Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum.

Natural compounds often have complex molecular structures and unknown molecular targets. These characteristics make them difficult to analyse using a classical pharmacological approach. Curcumin, the main curcuminoid of turmeric, is a complex molecule possessing wide-ranging biological activities, cellular mechanisms and roles in potential therapeutic treatment including Alzheimer's disease and cancer. Here, we investigate the physiological effects and molecular targets of curcumin in Dictyostelium discoideum We show curcumin causes acute effects on cell behaviour, reduces cell growth, and slows multicellular development. We then employ a range of structurally related compounds to show the distinct role of different structural groups cell behaviour, growth, and development, highlighting active moieties in cell function, and showing that these cellular effects are unrelated to the well-known antioxidant activity of curcumin. Molecular mechanisms underlying the effect of curcumin and one synthetic analogue (EF24) were then investigated to identify a curcumin-resistant mutant lacking the protein phosphatase 2A regulatory subunit (PsrA) and an EF24-resistant mutant lacking the presenilin 1 orthologue (PsenB). Using in-silico docking analysis, we then show that curcumin may function through direct binding to a key regulatory region of PsrA. These findings reveal novel cellular and molecular mechanisms for the function of curcumin and related compounds

Environmental effects on galaxy evolution. II: quantifying the tidal features in NIR-images of the cluster Abell 85

This work is part of a series of papers devoted to investigate the evolution of cluster galaxies during their infall. In the present article we imaged in NIR a selected sample of galaxies through- out the massive cluster Abell 85 (z = 0.055). We obtained (JHK) photometry for 68 objects, reaching 1 mag/arcsec^2 deeper than 2MASS. We use these images to unveil asymmetries in the outskirts of a sample of bright galaxies and develop a new asymmetry index, alpha_An, which allows to quantify the degree of disruption by the relative area occupied by the tidal features on the plane of the sky. We measure the asymmetries for a subsample of 41 large area objects finding clear asymmetries in ten galaxies, most of them being in groups and pairs projected at different clustercentric distances, some of them located beyond R500 . Combining information on the Hi-gas content of blue galaxies and the distribution of sub-structures across Abell 85, with the present NIR asymmetry analysis, we obtain a very powerful tool to confirm that tidal mechanisms are indeed present and are currently affecting a fraction of galaxies in Abell 85. However, when comparing our deep NIR images with UV-blue images of two very disrupted (jellyfish) galaxies in this cluster, we discard the presence of tidal 1 interactions down to our detection limit. Our results suggest that ram-pressure stripping is at the origin of such spectacular disruptions. We conclude that across a complex cluster like Abell 85, environment mechanisms, both gravitational and hydrodynamical, are playing an active role in driving galaxy evolution.Comment: 30 pages, 13 figures, Accepted for Publication in A

Oxygen Activation by Mononuclear Mn, Co, and Ni Centers in Biology and Synthetic Complexes

The active sites of metalloenzymes that catalyze O2-dependent reactions generally contain iron or copper ions. However, several enzymes are capable of activating O2 at manganese or nickel centers instead, and a handful of dioxygenases exhibit activity when substituted with cobalt. This minireview summarizes the catalytic properties of oxygenases and oxidases with mononuclear Mn, Co, or Ni active sites, including oxalate-degrading oxidases, catechol dioxygenases, and quercetin dioxygenase. In addition, recent developments in the O2 reactivity of synthetic Mn, Co, or Ni complexes are described, with an emphasis on the nature of reactive intermediates featuring superoxo-, peroxo-, or oxo-ligands. Collectively, the biochemical and synthetic studies discussed herein reveal the possibilities and limitations of O2 activation at these three “overlooked” metals

Seismicity relocation and fault structure near the Leech River Fault Zone, southern Vancouver Island

Relatively low rates of seismicity and fault loading have made it challenging to correlate microseismicity to mapped surface faults on the forearc of southern Vancouver Island. Here we use precise relocations of microsciesmicity integrated with existing geologic data, to present the first identification of subsurface seismogenic structures associated with the Leech River fault zone (LRFZ) on southern Vancouver Island. We used HypoDD double difference relocation method to relocate 1253 earthquakes reported by the Canadian National Seismograph Network (CNSN) catalog from 1985 to 2015. Our results reveal an ~8-10 km wide, NNE-dipping zone of seismicity representing a subsurface structure along the eastern 30 km of the terrestrial LRFZ and extending 20 km farther eastward offshore, where the fault bifurcates beneath the Juan de Fuca Strait. Using a clustering analysis we identify secondary structures within the NNE-dipping fault zone, many of which are sub-vertical and exhibit right-lateral strike-slip focal mechanisms. We suggest that the arrangement of these near-vertical dextral secondary structures within a more general NE-dipping fault zone, located well beneath (10-15 km) the Leech River fault (LRF) as imaged by LITHOPROBE, may be a consequence of the reactivation of this fault system as a right-lateral structure in the crust with pre-existing NNE-dipping foliations. Our results provide the first confirmation of active terrestrial crustal faults on Vancouver Island using a relocation method. We suggest that slowly slipping active crustal faults, especially in regions with pre-existing foliations, may result in microseismicity along fracture arrays rather than along single planar structures

Catalytically active peptide–gold nanoparticle conjugates: Prospecting for artificial enzymes

The self‐assembly of peptides onto the surface of gold nanoparticles has emerged as a promising strategy towards the creation of artificial enzymes. The resulting high local peptide density surrounding the nanoparticle leads to cooperative and synergistic effects, which result in rate accelerations and distinct catalytic properties compared to the unconjugated peptide. This Minireview summarizes contributions to and progress made in the field of catalytically active peptide–gold nanoparticle conjugates. The origin of distinct properties, as well as potential applications, are also discussed

Divergent evolution of protein conformational dynamics in dihydrofolate reductase.

Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment