Lamp1 Deficiency Enhances Sensitivity to α-Synuclein and Oxidative Stress in Drosophila Models of Parkinson Disease

Parkinson disease (PD) is a common neurodegenerative condition affecting people predominantly at old age that is characterized by a progressive loss of midbrain dopaminergic neurons and by the accumulation of α-synuclein-containing intraneuronal inclusions known as Lewy bodies. Defects in cellular degradation processes such as the autophagy-lysosomal pathway are suspected to be involved in PD progression. The mammalian Lysosomal-associated membrane proteins LAMP1 and LAMP2 are transmembrane glycoproteins localized in lysosomes and late endosomes that are involved in autophagosome/lysosome maturation and function. Here, we show that the lack of Drosophila Lamp1, the homolog of LAMP1 and LAMP2, severely increased fly susceptibility to paraquat, a pro-oxidant compound known as a potential PD inducer in humans. Moreover, the loss of Lamp1 also exacerbated the progressive locomotor defects induced by the expression of PD-associated mutant α-synuclein A30P (α-synA30P) in dopaminergic neurons. Remarkably, the ubiquitous re-expression of Lamp1 in a mutant context fully suppressed all these defects and conferred significant resistance towards both PD factors above that of wild-type flies. Immunostaining analysis showed that the brain levels of α-synA30P were unexpectedly decreased in young adult Lamp1-deficient flies expressing this protein in comparison to non-mutant controls. This suggests that Lamp1 could neutralize α-synuclein toxicity by promoting the formation of non-pathogenic aggregates in neurons. Overall, our findings reveal a novel role for Drosophila Lamp1 in protecting against oxidative stress and α-synuclein neurotoxicity in PD models, thus furthering our understanding of the function of its mammalian homologs.     

Melanins from the Lichens Lobaria pulmonaria and Lobaria retigera as Eco-Friendly Adsorbents of Synthetic Dyes

Synthetic dyes are widely used in the industry; they are chemically stable, difficult to neutralize, and therefore they are a threat to the environment when released into wastewaters. The dyes have a significant impact on plant performance by impairing photosynthesis, inhibiting growth, and entering the food chain and may finally result in the toxicity, mutagenicity and carcinogenicity of food products. Implementation of the dark piment melanin for the adsorption of the synthetic dyes is a new ecologically friendly approach for bioremediation. The aim of the present work was to study the physico-chemical characteristics of melanins from the lichens Lobaria pulmonaria and Lobaria retigera, analyze their adsorption/desorption capacities towards synthetic dyes, and assess the capacity of melanins to mitigate toxicity of the dyes for a common soil bacterium Bacillus subtilis. Unique chelating properties of melanins determine the perspectives of the use of these high molecular weight polymers for detoxification of xenobiotics.     

The Finely Coordinated Action of SSB and NurA/HerA Complex Strictly Regulates the DNA End Resection Process in Saccharolobus solfataricus

Generation of the 3′ overhang is a critical step during homologous recombination (HR) and replication fork rescue processes. This event is usually performed by a series of DNA nucleases and/or helicases. The nuclease NurA and the ATPase HerA, together with the highly conserved MRE11/RAD50 proteins, play an important role in generating 3′ single-stranded DNA during archaeal HR. Little is known, however, about HerA-NurA function and activation of this fundamental and complicated DNA repair process. Herein, we analyze the functional relationship among NurA, HerA and the single-strand binding protein SSB from Saccharolubus solfataricus. We demonstrate that SSB clearly inhibits NurA endonuclease activity and its exonuclease activities also when in combination with HerA. Moreover, we show that SSB binding to DNA is greatly stimulated by the presence of either NurA or NurA/HerA. In addition, if on the one hand NurA binding is not influenced, on the other hand, HerA binding is reduced when SSB is present in the reaction. In accordance with what has been observed, we have shown that HerA helicase activity is not stimulated by SSB. These data suggest that, in archaea, the DNA end resection process is governed by the strictly combined action of NurA, HerA and SSB.     

Homogeneous Optical and Electronic Properties of Graphene Due to the Suppression of Multilayer Patches During CVD on Copper Foils

A synthesis method of strictly monolayer and fully homogeneous graphene across tens of centimeter squares, by chemical vapour deposition onto standard copper foils, is presented. The growth technique involves cyclic injection of a carbon precursor separated by idle times with constant hydrogen exposure. The formation of spurious multilayer patches, which accompanies the standard growth techniques based on continuous exposure to methane, is inhibited here, in a broad range of pressure and gas composition, including in two pressure regimes which are known to yield distinctive grain morphologies (dendritic versus hexagonal). Raman spectra confirm the absence of defects within the graphene films. A mechanism for growth/suppression of the multilayer patches based on the carbon storage at defective regions is proposed. The importance of multilayer suppression is highlighted in a comparative study showing the detrimental effect of patches on the performances of graphene transistors and on the optical transparency of stacked layers. The full‐layer graphene sheets are superiorly homogeneous in terms of their optical and electronic properties, and are thus suited for applications for high‐density integration as well as transparent electrodes with spatially continuous optical absorbance. Graphene transistors fabricated by the pulsed CVD method exhibit room‐temperature mobilities with a mean value of 5000 cm² V^?1 s^?1.     

