Pathway and single gene analyses of inhibited Caco-2 differentiation by ascorbate-stabilized quercetin suggest enhancement of cellular processes associated with development of colon cancer

The aim was to investigate mechanisms contributing to quercetin's previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anticarcinogenic potency. In a 10-day experiment, 40 microM quercetin stabilized by 1 mM ascorbate reduced Caco-2 differentiation up to 50% (p < 0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0 Affymetrix GeneChips(R), showed 1,743 affected genes on both days (p < 0.01). All 14 Caco-2 differentiation-associated genes showed decreased expression (p < 0.01), including intestinal alkaline phosphatase, that was confirmed technically (qRT-PCR) and functionally (enzyme-activity). The 1,743 genes contributed to 27 pathways (p < 0.05) categorized under six gene ontology (GO) processes, including apoptosis and cell-cycle. Genes within these GO-processes showed fold changes that suggest increased cell-survival and -proliferation. Furthermore, quercetin down-regulated expression of genes involved in tumor-suppression and phase II metabolism, and up-regulated oncogenes. Gene expression changes mediated by ascorbate-stabilized quercetin were concordant with those occurring in human colorectal carcinogenesis ( approximately 80-90%), but were opposite to those previously described for Caco-2 cells exposed to quercetin without ascorbate ( approximately 75-90%). In conclusion, gene expression among Caco-2 cells exposed to ascorbate-stabilized quercetin showed mechanisms contrary to what is expected for a cancer-preventive agent. Whether this unexpected in vitro effect is relevant in vivo, remains to be elucidated.     

A Framework for the Development of an Environmental Management System: A Case Study in a Thermal Power Plant

A framework for the development of an environmental management system that satisfies the requirements of the ISO 14001 standards is presented. The framework is developed for NB Power, a company producing electricity for the province of New Brunswick in Canada. A case study is carried out in a thermal power plant called Coleson Cove. An initial review of the existing environmental management programs is presented. The environmental policy is evaluated, and the environmental aspects and impacts of the plant's activities are identified and prioritized according to prespecified criteria of severity, frequency, degree of control, and existence of regulation. Environmental objectives and targets are set and recommendations are presented.     

Pharmaceutical Development of Nanostructured Vesicular Hydrogel Formulations of Rifampicin for Wound Healing

Chronic wounds exhibit elevated levels of inflammatory cytokines, resulting in the release of proteolytic enzymes which delay wound-healing processes. In recent years, rifampicin has gained significant attention in the treatment of chronic wounds due to an interesting combination of antibacterial and anti-inflammatory effects. Unfortunately, rifampicin is sensitive to hydrolysis and oxidation. As a result, no topical drug product for wound-healing applications has been approved. To address this medical need two nanostructured hydrogel formulations of rifampicin were developed. The liposomal vesicles were embedded into hydroxypropyl methylcellulose (HPMC) gel or a combination of hyaluronic acid and marine collagen. To protect rifampicin from degradation in aqueous environments, a freeze-drying method was developed. Before freeze-drying, two well-defined hydrogel preparations were obtained. After freeze-drying, the visual appearance, chemical stability, residual moisture content, and redispersion time of both preparations were within acceptable limits. However, the morphological characterization revealed an increase in the vesicle size for collagen–hyaluronic acid hydrogel. This was confirmed by subsequent release studies. Interactions of marine collagen with phosphatidylcholine were held responsible for this effect. The HPMC hydrogel formulation remained stable over 6 months of storage. Moving forward, this product fulfills all criteria to be evaluated in preclinical and clinical studies.     

RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic

ABCB4 (ATP-binding cassette subfamily B member 4) is an ABC transporter expressed at the canalicular membrane of hepatocytes where it ensures phosphatidylcholine secretion into bile. Genetic variations of ABCB4 are associated with several rare cholestatic diseases. The available treatments are not efficient for a significant proportion of patients with ABCB4-related diseases and liver transplantation is often required. The development of novel therapies requires a deep understanding of the molecular mechanisms regulating ABCB4 expression, intracellular traffic, and function. Using an immunoprecipitation approach combined with mass spectrometry analyses, we have identified the small GTPase RAB10 as a novel molecular partner of ABCB4. Our results indicate that the overexpression of wild type RAB10 or its dominant-active mutant significantly increases the amount of ABCB4 at the plasma membrane expression and its phosphatidylcholine floppase function. Contrariwise, RAB10 silencing induces the intracellular retention of ABCB4 and then indirectly diminishes its secretory function. Taken together, our findings suggest that RAB10 regulates the plasma membrane targeting of ABCB4 and consequently its capacity to mediate phosphatidylcholine secretion.     

