Ferritinophagy and α-Synuclein: Pharmacological Targeting of Autophagy to Restore Iron Regulation in Parkinson’s Disease

A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated α-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation.     

Circular RNAs in Pregnancy and the Placenta

The emerging field of circular RNAs (circRNAs) has identified their novel roles in the development and function of many cancers and inspired the interest of many researchers. circRNAs are also found throughout the healthy body, as well as in other pathological states, but while research into the function and abundance of circRNAs has progressed, our overall understanding of these molecules remains primitive. Importantly, recent studies are elucidating new roles for circRNAs in pregnancy, particularly in the placenta. Given that many of the genes responsible for circRNA production in cancer are also highly expressed in the placenta, it is likely that the same genes act in the production of circRNAs in the placenta. Furthermore, placental development can be referred to as ‘controlled cancer’, as it shares many key signalling pathways and hallmarks with tumour growth and metastasis. Hence, the roles of circRNAs in this field are important to study with respect to pregnancy success but also may provide novel insights for cancer progression. This review illuminates the known roles of circRNAs in pregnancy and the placenta, as well as demonstrating differential placental expressions of circRNAs between complicated and uncomplicated pregnancies.     

Development of the industrial relevance of catalysis and its physiochemical basis (1860-1940)

This was the period when industrial catalysis and the formulation of the relevant physiochemical principles developed simultaneously. The excellence of chemistry in Germany was recognised through Nobel Prizes being awarded to Nernst, Haber, Bosch and Ostwald all of whom had made significant contributions to heterogeneous catalysis which had, to some extent, been stimulated by the requirements of the First World War. The synthesis and oxidation of ammonia dominated the scene but also saw the emergence of catalytic hydrogenation through the work of Sabatier and also Fischer-Tropsch catalysis. Fundamental ideas on adsorption were put forward by Polanyi in Hungary, Langmuir in the USA and Eucken in Germany with Langmuir being awarded the Nobel Prize in 1932 for 'Discoveries and Inventions in Chemistry'. The concept of 'activation energy' was enunciated by Arrhenius, Nobel Prize winner in 1903. Concern was being raised concerning the nature of 'active centres' and the concept of activated adsorption was introduced by Rideal and Taylor while others such as Langmuir and J.K. Roberts paid attention to the preparation of “clean” surfaces with Otto Beeck making significant contributions through the use of evaporated metal lms as substrates. This revised version was published online in July 2006 with corrections to the Cover Date. This revised version was published online in July 2006 with corrections to the Cover Date.     

Mechanistic aspects of the heterogeneouscatalysts:the classical approach (1950-1980)

Strong “classical” heterogeneous catalysis groups were emerging in the USA (Boudart, Burwell, Emmett, Turkevich, Weisz),France (Imelik, Teichner), USSR (Boreskov, Kazansky, Balandin, Volkenstein), Netherlands (Schuit, Sachtler, van Reijen, Ponec), Poland (Haber) and the UK (Bond, Dowden, Eley, Kemball, Stone, Thompson, Webb and Wells). In the main there was an emphasis on ascertaining reaction mechanisms from monitoring the gas phase through for example exchange and kinetic studies, with less attention given to the surface although catalyst preparation and knowledge of solid state chemistry, particularly the role of defects in oxide surfaces and the electronic theory of catalysis, were recurring themes. Two spectroscopic techniques that were most significant in supporting the classical approach was infrared (widely used) and electron spin resonance (Che, Tench, Kazansky, Pink and Rooney). During the last decade of this period surface sensitive spectroscopies (X-ray photoelectron, Auger and Reflection Absorption Infrared) had become established but in the main were confined to the surface science schools (Pritchard, Chesters, King, Yates, Somorjai, Solymosi and Roberts) who were giving more attention to reactions and chemisorption (mainly CO!) at single crystal metal surfaces. This revised version was published online in July 2006 with corrections to the Cover Date. This revised version was published online in July 2006 with corrections to the Cover Date.     

