Aqua­[2-(5-ethyl-2-pyridyl-κN)-4-iso­propyl-4-methyl-5-oxo-4,5-dihydroxy­imidazol-1-ido-κN 1](5-methyl-1H-pyrazole-3-carboxyl­ato-κ2 N 2,O)copper(II) 1.33-hydrate

In the title complex, [Cu(C5H5N2O2)(C14H18N3O)(H2O)]·1.33H2O, the CuII ion is coordinated in a slightly distorted square-pyramidal environment. The basal plane is formed by two N atoms from a 2-(5-ethyl-2-pyridyl-κN)-4-isopropyl-4-methyl-5-oxo-4,5-dihydroxy­imidazol-1-ide ligand and by one O atom and one N atom from a 5-methyl-1H-pyrazole-3-carboxyl­ate ligand. The apical position is occupied by a water mol­ecule. In the crystal structure, O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds lead to a three-dimensional supra­molecular network

1-[3-(2-Nitro­phen­yl)-5-phenyl-2-pyrazolin-1-yl]ethanone

The title compound, C17H15N3O3, was prepared from 1-(2-nitro­phen­yl)-3-phenyl­prop-2-en-1-one and hydrazine. The dihedral angle between the benzene and phenyl rings is 74.55 (2)°. The pyrazoline ring is in a slight envelope conformation with the C atom bonded to the phenyl ring forming the flap. In the crystal structure, weak inter­molecular C—H⋯O hydrogen bonds connect mol­ecules into chains along [100]

Dual Specificity and Novel Structural Folding of Yeast Phosphodiesterase-1 for Hydrolysis of Second Messengers Cyclic Adenosine and Guanosine 3′,5′-Monophosphate

Cyclic nucleotide phosphodiesterases (PDEs) decompose second messengers cAMP and cGMP that play critical roles in many physiological processes. PDE1 of Saccharomyces cerevisiae has been subcloned and expressed in Escherichia coli. Recombinant yPDE1 has a KM of 110 μM and a kcat of 16.9 s–1 for cAMP and a KM of 105 μM and a kcat of 11.8 s–1 for cGMP. Thus, the specificity constant (kcat/KMcAMP)/(kcat/KMcGMP) of 1.4 indicates a dual specificity of yPDE1 for hydrolysis of both cAMP and cGMP. The crystal structures of unliganded yPDE1 and its complex with GMP at 1.31 Å resolution reveal a new structural folding that is different from those of human PDEs but is partially similar to that of some other metalloenzymes such as metallo-β-lactamase. In spite of their different structures and divalent metals, yPDE1 and human PDEs may share a common mechanism for hydrolysis of cAMP and cGMP

One-Step Multipurpose Surface Functionalization by Adhesive Catecholamine

Surface modification is one of the most important techniques in modern science and engineering. The facile introduction of a wide variety of desired properties onto virtually any material surface is an ultimate goal in surface chemistry. To achieve this goal, the incorporation of structurally diverse molecules onto any material surface is an essential capability for ideal surface modification. Here, a general strategy for surface modification is presented in which many diverse surfaces can be functionalized by immobilizing a wide variety of molecules. This strategy functionalizes surfaces by a one-step immersion of substrates in a one-pot mixture of a molecule and a catecholamine surface modification agent. This one-step procedure for surface modification represents a standard protocol to control interfacial properties.Armed Forces Institute of Regenerative Medicine (Award W81XWH-08-2-0034)National Institutes of Health (U.S.) (2R01DE016516-06

Elastic behaviour of nanophases in polyvinyl alcohol (PVA)/ bamboo charcoal (BC) nanocomposite films

