In Silico Analysis of the Apolipoprotein E and the Amyloid β Peptide Interaction: Misfolding Induced by Frustration of the Salt Bridge Network

The relationship between Apolipoprotein E (ApoE) and the aggregation processes of the amyloid β (Aβ) peptide has been shown to be crucial for Alzheimer's disease (AD). The presence of the ApoE4 isoform is considered to be a contributing risk factor for AD. However, the detailed molecular properties of ApoE4 interacting with the Aβ peptide are unknown, although various mechanisms have been proposed to explain the physiological and pathological role of this relationship. Here, computer simulations have been used to investigate the process of Aβ interaction with the N-terminal domain of the human ApoE isoforms (ApoE2, ApoE3 and ApoE4). Molecular docking combined with molecular dynamics simulations have been undertaken to determine the Aβ peptide binding sites and the relative stability of binding to each of the ApoE isoforms. Our results show that from the several ApoE isoforms investigated, only ApoE4 presents a misfolded intermediate when bound to Aβ. Moreover, the initial α-helix used as the Aβ peptide model structure also becomes unstructured due to the interaction with ApoE4. These structural changes appear to be related to a rearrangement of the salt bridge network in ApoE4, for which we propose a model. It seems plausible that ApoE4 in its partially unfolded state is incapable of performing the clearance of Aβ, thereby promoting amyloid forming processes. Hence, the proposed model can be used to identify potential drug binding sites in the ApoE4-Aβ complex, where the interaction between the two molecules can be inhibited

Cheatgrass is favored by warming but not CO\u3csub\u3e2\u3c/sub\u3e enrichment in a semi-arid grassland

levated CO2 and warming may alter terrestrial ecosystems by promoting invasive plants with strong community and ecosystem impacts. Invasive plant responses to elevated CO2 and warming are difficult to predict, however, because of the many mechanisms involved, including modification of phenology, physiology, and cycling of nitrogen and water. Understanding the relative and interactive importance of these processes requires multifactor experiments under realistic field conditions. Here, we test how free-air CO2 enrichment (to 600 ppmv) and infrared warming (+1.5 °C day/3 °C night) influence a functionally and phenologically distinct invasive plant in semi-arid mixed-grass prairie. Bromus tectorum (cheatgrass), a fast-growing Eurasian winter annual grass, increases fire frequency and reduces biological diversity across millions of hectares in western North America. Across 2 years, we found that warming more than tripled B. tectorum biomass and seed production, due to a combination of increased recruitment and increased growth. These results were observed with and without competition from native species, under wet and dry conditions (corresponding with tenfold differences in B. tectorum biomass), and despite the fact that warming reduced soil water. In contrast, elevated CO2 had little effect on B. tectorum invasion or soil water, while reducing soil and plant nitrogen (N). We conclude that (1) warming may expand B. tectorum’s phenological niche, allowing it to more successfully colonize the extensive, invasion-resistant northern mixed-grass prairie, and (2) in ecosystems where elevated CO2 decreases N availability, CO2 may have limited effects on B. tectorum and other nitrophilic invasive species

Clinical Significance of Right Ventricular Longitudinal Function Parameters After Aortic Valve Replacement

[No abstract available

Triazacyclohexane (tach) complexes of high-valent rhenium: syntheses of [(R(3)tach)ReO(3)](+) (R = -CH(3), -CH(2)C(6)H(5)) and its substitution reactions

N-Alkylated derivatives of 1,3,5-triazacyclohexane (tach) are versatile, facially coordinating ligands. We present the syntheses and full characterization of two new complexes of the (R(3)tach)ReO3](+) type. In these complexes, the tach ligand is readily substituted by bi- and tridentate ligands; hence, they can be considered as sources of the ReO3](+) motif for Re-VII complexes