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The coordination chemistry of transition metal ions (Fe, Cu, Zn) with the amyloid-β (Aβ) peptides has attracted a lot of attention in recent years due to its repercussions in Alzheimer's disease (AD). Aβ peptide undergoes self-aggregation to form amyloid plaques and soluble oligomers, which are believed to play a central role in AD pathology. Metal ions and Aβ-metal adducts can generate toxic radical species capable of modifying biomolecules, ultimately causing death of the neuronal cells. The impact of these metal ions on Aβ aggregation and neurotoxic species formation is still not well understood. A large number of reports indicate that transition metal ions such as Cu and Zn have significant effects on Aβ peptide aggregation and stabilization of neurotoxic soluble Aβ aggregates; some of these reports are contradictory too. A review on the effects of Cu and Zn metal ions on Aβ peptide aggregation due to their coordination with these peptides is presented herein. The review includes brief discussions with regards to the levels of Cu and Zn in an AD affected brain, structures of Aβ peptides, and the coordination of Aβ peptides with Cu and Zn. In the current scenario, a consensus appears to be emerging regarding the coordination mode and the effect of metal ions (especially Cu and Zn) on the aggregation of Aβ peptides. Towards the end, a short discussion on current research trends in the field of bifunctional metal chelators for tackling the metal effect on Aβ aggregation and toxicity has also been presented. It is expected that this review would aid in gaining a better understanding of the current status of various aspects of AD from an inorganic chemistry perspective.

Copper plays key roles in catalytic and regulatory biochemical reactions essential for normal growth, development, and health. Dietary copper deficiencies or mutations in copper homeostasis genes can lead to abnormal musculoskeletal development, cognitive disorders, and poor growth. In yeast and mammals, copper is acquired through the activities of the CTR1 family of high-affinity copper transporters. However, the mechanisms of systemic responses to dietary or tissue-specific copper deficiency remain unclear. Here, taking advantage of the animal model Caenorhabditis elegans for studying whole-body copper homeostasis, we investigated the role of a C. elegans CTR1 homolog, CHCA-1, in copper acquisition and in worm growth, development, and behavior. Using sequence homology searches, we identified 10 potential orthologs to mammalian CTR1 Among these genes, we found that chca-1 , which is transcriptionally up-regulated in the intestine and hypodermis of C. elegans during copper deficiency, is required for normal growth, reproduction, and maintenance of systemic copper balance under copper deprivation. The intestinal copper transporter CUA-1 normally traffics to endosomes to sequester excess copper, and we found here that loss of chca-1 caused CUA-1 to mislocalize to the basolateral membrane under copper overload conditions. Moreover, animals lacking chca-1 exhibited significantly reduced copper avoidance behavior in response to toxic copper conditions compared with WT worms. These results establish that CHCA-1-mediated copper acquisition in C. elegans is crucial for normal growth, development, and copper-sensing behavior., (© 2018 Yuan et al.)

Copper plays key catalytic and regulatory roles in biochemical processes essential for normal growth, development, and health. Defects in copper metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular disease and are associated with other pathophysiological states. Consequently, it is critical to understand the mechanisms by which organisms control the acquisition, distribution, and utilization of copper. The intestinal enterocyte is a key regulatory point for copper absorption into the body; however, the mechanisms by which intestinal cells transport copper to maintain organismal copper homeostasis are poorly understood. Here, we identify a mechanism by which organismal copper homeostasis is maintained by intestinal copper exporter trafficking that is coordinated with extraintestinal copper levels in Caenorhabditis elegans Specifically, we show that CUA-1, the C. elegans homolog of ATP7A/B, localizes to lysosome-like organelles (gut granules) in the intestine under copper overload conditions for copper detoxification, whereas copper deficiency results in a redistribution of CUA-1 to basolateral membranes for copper efflux to peripheral tissues. Worms defective in gut granule biogenesis exhibit defects in copper sequestration and increased susceptibility to toxic copper levels. Interestingly, however, a splice isoform CUA-1.2 that lacks a portion of the N-terminal domain is targeted constitutively to the basolateral membrane irrespective of dietary copper concentration. Our studies establish that CUA-1 is a key intestinal copper exporter and that its trafficking is regulated to maintain systemic copper homeostasis. C. elegans could therefore be exploited as a whole-animal model system to study regulation of intra- and intercellular copper trafficking pathways., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

