Chapter 1 Transmissible Spongiform Encephalopathy: from the High Middle Ages to Daniel Carlton Gajdusek Paul Brown Chapter 2 The Rich Chemistry of the Copper and Zinc Sites in Cellular Prion Protein Glenn L. Millhauser Chapter 3 Role of Cellular Prion Protein in the Amyloid-ss Oligomer Pathophysiology of Alzheimer's Disease Adam C. Kaufman, Stephen M. Strittmatter Chapter 4 Cellular Prion Protein and Cancers Wei Xin, Man-sun Sy, Chaoyang Li Chapter 5 Insoluble Cellular Prion Protein Wen-Quan Zou Chapter 6 Protein Misfolding Cyclic Amplification Fabio Moda, Sandra Pritzkow, Claudio Soto Chapter 7 Cofactor Involvement in Prion Propagation Surachai Supattapone, Michael B. Miller Chapter 8 Prion Protein Conversion and Lipids Jiyan Ma Chapter 9 New Perspectives on Prion Conversion: Introducing a Mechanism of Deformed Templating Ilia V. Baskakov Chapter 10 Infectious and Pathogenic Forms of Prion Protein Emiliano Biasini, David A. Harris Chapter 11 Cellular Mechanisms of Propagation and Clearance Hermann M. Schatzl Chapter 12 Molecular Mechanisms Encoding Quantitative and Qualitative Traits of Prion Strains Jiri G. Safar Chapter 13 Modeling the Cell Biology of Prions Richard Rubenstein, Robert B. Petersen Chapter 14 Prion Strain Interference Charles R. Schutt, Ronald A. Shikiya, Jason C. Bartz Chapter 15 Introduction to Yeast and Fungal Prions Reed B. Wickner Chapter 16 Yeast Prions are Pathogenic, in-register Parallel Amyloids Reed B. Wickner, Herman K. Edskes, David A. Bateman, Amy C. Kelly, Anton Gorkovskiy

Physiology and pathophysiology

Modulation of cellular processes by histone and non-histone protein acetylation

The circadian clock controls metabolic and physiological processes through finely tuned molecular mechanisms. The clock is remarkably plastic and adapts to exogenous "zeitgebers," such as light and nutrition. How a pathological condition in a given tissue influences systemic circadian homeostasis in other tissues remains an unanswered question of conceptual and biomedical importance. Here, we show that lung adenocarcinoma operates as an endogenous reorganizer of circadian metabolism. High-throughput transcriptomics and metabolomics revealed unique signatures of transcripts and metabolites cycling exclusively in livers of tumor-bearing mice. Remarkably, lung cancer has no effect on the core clock but rather reprograms hepatic metabolism through altered pro-inflammatory response via the STAT3-Socs3 pathway. This results in disruption of AKT, AMPK, and SREBP signaling, leading to altered insulin, glucose, and lipid metabolism. Thus, lung adenocarcinoma functions as a potent endogenous circadian organizer (ECO), which rewires the pathophysiological dimension of a distal tissue such as the liver. PAPERCLIP.

Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis

Synthetic molecular probes, chemosensors, and nanosensors used in combination with innovative assay protocols hold great potential for the development of robust, low-cost, and fast-responding sensors that are applicable in biofluids (urine, blood, and saliva). Particularly, the development of sensors for metabolites, neurotransmitters, drugs, and inorganic ions is highly desirable due to a lack of suitable biosensors. In addition, the monitoring and analysis of metabolic and signaling networks in cells and organisms by optical probes and chemosensors is becoming increasingly important in molecular biology and medicine. Thus, new perspectives for personalized diagnostics, theranostics, and biochemical/medical research will be unlocked when standing limitations of artificial binders and receptors are overcome. In this review, we survey synthetic sensing systems that have promising (future) application potential for the detection of small molecules, cations, and anions in aqueous media and biofluids. Special attention was given to sensing systems that provide a readily measurable optical signal through dynamic covalent chemistry, supramolecular host–guest interactions, or nanoparticles featuring plasmonic effects. This review shall also enable the reader to evaluate the current performance of molecular probes, chemosensors, and nanosensors in terms of sensitivity and selectivity with respect to practical requirement, and thereby inspiring new ideas for the development of further advanced systems.

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Molecular Probes, Chemosensors, and Nanosensors for Optical Detection of Biorelevant Molecules and Ions in Aqueous Media and Biofluids

Faculty of 1000 evaluation for NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus.

Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

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Xiaobo Zhou

Papers

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential.