Novel role for the CDK-activating kinase Cak1 in actively growing cells

Cdc28 is the main cyclin-dependent kinase (CDK) directing the yeast cell cycle. Besides cyclin binding, Cdc28 requires phosphorylation by Cak1 (CDK-activating kinase) to achieve full activity. In previous work, our laboratory isolated carboxy-terminal cdc28CST mutants that display high temperature sensitivity and chromosome instability. These phenotypes are suppressed by increasing the copy numbers of Cak1 in its catalytically active or inactive form. The cdc28CST mutants are also extremely sensitive to changes in Cak1 integrity and dosage. These results indicated that besides the activating phosphorylation by Cak1, the interaction between Cak1 and the carboxyl terminus of Cdc28 is important to maintain stable and active Cdc28 complexes. In this thesis, I discuss recent results that suggest that Cdc28 is highly dependent on Cak1 levels, even in wild type cells. Because actively growing cells require cycles of high CDK activity, we hypothesize that this can be achieved only by maintaining an optimum Cdc28:Cak1 ratio. We found that alteration of this ratio by increasing Cdc28 copy numbers is deleterious, but this effect is suppressed by concomitant increase of the copy numbers of Cak1 (catalytically active or inactive). We found that there is a very good correlation between active cell growth and Cak1 levels. Based on these results we propose the following model: When cells sense depletion of nutrients and must cease dividing, Cak1 is degraded to alter the Cdc28:Cak1 ratio leading to quick inactivation of Cdc28. According to this model, Cak1 functions as an assembly factor for Cdc28 CDK complexes coordinating nutrient availability and cell growth in yeast

Menthol Enhances an Antiproliferative Activity of 1α,25-Dihydroxyvitamin D3 in LNCaP Cells

1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the most active form of vitamin D3, and its analogues have therapeutic benefits for prostate cancer treatment. However, the development of hypercalcemia is an obstacle to clinical applications of 1α,25(OH)2D3 for cancer therapy. In this study, we provide evidence that menthol, a key component of peppermint oil, increases an anti-proliferation activity of 1α,25(OH)2D3 in LNCaP prostate cancer cells. We found that menthol per se does not exhibit antiproliferative activity, but it is able to enhance 1α,25(OH)2D3-mediated growth inhibition in LNCaP cells. Fluorometric assays using Fura-2 showed that 1α,25(OH)2D3 does not induce acute Ca2+ response, whereas menthol evokes an increase in [Ca2+]i, which suggests that cross-talks of menthol-induced Ca2+ signaling with 1α,25(OH)2D3-mediated growth inhibition pathways. In addition, Western blot analysis revealed that 1α,25(OH)2D3 and menthol cooperatively modulate the expression of bcl-2 and p21 which provides the insight into the molecular mechanisms underlying the enhanced 1α,25(OH)2D3-mediated growth inhibition by menthol. Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1α,25(OH)2D3

Comparison of air pollution and the prevalence of allergy-related diseases in Incheon and Jeju City

PurposeA high level of air pollutants can increase the number of patients with allergy-related diseases such as asthma and allergic rhinitis (AR). To analyze the association between air pollution and allergic disease, we investigated 2 areas in Korea: Incheon, an industrial area, and Jeju, a non-industrialized area.MethodsSecond grade students at elementary schools (11 schools in Incheon and 45 schools in Jeju) were examined in a cross-sectional study. A questionnaire was used and a skin prick test was performed. The levels of NO2, CO2, O3, particulate matter (PM) PM10/2.5, formaldehyde, tVOCs, and dust mites in the classrooms and grounds were determined.ResultsThe levels of outdoor CO, PM10, and PM2.5 were significantly higher in Incheon (P<0.01). The levels of indoor CO, CO2, PM10, PM2.5 were significantly higher in Incheon (P<0.01). The prevalence rates of AR symptoms at any time, AR symptoms during the last 12 months, diagnosis of rhinitis at any time, and AR treatment during the last 12 months were significantly higher in Incheon (P<0.01). The prevalence rate of wheezing or whistling at any time, and wheezing during the last 12 months were significantly higher in Incheon (P<0.01).ConclusionWe found that the children living in Incheon, which was more polluted than Jeju, had a higher rate of AR and asthma symptoms compared to children in Jeju. To determine the effect of air pollution on the development of the AR and asthma, further studies are needed

