171 research outputs found
Governance of interdependent ecosystem services and common-pool resources
Environmental governance is recognized as a key issue in many natural and social sciences. It is highly relevant for ecosystem services and common-pool resources as well. Both fields overlap yet have typically been studied separately. Therefore, this study aimed a) to examine the emerging body of literature that incorporates concepts from both fields of research and considers governance challenges, and b) to identify policy tools and recommendations presented for addressing those challenges. The analysis of thirty-nine selected peer-review papers revealed the multiplicity of interacting governance challenges with three major categories: environmental, socioeconomic, and problems of governance itself. Governance is impeded by institutional mismatches, exclusion of local actors, corruption, and perverse policies. The proposed policy recommendations most often suggest changes in institutional arrangements and increasing scientific understanding. Meeting human needs, and increasing social equity and justice were recognized broadly as integral for improving governance, yet correlations among governance problems and solutions appear elusive. These findings extend theoretical reasoning, while carrying practical implications for policy, governance and environmental stewardship. The analysis implies that policies to improve human conditions will be key for improved environmental governance, but more research is needed to learn which types of policy recommendations prove successful given diverse local contexts
Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates
The presence of oligomeric aggregates, which is often observed during the
process of amyloid formation, has recently attracted much attention since it
has been associated with neurodegenerative conditions such as Alzheimer's and
Parkinson's diseases. We provide a description of a sequence-indepedent
mechanism by which polypeptide chains aggregate by forming metastable
oligomeric intermediate states prior to converting into fibrillar structures.
Our results illustrate how the formation of ordered arrays of hydrogen bonds
drives the formation of beta-sheets within the disordered oligomeric aggregates
that form early under the effect of hydrophobic forces. Initially individual
beta-sheets form with random orientations, which subsequently tend to align
into protofilaments as their lengths increases. Our results suggest that
amyloid aggregation represents an example of the Ostwald step rule of first
order phase transitions by showing that ordered cross-beta structures emerge
preferentially from disordered compact dynamical intermediate assemblies.Comment: 14 pages, 4 figure
Discrete molecular dynamics simulations of peptide aggregation
We study the aggregation of peptides using the discrete molecular dynamics
simulations. At temperatures above the alpha-helix melting temperature of a
single peptide, the model peptides aggregate into a multi-layer parallel
beta-sheet structure. This structure has an inter-strand distance of 0.48 nm
and an inter-sheet distance of 1.0 nm, which agree with experimental
observations. In this model, the hydrogen bond interactions give rise to the
inter-strand spacing in beta-sheets, while the Go interactions among side
chains make beta-strands parallel to each other and allow beta-sheets to pack
into layers. The aggregates also contain free edges which may allow for further
aggregation of model peptides to form elongated fibrils.Comment: 15 pages, 8 figure
Dimer Formation Enhances Structural Differences between Amyloid β-Protein (1–40) and (1–42): An Explicit-Solvent Molecular Dynamics Study
Amyloid -protein (A) is central to the pathology of Alzheimer's disease. A 5% difference in the primary structure of the two predominant alloforms, A and A, results in distinct assembly pathways and toxicity properties. Discrete molecular dynamics (DMD) studies of A and A assembly resulted in alloform-specific oligomer size distributions consistent with experimental findings. Here, a large ensemble of DMD–derived A and A monomers and dimers was subjected to fully atomistic molecular dynamics (MD) simulations using the OPLS-AA force field combined with two water models, SPCE and TIP3P. The resulting all-atom conformations were slightly larger, less compact, had similar turn and lower -strand propensities than those predicted by DMD. Fully atomistic A and A monomers populated qualitatively similar free energy landscapes. In contrast, the free energy landscape of A dimers indicated a larger conformational variability in comparison to that of A dimers. A dimers were characterized by an increased flexibility in the N-terminal region D1-R5 and a larger solvent exposure of charged amino acids relative to A dimers. Of the three positively charged amino acids, R5 was the most and K16 the least involved in salt bridge formation. This result was independent of the water model, alloform, and assembly state. Overall, salt bridge propensities increased upon dimer formation. An exception was the salt bridge propensity of K28, which decreased upon formation of A dimers and was significantly lower than in A dimers. The potential relevance of the three positively charged amino acids in mediating the A oligomer toxicity is discussed in the light of available experimental data
Fluctuations and correlations in sandpile models
We perform numerical simulations of the sandpile model for non-vanishing
driving fields and dissipation rates . Unlike simulations
performed in the slow driving limit, the unique time scale present in our
system allows us to measure unambiguously response and correlation functions.
