A Minimal Fragment of MUC1 Mediates Growth of Cancer Cells

The MUC1 protein is aberrantly expressed on many solid tumor cancers. In contrast to its apical clustering on healthy epithelial cells, it is uniformly distributed over cancer cells. However, a mechanistic link between aberrant expression and cancer has remained elusive. Herein, we report that a membrane-bound MUC1 cleavage product, that we call MUC1*, is the predominant form of the protein on cultured cancer cells and on cancerous tissues. Further, we demonstrate that transfection of a minimal fragment of MUC1, MUC1*1110, containing a mere forty-five (45) amino acids of the extracellular domain, is sufficient to confer the oncogenic activities that were previously attributed to the full-length protein. By comparison of molecular weight and function, it appears that MUC1* and MUC1*1110 are approximately equivalent. Evidence is presented that strongly supports a mechanism whereby dimerization of the extracellular domain of MUC1* activates the MAP kinase signaling cascade and stimulates cell growth. These findings suggest methods to manipulate this growth mechanism for therapeutic interventions in cancer treatments

Future energy-optimised buildings — Addressing the impact of climate change on buildings

Building energy optimisation is generally performed under present climate conditions with fixed simulation parameters (e.g. internal loads). However, climate change and variations in simulation parameters over the building's life span may impact the optimised design. A key question is whether a particular energy-optimised design under present climate conditions would remain energy-optimised in the future. Accordingly, in this paper, a new simulation-based optimisation method is developed, which uses climate models and Ant Colony Optimisation to compare the energy-optimised designs under present and future climates. To demonstrate its potential, this method is applied to a typical office building in two Australian cities, Brisbane and Canberra. The results show that optimising under future climate conditions can lead to different optimal building designs. For Brisbane, the energy difference between optimising under present and future climate conditions is small, but in Canberra the cooling load is increased by up to 6%. This suggests that optimising the studied office building under present climate conditions is acceptable for Brisbane, while considering future climate may yield some savings in Canberra. Results also show that the energy-optimised building configuration for both future and present climates in Brisbane is less sensitive to changes in the load scenario than in Canberra.</p

Correlation of systemic lupus erythematosus disease activity with classical complement (CH50) function and related protein levels

&quot;nBackground: The components of the classical complement pathway play an important role in the pathogenesis of systemic lupus erythematosus (SLE) and are reportedly useful biomarkers of disease activity. In this study, we evaluate disease activity, complement function (total hemolytic complement, CH50) and complement protein levels (C3, C4, C3d, C4d, SC5b-9), comparing the results of patients with active disease versus those with inactive disease.&quot;n&quot;nMethods: This cross-sectional study included 78 hospitalized women with SLE, 24 of whom were in the active group, with SLE disease activity indexes (SLEDAI.2K) of &amp;gt;6, and 54 in the inactive group, with SLEDAI.2K of &amp;le;6. Serum CH50 was measured using a red blood cell hemolytic assay. C3 and C4 levels were determined by nephlometry and plasma levels of C3d, C4d, SC5b-9 by ELISA. The data were statistically analyzed using SPSS.&quot;n&quot;nResults: The mean (&amp;plusmn;standard error) C4d levels of the inactive group were significantly higher than those of the active group (23.39&amp;plusmn;1.1&amp;micro;g/ml and 16.9&amp;plusmn;1.6&amp;micro;g/ml, respectively; p=0.003). There was also a significant correlation between C3 and C4 levels (p=0.807). The mean values of the other proteins (C3, C4, CH50, SC5b-9, and C3d circulating immune complex concentrations) were not significantly different between the inactive group vs. the active group: 89.35&amp;plusmn;6.8 vs. 85.54&amp;plusmn;7.6mg/dl, 18.33&amp;plusmn;2.3 vs. 20.45&amp;plusmn;2.4mg/dl, 149.03&amp;plusmn;4.3 vs. 157&amp;plusmn;4.3U, 1414.4&amp;plusmn;114.94 vs. 1471.1&amp;plusmn;216.9ng/ml, 9.43&amp;plusmn;0.96 vs. 13.31&amp;plusmn;3.16&amp;micro;gEq/ml, respectively (p&amp;gt;0.05).&quot;n&quot;nConclusions: According to our results, C4d levels may be used as a biomarker of disease activity. The significant correlation between C3 and C4 may confirm the activity of the classical pathway in SLE patients.&quot;n&quot;nKeywords: Systemic lupus erythematosus, CH50, C3, C4, C3d, C4d, SC5b-9, inactive, flare

Vision-related Quality of Life After Bilateral Implantation of Monofocal and Multifocal Intraocular Lenses

