Relationship of dietary natural folate and synthetic folic acid co-exposure patterns with biological aging: findings from NHANES 2003-2018.

: The mandatory folic acid fortification program in the United States has inevitably exposed most Americans to both natural folate and synthetic folic acid. We aim to examine the association of dietary folate co-exposure patterns with biological aging indicators. : A total of 18 889 participants were enrolled from 2003 to 2018.

The influence of "small private online course + flipped classroom" teaching on physical education students' learning motivation from the perspective of self-determination theory.

Objective: The study aimed to enhance the learning motivation of college physical education students and improve their learning outcomes. Based on the perspective of the self-determination theory, this study explores the influence of "Small Private Online Course (SPOC) + flipped classroom" teaching on the learning motivation of students majoring in physical education and profoundly analyzes the influencing factors and promotion paths of learning motivation using this model.

Materials And Methods: A total of four classes (64 students) of physical education majors in a university were selected and randomly divided into an experimental group (34 students) and a control group (30 students).

The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease.

Innate immunity is associated with Alzheimer's disease, but the influence of immune activation on the production of amyloid-β is unknown. Here we identify interferon-induced transmembrane protein 3 (IFITM3) as a γ-secretase modulatory protein, and establish a mechanism by which inflammation affects the generation of amyloid-β. Inflammatory cytokines induce the expression of IFITM3 in neurons and astrocytes, which binds to γ-secretase and upregulates its activity, thereby increasing the production of amyloid-β.

Lasso peptides: structure, function, biosynthesis, and engineering.

Lasso peptides are a class of ribosomally-synthesized and posttranslationally-modified natural products with diverse bioactivities. This review describes the structure and function of all known lasso peptides (as of mid-2012) and covers our current knowledge about the biosynthesis of those molecules. The isolation and characterization of lasso peptides are also covered as are bioinformatics strategies for the discovery of new lasso peptides from genomic sequence data.

The role of a conserved threonine residue in the leader peptide of lasso peptide precursors.

The conserved threonine (Thr) residue in the penultimate position of the leader peptide of lasso peptides microcin J25 and capistruin can be effectively replaced by several amino acids close in size and shape to Thr. These findings suggest a model for lasso peptide biosynthesis in which the Thr sidechain is a recognition element for the lasso peptide maturation machinery.

Construction of a single polypeptide that matures and exports the lasso peptide microcin J25.

Roped in: The lasso peptide microcin J25 (MccJ25) is matured by two enzymes and is exported by a putative ABC transporter. We probed the function of the maturation enzymes using mutagenesis. We demonstrate that fusions of the enzymes with intervening linkers can produce MccJ25.

Sequence diversity in the lasso peptide framework: discovery of functional microcin J25 variants with multiple amino acid substitutions.

Microcin J25 (MccJ25) is a ribosomally synthesized antimicrobial peptide that has an unusual threaded lasso structure in which the C-terminal "tail" of the peptide is fed through a macrocyclic "ring" formed by the N-terminal residues. Production of MccJ25 in Escherichia coli is dependent upon a four-gene cluster encoding the structural gene mcjA, two maturation enzymes mcjB and mcjC, and an immunity factor, mcjD, in the form of an MccJ25 export pump. Here we have developed a system for orthogonal control of the expression of mcjA and mcjD, thus permitting independent control of MccJ25 production and export/immunity in E.

Computational design of the lasso peptide antibiotic microcin J25.

Microcin J25 (MccJ25) is a 21 amino acid (aa) ribosomally synthesized antimicrobial peptide with an unusual structure in which the eight N-terminal residues form a covalently cyclized macrolactam ring through which the remaining 13 aa tail is fed. An open question is the extent of sequence space that can occupy such an extraordinary, highly constrained peptide fold. To begin answering this question, here we have undertaken a computational redesign of the MccJ25 peptide using a two-stage sequence selection procedure based on both energy minimization and fold specificity.

Much of the microcin J25 leader peptide is dispensable.

The antimicrobial peptide microcin J25 (MccJ25) is matured by two enzymes, McjB and McjC, from a 58 amino acid (aa) preprotein, McjA, into its final 21 aa lasso topology. Herein we have investigated the role of the leader peptide of McjA and found that only the eight C-terminal amino acids of this leader peptide are required for maturation of MccJ25. There is a high content of lysine residues in the McjA leader peptide, but herein we also demonstrate that these charged amino acids do not play a major role in the maturation of MccJ25.

Engineered gene clusters for the production of the antimicrobial peptide microcin J25.

Microcin J25 (MccJ25) is an antimicrobial peptide produced by isolates of Escherichia coli with activity against closely related species. Production and export of mature MccJ25 in E. coli requires four genes that are organized on a plasmid-borne cluster in natural producer strains.