451 research outputs found
Macroscopic synthesis and characterization of giant fullerenes
Thermal treatment of carbon soot produced by arc evaporation of nickel-filled graphite rods in 500 Torr of helium gives giant fullerenes showing characteristic IR, Raman, NMR and powder XRD signatures. Transmission electron micrographs show faceted structures with pentagonal, hexagonal and spherical shapes. The simplicity and similarity of the IR spectrum with those of smaller fullerenes suggest that the material is a form of large fullerenes. Chemical treatment of the material gives carbon onions
Lack of evidence for MHC-unrestricted (atypical) recognition of mucin by mucinous pancreatic tumour-reactive T-cells
Cytotoxic T-cells generated against heterologous, mucinous pancreatic tumour cells were shown to recognize mucin in a major histocombatibility complex (MHC)-unrestricted fashion. In contrast, the present study demonstrates a typical allogeneic response of heterologous cytotoxic T-cells established against mucin-expressing pancreatic tumour cells. Heterologous cytotoxic T cells lysed targets that were used as stimulators and other targets that shared human leucocyte antigen (HLA) with the stimulator. These cytotoxic T-cells lysed mucin-expressing stimulator cells but not autologous tumour cells in spite of expressing mucin on their surface. Likewise, tumour-infiltrating CD4+T-cells proliferated against its own tumour cell target, while such T-cells did not respond to heterologous, mucin-expressing pancreatic tumour cells. Culturing heterologous tumour-specific cytotoxic T-cells with purified pancreatic tumour cell-mucin rendered them unresponsive to their target cells. Furthermore, purified mucin did not produce a mucin-specific response in mucinous pancreatic tumour patients' primary T-cells even in the presence of antigen-presenting cells. Our study finds no evidence for MHC-unrestricted recognition of mucin by pancreatic cancer patients' T-cells. © 2000 Cancer Research Campaig
O-GlcNAcase Fragment Discovery with Fluorescence Polarimetry
The
attachment of the sugar N-acetyl-D-glucosamine (GlcNAc) to
specific serine and threonine residues on proteins is referred to
as protein O-GlcNAcylation. O-GlcNAc transferase (OGT) is the enzyme
responsible for carrying out the modification, while O-GlcNAcase (OGA)
reverses it. Protein O-GlcNAcylation has been implicated in a wide
range of cellular processes including transcription, proteostasis,
and stress response. Dysregulation of O-GlcNAc has been linked to
diabetes, cancer, and neurodegenerative and cardiovascular disease.
OGA has been proposed to be a drug target for the treatment of Alzheimer’s
and cardiovascular disease given that increased O-GlcNAc levels appear
to exert a protective effect. The search for specific, potent, and
drug-like OGA inhibitors with bioavailability in the brain is therefore
a field of active research, requiring orthogonal high-throughput assay
platforms. Here, we describe the synthesis of a novel probe for use
in a fluorescence polarization based assay for the discovery of inhibitors
of OGA. We show that the probe is suitable for use with both human
OGA, as well as the orthologous bacterial counterpart from <i>Clostridium perfringens</i>, <i>Cp</i>OGA, and the
lysosomal hexosaminidases HexA/B. We structurally characterize <i>Cp</i>OGA in complex with a ligand identified from a fragment
library screen using this assay. The versatile synthesis procedure
could be adapted for making fluorescent probes for the assay of other
glycoside hydrolases
PEG Branched Polymer for Functionalization of Nanomaterials with Ultralong Blood Circulation
Nanomaterials have been actively pursued for biological and medical
applications in recent years. Here, we report the synthesis of several new
poly(ethylene glycol) grafted branched-polymers for functionalization of
various nanomaterials including carbon nanotubes, gold nanoparticles (NP) and
gold nanorods (NRs), affording high aqueous solubility and stability for these
materials. We synthesize different surfactant polymers based upon
poly-(g-glutamic acid) (gPGA) and poly(maleic anhydride-alt-1-octadecene)
(PMHC18). We use the abundant free carboxylic acid groups of gPGA for attaching
lipophilic species such as pyrene or phospholipid, which bind to nanomaterials
via robust physisorption. Additionally, the remaining carboxylic acids on gPGA
or the amine-reactive anhydrides of PMHC18 are then PEGylated, providing