Purpose: To evaluate vision-related quality of life in two sets of patients after routine Cataract surgery implanting with traditional versus multifocal intraocular lens (IOLs). Methods: In a cross-sectional prospective study, 58 and 33 candidates for Cataract surgery were divided into traditional (Acrysof SN60WF, Alcon Laboratories, Inc) and multifocal IOL (AcrySof IQ PanOptix IOL TFNT00, Alcon Laboratories, Inc.) groups, respectively. The primary outcome was VFQ-25 scores. The secondary outcomes were making comparisons between the two IOL types in the near vision and the driving items. Results: The mean patients' age in traditional and multifocal IOL groups was 60.85 ± 7.40 (55% female) and 59.85 ± 8.95 (36% female) years, respectively. The mean VFQ-25 total scores in traditional and multifocal IOL groups before and after surgery were 63.69 ± 4.95 and 72.15 ± 9.66, and 98.08 ± 0.70 and 95.70 ± 1.30, respectively (P = 0.001 &amp; 0.001). The mean scores of night driving in traditional and multifocal IOL groups were 38.79 ± 20.50 and 44.35 ± 21.12 (P = 0.1) before surgery which improved to 97.41 ± 7.68 and 56.45 ± 11.12 after surgery, respectively (P = 0.001). The mean scores of near vision in traditional and multifocal IOL groups were 46.83 ± 10.56 and 50.53 ± 8.58 (P = 0.2) before surgery which improved to 89.94 ± 4.87 and 100.00 ± 0.00 after surgery, respectively (P = 0.001). Conclusion: Vision-related quality of life after Cataract surgery with either type of traditional or multifocal (PanOptix) IOLs improved to an excellent level. Traditional IOLs provided more satisfaction in nighttime driving while multifocal IOLs provided increased satisfaction in near and intermediate vision

Fourier Analysis of Keratometric Data in Epithelium Removal Versus Epithelial Disruption Corneal Cross-linking

Purpose: To compare epithelium-removal and epithelium-disruption corneal crosslinking (CXL) methods in Fourier analysis of keratometric data and clinical outcomes. Methods: In this double-masked randomized clinical trial, each eye of 34 patients with bilateral keratoconus was randomly allocated to either the epithelium-removal or epithelium-disruption CXL treatment groups. Ocular examination, refraction, uncorrected and best spectacle-corrected visual acuity (UCVA and BSCVA, respectively) measurements, and Pentacam imaging (keratometry, pachymetry, and Fourier analysis) were performed at baseline and at six-month follow-up period. Results: Patients' mean age was 23.3 ± 3.6 years. The preoperative thickness of the thinnest point was 459.20 ± 37.40 μm and 455.80 ± 32.70 μm in the epithelium removal and epithelial-disruption CXL groups, respectively (P = ?). The corresponding figures were 433.50 ± 33.50 μm and 451.90 ± 39.70 μm, respectively, six months after the treatment (P = 0.0001). The irregularity component was 0.030 ± 0.016 μm in the epithelium-removal group and 0.028 ± 0.011 μm in the epithelium-disruption group preoperatively (P = ?). This measurement was 0.031 ± 0.016 μm and 0.024 ± 0.009 μm, respectively at month 6 (P = 0.04). The epithelium-disruption CXL group had better results in terms of the thickness of the thinnest point and the irregularity component as compared to the epithelium-removal group. The two study groups were comparable in spherical equivalent, mean keratometry, UCVA, BSCVA, or other Fourier analysis components (spherical R min, spherical eccentricity, central, peripheral regular astigmatism, and maximum decentration) (P &gt; 0.05). Conclusion: This study shows that epithelium-disruption CXL is superior to epithelium removal CXL regarding the short-term changes in pachymetry and corneal irregularity. Other evaluated parameters were comparable between the two techniques within the six-month follow-up period

MUC1* mediates the growth of human pluripotent stem cells.

The MUC1 protein is aberrantly expressed on an estimated 75% of all human solid tumor cancers. We recently reported that a transmembrane cleavage product, MUC1*, is the predominant form of the protein on cancer cells [1]. Further, our evidence indicated that MUC1* functions as a growth factor receptor on tumor cells, while the full-length protein appeared to have no growth promoting activity. Here, we report that MUC1* acts as a growth factor receptor on undifferentiated human embryonic stem cells (hESCs). Cleavage of the full-length ectodomain to form MUC1*, a membrane receptor, appears to make binding to its ligand, NM23, possible. Unexpectedly, we found that newly differentiated cells no longer express the cleaved form, MUC1*, or its ligand, NM23. Newly differentiated stem cells exclusively present full-length MUC1. Antibody-induced dimerization of the MUC1* receptor on hESCs stimulated cell growth to a far greater degree than currently used methods that require the addition of exogenous basic fibroblast growth factor (bFGF) as well as factors secreted by fibroblast "feeder cells". Further, MUC1* mediated growth was shown to be independent of growth stimulated by bFGF or the milieu of factors secreted by feeder cells. Stimulating the MUC1* receptor with either the cognate antibody or its ligand NM23 enabled hESC growth in a feeder cell-free system and produced pluripotent colonies that resisted spontaneous differentiation. These findings suggest that this primal growth mechanism could be utilized to propagate large numbers of pluripotent stem cells for therapeutic interventions