Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

In the last decade, clear evidence has emerged that the cellular components of skeletal muscle are important sites for the release of proteins and peptides called “myokines”, suggesting that skeletal muscle plays the role of a secretory organ. After their secretion by muscles, these factors serve many biological functions, including the exertion of complex autocrine, paracrine and/or endocrine effects. In sum, myokines affect complex multi-organ processes, such as skeletal muscle trophism, metabolism, angiogenesis and immunological response to different physiological (physical activity, aging, etc.) or pathological states (cachexia, dysmetabolic conditions, chronic inflammation, etc.). The aim of this review is to describe in detail a number of myokines that are, to varying degrees, involved in skeletal muscle aging processes and belong to the group of proteins present in the functional environment surrounding the muscle cell known as the “Niche”. The particular myokines described are those that, acting both from within the cell and in an autocrine manner, have a defined relationship with the modulation of oxidative stress in muscle cells (mature or stem) involved in the regulatory (metabolic or regenerative) processes of muscle aging. Myostatin, IGF-1, NGF, S100 and irisin are examples of specific myokines that have peculiar features in their mechanisms of action. In particular, the potential role of one of the most recently characterized myokines—irisin, directly linked to an active lifestyle—in reducing if not reversing senescence-induced oxidative damage is discussed in terms of its possible application as an agent able to counteract the deleterious effects of muscle aging.     

Genes Implicated in Familial Parkinson’s Disease Provide a Dual Picture of Nigral Dopaminergic Neurodegeneration with Mitochondria Taking Center Stage

The mechanism of nigral dopaminergic neuronal degeneration in Parkinson’s disease (PD) is unknown. One of the pathological characteristics of the disease is the deposition of α-synuclein (α-syn) that occurs in the brain from both familial and sporadic PD patients. This paper constitutes a narrative review that takes advantage of information related to genes (SNCA, LRRK2, GBA, UCHL1, VPS35, PRKN, PINK1, ATP13A2, PLA2G6, DNAJC6, SYNJ1, DJ-1/PARK7 and FBXO7) involved in familial cases of Parkinson’s disease (PD) to explore their usefulness in deciphering the origin of dopaminergic denervation in many types of PD. Direct or functional interactions between genes or gene products are evaluated using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The rationale is to propose a map of the interactions between SNCA, the gene encoding for α-syn that aggregates in PD, and other genes, the mutations of which lead to early-onset PD. The map contrasts with the findings obtained using animal models that are the knockout of one of those genes or that express the mutated human gene. From combining in silico data from STRING-based assays with in vitro and in vivo data in transgenic animals, two likely mechanisms appeared: (i) the processing of native α-syn is altered due to the mutation of genes involved in vesicular trafficking and protein processing, or (ii) α-syn mutants alter the mechanisms necessary for the correct vesicular trafficking and protein processing. Mitochondria are a common denominator since both mechanisms require extra energy production, and the energy for the survival of neurons is obtained mainly from the complete oxidation of glucose. Dopamine itself can result in an additional burden to the mitochondria of dopaminergic neurons because its handling produces free radicals. Drugs acting on G protein-coupled receptors (GPCRs) in the mitochondria of neurons may hopefully end up targeting those receptors to reduce oxidative burden and increase mitochondrial performance. In summary, the analysis of the data of genes related to familial PD provides relevant information on the etiology of sporadic cases and might suggest new therapeutic approaches.     

A Breach in Plant Defences: Pseudomonas syringae pv. actinidiae Targets Ethylene Signalling to Overcome Actinidia chinensis Pathogen Responses

Ethylene interacts with other plant hormones to modulate many aspects of plant metabolism, including defence and stomata regulation. Therefore, its manipulation may allow plant pathogens to overcome the host’s immune responses. This work investigates the role of ethylene as a virulence factor for Pseudomonas syringae pv. actinidiae (Psa), the aetiological agent of the bacterial canker of kiwifruit. The pandemic, highly virulent biovar of this pathogen produces ethylene, whereas the biovars isolated in Japan and Korea do not. Ethylene production is modulated in planta by light/dark cycle. Exogenous ethylene application stimulates bacterial virulence, and restricts or increases host colonisation if performed before or after inoculation, respectively. The deletion of a gene, unrelated to known bacterial biosynthetic pathways and putatively encoding for an oxidoreductase, abolishes ethylene production and reduces the pathogen growth rate in planta. Ethylene production by Psa may be a recently and independently evolved virulence trait in the arms race against the host. Plant- and pathogen-derived ethylene may concur in the activation/suppression of immune responses, in the chemotaxis toward a suitable entry point, or in the endophytic colonisation.     

