Microwave treatment of the cornea leads to localised disruption of the extracellular matrix

Microwave keratoplasty is a thermo-refractive surgical procedure that can correct myopia (short-sightedness) and pathologic corneal steepening by using microwave energy to cause localised shrinkage around an annulus of the cornea leading to its flattening and vision correction. The effects on the corneal extracellular matrix, however, have not yet been evaluated, thus the current study to assess post-procedure ultrastructural changes in an in-vivo rabbit model. To achieve this a series of small-angle x-ray scattering (SAXS) experiments were carried out across whole transects of treated and untreated rabbit corneas at 0.25 mm intervals, which indicated no significant change in collagen intra-fibrillar parameters (i.e. collagen fibril diameter or axial D-period), whereas inter-fibrillar measures (i.e. fibril spacing and the degree of spatial order) were markedly altered in microwave-treated regions of the cornea. These structural matrix alterations in microwave-treated corneas have predicted implications for corneal biomechanical strength and tissue transparency, and, we contend, potentially render microwave-treated corneas resistant to surgical stabilization using corneal cross-linking procedures currently employed to combat refractive error caused by corneal steepening

Search for solar axions in XMASS, a large liquid-xenon detector

XMASS, a low-background, large liquid-xenon detector, was used to search for solar axions that would be produced by bremsstrahlung and Compton effects in the Sun. With an exposure of 5.6ton days of liquid xenon, the model-independent limit on the coupling for mass $\ll$ 1keV is $|g_{aee}|< 5.4\times 10^{-11}$ (90% C.L.), which is a factor of two stronger than the existing experimental limit. The bounds on the axion masses for the DFSZ and KSVZ axion models are 1.9 and 250eV, respectively. In the mass range of 10-40keV, this study produced the most stringent limit, which is better than that previously derived from astrophysical arguments regarding the Sun to date

Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation

Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. © 2013 Goh et al

The Mitotic Arrest Deficient Protein MAD2B Interacts with the Small GTPase RAN throughout the Cell Cycle

Contains fulltext : 81260.pdf (publisher's version ) (Open Access)BACKGROUND: Previously, we identified the mitotic arrest deficient protein MAD2B (MAD2L2) as a bona fide interactor of the renal cell carcinoma (RCC)-associated protein PRCC. In addition, we found that fusion of PRCC with the transcription factor TFE3 in t(X;1)(p11;q21)-positive RCCs results in an impairment of this interaction and, concomitantly, an abrogation of cell cycle progression. Although MAD2B is thought to inhibit the anaphase promoting complex (APC) by binding to CDC20 and/or CDH1(FZR1), its exact role in cell cycle control still remains to be established. METHODOLOGY/PRINCIPAL FINDINGS: Using a yeast two-hybrid interaction trap we identified the small GTPase RAN, a well-known cell cycle regulator, as a novel MAD2B binding protein. Endogenous interaction was established in mammalian cells via co-localization and co-immunoprecipitation of the respective proteins. The interaction domain of RAN could be assigned to a C-terminal moiety of 60 amino acids, whereas MAD2B had to be present in its full-length conformation. The MAD2B-RAN interaction was found to persist throughout the cell cycle. During mitosis, co-localization at the spindle was observed. CONCLUSIONS/SIGNIFICANCE: The small GTPase RAN is a novel MAD2B binding protein. This novel protein-protein interaction may play a role in (i) the control over the spindle checkpoint during mitosis and (ii) the regulation of nucleocytoplasmic trafficking during interphase

A Vaccine against Nicotine for Smoking Cessation: A Randomized Controlled Trial

BACKGROUND: Tobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period. METHODOLOGY/PRINCIPAL FINDINGS: 229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qbeta (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012). CONCLUSIONS: Whereas Nicotine-Qbeta did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction. TRIAL REGISTRATION: Swiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616