Frontal lobe mucocoele secondary to an extensive frontal sinus osteoma

ABSTRACT Osteomas are benign slow growing tumours of the paranasal sinuses. The frontal and ethmoidal sinuses are most commonly affected. We present an unusual case of a 42-year-old Malay lady who had a frontal lobe mucocoele, secondary to an extensive frontal sinus osteoma with orbital and intracranial extension, and presenting primarily with orbital proptosis. She was successfully managed by a multi specialty team

Carbon Nanotubes Generated from Polyphenyl Acetylene

The carbonization of polyphenyl acetylene in alumina matrix yields uniform, cylindrical, monodisperse carbon nanotubes with outer diameter almost equal to pore diameter of the alumina membrane used. The electrochemical characteristics reveal that the charge transfer at the composite electrode based on carbon nanotube might be higher compared to that of planar graphite, glassy carbon and composite electrode based on commercially available Vulcan XC72R carbon. Pt-Ru nanoparticles are highly dispersed inside the tube with an average particle size of 1.7 nm as revealed by HR-TEM images

Oncolytic viruses as therapeutic cancer vaccines

Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity. With this favorable immune backdrop, genetic engineering of OVs and rational combinations further potentiate OVs as cancer vaccines. OVs armed with GM-CSF (such as T-VEC and Pexa-Vec) or other immunostimulatory genes, induce potent anti-tumor immunity in both animal models and human patients. Combination with other immunotherapy regimens improve overall therapeutic efficacy. Coadministration with a HDAC inhibitor inhibits innate immunity transiently to promote infection and spread of OVs, and significantly enhances anti-tumor immunity and improves the therapeutic index. Local administration or OV mediated-expression of ligands for Toll-like receptors can rescue the function of tumor-infiltrating CD8+ T cells inhibited by the immunosuppressive tumor microenvironment and thus enhances the antitumor effect. Combination with cyclophosphamide further induces ICD, depletes Treg, and thus potentiates antitumor immunity. In summary, OVs properly armed or in rational combinations are potent therapeutic cancer vaccines. © 2013 Bartlett et al.; licensee BioMed Central Ltd

19F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy

Studying polysaccharide-protein interactions under physiological conditions by conventional techniques is challenging. Ideally, macromolecules could be followed by both in vitro spectroscopy experiments as well as in tissues using microscopy, to enable a proper comparison of results over these different scales but, often, this is not feasible. The cell surface and extracellular matrix polysaccharides, glycosaminoglycans (GAGs) lack groups that can be detected selectively in the biological milieu. The introduction of 19F labels into GAG polysaccharides is explored and the interaction of a labelled GAG with the heparin-binding protein, antithrombin, employing 19F NMR spectroscopy is followed. Furthermore, the ability of 19F labelled GAGs to be imaged using CARS microscopy is demonstrated. 19F labelled GAGs enable both 19F NMR protein-GAG binding studies in solution at the molecular level and non-linear microscopy at a microscopic scale to be conducted on the same material, essentially free of background signals

Multivalent helix mimetics for PPI-inhibition.

The exploitation of multivalent ligands for the inhibition of protein-protein interactions has not yet been explored as a supramolecular design strategy. This is despite the fact that protein-protein interactions typically occur within the context of multi-protein complexes and frequently exploit avidity effects or co-operative binding interactions to achieve high affinity interactions. In this paper we describe preliminary studies on the use of a multivalent N-alkylated aromatic oligoamide helix mimetic for inhibition of p53/hDM2 and establish that protein dimerisation is promoted, rather than enhanced binding resulting from a higher effective concentration of the ligand. This journal i

Influence of calcination temperature on structural and magnetic properties of nanocomposites formed by Co-ferrite dispersed in sol-gel silica matrix using tetrakis(2-hydroxyethyl) orthosilicate as precursor

Effects of calcination temperatures varying from 400 to 1000°C on structural and magnetic properties of nanocomposites formed by Co-ferrite dispersed in the sol-gel silica matrix using tetrakis(2-hydroxyethyl) orthosilicate (THEOS) as water-soluble silica precursor have been investigated. Studies carried out using XRD, FT-IR, TEM, STA (TG-DTG-DTA) and VSM techniques. Results indicated that magnetic properties of samples such as superparamagnetism and ferromagnetism showed great dependence on the variation of the crystallinity and particle size caused by the calcination temperature. The crystallization, saturation magnetization Ms and remenant magnetization Mr increased as the calcination temperature increased. But the variation of coercivity Hc was not in accordance with that of Ms and Mr, indicating that Hc is not determined only by the crystallinity and size of CoFe2O4 nanoparticles. TEM images showed spherical nanoparticles dispersed in the silica network with sizes of 10-30 nm. Results showed that the well-established silica network provided nucleation locations for CoFe2O4 nanoparticles to confinement the coarsening and aggregation of nanoparticles. THEOS as silica matrix network provides an ideal nucleation environment to disperse CoFe2O4 nanoparticles and thus to confine them to aggregate and coarsen. By using THEOS as water-soluble silica precursor over the currently used TEOS and TMOS, the organic solvents are not needed owing to the complete solubility of THEOS in water. Synthesized nanocomposites with adjustable particle sizes and controllable magnetic properties make the applicability of Co-ferrite even more versatile

Modular protein-RNA interactions regulating mRNA metabolism: a role for NMR

Here we review the role played by transient interactions between multi-functional proteins and their RNA targets in the regulation of mRNA metabolism, and we describe the important function of NMR spectroscopy in the study of these systems. We place emphasis on a general approach for the study of different features of modular multi-domain recognition that uses well-established NMR techniques and that has provided important advances in the general understanding of post-transcriptional regulation

Novel SOX10 Indel Mutations Drive Schwannomas Through Impaired Transactivation of Myelination Gene Programs

BACKGROUND: Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas. METHODS: We performed comprehensive genomic profiling on a cohort of 96 human schwannomas, as well as DNA methylation profiling on a subset. Functional studies including RNA sequencing, chromatin immunoprecipitation-DNA sequencing, electrophoretic mobility shift assay, and luciferase reporter assays were performed in a fetal glial cell model following transduction with wildtype and tumor-derived mutant isoforms of SOX10. RESULTS: We identified that nearly one-third of sporadic schwannomas lack alterations in known nerve sheath tumor genes and instead harbor novel recurrent in-frame insertion/deletion mutations in SOX10, which encodes a transcription factor responsible for controlling Schwann cell differentiation and myelination. SOX10 indel mutations were highly enriched in schwannomas arising from nonvestibular cranial nerves (eg facial, trigeminal, vagus) and were absent from vestibular nerve schwannomas driven by NF2 mutation. Functional studies revealed these SOX10 indel mutations have retained DNA binding capacity but impaired transactivation of glial differentiation and myelination gene programs. CONCLUSIONS: We thus speculate that SOX10 indel mutations drive a unique subtype of schwannomas by impeding proper differentiation of immature Schwann cells