Effects of statins on the secretion of human serum albumin in cultured HepG2 cells

Statins reduce cholesterol biosynthesis by inhibiting HMG-CoA reductase and thereby lower total cholesterol and LDL cholesterol levels in serum, which in turn lower the incidence of cardiovascular disease (CVD). Statins are also known to modulate various cellular functions such as gene expression, cell proliferation, and programmed cell death through inhibition of downstream intermediates in cholesterol synthesis. In this study, we have investigated the possible effects of statins on the secretion of serum albumin from cultured HepG2 cells since high levels of serum albumin are associated with reduced risks for CVD and statins are effective in lowering the risk of CVD through other effects in addition to their effects on serum total cholesterol and LDL cholesterol levels, known as pleiotropic effects. Our results showed that simvastatin increased HSA secretion up to 32.3% compared to the control group. Among 3 statin analogs we tested, simvastatin exhibited the highest stimulatory effects on HSA secretion compared to the control group. Our study also showed that the increased HSA secretions from HepG2 cells by simvastatin treatments were due to the increased rate of HSA synthesis, not due to the reduced posttranslational degradation rate of HSA. Our finding suggests another added benefit of statins' treatments in preventing CVD through stimulation of HSA biosynthesis

The importance of MpsABC for bacterial growth under atmospheric CO2 levels

Almost 50 years ago, carbon dioxide (CO2) dependent variants were described in non-autotrophic bacteria. However, the underlying mechanism of CO2-dependency are not clear. In this study, we demonstrate that the Staphylococcus aureus mpsAB operon does not only contribute to the production of membrane potential but is also vital for growth under atmospheric CO2 concentration. Deletion mutants of mpsA, mpsB, and mpsABC hardly grew under atmospheric air conditions but could be restored to near wild-type levels under elevated CO2 or bicarbonate concentrations. Uptake studies with radiolabeled sodium bicarbonate (NaH14CO3) revealed that MpsAB represents a bicarbonate/dissolved inorganic carbon (DIC) transporter. Additionally, an Escherichia coli carbonic anhydrase (CA) can mutant which is unable to grow under atmospheric air but can grow when elevated CO2 is present, can be complemented by S. aureus mpsAB and vice versa. This mutual complementation experiments indicate that both the DIC transporter and CA represent a DIC concentrating system that can functionally substitute each other. Compared to the wild type, production of hemolytic toxins are less in S. aureus mps mutants and they also display less virulence in mouse model of infection. Phylogenetic analysis reveals that MpsAB homologs are ubiquitous in bacteria and frequently occur side-by-side on the genome. Interestingly, the majority of bacteria possess homologs of either MpsAB or CA, while both are present in some highly pathogenic species. Taken together, MpsAB is proposed to act as a DIC transporter or bicarbonate concentrating system, potentially operating as a sodium bicarbonate cotransporter. In a separate work, the mechanisms behind the host cell internalization triggered by Lpl proteins was elucidated. Lipoprotein-like lipoproteins (Lpls) is encoded by the S. aureus lpl cluster on a pathogenicity island named νSaα island which consists of 10 lpls paralogue genes. By using recombinant Lpl1 protein as a model of Lpls, the host receptor for Lpl-induced S. aureus USA300 invasion of human keratinocytes was identified as human heat shock protein Hsp90 via pull-down assay. Synthetic peptides which covers the Lpl1 sequence resulted in double to five-fold higher rate of S. aureus invasion in HaCaT cells and in primary human keratinocytes. Lpl-Hsp90 interaction stimulates F-actin formation, leading to an endocytosis-like engulfment of S. aureus

Mobile Television: Challenges of Advanced Service Design

In this paper, we propose an integrative framework based on dynamic models of the evolution of industries. The main arguments are illustrated using the case of mobile TV. One main assertion is that the value network of mobile data services is much more complex than that of previous generations of mobile services, in particular voice and messaging. The new environment requires a significantly higher degree of coordination and integration between more participants in the value net and a consistent constellation of technology, policy and firm strategy. Unless such compatible arrangements are in place, mobile TV will not take off. The paper develops these themes theoretically and illustrates them with a detailed case study of mobile TV in South Korea as well as comments on the situation in Europe and the U.S. The private and public sectors in South Korea were capable of producing conditions in which mobile TV could flourish. Even so, significant challenges remain to create a financially sustainable mobile TV industry. In contrast, in Europe and the U.S. major obstacles to the development of mobile TV continue to exist. Unless these obstacles, including problems with spectrum policy, are addressed, mobile TV may not be able to develop its full market potential