extended hydrophilic groups, affording polymeric amphiphiles. We show that
single-walled carbon nanotubes (SWNTs), Au NPs and NRs functionalized by the
polymers exhibit high stability in aqueous solutions at different pHs, at
elevated temperatures and in serum. Morever, the polymer-coated SWNTs exhibit
remarkably long blood circulation (t1/2 22.1 h) upon intravenous injection into
mice, far exceeding the previous record of 5.4 h. The ultra-long blood
circulation time suggests greatly delayed clearance of nanomaterials by the
reticuloendothelial system (RES) of mice, a highly desired property for in vivo
applications of nanomaterials, including imaging and drug delivery
Morphology of supported polymer electrolyte ultra-thin films: a numerical study
Morphology of polymer electrolytes membranes (PEM), e.g., Nafion, inside PEM
fuel cell catalyst layers has significant impact on the electrochemical
activity and transport phenomena that determine cell performance. In those
regions, Nafion can be found as an ultra-thin film, coating the catalyst and
the catalyst support surfaces. The impact of the hydrophilic/hydrophobic
character of these surfaces on the structural formation of the films has not
been sufficiently explored yet. Here, we report about Molecular Dynamics
simulation investigation of the substrate effects on the ionomer ultra-thin
film morphology at different hydration levels. We use a mean-field-like model
we introduced in previous publications for the interaction of the hydrated
Nafion ionomer with a substrate, characterized by a tunable degree of
hydrophilicity. We show that the affinity of the substrate with water plays a
crucial role in the molecular rearrangement of the ionomer film, resulting in
completely different morphologies. Detailed structural description in different
regions of the film shows evidences of strongly heterogeneous behavior. A
qualitative discussion of the implications of our observations on the PEMFC
catalyst layer performance is finally proposed
RAPID: Resource of Asian Primary Immunodeficiency Diseases
Availability of a freely accessible, dynamic and integrated database for primary immunodeficiency diseases (PID) is important both for researchers as well as clinicians. To build a PID informational platform and also as a part of action to initiate a network of PID research in Asia, we have constructed a web-based compendium of molecular alterations in PID, named Resource of Asian Primary Immunodeficiency Diseases (RAPID), which is available as a worldwide web resource at http://rapid.rcai.riken.jp/. It hosts information on sequence variations and expression at the mRNA and protein levels of all genes reported to be involved in PID patients. The main objective of this database is to provide detailed information pertaining to genes and proteins involved in primary immunodeficiency diseases along with other relevant information about protein–protein interactions, mouse studies and microarray gene-expression profiles in various organs and cells of the immune system. RAPID also hosts a tool, mutation viewer, to predict deleterious and novel mutations and also to obtain mutation-based 3D structures for PID genes. Thus, information contained in this database should help physicians and other biomedical investigators to further investigate the role of these molecules in PID
Stability, Electronic Structure and Vibrational Modes of Ti_8C_12 Dimer
We present our density functional results of the geometry, electronic
structure and dissociation energy of Ti_8C_12 dimer. We show that as opposed to
the currently held view that Ti_8C_12 are highly stable monodispersed clusters,
the neutral Ti_8C_12 clusters form covalent bonds and form stable dimers. We
determine that the Ti atoms bond weakly (0.9 eV/bond) to organic ligands such
as ammonia. Alternatively the Met-Car dimer has a cohesive energy of 4.84 eV or
approximately 1.2 eV per bond. While Met-Car dimers are stable, formation of
these dimers may be quenched in an environment that contains a significant
population of organic ligands. The ionization and dissociation energies of the
dimer are of same order which prevents the observation of the dimer in the ion
mass spectroscopy. The analysis of the vibrational frequencies show the
lowest-energy structure to be dynamically stable. We also present infrared
absorption and Raman scattering spectra of the Ti_8C_12 dimer.Comment: 5 pages, 3 figures (Better quality figures available on request).
