Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) γ Activators and Pan-PPAR Partial Agonists

Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) γ to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPARγ ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8–C10) bind the PPARγ LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPARγ LBD, stronger partial agonists with full length PPARγ and exhibit full blockade of PPARγ phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPARγ also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/β-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPARγ modulators with useful clinical profiles among natural products

Tailoring Transportation Planning Decisions to Diverse Urban Environments

As the world's population continues to urbanize, providing efficient and effective logistics service to customers in urban areas has become an increasingly important, but difficult task. Recent vehicle routing studies suggest that logistics planners face numerous difficulties during decision-making due to certain complexities associated with the urban environment, but to date, specific challenges have remained unidentified. Using a multiple case study methodology, this research examines several environmental characteristics that influence vehicle routing decisions across eight U.S. urban centers, and contrasts decisions firms make when creating solutions to address these factors. Cross-case synthesis uncovered patterns connecting specific environmental characteristics with variations on traditional vehicle routing decisions. Results allow us to construct a theoretical framework and propositions to guide managers when tailoring urban logistics strategies to urban environments having different combinations of structural characteristics.This accepted article is published as Rose, W.J., Mollenkopf, D.A., Autry, C.W. and Williams, B.D. (2020), Tailoring Transportation Planning Decisions to Diverse Urban Environments. Decision Sciences, 51: 920-961. https://doi.org/10.1111/deci.12397. posted with permission. © 2019 Decision Sciences Institute<br

Neuropeptide S Receptor: Recent Updates on Nonpeptide Antagonist Discovery

Neuropeptide S (NPS) is a 20-amino acid peptide of great interest due to its possible involvement in several biological processes, including food intake, locomotion, wakefulness, arousal, and anxiety. Structure–activity relationship studies of NPS have identified key points for structural modifications with the goal of modulating NPS receptor (NPSR) agonist activity or achieving antagonism at the same receptor. Only limited information is available for nonpeptide NPSR antagonists. In the last year, several studies have been reported in literature which present various series of small molecules as antagonists of this receptor. The results allow a comparison of the structures and activities of these molecules, leading to the design of new ligands with increased potency and improved pharmacological and pharmacokinetic profiles. This work presents a brief overview of the available information regarding structural features and pharmacological characterization of published nonpeptide NPSR antagonists

Changing College Students’ Financial Knowledge, Attitudes, and Behavior through Seminar Participation

College students, Financial education, Financial knowledge, Financial behavior, Financial attitudes,

Family Structure and the Nature of Couple Relationships: Relationship Distress, Separation, Divorce, and Repartnering

The goal of this chapter is to review the current state of theoretical and empirical knowledge on the quality of the couple relationship and the family structure as determinants of parenting behavior. Ample evidence has accumulated over the past few decades that the functioning of the interparental relationship is pivotal for positive and supportive parenting. Supporting the spillover theory, relationship distress among parenting couples may increase child maladjustment, both directly and indirectly, by disrupted child-rearing and less optimal coparenting. In separated or divorced families, coparenting is a key concept to explain why some couples succeed in compartmentalizing their parenting from their spousal role. As such, cooperative coparenting has been firmly established as a central protective factor buffering the impact of parental separation on children. Based on the reviewed data among stepfamilies, it can be tentatively concluded that a cohabiting stepparent may become a significant new caregiver for the child, but only on condition of good stepparent–child relationship quality, which has emerged as crucially important for children’s adjustment in the new family environment. This chapter posits that the interparental relationship can be regarded as the key relation which is responsible for family functioning across different family types (nuclear, divorced, and stepfamilies). As a practical implication, it might, therefore, be wise to strengthen this core relationship as a potential leverage point to positively affect parents’ individual parenting and their joint coparental alliance