Exploring the mechanism of formation of native-like and precursor amyloid oligomers for the native acylphosphatase from Sulfolobus solfataricus

Over 40 human diseases are associated with the formation of well-defined proteinaceous fibrillar aggregates. Since the oligomers precursors to the fibrils are increasingly recognized to be the causative agents of such diseases, it is important to elucidate the mechanism of formation of these early species. The acylphosphatase from Sulfolobus solfataricus is an ideal system as it was found to form, under conditions in which it is initially native, two types of prefibrillar aggregates: (1) initial enzymatically active aggregates and (2) oligomers with characteristics reminiscent of amyloid protofibrils, with the latter originating from the structural reorganization of the initial assemblies. By studying a number of protein variants with a variety of biophysical techniques, we have identified the regions of the sequence and the driving forces that promote the first aggregation phase and show that the second phase consists in a cooperative conversion involving the entire globular fol

Low redshift constraints on energy-momentum-powered gravity models

There has been recent interest in the cosmological consequences of energy-momentum-powered gravity models, in which the matter side of Einstein's equations is modified by the addition of a term proportional to some power, $n$, of the energy-momentum tensor, in addition to the canonical linear term. In this work we treat these models as phenomenological extensions of the standard $\Lambda$CDM, containing both matter and a cosmological constant. We also quantitatively constrain the additional model parameters using low redshift background cosmology data that are specifically from Type Ia supernovas and Hubble parameter measurements. We start by studying specific cases of these models with fixed values of $n,$ which lead to an analytic expression for the Friedmann equation; we discuss both their current constraints and how the models may be further constrained by future observations of Type Ia supernovas for WFIRST complemented by measurements of the redshift drift by the ELT. We then consider and constrain a more extended parameter space, allowing $n$ to be a free parameter and considering scenarios with and without a cosmological constant. These models do not solve the cosmological constant problem per se. Nonetheless these models can phenomenologically lead to a recent accelerating universe without a cosmological constant at the cost of having a preferred matter density of around $\Omega_M\sim0.4$ instead of the usual $\Omega_M\sim0.3$. Finally we also briefly constrain scenarios without a cosmological constant, where the single component has a constant equation of state which needs not be that of matter; we provide an illustrative comparison of this model with a more standard dynamical dark energy model with a constant equation of state.Comment: 13+2 pages, 12+1 figures; A&A (in press

Virtual Functions Placement with Time Constraints in Fog Computing: a Matching Theory Perspective

This paper proposes two virtual function (VFs) placement approaches in a Fog domain. The considered solutions formulate a matching game with externalities, aiming at minimizing both the worst application completion time and the number of applications in outage, i.e., the number of applications with an overall completion time greater than a given deadline. The first proposed matching game is established between the VFs set and the Fog Nodes (FNs) set by taking into account the ordered sequence of services (i.e., chain) requested by each application. Conversely, the second proposed method overlooks the applications service chain structure in formulating the VF placement problem, with the aim at lowering the computation complexity without loosing the performance. Furthermore, in order to complete our analysis, the stability of the reached matchings has been theoretically proved for both the proposed solutions. Finally, performance comparisons of the proposed MT approaches with different alternatives are provided to highlight the superior performance of the proposed methods

The regions of the sequence most exposed to the solvent within the amyloidogenic state of a protein initiate the aggregation process.

Formation of misfolded aggregates is an essential part of what proteins can do. The process of protein aggregation is central to many human diseases and any aggregating event needs to be prevented within a cell and in protein design. In order to aggregate, a protein needs to unfold its native state, at least partially. The conformational state that is prone to aggregate is difficult to study, due to its aggregating potential and heterogeneous nature. Here, we use a systematic approach of limited proteolysis, in combination with electrospray ionisation mass spectrometry, to investigate the regions that are most flexible and solvent-exposed within the native, ligand-bound and amyloidogenic states of muscle acylphosphatase (AcP), a protein previously shown to form amyloid fibrils in the presence of trifluoroethanol. Seven proteases with different degrees of specificity have been used for this purpose. Following exposure to the aggregating conditions, a number of sites along the sequence of AcP become susceptible to proteolytic digestion. The pattern of proteolytic cleavages obtained under these conditions is considerably different from that of the native and ligand-bound conformations and includes a portion within the N-terminal tail of the protein (residues 6-7), the region of the sequence 18-23 and the position 94 near the C terminus. There is a significant overlap between the regions of the sequence found to be solvent-exposed from the present study and those previously identified to be critical in the rate-determining steps of aggregation from protein engineering approaches. This indicates that a considerable degree of solvent exposure is a feature of the portions of a protein that initiate the process of aggregation

Does degradation from selective logging and illegal activities differently impact forest resources? A case study in Ghana

Degradation, a reduction of the ecosystem’s capacity to supply goods and services, is widespread in tropical forests and mainly caused by human disturbance. To maintain the full range of forest ecosystem services and support the development of effective conservation policies, we must understand the overall impact of degradation on different forest resources. This research investigates the response to disturbance of forest structure using several indicators: soil carbon content, arboreal richness and biodiversity, functional composition (guild and wood density), and productivity. We drew upon large field and remote sensing datasets from different forest types in Ghana, characterized by varied protection status, to investigate impacts of selective logging, and of illegal land use and resources extraction, which are the main disturbance causes in West Africa. Results indicate that functional composition and the overall number of species are less affected by degradation, while forest structure, soil carbon content and species abundance are seriously impacted, with resources distribution reflecting the protection level of the areas. Remote sensing analysis showed an increase in productivity in the last three decades, with higher resiliency to change in drier forest types, and stronger productivity correlation with solar radiation in the short dry season. The study region is affected by growing anthropogenic pressure on natural resources and by an increased climate variability: possible interactions of disturbance with climate are also discussed, together with the urgency to reduce degradation in order to preserve the full range of ecosystem functions