The double-edged sword of rewards for participation in psychology experiments.

This quasi-experimental study examined participation rates and sample characteristics of participants recruited with and without the offer of course credit. In Sample 1, where course credit is not usually offered, credit was added in one condition (N = 195) and not in the other (N = 175). In Sample 2, where credit is usually offered, it was maintained in one condition (N = 92) and removed in the other (N = 178). Results in both samples revealed that participation rates were higher in the credit conditions; they plunged when customary rewards were taken away. Results also revealed evidence of sample bias. More specifically, the motivational characteristics of participants and nonparticipants differed in all conditions except the new credit condition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Connaissance des résultats et contr?le spatiotemporel dans une tache d'anticipation-co?ncidence chez des enfants de 6 à 10 ans.

Studied the effects of knowledge of results (KR), either spatial or temporal, on performance of a coincidence-timing task among Canadian children. Human subjects: 90 male and female Canadian children (aged 6–10 yrs). Ss were divided into 3 age groups (mean age 6.8 yrs, 8.3 yrs, and 10.2 yrs). Each age group was divided into 3 experimental groups: 1 group received spatial KR, 1 group received temporal KR, and 1 group received no KR during practice sessions for a coincidence-timing task. The task consisted of moving an object horizontally with the hand to a spot corresponding to the movement of a visual stimulus. The object was to reach the correct spot at the same time as the visual stimulus, which came from either the right or the left at speeds of 100 or 152 cm/s. The results were analyzed according to Ss' age, speed of stimulus, direction of stimulus, type of KR training, and whether or not the S's object arrived before or after the visual stimulus. A multivariate analysis of variance (MANOVA) was used. (English abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Directional control of rapid arm movements: The role of the kinetic visual feedback system.

Examined how vision of initial, terminal, or complete arm trajectory affected the movement control and accuracy of 6 right-handed volunteers when the amplitude and directional task constraints were varied. Evidence was found for the significant contribution of vision during the initial phase of rapid pointing movements when this phase is under the control of the kinetic channel. Movements having directional requirements were more accurate when vision of the initial portion of the trajectory was available. Times-to-peak acceleration and velocity were shorter and their respective amplitudes were generally higher when vision was available for the 1st 3rd of the trajectory than when it was not. Vision of the entire trajectory did not yield better precision than when vision was available for the initial phase of the movements only. The data support the existence of 2 supportive visual feedback systems. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relation between (bio-)chemical, morphological, and mechanical properties of thermally processed carrots as influenced by high-pressure pretreatment condition

Thermal texture evolution kinetics (90–110 °C) of nonpretreated and high-pressure pretreated (HP = 400 MPa, 60 °C, 15 min) carrots were determined using a multiparameter approach (cutting, compression). Alcohol Insoluble Residues (AIR) were extracted before and after thermal processing of the samples and the degree of methylation (DM) was estimated. The β-elimination kinetics of the water soluble pectin extract from the AIR was studied and related to the changes in material properties. Morphological changes and tissue-failure characteristics were monitored. The mechanical properties were strongly dependent on the processing temperature and the DM of the samples. Texture degradation rate constants were independent of the texture measurement method. Increasing temperature accelerated the β-elimination reaction (k _b) and the thermosoftening (k _x) rates, but pretreatment condition slowed down the rates. Interestingly, a strong correlation (r > 0.99) between k _b and k _x occurred. Thermal processing resulted in cell-wall thickening accompanied by a transition from cell rupture to cell separation, a process retarded by pretreatment condition.     

Effect of Pectinmethylesterase Infusion Methods and Processing Techniques on Strawberry Firmness

Strawberry halves were pretreated with fungal pectinmethylesterase (PME) and calcium chloride using, respectively, passive osmotic infusion, vacuum‐assisted infusion, and pressure‐assisted infusion with the aim to improve the firmness. The vacuum‐assisted procedure was observed to be the only method able to accomplish an uptake of infusion solution and hence capable of improving the firmness of the strawberries. Significantly less firmness increase was realized when tomato PME was vacuum‐infused instead of fungal PME. Strawberry halves were pretreated by vacuum‐assisted infusion with fungal PME and calcium chloride and were subsequently subjected to thermal treatments at 60 °C and 80 °C and pressure treatments at about 400 MPa and 550 MPa. For all treatments studied, the pretreated sample was significantly firmer compared with the reference sample. For the thermal processes, the residual firmness relative to the initial value before treatment was depending on the temperature of the treatment and not on the pretreatment. However, vacuum‐assisted infusion of PME and calcium could limit the portion of firmness loss due to pressure treatment to 30% compared with 80% for non‐pretreated fruits.