From Synthesis to Utilization: The Ins and Outs of Mitochondrial Heme

Heme is a ubiquitous and essential iron containing metallo-organic cofactor required for virtually all aerobic life. Heme synthesis is initiated and completed in mitochondria, followed by certain covalent modifications and/or its delivery to apo-hemoproteins residing throughout the cell. While the biochemical aspects of heme biosynthetic reactions are well understood, the trafficking of newly synthesized heme—a highly reactive and inherently toxic compound—and its subsequent delivery to target proteins remain far from clear. In this review, we summarize current knowledge about heme biosynthesis and trafficking within and outside of the mitochondria

Discovery of a single male Aedes aegypti (L.) in Merseyside, England

© The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The file attached is the published (publishers PDF) version of the article

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

Finite to infinite steady state solutions, bifurcations of an integro-differential equation

We consider a bistable integral equation which governs the stationary solutions of a convolution model of solid--solid phase transitions on a circle. We study the bifurcations of the set of the stationary solutions as the diffusion coefficient is varied to examine the transition from an infinite number of steady states to three for the continuum limit of the semi--discretised system. We show how the symmetry of the problem is responsible for the generation and stabilisation of equilibria and comment on the puzzling connection between continuity and stability that exists in this problem

Enhanced West Nile virus surveillance in the North Kent marshes, UK

Background As part of efforts to more fully understand the potential risks posed by West Nile virus (WNV) and Usutu virus (USUV) in the UK, and following on from previous reports of a potential bridge vector Culex modestus for these viruses, at wetland sites in North Kent, mosquito surveillance was undertaken more widely across the Isle of Sheppey, the Hoo Peninsula and the Kent mainland. Methods Larval surveys were conducted and Mosquito Magnet® adult traps were used to collect adult mosquitoes. Pools of female mosquitoes were tested for the presence of WNV using real-time reverse transcriptase polymerase chain reaction. A subset of samples was tested for USUV. Results Culex modestus was found in both the pre-imaginal and imago stage at all five locations surveyed, accounting for 90% of adult mosquitoes collected. WNV or USUV were not detected in any sample. Conclusions Although no mosquitoes have been shown to be virus positive, the field survey data from this study demonstrated the dominance of an important bridge vector species for WNV in this region. Its wide geographical distribution highlights the need to update risk assessments on WNV introduction, and to maintain vigilance for WNV in the South East of England

Mitochondrial contact site and cristae organizing system (MICOS) machinery supports heme biosynthesis by enabling optimal performance of ferrochelatase

Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied and its biosynthetic enzymes structurally characterized to varying extents. Nevertheless, understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Therefore, we investigated the molecular organization as well as the physical and genetic interactions of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and genetic analyses revealed dynamic association of Hem15 with Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS). Loss of MICOS negatively impacts Hem15 activity, affects the size of the Hem15 high-mass complex, and results in accumulation of reactive and potentially toxic tetrapyrrole precursors that may cause oxidative damage. Restoring intermembrane connectivity in MICOS-deficient cells mitigates these cytotoxic effects. These data provide new insights into how heme biosynthetic machinery is organized and regulated, linking mitochondrial architecture-organizing factors to heme homeostasis

Detecting modification of biomedical events using a deep parsing approach

<p>Abstract</p> <p>Background</p> <p>This work describes a system for identifying event mentions in bio-molecular research abstracts that are either speculative (e.g. <it>analysis of IkappaBalpha phosphorylation</it>, where it is not specified whether phosphorylation did or did not occur) or negated (e.g. <it>inhibition of IkappaBalpha phosphorylation</it>, where phosphorylation did <it>not </it>occur). The data comes from a standard dataset created for the BioNLP 2009 Shared Task. The system uses a machine-learning approach, where the features used for classification are a combination of shallow features derived from the words of the sentences and more complex features based on the semantic outputs produced by a deep parser.</p> <p>Method</p> <p>To detect event modification, we use a Maximum Entropy learner with features extracted from the data relative to the trigger words of the events. The shallow features are bag-of-words features based on a small sliding context window of 3-4 tokens on either side of the trigger word. The deep parser features are derived from parses produced by the English Resource Grammar and the <it>RASP </it>parser. The outputs of these parsers are converted into the Minimal Recursion Semantics formalism, and from this, we extract features motivated by linguistics and the data itself. All of these features are combined to create training or test data for the machine learning algorithm.</p> <p>Results</p> <p>Over the test data, our methods produce approximately a 4% absolute increase in F-score for detection of event modification compared to a baseline based only on the shallow bag-of-words features.</p> <p>Conclusions</p> <p>Our results indicate that grammar-based techniques can enhance the accuracy of methods for detecting event modification.</p

Modelling the strategies for age specific vaccination scheduling during influenza pandemic outbreaks

Finding optimal policies to reduce the morbidity and mortality of the ongoing pandemic is a top public health priority. Using a compartmental model with age structure and vaccination status, we examined the effect of age specific scheduling of vaccination during a pandemic influenza outbreak, when there is a race between the vaccination campaign and the dynamics of the pandemic. Our results agree with some recent studies on that age specificity is paramount to vaccination planning. However, little is known about the effectiveness of such control measures when they are applied during the outbreak. Comparing five possible strategies, we found that age specific scheduling can have a huge impact on the outcome of the epidemic. For the best scheme, the attack rates were up to 10% lower than for other strategies. We demonstrate the importance of early start of the vaccination campaign, since ten days delay may increase the attack rate by up to 6%. Taking into account the delay between developing immunity and vaccination is a key factor in evaluating the impact of vaccination campaigns. We provide a general framework which will be useful for the next pandemic waves as well

The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro

Background: Osteosarcoma (OS) affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6–12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death. Results: Taurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 μM taurolidine and less so in cells exposed to 250 μM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine’s effects may depend on the functional status of p53 in canine OS. Conclusion: Taurolidine’s cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.KEYWORDS: Carboplatin, In vitro, Apoptosis, Osteosarcoma, Taurolidine, DoxorubicinThis is the publisher’s final pdf. The published article is copyrighted by BioMed Central Ltd. and can be found at: http://www.biomedcentral.com

Assessment of the quality of fall detection and management in primary care in the Netherlands based on the ACOVE quality indicators

We determined adherence to nine fall-related ACOVE quality indicators to investigate the quality of management of falls in the elderly population by general practitioners in the Netherlands. Our findings demonstrate overall low adherence to these indicators, possibly indicating insufficiency in the quality of fall management. Most indicators showed a positive association between increased risk for functional decline and adherence, four of which with statistical significance