Copper (Cu) is an essential micronutrient required for the activity of redox-active enzymes involved in critical metabolic reactions, signaling pathways, and biological functions. Transporters and chaperones control Cu ion levels and bioavailability to ensure proper subcellular and systemic Cu distribution. Intensive research has focused on understanding how mammalian cells maintain Cu homeostasis, and how molecular signals coordinate Cu acquisition and storage within organs. In humans, mutations of genes that regulate Cu homeostasis or facilitate interactions with Cu ions lead to numerous pathologic conditions. Malfunctions of the Cu + -transporting ATPases ATP7A and ATP7B cause Menkes disease and Wilson disease, respectively. Additionally, defects in the mitochondrial and cellular distributions and homeostasis of Cu lead to severe neurodegenerative conditions, mitochondrial myopathies, and metabolic diseases. Cu has a dual nature in K E Y W O R D S cancer, copper, copper-dependent diseases, cuproproteins, Menkes disease, mitochondrial myopathies, Wilson disease

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Viral infections (like different types of influenza virus) are becoming alarmingly common often leading to epidemics. Since Viruses can multiply from genomic materials it can spread the infection quickly as well as cause other complications like birth defects, autoimmune disease and even cancer. Diagnostics of viral infection traditionally is performed using antigen-antibody reaction, which is time consuming and labor intensive. Also, viral infections can be latent or show false negative results when antibody reaction is tested. In-situ direct hybridization detection is possible by expensive, long and difficult radiation-based methods. Our group has developed a Carbon Nanotube (CNT) & Graphene based Bionanosensor (BNS) for rapid and direct detection of specific DNA sequences. In this technique, single-stranded (ss) DNA probe (known as priming) is immobilized on a substrate. This recognizes a specific complementary target DNA in a sample solution and gets hybridized leading to a detectable electrical signal. In this study we have expanded the scope of this BNS by using it to detect quick in-situ RNA hybridization. A sample of RNA was tested simultaneously in an array of 4 biosensors (each primed by the complementary sequence). The resistance across each of the biosensors was measured with a self-designed, feed-back controlled, balanced Wheatstone bridge circuit with an Arduino interface. A specific pattern related to hybridization was observed and a weighted average performed over 30 experiments. The sensors primed with the forward RNA was able to detect the complementary sequence in a mixed sample in 10 minutes from the starting time.

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Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical tool which presents high sensitivity in detection of the low concentration molecules and analytes. Its physical mechanism is based on strong confined electric fields in the tiny gaps between metallic nanostructures. In this work, two different sizes of polystyrene (PS) spheres were mixed to fabricate large-area quasi-random nanoarray on silicon decorated with Ag film for SERS. With the tuning of the volume ratio of two different sizes of spheres and the thickness of Ag film, it will always exhibit higher SERS intensity than periodic nanoarray with only one size. The Finite-Difference Time-Domain (FDTD) simulation shows that this hybrid structure provides high density of hot spots around the hybrid nanostructure due to surface plasmons, and the produced long decay length of the enhanced electric field makes the SERS substrate a zero-gap system for sensitive detection of large biomolecules. And this SERS system achieved an enhancement factor of the order of 10 5 -10 6 in the detection of R6G molecules. The hybrid nanostructure is reproducible with a relative standard deviation of 10% .And the SERS substrates also produced sensitive Raman signals on long Ab and hIAPP fibrils, which is potential for sensitive detection of amyloid aggregates that are related to Alzheimer's disease and type 2 diabetes (T2D). Our study demonstrates that the Ag-Film-Functionalized mixed PS spheres substrates may serve as good SERS substrates in the detection for biomedical and chemical analytes.