Epitope mapping using mRNA display and a unidirectional nested deletion library

In vitro selection targeting an anti-polyhistidine monoclonal antibody was performed using mRNA display with a random, unconstrained 27-mer peptide library. After six rounds of selection, epitope-like peptides were identified that contain two to five consecutive, internal histidines and are biased for arginine residues, without any other identifiable consensus. The epitope was further refined by constructing a high-complexity, unidirectional fragment library from the final selection pool. Selection by mRNA display minimized the dominant peptide from the original selection to a 15-residue functional sequence (peptide Cmin: RHDAGDHHHHHGVRQ; K(D) = 38 nM). Other peptides recovered from the fragment library selection revealed a separate consensus motif (ARRXA) C-terminal to the histidine track. Kinetics measurements made by surface plasmon resonance, using purified Fab (antigen-binding fragment) to prevent avidity effects, demonstrate that the selected peptides bind with 10- to 75-fold higher affinities than a hexahistidine peptide. The highest affinity peptides (K(D) approximately 10 nM) encode both a short histidine track and the ARRXA motif, suggesting that the motif and other flanking residues make important contacts adjacent to the core polyhistidine-binding site and can contribute >2.5 kcal/mol of binding free energy. The fragment library construction methodology described here is applicable to the development of high-complexity protein or cDNA expression libraries for the identification of protein-protein interaction domains.     

Toward rapid, "green", predictable microwave-assisted synthesis

Continuous and batch microwave reactors were constructed for efficient, "green" synthesis with low-boiling solvents at high temperature in closed vessels. Capabilities for rapid heating and cooling, concurrent heating and cooling, and differential heating facilitated novel chemical reactions and processes. Commercial microwave systems based on these developments are available. Times required for conventional reactions typically are decreased by 2-3 orders of magnitude. Green processes also have resulted through use of less or no catalyst, readily recyclable solvents, or media and yields that are often higher than normal. Complementary interactive software for calculating optimal conditions was developed.     

Acute effects of ingesting a commercial thermogenic drink on changes in energy expenditure and markers of lipolysis

Background  

To determine the acute effects of ingesting a thermogenic drink (Celsius, Delray Beach, FL) (TD) on changes in metabolism and lipolysis.     

Performance of Φ-Sulfo Fatty Methyl Ester Sulfonate Versus Linear Alkylbenzene Sulfonate,Secondary Alkane Sulfonate and α-Sulfo Fatty Methyl Ester Sulfonate

Sulfoxidation of fatty acid methyl esters with SO_2, O₂ and ultraviolet light of appropriate wavelength, has led to the synthesis of methyl esters sulfonates or sulfoxylates, known as Φ-MES, because of the possible random position of SO₃ group in the alkyl chain. Aqueous solutions based on the sulfoxylated methyl ester of palmitic acid (Φ-MES C16) have been studied and compared to the leading types of surfactants used today: linear alkylbenzene sulfonate (LAS) secondary alkane sulfonate (SAS) and α-sulfo fatty methyl ester sulfonate (α-MES) with regard to solubility, performance and skin compatibility. The experimental results obtained indicate that Φ-MES C16 can be regarded as a potential component of detergent formulations and most likely also of body care products.

Long term assessment of a hybrid electrochemical treatment

Monitoring the performance of systems installed to protect against/halt the corrosion of reinforcing steel in concrete is essential in ensuring that the reinforcing bar (rebar) is adequately protected and remains in a non‐corroding state. A chloride contaminated concrete test block containing a hybrid anode system has been periodically monitored over the past 4.5 years to assess the anode current output and thus, the protection offered to the steel. De‐polarisation and impedance analysis data have been acquired to calculate steel corrosion rates. Both tests indicated that the steel was passive in the concrete environment and that the anode was able to protect all of the embedded steel despite the difficult geometry of the sample. It was also found that after 2 years it was still possible to drive a high current from the installed anode.     

Chemical coupling of polypropylene systems containing nonglass fillers

Maleic anhydride (MAH) modified polypropylene (PP) was demonstrated to be a chemical coupling agent in filled PP compounds. Improved properties were shown for talc and wollastonite filled PP compounds with MAH modified PP as a coupling agent. Partial replacement of glass fiber with wollastonite showed no reduction in properties.