Heat Transfer Control of an Impinging Inclined Slot Jets on a Moving Wall

This work is devoted to the numerical study of the interaction of an inclined plane turbulent jet with a moving horizontal isothermal hot wall. The inclination of the jet allows the control of the stagnation point location. The numerical predictions based on statistical modeling are achieved using second order Reynolds stress turbulence model coupled to the enhanced wall treatment. The jet Reynolds number (Re), surface‐to‐jet velocity ratio (R_sj); and optimal inclination angle of the jet (α) are varied. The calculations are in good agreement with the available data. The numerical results show that the heat transfer is greatly influenced by the jet Re and the velocity of the moving wall. The local Nusselt number (Nu) decreases with increasing R_sj (until R_sj = 1). However, the optimal inclination of the jet enhances heat transfer and modifies significantly the stagnation point location. Average Nu is correlated according with the problem parameters as .     

Influence of cornstarch on thermomechanical behavior of poly(vinyl) chloride bioplastics

The diverse and ubiquitous consumption of polymers urges the necessity to make these materials easily available. However, the excessively used petrochemical-based polymers such as poly(vinyl) chloride (PVC) are nonbiodegradable, which is a motivation to modify it with “green” alternatives. In the present study, PVC (M_w = 48 000 g mol⁻¹⁾ has been incorporated with cornstarch (CS) to synthesize a series of 25 samples of bioplastics in addition to blank polymer samples. The films of five various thicknesses (0.1, 0.2, 0.3, 0.5, and 1.0 mm) have been synthesized using in situ polymerization. Each sample of pure PVC film and bioplastic has been induced with different concentrations of CS in the range of 1–5 wt %. The synthesized samples were subjected to the structural characterization by using Fourier transform infrared. Thermogravimetric analysis has demonstrated the three-step degradation with the improved stability of 250 °C. The 3% concentration of CS has shown the optimum storage modulus (E′) of 1 660 MPa from dynamic mechanical analysis and Tan δ as 0.50. The swelling test performed using water has shown an induction of hydrophilicity in PVC up to 4%. CS-induced bioplastics can be a potential ecofriendly alternative of conventional polymers. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48493.     

Structural Basis for Phospholyase Activity of a Class III Transaminase Homologue

Pyridoxal‐phosphate (PLP)‐dependent enzymes catalyse a remarkable diversity of chemical reactions in nature. A1RDF1 from Arthrobacter aurescens TC1 is a fold type I, PLP‐dependent enzyme in the class III transaminase (TA) subgroup. Despite sharing 28 % sequence identity with its closest structural homologues, including β‐alanine:pyruvate and γ‐aminobutyrate:α‐ketoglutarate TAs, A1RDF1 displayed no TA activity. Activity screening revealed that the enzyme possesses phospholyase (E.C. 4.2.3.2) activity towards O‐phosphoethanolamine (PEtN), an activity described previously for vertebrate enzymes such as human AGXT2L1, enzymes for which no structure has yet been reported. In order to shed light on the distinctive features of PLP‐dependent phospholyases, structures of A1RDF1 in complex with PLP (internal aldimine) and PLP ? PEtN (external aldimine) were determined, revealing the basis of substrate binding and the structural factors that distinguish the enzyme from class III homologues that display TA activity.     

Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin

In the present study, β-cyclodextrin-grafted chitosan nanoparticles (β-CD-g-CS NPs) were prepared using a new ionic gelation strategy involving a synergistic effect of NaCl (150 mmol/L), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, 10 mmol/L), and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD-g-CS NPs vs. the classical ionic gelation method. New HA/β-CD-g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid (HA) to the β-CD-g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w(HA):w(β-CD-g-CS) = 2:1 and furnished new spherical and smooth HA/β-CD-g-CS NPs. Furthermore, the stability of β- CD-g-CS NPs and HA/β-CD-g-CS NPs at 4°C in physiological medium (pH 7.4) was compared for 3 weeks period and showed that HA/β-CD-g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD-g-CS NPs. Finally, preliminary study of HA/β-CD-g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD-g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.