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Aromatic side-chain crosslinking in RiPP biosynthesis.
Nat Chem Biol
January 2025
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
Peptide cyclization is a defining feature of many bioactive molecules, particularly in the ribosomally synthesized and post-translationally modified peptide (RiPP) family of natural products. Although enzymes responsible for N- to C-terminal macrocyclization, lanthipeptide formation or heterocycle installation have been well documented, a diverse array of cyclases have been discovered that perform crosslinking of aromatic side chains. These enzymes form either biaryl linkages between two aromatic amino acids or a crosslink between one aliphatic amino acid and one aromatic amino acid.
View Article and Find Full Text PDFPhotoreceptor metabolic window unveils eye-body interactions.
Nat Commun
January 2025
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases, Guangzhou, China.
Photoreceptors are specialized neurons at the core of the retina's functionality, with optical accessibility and exceptional sensitivity to systemic metabolic stresses. Here we show the ability of risk-free, in vivo photoreceptor assessment as a window into systemic health and identify shared metabolic underpinnings of photoreceptor degeneration and multisystem health outcomes. A thinner photoreceptor layer thickness is significantly associated with an increased risk of future mortality and 13 multisystem diseases, while systematic analyses of circulating metabolomics enable the identification of 109 photoreceptor-related metabolites, which in turn elevate or reduce the risk of these health outcomes.
View Article and Find Full Text PDF3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.
Elife
January 2025
Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, United States.
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.
View Article and Find Full Text PDFRecent Advances in Diversity-Oriented Synthesis of N-containing Organic Molecules Through Carbodiimide-based Reactions.
Curr Org Synth
January 2025
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, I.R. Iran.
Carbodiimides (R-N=C=N-R) are well-known intermediates for the preparation of a variety of N-containing compounds, including heterocycles and amide linkages. Be-cause of their high reactivity and easy availability, carbodiimides have been broadly used as building blocks in the synthesis of structurally complex and diverse heterocyclic com-pounds in multi-component reactions (MCRs). Recent advances in diversity-oriented syn-thesis with carbodiimide-based MCRs are discussed in this minireview and are classified into different sections based on the key transformation involved in the reactions, such as heteroannulation and nucleophilic addition reactions which containing metal-catalyzed re-actions, multi-component reactions, and catalyst-free reactions subsections.
View Article and Find Full Text PDFAssociations of glycemic status with dynamic disease trajectories of atrial fibrillation and dementia.
J Prev Alzheimers Dis
January 2025
Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Background: Atrial fibrillation (AF) has been associated with elevated dementia risk, while few studies have examined the role of the optimal glycemic status in disease trajectories of AF and dementia.
Objectives: We aim to evaluate associations between glycemic status with disease trajectories of AF and dementia, as well as major dementia subtypes, including Alzheimer's disease and vascular dementia.
Design: Population-based cohort study.
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