Thioredoxin Reductase Inhibition for Cancer Therapy

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Radosveta Gencheva ◽  
Elias S.J. Arnér
Keyword(s):  
Cancer Therapy ◽  
Thioredoxin Reductase ◽  
Normal Activity ◽  
Annual Review ◽  
Publication Date ◽  
Nadph Oxidases ◽  
Thioredoxin Reductase 1 ◽  
Wide Range ◽  
Oxidative Challenge ◽  
Pharmacology And Toxicology

The cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, TXNRD1), and to some extent mitochondrial TrxR2 (TXNRD2), can be inhibited by a wide range of electrophilic compounds. Many such compounds also yield cytotoxicity toward cancer cells in culture or in mouse models, and most compounds are likely to irreversibly modify the easily accessible selenocysteine residue in TrxR1, thereby inhibiting its normal activity to reduce cytosolic thioredoxin (Trx1, TXN) and other substrates of the enzyme. This leads to an oxidative challenge. In some cases, the inhibited forms of TrxR1 are not catalytically inert and are instead converted to prooxidant NADPH oxidases, named SecTRAPs, thus further aggravating the oxidative stress, particularly in cells expressing higher levels of the enzyme. In this review, the possible molecular and cellular consequences of these effects are discussed in relation to cancer therapy, with a focus on outstanding questions that should be addressed if targeted TrxR1 inhibition is to be further developed for therapeutic use. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Measuring Pharmacogene Variant Function at Scale Using Multiplexed Assays

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Renee C. Geck ◽  
Gabriel Boyle ◽  
Clara J. Amorosi ◽  
Douglas M. Fowler ◽  
Maitreya J. Dunham
Keyword(s):  
Next Generation Sequencing ◽  
Functional Data ◽  
Genetic Variants ◽  
Genetic Information ◽  
Annual Review ◽  
Publication Date ◽  
Drug Selection ◽  
Functional Consequences ◽  
Pharmacology And Toxicology ◽  
Generation Sequencing

As costs of next-generation sequencing decrease, identification of genetic variants has far outpaced our ability to understand their functional consequences. This lack of understanding is a central challenge to a key promise of pharmacogenomics: using genetic information to guide drug selection and dosing. Recently developed multiplexed assays of variant effect enable experimental measurement of the function of thousands of variants simultaneously. Here, we describe multiplexed assays that have been performed on nearly 25,000 variants in eight key pharmacogenes ( ADRB2, CYP2C9, CYP2C19, NUDT15, SLCO1B1, TMPT, VKORC1, and the LDLR promoter), discuss advances in experimental design, and explore key challenges that must be overcome to maximize the utility of multiplexed functional data. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Basis of Navigation Across Species

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Cody A. Freas ◽  
Ken Cheng
Keyword(s):  
Large Scale ◽  
Error Reduction ◽  
Annual Review ◽  
Publication Date ◽  
Additional Component ◽  
Oscillatory Systems ◽  
Neural Architecture ◽  
Wide Range ◽  
Reduction Strategies ◽  
Cycling Behavior

Animals navigate a wide range of distances, from a few millimeters to globe-spanning journeys of thousands of kilometers. Despite this array of navigational challenges, similar principles underlie these behaviors across species. Here, we focus on the navigational strategies and supporting mechanisms in four well-known systems: the large-scale migratory behaviors of sea turtles and lepidopterans as well as navigation on a smaller scale by rats and solitarily foraging ants. In lepidopterans, rats, and ants we also discuss the current understanding of the neural architecture which supports navigation. The orientation and navigational behaviors of these animals are defined in terms of behavioral error-reduction strategies reliant on multiple goal-directed servomechanisms. We conclude by proposing to incorporate an additional component into this system: the observation that servomechanisms operate on oscillatory systems of cycling behavior. These oscillators and servomechanisms comprise the basis for directed orientation and navigational behaviors. Expected final online publication date for the Annual Review of Psychology, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Engineering Advances in Spray Drying for Pharmaceuticals

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
John M. Baumann ◽  
Molly S. Adam ◽  
Joel D. Wood
Keyword(s):  
Spray Drying ◽  
Oral Delivery ◽  
Process Development ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Annual Review ◽  
Publication Date ◽  
Dry Powders ◽  
Wide Range ◽  
Pharmaceutical Industries

Spray drying is a versatile technology that has been applied widely in the chemical, food, and, most recently, pharmaceutical industries. This review focuses on engineering advances and the most significant applications of spray drying for pharmaceuticals. An in-depth view of the process and its use is provided for amorphous solid dispersions, a major, growing drug-delivery approach. Enhanced understanding of the relationship of spray-drying process parameters to final product quality attributes has made robust product development possible to address a wide range of pharmaceutical problem statements. Formulation and process optimization have leveraged the knowledge gained as the technology has matured, enabling improved process development from early feasibility screening through commercial applications. Spray drying's use for approved small-molecule oral products is highlighted, as are emerging applications specific to delivery of biologics and non-oral delivery of dry powders. Based on the changing landscape of the industry, significant future opportunities exist for pharmaceutical spray drying. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 12 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Benjamin Steinhorn ◽  
Emrah Eroglu ◽  
Thomas Michel
Keyword(s):  
Dynamic Control ◽  
Cardiovascular Pharmacology ◽  
Redox Balance ◽  
Signaling Molecules ◽  
Annual Review ◽  
Publication Date ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Pharmacology And Toxicology ◽  
Intracellular Redox

Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein's specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellular redox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Chemical Stability of Proteins in Foods: Oxidation and the Maillard Reaction

