discriminate between multiple binding events. The software T-PIC (Tree shape Peak Identification for ChIP-Seq) is available at http://math.berkeley.edu/~vhower/tpic.htmlComment: 12 pages, 6 figure

Reconciling multiple societal objectives in cross-scale marine governance: Solomon Islands’ engagement in the Coral Triangle Initiative

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Environmental governance aims to reconcile an expanding set of societal objectives at ever-larger scales despite the challenges that remain in integrating conservation and development at smaller scales. We interrogate Solomon Islands’ engagement in the Coral Triangle Initiative on Coral Reefs, Fisheries and Food Security to contribute new insight on the scalar politics of multi-level marine governance. We show how regional objectives are re-interpreted and prioritized as they translate into national policy and practice. Our data suggest that enhanced coordination of finances and activities, integration of objectives in shared protocols and priority geographies, and a subtle shift in power relations between the state, donors, and implementation partners have resulted from processes of re-scaling. We discuss important procedural adjustments in cross-level and cross-scale governance across jurisdictional, institutional, and sectoral scales. We also reflect on the changing role of national governments in shifts toward large-scale, multi-national initiatives.LE acknowledges funding from the Australian Research Council Centre of Excellence for Coral Reef Studies. PJC and DB undertook this work as part of the CGIAR Research Program on Fish Agrifood Systems (FISH). Funding support for this study was provided by an Australian Centre for International Agricultural Research grant (FIS/2012/074)