Carbon fibre composites: integrated electrochemical sensors for wound management

The applicability of employing a carbon fibre mesh as an electrochemical sensing substructure for assessing urate transformations within wound exudates is evaluated. Prototype sensor assemblies have been designed and their response characteristics towards uric acid and other common physiological components are detailed. Modification of the carbon fibre sensor through surface anodisation and the application of cellulose acetate permselective barriers have been shown to lead to optimized responses and much greater sensitivity (1440% increase) and specificity. These could enable the accurate periodic monitoring of uric acid in wound fluid. The performance characteristics of the composite sensors in whole blood, serum and blister fluid have been investigated

Cryptosporidiosis in calves

Cryptosporidiosis is a widespread zoonotic parasitic disease affecting livestock all over the world. Despite its prevalence, there is very little evidence about transmission routes to young calves, and how it could affect them long-term. Many commonly used disinfectants on farm are unable to inactivate Cryptosporidium oocysts, and some commercially available disinfectants, which claim to work, do not appear to have sufficient evidence available to the research and farming community. This work shows multiple commercial disinfectants which have been directly compared against each other for their efficacy against Cryptosporidium oocysts. The idea that transmission could occur from adult cattle via direct contamination of calf pens with faecal material has been disputed in scientific literature. Older research suggests that adult cattle are not infected with the same species that the calves have, however more recent research with new oocyst concentration techniques has found this not to be the case. It is essential therefore that the genotypes of Cryptosporidium are determined to see if adult cattle pose a risk to their calves. Genotyping using microsatellite analysis gives a more in-depth look at the type of C. parvum present. The aim was, therefore, to determine the risk that adult cattle pose to their calves with regard to C. parvum oocyst transmission on both a dairy and a beef farm in Scotland. Using these methods, it was discovered that adult dairy cattle are unlikely to play a major role in the transmission of C. parvum to their calves. Most of the adult cattle on the dairy farm were predominantly shedding C. parvum however calves on the same farm presented with different multilocus genotype. On the beef farm, however, many of the adult cattle did share the same multilocus genotype as their calves, and so pose more of a risk for oocyst transmission to their calves. The species and genotypes of Cryptosporidium present in Scottish wildlife has very few published studies, therefore the aim was to determine the prevalence of C. parvum in samples from rabbits and pheasants in Scotland. Rabbit faecal samples collected from 18 farms from across Scotland revealed C. parvum to be the most prevalent species; an unusual discovery as it was previosuly believed that C. cuniculus was the most prevalent species in wild rabbits. Despite this the DNA was very difficult to genotype which may indicate that the oocyst load in the faeces of rabbits was small, or that the PCR may have been affected by inhibition. If there is little DNA present, rabbits are unlikely to pose a major threat to calves with regard to C. parvum oocyst transmission. The pheasants also presented with C. parvum as the most prevalent species, although very few shared the same genotype that was present in the calves at the pheasant samples location. Very few oocysts are required to cause cryptosporidiosis in a calf, so even if co-located wildlife do not appear to be shedding high numbers of oocysts, there is still a small risk of transmission present. Young calves affected with cryptosporidiosis tend to make a full recovery under the right management, and the clinical signs clear up within a couple of weeks. It is not known whether or not there is a long-term effect on the calves ability to gain weight following infection with the parasite. Therefore the aim was to compare calves with different levels of clinical cryptosporidiosis to calves with no signs of clinical disease and weigh these animals periodically until they went to market at 6 months of age. It was found that calves with severe disease gained significantly less weight than those with no clinical disease and even animals with mild cryptosporidiosis suffered reduced weight gain over 6 months. This result demonstrates the economic cost that the parasite could have to the farming community on a long-term basis. Commonly used disinfectants are typically ineffective against Cryptosporidium oocysts, and those that are on the market have very little evidence to support their efficacy. Therefore, seven commercial disinfectants were tested for their efficacy to inactivate Cryptosporidium oocysts based on excystation rate and sporozoite to shell ratio. It was identified that hydrogen peroxide and hydrogen peroxide-based disinfectants are the most successful at inactivating oocysts, but only when the disinfectant is freshly prepared. Testing the efficacy of disinfectants once the disinfectant had been made up for 7 days showed that the best performing disinfectant with regard to having the least degradation over seven days was KENOTMCOX. As many farmers are unlikely to make disinfectant up fresh every time it is used, it is useful to know that despite the high efficacy of some products, time since the product was prepared significantly reduces this. It was also found that pens contaminated with faecal material are likely to reduce the efficacy of hydrogen peroxide-based disinfectants and so it is important to clean pens before disinfection. Therefore, this PhD has addressed the knowledge gaps in the literature regarding the role of adult cattle, rabbits and pheasants in the transmission of C. parvum to calves. Neither one poses a major risk due to the low oocyst output and mixed C. parvum genotypes present. It is more likely therefore that calves maintain infection through widespread environmental contamination caused by other infected calves. This work has shown how infection with C. parvum in the first few weeks of life has a significant effect on the weight gain achieved over a 6-month period and so cryptosporidiosis has a significant effect on livestock production and on the profitability of the farm business. The efficacy of commercial disinfectants has provided the advice that disinfectants should be made up fresh and used on an area that has already been cleaned of faecal material in order to inactivate as many of the oocysts as possible

