Ruthenium(II)–Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells

Ru^II-arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new Ru^II-arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes ( 2 a , b and 5 ) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC₅₀=39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity.     

Promoting CM Student Success: Establishing an Academic Performance Benchmark Given Construction-Education Self-Efficacy,Motivation and Planned Behavior

High levels of self-efficacy, motivation and intentions to perform well are necessary to achieve high grade point averages (GPA) in demanding academic programs including engineering, mathematics and the sciences. However, scant research has investigated these constructs within the domain of construction management (CM) education. The Construction Training Attitudes and Intentions Scale (CTAIS), which adapts self-efficacy, motivation and planned behavior constructs to the construction-education domain, was administered among CM and Non-CM students (n = 633) enrolled in courses required for a bachelor degree at three American Council for Construction Education accredited programs. Significant differences (p < .001) in construction-education domain-level constructs were observed for CM and Non-CM majors providing evidence of face validity. CM majors (n = 587) were separated for ANOVA. Significant differences in self-efficacy (p = .014) and planned behavior (p = .001) were observed by GPA. Post-hoc analysis revealed differences in these constructs based on GPA above, or below, 3.0. CM majors (n = 587) were aggregated using the 3.0 GPA benchmark (GPA > 3.0, n = 328; GPA< 3.0, n = 239). T-test results revealed significantly higher levels of self-efficacy (p = .001) and planned behavior (p < .001) among students with GPAs above 3.0. This study provides CM educators with a domain-specific measure to target students for interventions that promote success. Limitations and opportunities for further research are discussed.     

Exo-mechanism proximity-accelerated alkylations: investigations of linkers, electrophiles and surface mutations in engineered cyclophilin-cyclosporin systems

Investigations on the scope and utility of exo-mechanism proximity-accelerated reactions in engineered receptor-ligand systems are reported. We synthesized a series of electrophilic cyclosporin (CsA) derivatives by varying electrophiles and linker lengths, prepared a series of nucleophilic cysteine mutations on the surface of cyclophilin A (Cyp), and examined their reactivity and specificity in proximity-accelerated reactions. Acrylamide and epoxide electrophiles afforded useful reactivity and high specificity for alkylation of engineered receptors in Jurkat cell extracts. We found that remote cysteines (>17 A from the ligand) could be alkylated with useful rates under physiological conditions. The results from mutations of the receptor surface suggest that the dominant factors governing the rates of proximity-accelerated reactions are related to the local environment of the reactive group on the protein surface. This study defines several parameters affecting reactivity in exo-mechanism proximity-accelerated reactions and provides guidance for the design of experiments for biological investigations involving proximity-accelerated reactions.     

Monitoring Insulin Aggregation via Capillary Electrophoresis

Early stages of insulin aggregation, which involve the transient formation of oligomeric aggregates, are an important aspect in the progression of Type II diabetes and in the quality control of pharmaceutical insulin production. This study is the first to utilize capillary electrophoresis (CE) with ultraviolet (UV) detection to monitor insulin oligomer formation at pH 8.0 and physiological ionic strength. The lag time to formation of the first detected species in the aggregation process was evaluated by UV-CE and thioflavin T (ThT) binding for salt concentrations from 100 mM to 250 mM. UV-CE had a significantly shorter (5-8 h) lag time than ThT binding (15-19 h). In addition, the lag time to detection of the first aggregated species via UV-CE was unaffected by salt concentration, while a trend toward an increased lag time with increased salt concentration was observed with ThT binding. This result indicates that solution ionic strength impacts early stages of aggregation and β-sheet aggregate formation differently. To observe whether CE may be applied for the analysis of biological samples containing low insulin concentrations, the limit of detection using UV and laser induced fluorescence (LIF) detection modes was determined. The limit of detection using LIF-CE, 48.4 pM, was lower than the physiological insulin concentration, verifying the utility of this technique for monitoring biological samples. LIF-CE was subsequently used to analyze the time course for fluorescein isothiocyanate (FITC)-labeled insulin oligomer formation. This study is the first to report that the FITC label prevented incorporation of insulin into oligomers, cautioning against the use of this fluorescent label as a tag for following early stages of insulin aggregation.     