The skipping strategy to reduce the effect of the autocorrelation on the <Emphasis Type="Italic">T</Emphasis><Superscript>2</Superscript> chart’s performance

In this article, we consider the T ² control chart for bivariate samples of size n with observations that are not only cross-correlated but also autocorrelated. The cross-covariance matrix of the sample mean vectors were derived with the assumption that the observations are described by a first-order vector autoregressive model—VAR (1). To counteract the undesired effect of autocorrelation, we build up the samples taking one item from the production line and skipping one, two, or more before selecting the next one. The skipping strategy always improves the chart’s performance, except when only one variable is affected by the assignable cause, and the observations of this variable are not autocorrelated. If only one item is skipped, the average run length (ARL) reduces in more than 30 %, on average. If two items are skipped, this number increases to 40 %.     

Cascade of Peritectic Reactions in the B-Fe-U System

The solidification paths for UFeB₄, UFe₃B₂ and UFe₄B, ternary compounds, situated along the U:(Fe,B) = 1:5 line in the B-Fe-U phase diagram, are proposed based on x-ray powder diffraction measurements, differential thermal analysis, heating curves and scanning electron microscopy observations complemented with energy and wavelength dispersive x-ray spectroscopies. The compounds melt incongruently and are formed by peritectic reactions. The present work demonstrates the existence of a cascade of peritectic reactions along the U:(Fe,B) = 1:5 composition line, establishes peritectic temperatures and proposes an isopleth diagram along this line.     

Co-gasification of coal and wastes in a pilot-scale installation. 2: Effect of catalysts in syngas treatment to achieve sulphur and nitrogen compounds abatement

Coal mixed with different types of wastes was co-gasified in a pilot-scale installation. The syngas produced was hot treated in two catalytic fixed-bed reactors. In the first one, dolomite was used and in the second reactor, a nickel-based catalyst was employed. Two different grade coals were tested, Puertollano and Colombian. Puertollano coal had high ash and sulphur contents, 42.5% and 2.4%, respectively, while ash and sulphur contents of Colombian coal were, respectively, 12.7% and 0.9%. Pine, bagasse, RDF and PE were the wastes mixed with both coals. After dolomite fixed-bed reactor, H₂S and NH₃ contents in syngas were much lower than those of the gas leaving the gasifier. For most coal and waste blends, NH₃ reductions changed between 30% and 50% depending on feedstock nitrogen content, while H₂S reductions achieved values from 68% to 74%, also depending on H₂S concentration in syngas. After syngas had gone through the nickel-based catalyst, it presented H₂S and NH₃ contents that allowed its use in boilers and gas engines for most coal and waste blends. The overall syngas treatment led to H₂S and NH₃ reductions higher than 97%. For most experiments, final H₂S and NH₃ concentration in syngas were below 20 ppmv and 30 ppmv, respectively.     

Effect of agglomerate properties on agglomerate stability in fluidized beds

Fluidized bed agglomeration is used to stabilize particulate mixtures and reduce dust emissions. This technology is applied to a variety of production processes for the pharmaceutical, chemical, fertilizer and food industries. In most of these applications, agglomerate stability is an essential criterion. Agglomerates and granules that do not conform to size and shape specifications may create problems in downstream processes, such as tableting, thus compromising process efficiency and product quality. When an agglomerate is formed in a fluidized bed, it can grow by incorporating other bed particles, split into smaller fragments, or be eroded by fluidized bed solids. The objective of the present study is to determine the critical agglomerate liquid content at which the rates of agglomerate growth and shrinkage are balanced when artificial agglomerates made from glass beads and water are introduced into a fluidized bed. This study examined the effects of agglomerate size, agglomerate density, liquid viscosity, binder concentration, and fluidizing gas velocity on the critical initial liquid content. This study found that small agglomerates and low density agglomerates displayed higher critical initial moisture contents. When the viscosity was increased by using sugar solutions, agglomerates were very stable and had very low critical initial moisture contents. The study also found that as the superficial gas velocity increased, the agglomerates started to fragment, rather than erode.     