Alpha synuclein determines ferroptosis sensitivity in dopaminergic neurons via modulation of ether-phospholipid membrane composition.

There is a continued unmet need for treatments that can slow Parkinson's disease progression due to the lack of understanding behind the molecular mechanisms underlying neurodegeneration. Since its discovery, ferroptosis has been implicated in several diseases and represents a therapeutic target in Parkinson's disease. Here, we use two highly relevant human dopaminergic neuronal models to show that endogenous levels of α-synuclein can determine the sensitivity of dopaminergic neurons to ferroptosis. We show that reducing α-synuclein expression in dopaminergic neurons leads to ferroptosis evasion, while elevated α-synuclein expression in patients' small-molecule-derived neuronal precursor cells with SNCA triplication causes an increased vulnerability to lipid peroxidation and ferroptosis. Lipid profiling reveals that ferroptosis resistance is due to a reduction in ether-linked phospholipids, required for ferroptosis, in neurons depleted of α-synuclein (α-syn). These results provide a molecular mechanism linking α-syn levels to the sensitivity of dopaminergic neurons to ferroptosis, suggesting potential therapeutic relevance

Bioavailable Trace Metals in Neurological Diseases

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron

Post translational changes to α-synuclein control iron and dopamine trafficking : a concept for neuron vulnerability in Parkinson's disease

Parkinson's disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain substantia nigra dopamine neurons that have a high α-synuclein (α-syn) and iron content. α-Syn is a neuronal protein that is highly modified post-translationally and central to the Lewy body neuropathology of the disease. This review provides an overview of findings on the role post translational modifications to α-syn have in membrane binding and intracellular vesicle trafficking. Furthermore, we propose a concept in which acetylation and phosphorylation of α-syn modulate endocytic import of iron and vesicle transport of dopamine during normal physiology. Disregulated phosphorylation and oxidation of α-syn mediate iron and dopamine dependent oxidative stress through impaired cellular location and increase propensity for α-syn aggregation. The proposition highlights a connection between α-syn, iron and dopamine, three pathological components associated with disease progression in sporadic Parkinson's disease

The Generation Challenge Programme Platform: Semantic Standards and Workbench for Crop Science

The Generation Challenge programme (GCP) is a global crop research consortium directed toward crop improvement through the application of comparative biology and genetic resources characterization to plant breeding. A key consortium research activity is the development of a GCP crop bioinformatics platform to support GCP research. This platform includes the following: (i) shared, public platform-independent domain models, ontology, and data formats to enable interoperability of data and analysis flows within the platform; (ii) web service and registry technologies to identify, share, and integrate information across diverse, globally dispersed data sources, as well as to access high-performance computational (HPC) facilities for computationally intensive, high-throughput analyses of project data; (iii) platform-specific middleware reference implementations of the domain model integrating a suite of public (largely open-access/-source) databases and software tools into a workbench to facilitate biodiversity analysis, comparative analysis of crop genomic data, and plant breeding decision making

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

The Generation Challenge Programme Platform: Semantic Standards and Workbench for Crop Science

The Generation Challenge programme (GCP) is a global crop research consortium directed toward crop improvement through the application of comparative biology and genetic resources characterization to plant breeding. A key consortium research activity is the development of a GCP crop bioinformatics platform to support GCP research. This platform includes the following: (i) shared, public platform-independent domain models, ontology, and data formats to enable interoperability of data and analysis flows within the platform; (ii) web service and registry technologies to identify, share, and integrate information across diverse, globally dispersed data sources, as well as to access high-performance computational (HPC) facilities for computationally intensive, high-throughput analyses of project data; (iii) platform-specific middleware reference implementations of the domain model integrating a suite of public (largely open-access/-source) databases and software tools into a workbench to facilitate biodiversity analysis, comparative analysis of crop genomic data, and plant breeding decision making.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Hindawi Publishing Corporation. The published article can be found at: http://www.hindawi.com/journals/ijpg/