Joint Blind Source Separation by Multiset Canonical Correlation Analysis

In this paper, we introduce a simple and effective scheme to achieve joint blind source separation (BSS) of multiple datasets using multiset canonical correlation analysis (M-CCA) [J. R. Kettenring, "Canonical analysis of several sets of variables", Biometrika, vol. 58, pp. 433-451, 1971]. We first propose a generative model of joint BSS based on the correlation of latent sources within and between datasets. We specify source separability conditions, and show that, when the conditions are satisfied, the group of corresponding sources from each dataset can be jointly extracted by M-CCA through maximization of correlation among the extracted sources. We compare source separation performance of the M-CCA scheme with other joint BSS methods and demonstrate the superior performance of the M-CCA scheme in achieving joint BSS for a large number of datasets, group of corresponding sources with heterogeneous correlation values, and complex-valued sources with circular and non-circular distributions. We apply M-CCA to analysis of functional magnetic resonance imaging (fMRI) data from multiple subjects and show its utility in estimating meaningful brain activations from a visuomotor task.     

Veteran interest in family involvement in PTSD treatment.

[Correction Notice: An erratum for this article was reported in Vol 7(3) of Psychological Services (see record 2010-17074-004). The copyright for the article was listed incorrectly. This article is in the Public Domain. The online version has been corrected.] The present study examined interest in family involvement in treatment and preferences concerning the focus of family oriented treatment for veterans (N = 114) participating in an outpatient Veterans Affairs outpatient posttraumatic stress disorder (PTSD) program. Most veterans viewed PTSD as a source of family stress (86%) and expressed interest in greater family involvement in their treatment (79%). These results suggest the need to consider increasing family participation in the clinical care of individuals with PTSD and to develop specialized family educational and support services for this population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of Viscoelasticity and HIV Transport as a Function of pH in a Reversibly Crosslinked Hydrogel

Materials that respond to physiological stimuli are important in developing advanced biomaterials for modern therapies. The reversibility of covalent crosslinks formed by phenylboronate (PBA) and salicylhydroxamate (SHA) has been exploited to provide a pH‐responsive gel for application to the vaginal tract. Dynamic rheology reveals that the gel frequency‐dependent viscoelastic properties are modulated by pH. At pH 4.8 the viscous component dominates throughout most of the frequency range. As the pH increases, the characteristic relaxation time continues to increase while the G′_Plateau levels off above pH 6. At pH 7.5, the elastic component dominates throughout the frequency sweep and is predominately independent of frequency. Particle tracking assesses the transport of both fluorescently labeled HIV‐1 and 100‐nm latex particles in the PBA–SHA crosslinked gel as a function of pH. At pH 4.8 the ensemble‐averaged mean squared displacement at lag times greater than three seconds reveals that transport of the HIV‐1 and 100‐nm particles becomes significantly impeded by the matrix, exhibiting diffusion coefficients less than 0.0002 µm² s^?1. This pH‐responsive gel thus displays properties that have the potential to significantly reduce the transport of HIV‐1 to susceptible tissues and thus prevent the first stage of male‐to‐female transmission of HIV‐1.     

Aqueous extract from the vegetative portion of Spanish black radish (Raphanus sativus L. var. niger) induces detoxification enzyme expression in HepG2 cells

The vegetative, or above ground, portion of radishes are not typically consumed and have not been characterized in terms of their phytochemical content or biological activity. The antioxidant capacity of the freeze-dried vegetative portion of mature Spanish black radishes (harvested 2 months after planting) was 3.7-, 3.6- and 2.9-fold greater than freeze-dried roots as assayed by ferric ion reducing antioxidant power (FRAP), total phenolics and oxygen radical absorbance capacity (ORAC), respectively. No carotenoids were detected in the roots, however the vegetative portion contained 905.0 and 421.2 μg/g of lutein and β-carotene, respectively. Despite differences in glucosinolate composition, a class of compounds related to the induction of detoxification enzymes, the aqueous extracts of roots and the vegetative portion similarly induced quinone reductase activity and the expression of multiple phase I and II detoxification enzymes in the HepG2 human hepatoma cell line. When juiced, the resulting freeze-dried juice and pulp of the vegetative portion maintained the ability to induce detoxification enzymes, although there were some differences in the phytochemical contents of these two dried materials. These data demonstrate that the ability of the vegetative portion of Spanish black radish, which has significantly greater antioxidant potential than roots, to induce detoxification enzyme expression was similar to that of the roots.