MA-[D-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic,Normalizes Glucose Tolerance and Episodic Memory in a Mouse Model of Type 2 Diabetes Mellitus and Alzheimer’s Disease-Like Cognitive Impairment

International Journal of Peptide Research and Therapeutics - In addition to its roles in regulating energy balance and glucose homeostasis, leptin greatly influences hippocampal learning and...     

Magnesium isotope fractionation during microbially enhanced forsterite dissolution

Bacillus subtilis endospore‐mediated forsterite dissolution experiments were performed to assess the effects of cell surface reactivity on Mg isotope fractionation during chemical weathering. Endospores present a unique opportunity to study the isolated impact of cell surface reactivity because they exhibit extremely low metabolic activity. In abiotic control assays, ²⁴Mg was preferentially released into solution during forsterite dissolution, producing an isotopically light liquid phase (δ²⁶Mg = ?0.39 ± 0.06 to ?0.26 ± 0.09‰) relative to the initial mineral composition (δ²⁶Mg = ?0.24 ± 0.03‰). The presence of endospores did not have an apparent effect on Mg isotope fractionation associated with the release of Mg from the solid into the aqueous phase. However, the endospore surfaces preferentially adsorbed ²⁴Mg from the dissolution products, which resulted in relatively heavy aqueous Mg isotope compositions. These aqueous Mg isotope compositions increased proportional to the fraction of dissolved Mg that was adsorbed, with the highest measured δ²⁶Mg (?0.08 ± 0.07‰) corresponding to the highest degree of adsorption (~76%). The Mg isotope composition of the adsorbed fraction was correspondingly light, at an average δ²⁶Mg of ?0.49‰. Secondary mineral precipitation and Mg adsorption onto secondary minerals had a minimal effect on Mg isotopes at these experimental conditions. Results demonstrate the isolated effects of cell surface reactivity on Mg isotope fractionation separate from other common biological processes, such as metabolism and organic acid production. With further study, Mg isotopes could be used to elucidate the role of the biosphere on Mg cycling in the environment.     

Disentangling the potential effects of land‐use and climate change on stream conditions

Land‐use and climate change are significantly affecting stream ecosystems, yet understanding of their long‐term impacts is hindered by the few studies that have simultaneously investigated their interaction and high variability among future projections. We modeled possible effects of a suite of 2030, 2060, and 2090 land‐use and climate scenarios on the condition of 70,772 small streams in the Chesapeake Bay watershed, United States. The Chesapeake Basin‐wide Index of Biotic Integrity, a benthic macroinvertebrate multimetric index, was used to represent stream condition. Land‐use scenarios included four Special Report on Emissions Scenarios (A1B, A2, B1, and B2) representing a range of potential landscape futures. Future climate scenarios included quartiles of future climate changes from downscaled Coupled Model Intercomparison Project ‐ Phase 5 (CMIP5) and a watershed‐wide uniform scenario (Lynch2016). We employed random forests analysis to model individual and combined effects of land‐use and climate change on stream conditions. Individual scenarios suggest that by 2090, watershed‐wide conditions may exhibit anywhere from large degradations (e.g., scenarios A1B, A2, and the CMIP5 25th percentile) to small degradations (e.g., scenarios B1, B2, and Lynch2016). Combined land‐use and climate change scenarios highlighted their interaction and predicted, by 2090, watershed‐wide degradation in 16.2% (A2 CMIP5 25th percentile) to 1.0% (B2 Lynch2016) of stream kilometers. A goal for the Chesapeake Bay watershed is to restore 10% of stream kilometers over a 2008 baseline; our results suggest meeting and sustaining this goal until 2090 may require improvement in 11.0%–26.2% of stream kilometers, dependent on land‐use and climate scenario. These results highlight inherent variability among scenarios and the resultant uncertainty of predicted conditions, which reinforces the need to incorporate multiple scenarios of both land‐use (e.g., development, agriculture, etc.) and climate change in future studies to encapsulate the range of potential future conditions.     

Elevated rates of positive selection drive the evolution of pestiferousness in the Colorado potato beetle (Leptinotarsa decemlineata,Say)

Contextualizing evolutionary history and identifying genomic features of an insect that might contribute to its pest status is important in developing early detection and control tactics. In order to understand the evolution of pestiferousness, which we define as the accumulation of traits that contribute to an insect population's success in an agroecosystem, we tested the importance of known genomic properties associated with rapid adaptation in the Colorado potato beetle (CPB), Leptinotarsa decemlineata Say. Within the leaf beetle genus Leptinotarsa, only CPB, and a few populations therein, has risen to pest status on cultivated nightshades, Solanum. Using whole genomes from ten closely related Leptinotarsa species native to the United States, we reconstructed a high‐quality species tree and used this phylogenetic framework to assess evolutionary patterns in four genomic features of rapid adaptation: standing genetic variation, gene family expansion and contraction, transposable element abundance and location, and positive selection at protein‐coding genes. Throughout approximately 20 million years of history, Leptinotarsa species show little evidence of gene family turnover and transposable element variation. However, there is a clear pattern of CPB experiencing higher rates of positive selection on protein‐coding genes. We determine that these rates are associated with greater standing genetic variation due to larger effective population size, which supports the theory that the demographic history contributes to rates of protein evolution. Furthermore, we identify a suite of coding genes under positive selection that are putatively associated with pestiferousness in the Colorado potato beetle lineage. They are involved in the biological processes of xenobiotic detoxification, chemosensation and hormone function.     

Prophylactic Application of MA-[d-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic,Prevents or Slows the Progression of Obesity,Insulin Resistance,and Cognitive Impairment in a Mouse Model of Type 2 Diabetes Mellitus

International Journal of Peptide Research and Therapeutics - Oral delivery of MA-[d-Leu-4]-OB3 has been shown to significantly improve energy balance, glycemic control, dyslipidemia, and episodic...