Vitamin D enzymes (CYP27A1, CYP27B1 and CYP24A1) and receptor expression in non-melanoma skin cancer

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Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective

Many heat shock proteins (HSPs) are essential to survival as a consequence of their role as molecular chaperones, and play a critical role in maintaining cellular proteostasis by integrating the fundamental processes of protein folding and degradation. HSPs are arguably among the most prominent classes of proteins that have been broadly linked to many human disorders, with changes in their expression profile and/or intracellular/extracellular location now being described as contributing to the pathogenesis of a number of different diseases. Although the concept was initially controversial, it is now widely accepted that HSPs have additional biological functions over and above their role in proteostasis (so-called ‘protein moonlighting’). Most importantly, these new insights are enlightening our understanding of biological processes in health and disease, and revealing novel and exciting therapeutic opportunities. This theme issue draws on therapeutic insights from established research on HSPs in cancer and other non-communicable disorders, with an emphasis on how the intracellular function of HSPs contrasts with their extracellular properties and function, and interrogates their potential diagnostic and therapeutic value to the prevention, management and treatment of chronic diseases

The use of a quartz crystal microbalance with dissipation for the measurement of protein–protein interactions: a qualitative and quantitative analysis of the interactions between molecular chaperones

Biotechnology research and innovation depends on the ability to understand the molecular mechanisms of biological processes such as protein–protein and protein–ligand interactions. Surface plasmon resonance (SPR) spectroscopy is now well established as a quantitative technique for monitoring biomolecular interactions. In this study, we examined the recently developed quartz crystal microbalance with dissipation (QCM-D) method as an alternative to SPR spectroscopy to investigate protein–protein interactions, in particular, for chaperone–co-chaperone interactions. In mammalian cells, the Hsp70/Hsp90 organizing protein (Hop) is a co-chaperone required for the association of the molecular chaperones, heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90). The objective of this research was to characterize qualitatively and quantitatively the interaction of Hsp70 with Hop. A truncated version of Hop consisting of only the C-terminal region and lacking the Hsp70-binding domain (GST-C-Hop) was used as a non-Hsp70- binding control. Immobilized GST-Hop was found to bind Hsp70 successfully, displaying a QCM-D response consistent with formation of a complex that became slightly more flexible as the concentration of bound Hsp70 increased. GST-C-Hop did not bind to Hsp70, thereby validating the specificity of the GST-Hop interaction with Hsp70. The kinetics of the interaction was followed at different concentrations of Hsp70, and an apparent thermodynamic dissociation constant (KD value) in the micromolar range was determined that correlated well with the value derived previously using SPR. This study represents a proof-of-principle that QCM-D can be applied to the analysis of chaperone–co-chaperone interactions. The economic and technical accessibility of QCM-D makes it a valuable tool for analyses of chaperone interactions, and protein– protein interactions in general

Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay

Background: The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents. Methods: In this study, the tumoursphere assay was validated in MCF-7 cells and used to screen novel marine algal compounds for potential anti-cancer stem cell (CSC) activity in vitro. Results: MCF-7 breast cancer cells were observed to generate tumourspheres or mammospheres after 3-5 days growth in anchorage-independent conditions and an apparent enrichment in potential CSCs was observed by an increase in the proportion of CD44high/CD24low marker-bearing cells and Oct4 expression compared to those in the bulk population grown in regular adherent conditions. Using this assay, a set of algal metabolites was screened for the ability to inhibit mammosphere development as a measure of potential anti-CSC activity. We report that the polyhalogenated monoterpene stereoisomers RU017 and RU018 isolated from the red alga Plocamium cornutum, both of which displayed no cytotoxicity against either adherent MCF-7 breast cancer or MCF-12A non-transformed breast epithelial cells, were able to prevent MCF-7 mammosphere formation in vitro. On the other hand, neither the brown algal carotenoid fucoxanthin nor the chemotherapeutic paclitaxel, both of which were toxic to adherent MCF-7 and MCF-12A cells, were able to inhibit mammosphere formation. In fact, pre-treatment with paclitaxel appeared to enhance mammosphere formation and development, a finding which is consistent with the reported resistance of CSCs to traditional chemotherapeutic agents. Conclusion: Due to the proposed clinical significance of CSC in terms of tumour initiation and metastasis, the identification of agents able to inhibit this subpopulation has clinical significance