Sulphur distribution in Illinois no. 6 coal subjected to different oxidation pre-treatments

The effect of different oxidation pre-treatments on the sulphur distribution in Illinois No. 6 coal (IBC-101) was studied using Atmospheric Pressure-Temperature Programmed Reduction (AP-TPR). Oxidation pre-treatments were carried out on demineralized coal with peroxyacetic acid (PAA) as a function of reaction time. For the longest reaction time the effect of PAA on the coal was compared to the effect of several other oxidants. AP-TPR results also show a clear effect of LiAlH₄ on the coal. Not only is pyrite removed, but there is also a decrease in other sulphur forms. Subsequent PAA oxidation causes an overall decrease of the AP-TPR signal, signifying the attack on organic as well as inorganic sulphur forms. With other oxidants, under the same conditions, only minor differences could be found after different treatments.     

3‐Amidocoumarins as Potential Multifunctional Agents against Neurodegenerative Diseases

Monoamine oxidase (MAO) generates reactive oxygen species (ROS), which cause neuronal cell death, causing neurodegeneration. Agents that are able to concurrently inhibit MAO and scavenge free radicals represent promising multifunctional neuroprotective agents that could be used to delay or slow the progression of neurodegenerative diseases. In this work, variously substituted 3‐amidocoumarins are described that exert neuroprotection in vitro against hydrogen peroxide in rat cortical neurons, as well as antioxidant activity in a 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH?) radical scavenging assay. Selective and reversible inhibitors of the MAO‐B isoform were identified. Interestingly, in the case of the 3‐benzamidocoumarins, substitution at position 4 with a hydroxy group abolishes MAO‐B activity, but the compounds remain active in the neuroprotection model. Further evaluation of 3‐heteroarylamide derivatives indicates that it is the nature of the heterocycle that determines the neuroprotective effects. Evaluation in a parallel artificial membrane permeability assay (PAMPA) highlighted the need to further improve the blood–brain barrier permeability of this compound class. However, the compounds described herein adhere to Lipinski′s rule of five, suggesting that this novel scaffold has desirable properties for the development of potential drug candidates.     

Ethyl Oleate and Ethyl Elaidate Ozonides: Thermal Decomposition and Photolysis

Highly pure ethyl oleate and ethyl elaidate were ozonized to their secondary ozonides (respectively EO-SOZ and EE-SOZ). The decomposition enthalpies of EO-SOZ and EE-SOZ were determined by DSC (Differential Scanning Calorimetry) and found, respectively, at --266 kJ/mol and --264 kJ/mol, a value much closer to the theoretically calculated upper limit of --278 kJ/mol than the decomposition enthalpy of --243 kJ/mol measured on EO-SOZ prepared from an ethyl oleate sample conforming to the European Pharmacopoeia. Although a considerable amount of heat was liberated, EO-SOZ and EE-SOZ cannot be defined as explosive based on their DSC traces at a heating rate of 10 °C/min. Pure EO-SOZ and EE-SOZ show a decomposition peak at the DSCs of 137 °C and 139 °C, respectively. The thermal decomposition of EO-SOZ and EE-SOZ was studied also by FT-IR spectroscopy showing that the decomposition involves the loss of the ozonide infrared band at 1110 cm^?1 and the formation of the expected decomposition products (pelargonic acid, pelargonaldehyde, ethyl azelate, etc.). The kinetics of the photochemical decomposition of EO-SOZ and EE-SOZ were studied by FT-IR spectroscopy, and the relative rate constants were determined. EO-SOZ when overozonized forms a spin adduct with nitrosobenzene and the relative nitroxyl radical was clearly detected by the Electron Spin Resonance (ESR). Secondary ozonation products known as trioxides may be responsible for these adducts.