Improvement of microstructure and corrosion properties of friction stir welded AA5754 by adding Zn interlayer

This study investigated the effect of Zn foil layers on the microstructure and corrosion characteristics of friction stir welded aluminum alloy 5754. Samples of various joints were prepared by applying different rotational and welding speeds, and their microstructures were evaluated via a metallographic technique and scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy elemental analysis. The anticorrosion behavior of joints in the absence and presence of a Zn interlayer was studied by cyclic potentiodynamic polarization test in 3.5wt% NaCl aqueous solution, and sound welds were obtained in the presence of the Zn interlayer foil. The results revealed that the joint made at a rotational speed of 800 r/min and traveling speed of 15 mm/min achieved a chemical composition identical to that of aluminum alloy 7xxx series, and as such, it showed the best resistance to corrosion.     

The functional importance of co-evolving residues in proteins

Computational approaches for detecting co-evolution in proteins allow for the identification of protein–protein interaction networks in different organisms and the assignment of function to under-explored proteins. The detection of co-variation of amino acids within or between proteins, moreover, allows for the discovery of residue–residue contacts and highlights functional residues that can affect the binding affinity, catalytic activity, or substrate specificity of a protein. To explore the functional impact of co-evolutionary changes in proteins, a combined experimental and computational approach must be recruited. Here, we review recent studies that apply computational and experimental tools to obtain novel insight into the structure, function, and evolution of proteins. Specifically, we describe the application of co-evolutionary analysis for predicting high-resolution three-dimensional structures of proteins. In addition, we describe computational approaches followed by experimental analysis for identifying specificity-determining residues in proteins. Finally, we discuss studies addressing the importance of such residues in terms of the functional divergence of proteins, allowing proteins to evolve new functions while avoiding crosstalk with existing cellular pathways or forming reproductive barriers and hence promoting speciation.     

A role for mitochondria in NLRP3 inflammasome activation

An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.     

Local charge of the ν = 5/2 fractional quantum Hall state

Electrons moving in two dimensions under the influence of strong magnetic fields effectively lose their kinetic energy and display exotic behaviour dominated by Coulomb forces. When the ratio of electrons to magnetic flux quanta in the system (ν) is near 5/2, the electrons are predicted to condense into a correlated phase with fractionally charged quasiparticles and a ground-state degeneracy that grows exponentially as these quasiparticles are introduced. The only way for electrons to transform between the many ground states would be to braid the fractional excitations around each other. This property has been proposed as the basis of a fault-tolerant quantum computer. Here we present observations of localized quasiparticles at ν = 5/2, confined to puddles by disorder. Using a local electrometer to compare how quasiparticles at ν = 5/2 and ν = 7/3 charge these puddles, we were able to extract the ratio of local charges for these states. Averaged over several disorder configurations and samples, we found the ratio to be 4/3, suggesting that the local charges are = e/3 and = e/4, where e is the charge of an electron. This is in agreement with theoretical predictions for a paired state at ν = 5/2. Confirming the existence of localized e/4 quasiparticles shows that proposed interferometry experiments to test statistics and computational ability of the state at ν = 5/2 would be possible.     

Interaction of reelin signaling and Lis1 in brain development

Loss-of-function mutations in RELN (encoding reelin) or PAFAH1B1 (encoding LIS1) cause lissencephaly, a human neuronal migration disorder. In the mouse, homozygous mutations in Reln result in the reeler phenotype, characterized by ataxia and disrupted cortical layers. Pafah1b1(+/-) mice have hippocampal layering defects, whereas homozygous mutants are embryonic lethal. Reln encodes an extracellular protein that regulates layer formation by interacting with VLDLR and ApoER2 (Lrp8) receptors, thereby phosphorylating the Dab1 signaling molecule. Lis1 associates with microtubules and modulates neuronal migration. We investigated interactions between the reelin signaling pathway and Lis1 in brain development. Compound mutant mice with disruptions in the Reln pathway and heterozygous Pafah1b1 mutations had a higher incidence of hydrocephalus and enhanced cortical and hippocampal layering defects. Dab1 and Lis1 bound in a reelin-induced phosphorylation-dependent manner. These data indicate genetic and biochemical interaction between the reelin signaling pathway and Lis1.     

Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint

During electron transport, the mitochondrion generates ATP and reactive oxygen species (ROS), a group of partially reduced and highly reactive metabolites of oxygen. In this in vivo genetic analysis in Drosophila melanogaster, we establish that disruption of complex I of the mitochondrial electron transport chain specifically retards the cell cycle during the G1-S transition. The mechanism involves a specific signaling cascade initiated by ROS and transduced by ASK-1, JNK, FOXO and the Drosophila p27 homolog, Dacapo. On the basis of our data combined with previous analyses of the system, we conclude that mitochondrial dysfunction activates at least two retrograde signals to specifically enforce a G1-S cell cycle checkpoint. One such signal involves an increase in AMP production and downregulation of cyclin E protein; another independent pathway involves increased ROS and upregulation of Dacapo. Thus, our results indicate that the mitochondrion can use AMP and ROS at sublethal concentrations as independent signaling molecules to modulate cell cycle progression.     

Effects of Eriobotrya japonica (Lindl.) flower extracts on mercuric chloride-induced hepatotoxicity in rats

Mercury(II) is an important factor in hepatotoxicity that can enter the body through marine diets and amalgams.In the present study,the protective effect of the Eriobotrya japonica flower extract(EJFE) on HgCl 2-induced hepatotoxicity was investigated.Five mg/kg of mercuric chloride in drinking water was given to rats either with saline or EJFE(100 and 200 mg/kg as intraperitoneal(IP)) for 30 d.The mercury levels in different groups of liver tissues of the rats were measured with flameless atomic absorption spectroscopy(F-AAS).Also,mercury accumulation in the liver of the rats was modeled by using a parallel chemical kinetic model.The results showed that HgCl 2-induced oxidative damage led to a significant decrease in glutathione(GSH) and the total antioxidant capacity(TAC) levels,and to a significant increase in lipid peroxidation level.Accumulated mercury was 14.47% more in the livers of the stress groups than in those of the control groups(P<0.001),whereas the amount of Hg was adjusted to 13.49% and 13.93% in groups treated with 100 and 200 mg/kg of EJFE respectively,as compared with stress groups(P<0.001).HPLC analysis of EJFE revealed that hesperetin and gallic acid are the major antioxidants in EJFE.Results demonstrate that flowers of the Eriobotrya japonica cause a significant protection against HgCl 2 induced hepatotoxicity in all diagnostic parameters by strengthening the antioxidant defense mechanisms and they may have a therapeutic function in free radical mediated diseases.