The chronic exposure of humans to the toxic metal cadmium (Cd), either occupational or from food and air, causes various diseases, including neurodegenerative conditions, dysfunction of vital organs, and cancer. While the toxicology of Cd and its effect on the homeostasis of biologically relevant elements is increasingly recognized, the spatial distribution of Cd and other elements in Cd toxicity-caused diseases is still poorly understood. Here, we use Caenorhabditis elegans as a non-mammalian multicellular model system to determine the distribution of Cd at the tissue and cellular resolution and its effect on the internal levels and the distribution of biologically relevant elements. Using inductively coupled plasma-mass spectrophotometry (ICP-MS), we show that exposure of worms to Cd not only led to its internal accumulation but also significantly altered the C. elegans ionome. Specifically, Cd treatment was associated with increased levels of toxic elements such as arsenic (As) and rubidium (Rb) and a decreased accumulation of essential elements such as zinc (Zn), copper (Cu), manganese (Mn), calcium (Ca), cobalt (Co) and, depending on the Cd-concentration used in the assay, iron (Fe). We regarded these changes as an ionomic signature of Cd toxicity in C. elegans. We also show that supplementing nematode growth medium with Zn but not Cu, rescues Cd toxicity and that mutant worms lacking Zn transporters CDF-1 or SUR-7, or both are more sensitive to Cd toxicity. Finally, using synchrotron X-Ray fluorescence Microscopy (XRF), we showed that Cd significantly alters the spatial distribution of mineral elements. The effect of Cd on the distribution of Fe was particularly striking: while Fe was evenly distributed in intestinal cells of worms grown without Cd, in the presence of Cd, Fe, and Cd co-localized in punctum-like structures in the intestinal cells. Together, this study advances our understanding of the effect of Cd on the accumulation and distribution of biologically relevant elements. Considering that C. elegans possesses the principal tissues and cell types as humans, our data may have important implications for future therapeutic developments aiming to alleviate Cd-related pathologies in humans. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research is to show the characteristics of a Cu–Ti dissimilar interface produced by a wire arc-based additive manufacturing process. The purpose of this research was to determine the viability of the Cu–Ti interface for the fabrication of functionally graded structures (FGS) using the wire arc additive manufacturing (WAAM) process. Design/methodology/approach: This paper used the WAAM process with variable current vis-à-vis heat input to demonstrate multiple Ti-6Al-4V (Ti64) and C11000 dissimilar fabrications. The hardness and microstructure of the dissimilar interfaces were investigated thoroughly. The formation of Cu–Ti intermetallic at the Ti64/Cu fusion interface is been revealed by scanning electron microscopy and energy dispersive X-ray analysis, while X-ray diffraction was used to identify various Cu–Ti intermetallic phases. The effect of microstructure on interfacial sensitivity and hardness are also investigated. Findings: The formation of CuTi intermetallic and the β-phase transformation in Ti-6Al-4V are found to be heat input dependent. The Cu diffusion length increases as the heat input for Ti64 deposition increases, resulting in a greater Cu–Ti intermetallic thickness. The Cu–Ti interface properties improve when the heat input is less than approximately 250 J/mm or the deposition current is less than 90 A. The microhardness ranges from 55 to 650 HV from the Cu-side to the interface and from 650 to 350 HV from the interface to the Ti-side. Higher current increases interface hardness, which increases brittleness and makes the interface more prone to interfacial cracking. Originality/value: Nonlinear components are needed for a variety of extreme engineering applications, which can be met by FGS with varying microstructure, composition and properties. FGS produced using the WAAM process is a novel concept that requires further investigation. Despite numerous studies on Ti-clad Cu, information on Cu–Ti interface characteristics is lacking. Furthermore, the suitability of the WAAM process for the development of Cu–Ti FGS is unknown. As a result, the goal of this research article is to fill these gaps by providing preliminary information on the feasibility of developing Cu–Ti FGS via the WAAM process. [ABSTRACT FROM AUTHOR]

The present work investigates the novel route for the synthesis of Fe-Cu alloy using electric discharge machining (EDM). The Synthesis of Fe-Cu alloy is difficult by equilibrium processes because of their immiscible nature. An attempt was made to investigate the synthesis of Fe-Cu alloy by EDM process where the discharge can lead to a very high temperature and subsequent quenching to result in alloy formation. The electrode was made up of copper and die steel was used as workpiece. The characterization of generated debris was carried out by X-ray diffraction analysis, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM). The nano-phase granular particles of Fe-Cu alloy were confirmed by TEM and selected area diffraction pattern analysis. SEM morphology results reveal that the generated particles were both, spherical and non-spherical shape and size ranging between 50 nm and 30 µm. The EDS analysis indicates that the spherical particles were Fe-rich and non-spherical particles were Cu-rich. [ABSTRACT FROM AUTHOR]

Abstract: Reaction of the ligand N-methyl-N-((6-pivaloylamido-2-pyridyl)methyl)-N-(2-pyridylethyl)amine (mpppa) with equimolar amounts of [Cu(H2O)6][ClO4]2 or CuCl2 ·2H2O in MeCN afforded mononuclear copper(II) complexes [Cu(mpppa)][ClO4]2 (1) and [Cu(mpppa)Cl2] (2). Crystal structure analysis reveals CuN3O (two pyridyl, an aliphatic amine, and an amide oxygen) coordination in 1 and CuN3Cl2 (two pyridyl, an aliphatic amine, and two chlorides) coordination in 2. Crystal packing diagram of 1 reveals that one of the perchlorate counteranions provides weak coordination to copper(II) centers and in turn the copper(II) centers assume pseudo-six-coordination, generating 1D chain. Notably, one of the copper(II)-coordinated chloride ions in 2 participates in an intramolecular N–H⋯Cl interaction. Intermolecular C–H⋯Cl interactions in the solid state generate helical structure. Spectroscopic (IR, UV–Vis, and EPR) and redox properties of the two complexes have been investigated and compared. [Copyright &y& Elsevier]