Global

Highlights issues to be aware of when designing adaptation policy and calls for greater attention to the social justice implications in the policy design process.
Schematic representation of the mechanism by which readthrough compounds restore channel function in G542X-CFTR–expressing cells. PTC refers to the premature termination codon.
Cystic fibrosis (CF) is caused by a mutation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which disrupts an ion channel involved in hydration maintenance via anion homeostasis. Nearly 5% of CF patients possess one or more copies of the G542X allele, which results in a stop codon at residue 542, preventing full-length CFTR protein synthesis. Identifying small-molecule modulators of mutant CFTR biosynthesis that affect the readthrough of this and other premature termination codons to synthesize a fully functional CFTR protein represents a novel target area of drug discovery. We describe the implementation and integration for large-scale screening of a homogeneous, 1536-well functional G542X-CFTR readthrough assay. The assay uses HEK 293 cells engineered to overexpress the G542X-CFTR mutant, whose functional activity is monitored with a membrane potential dye. Cells are co-incubated with a CFTR amplifier and CFTR corrector to maximize mRNA levels and trafficking of CFTR to the cell surface. Compounds that allow translational readthrough and synthesis of functional CFTR chloride channels are reflected by changes in membrane potential in response to cAMP stimulation with forskolin and CFTR channel potentiation with genistein. Assay statistics yielded Z′ values of 0.69 ± 0.06. As further evidence of its suitability for high-throughput screening, we completed automated screening of approximately 666,000 compounds, identifying 7761 initial hits. Following secondary and tertiary assays, we identified 188 confirmed hit compounds with low and submicromolar potencies. Thus, this approach takes advantage of a phenotypic screen with high-throughput scalability to identify new small-molecule G542X-CFTR readthrough modulators.
Elsevier,

Economic Effects of Natural Disasters, Theoretical Foundations, Methods, and Tools, 2021, Pages 77-95

This book chapter advances SDG 5 and 13 by unpacking the gendered nature of economic dimensions of climate change and identifing that climate change needs to be seen as a pervasive economic issue impacting men and women differently.
This book chapter advances SDG #3 and #10 by providing therapeutic strategies that can be employed in clinical trials for AD in DS will be discussed as well as their underlying scientific rationale.
This book chapter advances SDG #3 and #10 by providing a brief history of PET imaging and the radiotracers that have had a significant impact for measuring the three signature AD-related neuropathologies related to AD and provides an overview of the research utilizing PET imaging in the DS population
This book chapter advances SDG #3 and #10 by discussing the advantages of performing genetic studies in people with DS, and then discussing the role of reported genes that are known to be associated with AD risk in adults with DS or in the general population. It also discusses how future longitudinal multiomic and imaging study can enhance our understanding of the biology of AD.
Elsevier,

Alzheimer’s Disease: Understanding Biomarkers, Big Data, and Therapy, Volume , 1 January 2021

This book chapter advances SDG #3 and #10 by discussing the operational aspects of deep learning solutions for Alzheimer’s disease, including the review of the advantages and limitations of using deep learning, and future directions on the applications of deep learning to Alzheimer’s disease.
This book chapter advances SDG #3 and #10 by systematically appraises the concepts and promising benefits of AI technology within healthcare for AD risk prediction across communities, and its possible concerns to be tackled prior to large-scale implementation.
Elsevier,

Alzheimer’s Disease: Understanding Biomarkers, Big Data, and Therapy, Volume , 1 January 2021

This book chapter advances SDG #3 and #10 by providing evidence that behavioral treatments are more effective than most pharmacological therapies at managing depression in Alzheimer’s disease.
This book chapter advances SDG #3 and #10 by stressing that a population health approach and a focus on promoting equity in health and access to care are critical to reducing the risk of AD and other dementias.

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