Physical Review B (Rapid Communication) (2002, in press
Polymer-Nanoparticle Complexes : from Dilute Solution to Solid State
We report on the formation and the structural properties of supermicellar
aggregates also called electrostatic complexes, made from mineral nanoparticles
and polyelectrolyte-neutral block copolymers in aqueous solutions. The mineral
particles put under scrutiny are ultra-fine and positively charged yttrium
hydroxyacetate nanoparticles. Combining light, neutron and x-ray scattering
experiments, we have characterized the sizes and the aggregation numbers of the
organic-inorganic complexes. We have found that the hybrid aggregates have
typical sizes in the range 100 nm and exhibit a remarkable colloidal stability
with respect to ionic strength and concentration variations. Solid films with
thicknesses up to several hundreds of micrometers were cast from solutions,
resulting in a bulk polymer matrix in which nanoparticle clusters are dispersed
and immobilized. It was found in addition that the structure of the complexes
remains practically unchanged during film casting.Comment: 18 pages, 11 figures, 2 table
Evaluation of antiarthritic activity of Strychnos potatorum Linn seeds in Freund's adjuvant induced arthritic rat model
<p>Abstract</p> <p>Background</p> <p><it>Strychnos potatorum </it>Linn (Loganiaceae) is a moderate sized tree found in southern and central parts of India, Sri Lanka and Burma. In traditional system of medicine, <it>Strychnos potatorum </it>Linn seeds were used for various ailments including inflammation, diabetes etc. To investigate the folkloric use of the seeds the present study was carried out on Freund's adjuvant induced arthritic rats.</p> <p>Methods</p> <p>The present study states the effect of the aqueous extract (SPE) and the whole seed powder (SPP) of <it>Strychnos potatorum </it>Linn seeds on the Freund's complete adjuvant (FCA) induced arthritic rat paw edema, body weight changes and alterations in haematological and biochemical parameters in both developing and developed phases of arthritis. Histopathology of proximal interphalangeal joints and radiology of hind legs were studied.</p> <p>Results</p> <p>In FCA induced arthritic rats, there was significant increase in rat paw volume and decrease in body weight increment, whereas SPP and SPE treated groups, showed significant reduction in paw volume and normal gain in body weight. The altered haematological parameters (Hb, RBC, WBC and ESR) and biochemical parameters (blood urea, serum creatinine, total proteins and acute phase proteins) in the arthritic rats were significantly brought back to near normal by the SPP and SPE treatment at the dose of 200 mg/kg/p.o in both developing and developed phases of arthritis. Further the histopathological and radiological studies revealed the antiarthritic activity of SPP and SPE by indicating fewer abnormalities in these groups when compared to the arthritic control group.</p> <p>Conclusion</p> <p>In conclusion, both SPP and SPE at the specified dose level of 200 mg/kg, p.o. showed reduction in rat paw edema volume and it could significantly normalize the haematological and biochemical abnormalities in adjuvant induced arthritic rats in both developing and developed phases of FCA induced arthritis. Further the histopathological and radiological studies confirmed the antiarthritic activity of SPP and SPE.</p
A mutant O-GlcNAcase enriches Drosophila developmental regulators
YesProtein O-GlcNAcylation is a reversible post-translational modification of serines/threonines on
nucleocytoplasmic proteins. It is cycled by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase
(O-GlcNAcase or OGA). Genetic approaches in model organisms have revealed that protein O-GlcNAcylation is
essential for early embryogenesis. Drosophila melanogaster OGT/supersex combs (sxc) is a polycomb gene,
null mutants of which display homeotic transformations and die at the pharate adult stage. However, the identities
of the O-GlcNAcylated proteins involved, and the underlying mechanisms linking these phenotypes to embryonic
development, are poorly understood. Identification of O-GlcNAcylated proteins from biological samples is
hampered by the low stoichiometry of this modification and limited enrichment tools. Using a catalytically inactive
bacterial O-GlcNAcase mutant as a substrate trap, we have enriched the O-GlcNAc proteome of the developing
Drosophila embryo, identifying, amongst others, known regulators of Hox genes as candidate conveyors of OGT
function during embryonic development.Wellcome Trust Investigator Award (110061); MRC grant (MC_UU_12016/5); and Royal Society Research Grant
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