Standardization of the Manufacturing Process of Bee Venom Pharmacopuncture Containing Melittin as the Active Ingredient

Background. Pharmacopuncture is a unique treatment in oriental medicine that combines chemical stimulation with conventional acupuncture. However, there are no standardized methods for preparing the herbal medicines used in pharmacopuncture, and it is not clear whether the active ingredients are safe and stable. Several studies have investigated nonstandardized preparation processes, but few investigations have addressed safety and preparation methods. Pharmacopuncture may provide an alternative treatment for incurable diseases. However, it must be as valid and safe as standardized medicine. In this way, the present project may contribute to the industrialization of medicine in Korea. It may also expand health insurance coverage by promoting evidence-based medical insurance benefits. Thus, the present study attempted to standardize and improve the raw materials, preparation, and efficacy of bee venom pharmacopuncture (BVP), which is a highly effective technique in oriental medicine. Method. To purify the crude bee venom, the extract was subjected to a stepped-gradient open column (ODS-A; 120 Å, 150 mesh). Using this method, the yield of melittin was significantly increased and the allergen proteins were effectively removed. The melittin content of the purified bee venom was determined using HPLC, and the product was then diluted to 0.1 mg/mL using injection water in preparation for BVP. Results. In the present study, we standardized the purification process to provide safe and stable BVP by increasing the main effective components and eliminating allergens. This study will be seminal in the industrialization and regulation of BVP. Conclusion. We developed an effective strategy for melittin purification and allergen removal from bee venom to create safe BVP

The Impact of Slow Infusion Intermittent Feeding on Gavage Feeding-Associated Cardiorespiratory Deterioration in Neonatal Intensive Care Unit Infants

Purpose Infants in the neonatal intensive care unit (NICU) often show cardiorespiratory deterioration during gavage feeding. We aimed to determine whether slow infusion intermittent feeding (SIIF) can reduce respiratory deterioration during gavage feeding in preterm infants in the NICU. Methods Data on preterm infants whose gavage feeding method was changed to SIIF (1-­­hour infusion with an infusion pump and 2-­hour rest within a 3­-hour interval) from bolus gravity feeding (2-­ or 3-­hour interval) due to feeding­-associated cardiorespiratory deterioration were retrospectively reviewed. A significant cardiorespiratory event was defined as a saturation level below 80% or heart rate below 80 bpm. We compared the frequency of cardiorespiratory events and the level of respiratory support 24 hours before and after the application of SIIF. Results A total of 34 infants were enrolled and analyzed. The total frequency of desaturation or bradycardia significantly decreased after SIIF application (8.94 vs. 5.03, P=0.001). The frequency of feeding-­related bradycardia and desaturation also significantly decreased (4.15 vs. 1.68, P=0.008). Out of 34 patients, 11 (32.4%) had a decreased level of ventilator support within 1 day after SIIF. The respiratory severity scores of the 10 patients who received invasive ventilator support decreased significantly after SIIF (5.24 vs. 4.59, P=0.032). Conclusion SIIF significantly decreased gavage feeding­-associated cardiorespiratory events and reduced respiratory support in approximately one-­third of subjects. Therefore, SIIF may be a therapeutic option for gavage feed-­associated respiratory deterioration in preterm infants in the NICU

Positional vertigo afterwards maxillary dental implant surgery with bone regeneration