Polyvinyl alcohol (PVA) nanocomposite films reinforced with bamboo charcoal (BC) nanoparticles were successfully fabricated via solution casting and their nanomechanical properties in terms of material phases were determined by a peak force quantitative nanomechanical tapping mode (PFQNM). Our experimental results revealed that the elastic modulus of PVA semicrystalline phase in stack-bundle form was 24± 4.2 GPa with the semicrystalline phase width being 20-76 nm, as opposed to 11.4± 3.1 GPa and 18-65 nm for corresponding PVA amorphous phase accordingly. The incorporation of BC nanoparticles enhanced the elastic moduli of both crystalline and amorphous phases of PVA by ~51% and ~100%, respectively. Moreover, the phase width was decreased to be in range of 5-53 nm for crystalline phase and 4-35 nm for amorphous phase

ENTH and ANTH domain proteins participate in AP2-independent clathrin-mediated endocytosis

Clathrin-mediated endocytosis (CME) is a major route of entry into eukaryotic cells. A core of evolutionarily ancient genes encodes many components of this system but much of our mechanistic understanding of CME is derived from a phylogenetically narrow sampling of a few model organisms. In the parasite Trypanosoma brucei, which is distantly related to the better characterised animals and fungi, exceptionally fast endocytic turnover aids its evasion of the host immune system. Although clathrin is absolutely essential for this process, the adaptor protein complex 2 (AP2) has been secondarily lost, suggesting mechanistic divergence. Here, we characterise two phosphoinositide-binding monomeric clathrin adaptors, T. brucei (Tb)EpsinR and TbCALM, which in trypanosomes are represented by single genes, unlike the expansions present in animals and fungi. Depletion of these gene products reveals essential, but partially redundant, activities in CME. Ultrastructural analysis of TbCALM and TbEpsinR double-knockdown cells demonstrated severe defects to clathrin-coated pit formation and morphology associated with a dramatic inhibition of endocytosis. Depletion of TbCALM alone, however, produced a distinct lysosomal segregation phenotype, indicating an additional non-redundant role for this protein. Therefore, TbEpsinR and TbCALM represent ancient phosphoinositide-binding proteins with distinct and vital roles in AP2-independent endocytosis

Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect

Network Archaeology: Uncovering Ancient Networks from Present-day Interactions

Often questions arise about old or extinct networks. What proteins interacted in a long-extinct ancestor species of yeast? Who were the central players in the Last.fm social network 3 years ago? Our ability to answer such questions has been limited by the unavailability of past versions of networks. To overcome these limitations, we propose several algorithms for reconstructing a network's history of growth given only the network as it exists today and a generative model by which the network is believed to have evolved. Our likelihood-based method finds a probable previous state of the network by reversing the forward growth model. This approach retains node identities so that the history of individual nodes can be tracked. We apply these algorithms to uncover older, non-extant biological and social networks believed to have grown via several models, including duplication-mutation with complementarity, forest fire, and preferential attachment. Through experiments on both synthetic and real-world data, we find that our algorithms can estimate node arrival times, identify anchor nodes from which new nodes copy links, and can reveal significant features of networks that have long since disappeared.Comment: 16 pages, 10 figure

Metal-enhanced fluorescence of colloidal nanocrystals with nanoscale control

Engineering the spectral properties of fluorophores, such as the enhancement of luminescence intensity, can be achieved through coupling with surface plasmons in metallic nanostructures This process, referred to as metal-enhanced fluorescence, offers promise for a range of applications, including LEDs, sensor technology, microarrays and single-molecule studies. It becomes even more appealing when applied to colloidal semiconductor nanocrystals, which exhibit size-dependent optical properties, have high photochemical stability, and are characterized by broad excitation spectra and narrow emission bands. Other approaches have relied upon the coupling of fluorophores (typically organic dyes) to random distributions of metallic nanoparticles or nanoscale roughness in metallic films. Here, we develop a new strategy based on the highly reproducible fabrication of ordered arrays of gold nanostructures coupled to CdSe/ZnS nanocrystals dispersed in a polymer blend. We demonstrate the possibility of obtaining precise control and a high spatial selectivity of the fluorescence enhancement process