Genetic strategies to understand physiological pathways regulating body weight

Body weight is a highly heritable trait across species. In humans, genetic variation plays a major role in determining the inter-individual differences in susceptibility or resistance to environmental factors which influence energy intake and expenditure. In this review, I discuss how genetic studies have contributed to our understanding of the central pathways that govern energy homeostasis. The study of individuals harboring highly penetrant genetic variants that disrupt the leptin–melanocortin pathway has informed our understanding of the physiological pathways involved in mammalian energy homeostasis.     

Shoot endophytic plant growth-promoting bacteria reduce cadmium toxicity and enhance switchgrass (<Emphasis Type="Italic">Panicum virgatum</Emphasis> L.) biomass

The aims of the study were to increase the biomass and to alleviate the deleterious effects of cadmium (Cd) in the switchgrass cultivars (Panicum virgatum L.) Alamo and Cave-in-Rock (CIR) under cadmium (Cd) stress using Cd-tolerant shoot endophytic plant growth-promoting bacteria (PGPB). Four shoot endophytic bacterial strains, viz. Bc09, So23, E02, and Oj24, were isolated from the above-ground parts of plants grown in a Cd-polluted soil and were successfully identified by 16S rRNA gene sequencing as Pseudomonas grimontii, Pantoea vagans, Pseudomonas veronii, and Pseudomonas fluorescens, respectively. These four strains were adapted to high CdCl₂ concentrations as they had higher Cd uptake capacities. In addition, they possessed a huge amount of growth regulatory activities e.g., indole acetic acid production, 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) activity, and phosphate solubilization. Growth particularly the height and biomass of both cultivars increased significantly in response to PGPB inoculation in the 20 µM CdCl₂ stress. The shoot biomass of the PGPB-inoculated Alamo was higher than the CIR under Cd stress. Interestingly, the level of Cd inside PGPB-inoculated plant tissues and the translocation factors were lower compared with the noninoculated Cd control plants. CIR plants exhibited higher Cd content than Alamo plants. Through confocal microscopy, green fluorescence was observed in roots and leaf tissues 2 days after the inoculation of green fluorescent protein (GFP)-labeled bacteria in Alamo, which confirmed the successful colonization of bacteria inside the plant tissues. These shoot endophytic PGPB and switchgrass interactions are useful for the sustainable biomass production of bioenergy crop in a Cd-contaminated environment.     

A Novel Gene Controlling the Timing of Courtship Initiation in Drosophila melanogaster

Over the past 35 years, developmental geneticists have made impressive progress toward an understanding of how genes specify morphology and function, particularly as they relate to the specification of each physical component of an organism. In the last 20 years, male courtship behavior in Drosophila melanogaster has emerged as a robust model system for the study of genetic specification of behavior. Courtship behavior is both complex and innate, and a single gene, fruitless (fru), is both necessary and sufficient for all aspects of the courtship ritual. Typically, loss of male-specific Fruitless protein function results in male flies that perform the courtship ritual incorrectly, slowly, or not at all. Here we describe a novel requirement for fru: we have identified a group of cells in which male Fru proteins are required to reduce the speed of courtship initiation. In addition, we have identified a gene, Trapped in endoderm 1 (Tre1), which is required in these cells for normal courtship and mating behavior. Tre1 encodes a G-protein-coupled receptor required for establishment of cell polarity and cell migration and has previously not been shown to be involved in courtship behavior. We describe the results of feminization of the Tre1-expressing neurons, as well as the effects on courtship behavior of mutation of Tre1. In addition, we show that Tre1 is expressed in a sexually dimorphic pattern in the central and peripheral nervous systems and investigate the role of the Tre1 cells in mate identification.     

Total synthesis,structural, and biological evaluation of stylissatin A and related analogs

The natural product cyclic peptide stylissatin A ( 1a ) was reported to inhibit nitric oxide production in LPS‐stimulated murine macrophage RAW 264.7 cells. In the current study, solid‐phase total synthesis of stylissatin A was performed by using a safety‐catch linker and yielded the peptide with a trans‐Phe⁷‐Pro⁶ linkage, whereas the natural product is the cis rotamer at this position as evidenced by a marked difference in NMR chemical shifts. In order to preclude the possibility of 1b being an epimer of the natural product, we repeated the synthesis using d ‐allo‐Ile in place of l ‐Ile and a different site for macrocyclization. The resulting product (d ‐allo‐Ile²)‐stylissatin A ( 1c ) was also found to have the trans‐Phe⁷‐Pro⁶ peptide conformations like rotamer 1b . Applying the second route to the synthesis of stylissatin A itself, we obtained stylissatin A natural rotamer 1a accompanied by rotamer 1b as the major product. Rotamers 1a , 1b , and the epimer 1c were separable by HPLC, and 1a was found to match the natural product in structure and biological activity. Six related analogs 2–7 of stylissatin A were synthesized on Wang resin and characterized by spectral analysis. The natural product ( 1a ), the rotamer ( 1b ), and (d ‐allo‐Ile²)‐stylissatin A ( 1c ) exhibited significant inhibition of NO^.. Further investigations were focused on 1b , which also inhibited proliferation of T‐cells and inflammatory cytokine IL‐2 production. The analogs 2–7 weakly inhibited NO^. production, but strongly inhibited IL‐2 cytokine production compared with synthetic peptide 1b . All analogs inhibited the proliferation of T‐cells, with analog 7 having the strongest effect. In the analogs, the Pro⁶ residue was replaced by Glu/Ala, and the SAR indicates that the nature of this residue plays a role in the biological function of these peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.