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Mahesha M. Poojary ◽  
Marianne N. Lund
Keyword(s):  
Maillard Reaction ◽  
Protein Oxidation ◽  
Oxidation Products ◽  
Protein Carbonyls ◽  
Annual Review ◽  
Publication Date ◽  
Food Protein ◽  
Food Proteins ◽  
Wide Range ◽  
Specific Oxidation

Protein is a major nutrient present in foods along with carbohydrates and lipids. Food proteins undergo a wide range of modifications during food production, processing, and storage. In this review, we discuss two major reactions, oxidation and the Maillard reaction, involved in chemical modifications of food proteins. Protein oxidation in foods is initiated by metal-, enzyme-, or light-induced processes. Food protein oxidation results in the loss of thiol groups and the formation of protein carbonyls and specific oxidation products of cysteine, tyrosine, tryptophan, phenylalanine, and methionine residues, such as disulfides, dityrosine, kynurenine, m-tyrosine, and methionine sulfoxide. The Maillard reaction involves the reaction of nucleophilic amino acid residues with reducing sugars, which yields numerous heterogeneous compounds such as α-dicarbonyls, furans, Strecker aldehydes, advanced glycation end-products, and melanoidins. Both protein oxidation and the Maillard reaction result in the loss of essential amino acids but may positively or negatively impact food structure and flavor. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Freshwater Scarcity

2021 ◽  
Vol 46 (1) ◽  
Author(s):  
Peter H. Gleick ◽  
Heather Cooley
Keyword(s):  
Fresh Water ◽  
Water Scarcity ◽  
Sustainable Management ◽  
Ecosystem Health ◽  
Annual Review ◽  
Publication Date ◽  
Wide Range ◽  
Use Efficiency ◽  
Alternative Sources ◽  
Violent Conflicts

The availability and use of fresh water are critical for human health and for economic and ecosystem stability. But the growing mismatch between human demands and natural freshwater availability is contributing to water scarcity, affecting industrial and agricultural production and a wide range of social, economic, and political problems, including poverty, deterioration of ecosystem health, and violent conflicts. Understanding and addressing different forms of water scarcity are vital for moving toward more sustainable management and use of fresh water. We provide here a review of concepts and definitions of water scarcity, metrics and indicators used to evaluate scarcity together with strategies for addressing and reducing the adverse consequences of water scarcity, including the development of alternative sources of water, improvements in water-use efficiency, and changes in systems of water management and planning. Expected final online publication date for the Annual Review of Environment and Resources, Volume 46 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Neural Network Potentials: A Concise Overview of Methods

2022 ◽  
Vol 73 (1) ◽  
Author(s):  
Emir Kocer ◽  
Tsz Wai Ko ◽  
Jörg Behler
Keyword(s):  
Machine Learning ◽  
Atomic Structure ◽  
Electrostatic Interactions ◽  
Large Scale ◽  
Machine Learning Algorithms ◽  
Annual Review ◽  
Publication Date ◽  
Great Success ◽  
Concise Overview ◽  
Wide Range

In the past two decades, machine learning potentials (MLPs) have reached a level of maturity that now enables applications to large-scale atomistic simulations of a wide range of systems in chemistry, physics, and materials science. Different machine learning algorithms have been used with great success in the construction of these MLPs. In this review, we discuss an important group of MLPs relying on artificial neural networks to establish a mapping from the atomic structure to the potential energy. In spite of this common feature, there are important conceptual differences among MLPs, which concern the dimensionality of the systems, the inclusion of long-range electrostatic interactions, global phenomena like nonlocal charge transfer, and the type of descriptor used to represent the atomic structure, which can be either predefined or learnable. A concise overview is given along with a discussion of the open challenges in the field. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 73 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Score-Driven Time Series Models

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Andrew C. Harvey
Keyword(s):  
Time Series ◽  
Circular Data ◽  
Annual Review ◽  
Time Series Models ◽  
Publication Date ◽  
Time Series Modeling ◽  
Dynamic Correlation ◽  
Switching Regimes ◽  
Wide Range ◽  
Application Volume

The construction of score-driven filters for nonlinear time series models is described, and they are shown to apply over a wide range of disciplines. Their theoretical and practical advantages over other methods are highlighted. Topics covered include robust time series modeling, conditional heteroscedasticity, count data, dynamic correlation and association, censoring, circular data, and switching regimes. Expected final online publication date for the Annual Review of Statistics and Its Application, Volume 9 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Dynamics of Atrial Fibrillation Mechanisms and Comorbidities

2020 ◽  
Vol 83 (1) ◽  
Author(s):  
Jordi Heijman ◽  
Dominik Linz ◽  
Ulrich Schotten
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Dynamic Interaction ◽  
Future Research ◽  
Annual Review ◽  
Publication Date ◽  
Atrial Remodeling ◽  
Dynamic Changes ◽  
Wide Range

Atrial fibrillation (AF) contributes to morbidity and mortality of millions of individuals. Its molecular, cellular, neurohumoral, and hemodynamic pathophysiological mechanisms are complex, and there is increasing awareness that a wide range of comorbidities can contribute to AF-promoting atrial remodeling. Moreover, recent research has highlighted that AF risk is not constant and that the temporal variation in concomitant conditions contributes to the complexity of AF dynamics. In this review, we provide an overview of fundamental AF mechanisms related to established and emerging comorbidities or risk factors and their role in the AF-promoting effects. We focus on the accumulating evidence for the relevance of temporally dynamic changes in these risk factors and the consequence for AF initiation and maintenance. Finally, we highlight the important implications for future research and clinical practice resulting from the dynamic interaction between AF risk factors and mechanisms. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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