FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective

Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.     

In Vivo Silencing of Genes Coding for dTip60 Chromatin Remodeling Complex Subunits Affects Polytene Chromosome Organization and Proper Development in Drosophila melanogaster

Chromatin organization is developmentally regulated by epigenetic changes mediated by histone-modifying enzymes and chromatin remodeling complexes. In Drosophila melanogaster, the Tip60 chromatin remodeling complex (dTip60) play roles in chromatin regulation, which are shared by evolutionarily-related complexes identified in animal and plants. Recently, it was found that most subunits previously assigned to the dTip60 complex are shared by two related complexes, DOM-A.C and DOM-B.C, defined by DOM-A and DOM-B isoforms, respectively. In this work, we combined classical genetics, cell biology, and reverse genetics approaches to further investigate the biological roles played during Drosophila melanogaster development by a number of subunits originally assigned to the dTip60 complex.     

Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.     

Cowpea resistance and bioactivity of two diatomaceous earths against Callosobruchus maculatus (F.) (Coleoptera: Chrysomelidae) on three cowpea varieties

The bruchid, Callosobruchus maculatus (F.) is the most important pest of stored cowpea in tropical climates. Experiments were conducted to evaluate the susceptibility of three cowpea varieties and the bioactivity of SilicoSec® and FossilShield® against this insect pest under ambient laboratory conditions at the contents 0, 0.5, 1, 1.5 and 2 g/kg of cowpea. The Dobie susceptibility index for cowpea genotypes was estimated to compare their relative tolerance to this insect pest. Adult mortality was assessed after 1, 2, 4 and 6 days of exposure followed by the evaluation of the F₁ progeny. Population increase, percentage seed damage and weight loss were assessed after three months of storage. The results showed that the CRPS and TN5-78 varieties were highly susceptible to C. maculatus, while Lori variety was moderately susceptible to the weevil. SilicoSec® and FossilShield® caused a significant and increasing bruchid mortality according to the dose rates and periods of exposure. Malathion 5% caused complete mortality after one day exposure time. SilicoSec® was more effective than FossilShield® on the three varieties of cowpea. The greatest dose of SilicoSec® and FossilShield® (2 g/kg) caused 100% mortality on all three varieties; 4 days of exposure in the Lori variety was the shortest exposure time leading to complete mortality. Regarding LD₅₀ and LD₉₅ values, it was observed that C. maculatus adults are more susceptible to SilicoSec® than to FossilShield®.The two formulations of diatomaceous earth (1.5 g/kg) reduced the F₁ progeny by more than 70%, and produced less than 10% of seed damage and weight loss for the three varieties of cowpea. The varietal resistance and the use of diatomaceous earth against C. maculatus in storage could represent an alternative to Malagrain® for the protection of the cowpea.     

Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disorders caused by a loss of tolerance to endogenous nuclear antigens triggering an aberrant autoimmune response targeting various tissues. Lupus nephritis (LN), a major cause of morbidity and mortality in patients with SLE, affects up to 60% of patients. The recent insights into the genetic and molecular basis of SLE and LN paved the way for newer therapies to be developed for these patients. Apart from the traditional B-cell-centered view of this disease pathogenesis, acknowledging that multiple extrarenal and intrarenal pathways contribute to kidney-specific autoimmunity and injury may help refine the individual therapeutic and prognostic characterization of such patients. Accordingly, the formerly induction-maintenance treatment strategy was recently challenged with the exciting results obtained from the trials that evaluated add-on therapy with voclosporin, belimumab, or Obinutuzumab. The scope of this review is to provide an insight into the current knowledge of LN pathogenesis and future therapeutic strategies.     

Protective nature of nano-TiN coatings shaped by EPD on Ti substrates

The hardness and corrosion resistance of TiN coatings, processed by Electrophoretic Deposition (EPD) to cover polished and unpolished Ti substrates, have been evaluated. A deposition time of 5 min has been enough to obtain a cohesive layer of 7–8 μm in thickness. The coatings were thermally treated in vacuum atmosphere at 1200 °C for 1 h with heating and cooling rates of 5 °C min^?1. The surfaces have been covered homogeneously optimizing the properties of the Ti substrates. Uniform and dense TiN coatings have been obtained onto polished substrates, while on unpolished Ti the nitrogen diffuses toward the substrate, moderately dissolving TiN coating. The nanohardness values of the polished samples have been increased from 2.8–4.8 GPa up to 6.5–8.5 GPa. Besides, the corrosion current density has been reduced more than one order of magnitude obtaining a protective efficiency of 82%. These values have been compared with other works in literature where authors used complex and costly processing techniques, demonstrating the strong impact of the colloidal processing over the specific properties of the material.     

Evolution on neutral networks accelerates the ticking rate of the molecular clock

Large sets of genotypes give rise to the same phenotype, because phenotypic expression is highly redundant. Accordingly, a population can accept mutations without altering its phenotype, as long as the genotype mutates into another one on the same set. By linking every pair of genotypes that are mutually accessible through mutation, genotypes organize themselves into neutral networks (NNs). These networks are known to be heterogeneous and assortative, and these properties affect the evolutionary dynamics of the population. By studying the dynamics of populations on NNs with arbitrary topology, we analyse the effect of assortativity, of NN (phenotype) fitness and of network size. We find that the probability that the population leaves the network is smaller the longer the time spent on it. This progressive ‘phenotypic entrapment’ entails a systematic increase in the overdispersion of the process with time and an acceleration in the fixation rate of neutral mutations. We also quantify the variation of these effects with the size of the phenotype and with its fitness relative to that of neighbouring alternatives.     

Nonlinear adaptive filtering using kernel‐based algorithms with dictionary adaptation

Nonlinear adaptive filtering has been extensively studied in the literature, using, for example, Volterra filters or neural networks. Recently, kernel methods have been offering an interesting alternative because they provide a simple extension of linear algorithms to the nonlinear case. The main drawback of online system identification with kernel methods is that the filter complexity increases with time, a limitation resulting from the representer theorem, which states that all past input vectors are required. To overcome this drawback, a particular subset of these input vectors (called dictionary) must be selected to ensure complexity control and good performance. Up to now, all authors considered that, after being introduced into the dictionary, elements stay unchanged even if, because of nonstationarity, they become useless to predict the system output. The objective of this paper is to present an adaptation scheme of dictionary elements, which are considered here as adjustable model parameters, by deriving a gradient‐based method under collinearity constraints. The main interest is to ensure a better tracking performance. To evaluate our approach, dictionary adaptation is introduced into three well‐known kernel‐based adaptive algorithms: kernel recursive least squares, kernel normalized least mean squares, and kernel affine projection. The performance is evaluated on nonlinear adaptive filtering of simulated and real data sets. As confirmed by experiments, our dictionary adaptation scheme allows either complexity reduction or a decrease of the instantaneous quadratic error, or both simultaneously. Copyright © 2015 John Wiley & Sons, Ltd.     

Revisiting Linus’s law: Benefits and challenges of open source software peer review

Open source projects leverage a large number of people to review products and improve code quality. Differences among participants are inevitable and important to this collaborative review process—participants with different expertise, experience, resources, and values approach the problems differently, increasing the likelihood of finding more bugs and fixing the particularly difficult ones. To understand the impacts of member differences on the open source software peer review process, we examined bug reports of Mozilla Firefox. These analyses show that the various types of member differences increase workload as well as frustration and conflicts. However, they facilitate situated learning, problem characterization, design review, and boundary spanning. We discuss implications for work performance and community engagement, and suggest several ways to leverage member differences in the open source software peer review process.     

Transposable Elements and Stress in Vertebrates: An Overview

Since their identification as genomic regulatory elements, Transposable Elements (TEs) were considered, at first, molecular parasites and later as an important source of genetic diversity and regulatory innovations. In vertebrates in particular, TEs have been recognized as playing an important role in major evolutionary transitions and biodiversity. Moreover, in the last decade, a significant number of papers has been published highlighting a correlation between TE activity and exposition to environmental stresses and dietary factors. In this review we present an overview of the impact of TEs in vertebrate genomes, report the silencing mechanisms adopted by host genomes to regulate TE activity, and finally we explore the effects of environmental and dietary factor exposures on TE activity in mammals, which is the most studied group among vertebrates. The studies here reported evidence that several factors can induce changes in the epigenetic status of TEs and silencing mechanisms leading to their activation with consequent effects on the host genome. The study of TE can represent a future challenge for research for developing effective markers able to detect precocious epigenetic changes and prevent human diseases.