Benign paroxysmal positional vertigo (BPPV) is the most common form of vertigo. It is caused by loose otoconia from the utricle which, in certain positions, displaced the cupula of the posterior semicircular canal. BPPV most often is a result of aging. It also can occur after a blow to the head. Less common causes include a prolonged positioning on the back (supine) during some surgical procedures. Additionally one can include in this ethiopathogenesis the positioning required during the maxillary dental implant surgery with bone regeneration related to a forced head positioning and inner ear trauma induced by dental turbine noise working in the maxillary bone. Two cases of patients who suffered BPPV after undergoing maxillary dental implant with bone regeneration procedures are reported. Diagnosis and treatment are also described

Combined Effects of Surface Morphology and Mechanical Straining Magnitudes on the Differentiation of Mesenchymal Stem Cells without Using Biochemical Reagents

Existing studies examining the control of mesenchymal stem cell (MSC) differentiation into desired cell types have used a variety of biochemical reagents such as growth factors despite possible side effects. Recently, the roles of biomimetic microphysical environments have drawn much attention in this field. We studied MSC differentiation and changes in gene expression in relation to osteoblast-like cell and smooth muscle-like cell type resulting from various microphysical environments, including differing magnitudes of tensile strain and substrate geometries for 8 days. In addition, we also investigated the residual effects of those selected microphysical environment factors on the differentiation by ceasing those factors for 3 days. The results of this study showed the effects of the strain magnitudes and surface geometries. However, the genes which are related to the same cell type showed different responses depending on the changes in strain magnitude and surface geometry. Also, different responses were observed three days after the straining was stopped. These data confirm that controlling microenvironments so that they mimic those in vivo contributes to the differentiation of MSCs into specific cell types. And duration of straining engagement was also found to play important roles along with surface geometry

Assesment of safety analysis code on integral effect test with SNUF

Paper presented at the 9th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Malta, 16-18 July, 2012.A Safety and Performance Analysis CodE (SPACE) is a thermal-hydraulics computer code under development of South Korea for analysis of complicated phenomena in the nuclear power plants including anticipated transients and postulated accidents. This study assessed the SPACE code capability for prediction of the direct vessel injection (DVI) system, which is adopted as a key safety system in the APR1400 reactor. This study mainly focused on the DVI line break accident, one of the postulated SBLOCA accidents that might result in loss of main coolant water and a quarter of safety injection water simultaneously, for assessment of the code. In order to evaluate the code prediction capability on the phenomena associated with the downcomer seal clearing at the DVI line break, this study selected the SNUF DVI break experiment as the experimental benchmark. This experiment is a reduced-height and reduced-pressure (RHRP) integral test facility designed for simulation of the primary loop of APR1400 designed in Korea. As a result, the SPACE showed reliable agreement with the experimental data on seal clearing phenomena well predicting both the start point of downcomer seal clearance and loop seal clearance. In the DVI system, downcomer seal clearing appears to be more important than loop seal clearing because the vapor generated from core flows through downcomer to broken DVI line. Therefore, the core collapsed level increases as the vapor pressure decreases in the coredc201

Derivation of continuum stochastic equations for discrete growth models

We present a formalism to derive the stochastic differential equations (SDEs) for several solid-on-solid growth models. Our formalism begins with a mapping of the microscopic dynamics of growth models onto the particle systems with reactions and diffusion. We then write the master equations for these corresponding particle systems and find the SDEs for the particle densities. Finally, by connecting the particle densities with the growth heights, we derive the SDEs for the height variables. Applying this formalism to discrete growth models, we find the Edwards-Wilkinson equation for the symmetric body-centered solid-on-solid (BCSOS) model, the Kardar-Parisi-Zhang equation for the asymmetric BCSOS model and the generalized restricted solid-on-solid (RSOS) model, and the Villain--Lai--Das Sarma equation for the conserved RSOS model. In addition to the consistent forms of equations for growth models, we also obtain the coefficients associated with the SDEs.Comment: 5 pages, no figur