Pickling C. botulinumtoxin formation in finished product Maximum finished product pH in the loin muscle of 5.0 Finished product pH in the loin muscle Collect sample of product from each pickling tank at the end of each pickling cycle and analyze for pH using a pH meter Each pickling tank, each cycle QC personnel Continue pickling process until pH meets the CL Analytical results Daily calibration of pH meter

Food and Drug Administration Center for Food Safety and Applied Nutrition

Copper is an essential element in many biological processes. The critical functions associated with copper have resulted from evolutionary harnessing of its potent redox activity. This same property also places copper in a unique role as a key modulator of cell signal transduction pathways. These pathways are the complex sequence of molecular interactions that drive all cellular mechanisms and are often associated with the interplay of key enzymes including kinases and phosphatases but also including intracellular changes in pools of smaller molecules. A growing body of evidence is beginning to delineate the how, when and where of copper-mediated control over cell signal transduction. This has been driven by research demonstrating critical changes to copper homeostasis in many disorders including cancer and neurodegeneration and therapeutic potential through control of disease-associated cell signalling changes by modulation of copper-protein interactions. This timely review brings together for the first time the diverse actions of copper as a key regulator of cell signalling pathways and discusses the potential strategies for controlling disease-associated signalling processes using copper modulators. It is hoped that this review will provide a valuable insight into copper as a key signal regulator and stimulate further research to promote our understanding of copper in disease and therapy.

Copper as a key regulator of cell signalling pathways

Increasing biochemical and genetic evidence confirms that myristoylation is an evolutionary conserved process of lipid modification in many eukaryotic and viral proteins. The discovery that the N-terminal blocking group of cyclic AMP-dependent protein kinase is a myristic acid, some 33 years ago, led to the birth of the field of ‘myristoylation’, dedicated to understanding the significance of protein myristoylation. Although the field is in its infancy, an increasing number of studies have appeared addressing the mechanisms and significance of N-myristoylation in various aspects of cellular signaling. N-Myristoylation is known to occur in mammalian, plant, viral and fungal proteins. Many proteins involved in a variety of signal cascades and cellular differentiation are myristoylated. These include the catalytic subunit of cAMP-dependent protein kinase, the β-subunit of calcineurin, the α-subunit of several G-proteins, the cellular and transforming forms of pp60src. Given the indispensible role of myristoylation in cellular functions, in this review, we examine the myriad functional implications of myristoylation with respect to immune function and regulation.

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Myristoylation: An Important Protein Modification in the Immune Response.

Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.

Turning Tumor-Promoting Copper into an Anti-Cancer Weapon via High-Throughput Chemistry

Synthesis, characterization, molecular modeling and antioxidant activity of (1E,5E)-1,5-bis(1-(pyridin-2-yl)ethylidene)carbonohydrazide (H2APC) and its zinc(II), cadmium(II) and mercury(II) complexes

Copper(II) and manganese(III) complexes of N'-[(2-hydroxy phenyl) carbonothioyl] pyridine-2-carbohydrazide: novel therapeutic agents for cancer.

Metal-assisted transformation of N-benzoyldithiocarbazate to 5-phenyl-1,3,4-oxadiazole-2-thiol in the presence of ethylenediamine, and its first row transition metal complexes

In the title compound, C8H6N2OS, the planar oxadiazole ring is effectively coplanar with the phenyl ring. This facilitates the formation of N—H⋯S inter­actions, leading to a thione tautomer in the solid state, and the formation of centrosymmetric dimers.

5-Phenyl-1,3,4-oxadiazole-2(3H)-thione

Problem statement: Interaction between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component. Herb traditionally used to decrease glucose concentrations in diabetes could theoretically precipitate hypoglycaemia if taken in combination with conventional drugs. Approach: The present study was undertaken to determine the interaction of Glibenclamide, a Sulphonylurea with Trigonella foenum-graecum seed extract, an herbal drug widely used as a antidiabetic agent. The pharmacodynamic interaction was evaluated in streptozotocin induced diabetic rats. Glibenclamide was given orally in two different doses of 0.25 and 0.50 mg kg-1. Trigonella seed extract was administered at a dose of 20 mL kg-1. The blood glucose estimation was carried out. Results: Both glibenclamide and Trigonella seed extract showed hypoglycemic effect. The hypoglycemic effect observed with combination of glibenclamide and Trigonella seed extract was significantly more than either of drug given alone. Conclusion: It is concluded that Trigonella seed extract shows synergistic effect with glibenclamide. This could be important in reducing the dose of glibenclamide to achieve enhanced therapeutic effect with minimum adverse effect.

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Pratibha Tripathi

Papers

Copper(II) and manganese(III) complexes of N'-[(2-hydroxy phenyl) carbonothioyl] pyridine-2-carbohydrazide: novel therapeutic agents for cancer.

Metal-assisted transformation of N-benzoyldithiocarbazate to 5-phenyl-1,3,4-oxadiazole-2-thiol in the presence of ethylenediamine, and its first row transition metal complexes

5-Phenyl-1,3,4-oxadiazole-2(3H)-thione

Interaction of Aqueous Extract of Trigonella Foenum-Graecum Seeds with Glibenclamide in Streptozotocin Induced Diabetic Rats

Bioactivity of novel transition metal complexes of N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide.