Modulation of EGFR activity by molecularly imprinted polymer nanoparticles targeting intracellular epitopes

In recent years, molecularly imprinted polymer nanoparticles (nanoMIPs) have proven to be an attractive alternative to antibodies in diagnostic and therapeutic applications. However, several key questions remain: how suitable are intracellular epitopes as targets for nanoMIP binding? And to what extent can protein function be modulated via targeting specific epitopes? To investigate this, three extracellular and three intracellular epitopes of epidermal growth factor receptor (EGFR) were used as templates for the synthesis of nanoMIPs which were then used to treat cancer cells with different expression levels of EGFR. It was observed that nanoMIPs imprinted with epitopes from the intracellular kinase domain and the extracellular ligand binding domain of EGFR caused cells to form large foci of EGFR sequestered away from the cell surface, caused a reduction in autophosphorylation, and demonstrated effects on cell viability. Collectively, this suggests that intracellular domain-targeting nanoMIPs can be a potential new tool for cancer therapy

Structural diversity in binary nanoparticle superlattices

Assembly of small building blocks such as atoms, molecules and nanoparticles into macroscopic structures - that is, 'bottom up' assembly - is a theme that runs through chemistry, biology and material science. Bacteria(1), macromolecules(2) and nanoparticles(3) can self-assemble, generating ordered structures with a precision that challenges current lithographic techniques. The assembly of nanoparticles of two different materials into a binary nanoparticle superlattice (BNSL)(3-7) can provide a general and inexpensive path to a large variety of materials (metamaterials) with precisely controlled chemical composition and tight placement of the components. Maximization of the nanoparticle packing density has been proposed as the driving force for BNSL formation(3,8,9), and only a few BNSL structures have been predicted to be thermodynamically stable. Recently, colloidal crystals with micrometre-scale lattice spacings have been grown from oppositely charged polymethyl methacrylate spheres(10,11). Here we demonstrate formation of more than 15 different BNSL structures, using combinations of semiconducting, metallic and magnetic nanoparticle building blocks. At least ten of these colloidal crystalline structures have not been reported previously. We demonstrate that electrical charges on sterically stabilized nanoparticles determine BNSL stoichiometry; additional contributions from entropic, van der Waals, steric and dipolar forces stabilize the variety of BNSL structures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62551/1/nature04414.pd

VEGF and eNOS genes polymorphism features in patients with diabetes mellitus with and without initial non-proliferative diabetic retinopathy

The endothelial NO synthase (eNOS) and vascular endothelial growth factor (VEGF) imbalance and the polymorphism of these genes may be the predisposition for diabetic retinopathy (DR) development and progression.The aim: to analyze VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes polymorphism and their combinations in patients with type 2 diabetes mellitus (DM2) with and without initial non-proliferative DR.Materials and methods. The study included 200 patients with type 2 diabetes (155 women and 45 men, age – 43–70 years): 111 people without and 89 people with DR. The polymorphism of the regulatory regions of VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes was studied using restriction fragment length polymorphism analysis and TaqMan Real-Time PCR by. Statistical processing was carried out using the software packages Statistica 10.0, SPSS Statistics 23 and the package of original programs for volumetric processing of bioinformation.Results. The VEGF-2578 heterozygosity and two complex genotypes – VEGF-2578CA:VEGF+936CC and NOS3-786CT:VEGF-2578CA:VEGF+936CC – signifi cantly decreased in patients with DR. The predisposition to early DR development to minor genotype of eNOS gene in the NOS3-786CC:VEGF+936CT complex and signifi cantly decreased the homozygous wild-type eNOS genotype in DM2 patients with ophthalmopathology were shown. NOS3-86TT:VEGF2578AA genotype signifi cantly decreased in group with retinopathy developing and the glycated hemoglobin high level.Conclusion. Along with the clinical risk factors for the development of DR in DM2, the genetic polymorphism of the regulatory regions of the genes analyzed by us has a signifi cant weight. When analyzing potential genetic markers, it is important to consider possible joint epistatic/hypostatic effects. The complex analysis of polymorphic gene can help early prognosis of the DR development

Preparation of stable magnetic nanofluids containing Fe3O4@PPy nanoparticles by a novel one-pot route

Stable magnetic nanofluids containing Fe3O4@Polypyrrole (PPy) nanoparticles (NPs) were prepared by using a facile and novel method, in which one-pot route was used. FeCl3·6H2O was applied as the iron source, and the oxidizing agent to produce PPy. Trisodium citrate (Na3cit) was used as the reducing reagent to form Fe3O4 NPs. The as-prepared nanofluid can keep long-term stability. The Fe3O4@PPy NPs can still keep dispersing well after the nanofluid has been standing for 1 month and no sedimentation is found. The polymerization reaction of the pyrrole monomers took place with Fe3+ ions as the initiator, in which these Fe3+ ions remained in the solution adsorbed on the surface of the Fe3O4 NPs. Thus, the core-shell NPs of Fe3O4@PPy were obtained. The particle size of the as-prepared Fe3O4@PPy can be easily controlled from 7 to 30 nm by the polymerization reaction of the pyrrole monomers. The steric stabilization and weight of the NPs affect the stability of the nanofluids. The as-prepared Fe3O4@PPy NPs exhibit superparamagnetic behavior

Identification and characterisation of tomato torrado virus, a new plant picorna-like virus from tomato

A new virus was isolated from tomato plants from the Murcia region in Spain which showed symptoms of ‘torrado disease’ very distinct necrotic, almost burn-like symptoms on leaves of infected plants. The virus particles are isometric with a diameter of approximately 28 nm. The viral genome consists of two (+)ssRNA molecules of 7793 (RNA1) and 5389 nts (RNA2). RNA1 contains one open reading frame (ORF) encoding a predicted polyprotein of 241 kDa that shows conserved regions with motifs typical for a protease-cofactor, a helicase, a protease and an RNA-dependent RNA polymerase. RNA2 contains two, partially overlapping ORFs potentially encoding proteins of 20 and 134 kDa. These viral RNAs are encapsidated by three proteins with estimated sizes of 35, 26 and 23 kDa. Direct protein sequencing mapped these coat proteins to ORF2 on RNA2. Phylogenetic analyses of nucleotide and derived amino acid sequences showed that the virus is related to but distinct from viruses belonging to the genera Sequivirus, Sadwavirus and Cheravirus. This new virus, for which the name tomato torrado virus is proposed, most likely represents a member of a new plant virus genus

Synthesis and characterization of hybrid nanostructures

There has been significant interest in the development of multicomponent nanocrystals formed by the assembly of two or more different materials with control over size, shape, composition, and spatial orientation. In particular, the selective growth of metals on the tips of semiconductor nanorods and wires can act to couple the electrical and optical properties of semiconductors with the unique properties of various metals. Here, we outline our progress on the solution-phase synthesis of metal-semiconductor heterojunctions formed by the growth of Au, Pt, or other binary catalytic metal systems on metal (Cd, Pb, Cu)-chalcogenide nanostructures. We show the ability to grow the metal on various shapes (spherical, rods, hexagonal prisms, and wires). Furthermore, manipulating the composition of the metal nanoparticles is also shown, where PtNi and PtCo alloys are our main focus. The magnetic and electrical properties of the developed hybrid nanostructures are shown

Morphology-Controllable Synthesis of CeO2on a Pt Electrode

Nanoscale cerium dioxides with shape of nanoparticles, nanorods, and nanotubes were electrochemically synthesized. The morphology of CeO2was modulated by changing electrode potential and potential direction. CeO2nanorods and CeO2nanotubes were synthesized via the potentiostatic and cyclic voltammeteric methods, respectively. The morphology and structure of the obtained CeO2were characterized by field emission scanning electron microscope (FESEM) and X-ray diffraction (XRD). A possible formation mechanism has been suggested to illuminate the relationship between the preparation condition and the morphology of CeO2

Core Proteome of the Minimal Cell: Comparative Proteomics of Three Mollicute Species

Mollicutes (mycoplasmas) have been recognized as highly evolved prokaryotes with an extremely small genome size and very limited coding capacity. Thus, they may serve as a model of a ‘minimal cell’: a cell with the lowest possible number of genes yet capable of autonomous self-replication. We present the results of a comparative analysis of proteomes of three mycoplasma species: A. laidlawii, M. gallisepticum, and M. mobile. The core proteome components found in the three mycoplasma species are involved in fundamental cellular processes which are necessary for the free living of cells. They include replication, transcription, translation, and minimal metabolism. The members of the proteome core seem to be tightly interconnected with a number of interactions forming core interactome whether or not additional species-specific proteins are located on the periphery. We also obtained a genome core of the respective organisms and compared it with the proteome core. It was found that the genome core encodes 73 more proteins than the proteome core. Apart of proteins which may not be identified due to technical limitations, there are 24 proteins that seem to not be expressed under the optimal conditions

Observation of a J^PC = 1-+ exotic resonance in diffractive dissociation of 190 GeV/c pi- into pi- pi- pi+

The COMPASS experiment at the CERN SPS has studied the diffractive dissociation of negative pions into the pi- pi- pi+ final state using a 190 GeV/c pion beam hitting a lead target. A partial wave analysis has been performed on a sample of 420000 events taken at values of the squared 4-momentum transfer t' between 0.1 and 1 GeV^2/c^2. The well-known resonances a1(1260), a2(1320), and pi2(1670) are clearly observed. In addition, the data show a significant natural parity exchange production of a resonance with spin-exotic quantum numbers J^PC = 1-+ at 1.66 GeV/c^2 decaying to rho pi. The resonant nature of this wave is evident from the mass-dependent phase differences to the J^PC = 2-+ and 1++ waves. From a mass-dependent fit a resonance mass of 1660 +- 10+0-64 MeV/c^2 and a width of 269+-21+42-64 MeV/c^2 is deduced.Comment: 7 page, 3 figures; version 2 gives some more details, data unchanged; version 3 updated authors, text shortened, data unchange