One Hundred and One Practical Non-Flesh Recipes

https://knowledge.e.southern.edu/foodiesguide-1910/1000/thumbnail.jp

Molecular analysis of the Vibrio alginolyticus sucrose utilization system cloned into Escherichia coli

Bibliography: pages 135-150.This dissertation represents a continuation of the research on the sucrose utilization system of the aerobic, collagenolytic, halotolerant, Gram-negative bacterium Vibrio alginolyticus. The V. alginolyticus sucrose utilization system originally cloned into Escherichia coli on plasmid pVS100 involves a sucrase enzyme (gene scrB), and a sucrose uptake system. Synthesis of the sucrase and sucrose uptake system in V. alginolyticus and E. coli(pVS100) is regulated. The nucleotide sequence and analysis of DNA regions encoding the sucrose uptake and regulatory functions are presented here. An investigation of the expression of the. V. alginolyticus sucrose utilization system in Bacillus subtilis is also presented

Exploration of new catalytic methodologies for heterocyclic synthesis and C-C Bond Formation.

Amino boronate based bifiinctional molecules have the potential to be powerful catalysts. Herein, a number of approaches to the bifimctional benzimidazole catalyst 1 are described, and the synthesis of a number of analogues are explored. Investigations into the potential of 2-(2-boronobenzene)- 2N-n-butylbenzimidazole sodium hydroxide salt 1 as a catalyst for a number of synthetic transformations, including an aza-version of the Baeyer-Villiger reaction (Equation 1), are described The 2-(2-boronobenzene)-N-n-butylbenzimidazole sodium hydroxide salt 1 is shown to be active in the aldol condensation reaction (Equation 2)， Knoevenagel reaction, and evidence for the promotion of the Michael reaction by 1 is presented. The mechanism by which the aldol condensation reaction is promoted by 1 is explored through kinetic studies

Dependence of Mesomorphic Behaviour of Methylene-Linked Dimers and the Stability of the NTB/NX Phase upon Choice of Mesogenic Units and Terminal Chain Length

Twelve symmetrical dimeric materials consisting of a nonamethylene (C9) spacer and either phenyl 4-(4'-alkylphenyl)benzoate, phenyl 4-(4'-alkylcyclohexyl)benzoate or phenyl 4-(4'-alkylbicyclohexyl)carboxylate mesogenic units were prepared and their mesogenic behaviour characterised by POM, DSC and XRD. All of the materials exhibited nematic phases with clearing points in excess of 200°C. Four compounds were found to exhibit the twist-bend nematic phase, with one material exhibiting a transition from the NTB phase into an anticlinic smectic 'X' phase. Across all three series of compounds the length of terminal chain is seen to dictate, to some degree, the type of mesophase formed: shorter terminal chains favour nematic and NTB mesophases, whereas longer terminal aliphatic chains were found to promote smectic phases

A Monte Carlo calculation of neutron reflection from various curved surfaces

Plane parallel neutron beams normally incident upon the curved surface of a solid reflector are studied with the Monte Carlo method. The geometries studied are cylindrical, parabolic, and hemispherical. It is shown that when the curved surface is cylindrical, a small focusing effect occurs in the reflected neutron beam. Parabolic and hemispherical surfaces do not show focusing . A study of the factors which determine the spatial dependence of the reflected flux shows that the probability of emergence of a neutron, traveling a fixed distance from a point inside the reflector, depends upon the curvature of the surface. It is only for cylindrical geometry that this probability as a function of distance shows a peak which results in focusing --Abstract, page ii