We discuss the dynamic scaling of the model and show that
fluctuation-dissipation relations are not obeyed in this system.Comment: 5 pages, latex, 4 postscript figure
A Bethe lattice representation for sandpiles
Avalanches in sandpiles are represented throughout a process of percolation
in a Bethe lattice with a feedback mechanism. The results indicate that the
frequency spectrum and probability distribution of avalanches resemble more to
experimental results than other models using cellular automata simulations.
Apparent discrepancies between experiments are reconciled. Critical behavior is
here expressed troughout the critical properties of percolation phenomena.Comment: 5 pages, 4 figures, submitted for publicatio
A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation
Nanoparticles introduced in living cells are capable of strongly promoting
the aggregation of peptides and proteins. We use here molecular dynamics
simulations to characterise in detail the process by which nanoparticle
surfaces catalyse the self- assembly of peptides into fibrillar structures. The
simulation of a system of hundreds of peptides over the millisecond timescale
enables us to show that the mechanism of aggregation involves a first phase in
which small structurally disordered oligomers assemble onto the nanoparticle
and a second phase in which they evolve into highly ordered beta-sheets as
their size increases
Conformational Preferences of a 14-Residue Fibrillogenic Peptide from Acetylcholinesteraseâ€
A 14-residue fragment from near the C-terminus of the enzyme acetylcholinesterase (AChE) is believed to have a neurotoxic/neurotrophic effect acting via an unknown pathway. While the peptide is α-helical in the full-length enzyme, the structure and association mechanism of the fragment are unknown. Using multiple molecular dynamics simulations, starting from a tetrameric complex of the association domain of AChE and systematicall disassembled subsets that include the peptide fragment, we show that the fragment is incapable of retaining its helicity in solution. Extensive replica exchange Monte Carlo folding and unfolding simulations in implicit solvent with capped and uncappted termini failed to converge to any consistent cluster of structures, suggesting that the fragment remains largely unstructured in solution under the conditions considered. Furthermore, extended molecular dynamics simulations of two steric zipper models show that the peptide is likely to form a zipper with antiparallel sheets and that peptides with mutations known to prevent fibril formation likely do so by interfering with this packing. The results demonstrate how the local environment of a peptide can stabilize a particular conformation
Europium as an inhibitor of Amyloid-β(1-42) induced membrane permeation
Soluble Amyloid-beta (Aβ) oligomers are a source of cytotoxicity in Alzheimer's disease (AD). The toxicity of Aβ oligomers may arise from their ability to interact with and disrupt cellular membranes mediated by GM1 ganglioside receptors within these membranes. Therefore, inhibition of Aβ–membrane interactions could provide a means of preventing the toxicity associated with Aβ. Here, using Surface Plasmon field-enhanced Fluorescence Spectroscopy, we determine that the lanthanide, Europium III chloride (Eu3+), strongly binds to GM1 ganglioside-containing membranes and prevents the interaction with Aβ42 leading to a loss of the peptides ability to cause membrane permeation. Here we discuss the molecular mechanism by which Eu3+ inhibits Aβ42-membrane interactions and this may lead to protection of membrane integrity against Aβ42 induced toxicity
Finite Size Effects in Simulations of Protein Aggregation
It is becoming increasingly clear that the soluble protofibrillar species that proceed amyloid fibril formation are associated with a range of neurodegenerative disorders such as Alzheimer's and Parkinson diseases. Computer simulations of the processes that lead to the formation of these oligomeric species are starting to make significant contributions to our understanding of the determinants of protein aggregation. We simulate different systems at constant concentration but with a different number of peptides and we study the how the finite number of proteins affects the underlying free energy of the system and therefore the relative stability of the species involved in the process. If not taken into account, this finite size effect can undermine the validity of theoretical predictions regarding the relative stability of the species involved and the rates of conversion from one to the other. We discuss the reasons that give rise to this finite size effect form both a probabilistic and energy fluctuations point of view and also how this problem can be dealt by a finite size scaling analysis
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