Applications of Different Weighting Schemes to Improve Pathway-Based Analysis

Conventionally, pathway-based analysis assumes that genes in a pathway equally contribute to a biological function, thus assigning uniform weight to genes. However, this assumption has been proved incorrect, and applying uniform weight in the pathway analysis may not be an appropriate approach for the tasks like molecular classification of diseases, as genes in a functional group may have different predicting power. Hence, we propose to use different weights to genes in pathway-based analysis and devise four weighting schemes. We applied them in two existing pathway analysis methods using both real and simulated gene expression data for pathways. Among all schemes, random weighting scheme, which generates random weights and selects optimal weights minimizing an objective function, performs best in terms of P value or error rate reduction. Weighting changes pathway scoring and brings up some new significant pathways, leading to the detection of disease-related genes that are missed under uniform weight

Triclinic Na3.12Co2.44(P2O7)(2) as a High Redox Potential Cathode Material for Na-Ion Batteries

Two types of sodium cobalt pyrophosphates, triclinic Na3.12Co2.44(P2O7)(2) and orthorhombic Na2CoP2O7, are compared as high-voltage cathode materials for Na-ion batteries. Na2CoP2O7 shows no electrochemical activity, delivering negligible capacity. In contrast, Na3.12Co2.44(P2O7)(2) exhibits good electrochemical performance, such as high redox potential at ca. 4.3 V (vs. Na/Na+) and stable capacity retention over 50 cycles, although Na3.12Co2.44(P2O7)(2) delivered approximately 40 mA h g(-1). This is attributed to the fact that Na2CoP2O7 (similar to 3.1 angstrom) has smaller diffusion channel size than Na3.12Co2.44(P2O7)(2) (similar to 4.2 angstrom). Moreover, the electrochemical performance of Na3.12Co2.44(P2O7)(2) is examined using Na cells and Li cells. The overpotential of Na cells is smaller than that of Li cells. This is due to the fact that Na3.12Co2.44(P2O7)(2) has a smaller charge transfer resistance and higher diffusivity for Na+ ions than Li+ ions. This implies that the large channel size of Na3.12Co2.44(P2O7)(2) is more appropriate for Na+ ions than Li+ ions. Therefore, Na3.12Co2.44(P2O7)(2) is considered a promising high-voltage cathode material for Na-ion batteries, if new electrolytes, which are stable above 4.5 V vs. Na/Na+, are introduced.

Combination of Medicinal Herbs KIOM-79 Reduces Advanced Glycation End Product Accumulation and the Expression of Inflammatory Factors in the Aorta of Zucker Diabetic Fatty Rats

Previous studies have reported that KIOM-79 shows a strong inhibitory effect on AGE formation and inhibited a proinflammatory state in a murine macrophage cell line. In the present study, we investigated the effect of KIOM-79 on AGE accumulation and vascular inflammation in the aorta of Zucker diabetic fatty (ZDF) rats, a commonly used model of type 2 diabetes. Seven-week-old male ZDF rats were treated with KIOM-79 (50 mg/kg) once a day orally for 13 weeks. We examined the dissected aortas for AGE accumulation, expression of the receptor for AGEs (RAGE), and the expression of proinflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and vascular adhesion molecule-1 (VCAM-1). Nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were also measured by Southwestern histochemistry, electrophoretic mobility shift assay (EMSA), and immunohistochemistry, respectively. KIOM-79 markedly reduced the accumulation of AGEs and the expression of RAGE in the aorta. We also found that KIOM-79 attenuated the expression of inflammatory factors including NF-κB, MCP-1, VEGF, VCAM-1, and iNOS in the aortas of ZDF rats. These data suggest that KIOM-79 may prevent or retard the development of inflammation in diabetic vascular disease

The MpsAB Bicarbonate Transporter Is Superior to Carbonic Anhydrase in Biofilm-Forming Bacteria with Limited CO 2 Diffusion

CO2 and bicarbonate are required for carboxylation reactions, which are essential in most bacteria. To provide the cells with sufficient CO2, there exist two dissolved inorganic carbon supply (DICS) systems: the membrane potential-generating system (MpsAB) and the carbonic anhydrase (CA). Recently, it has been shown that MpsAB is a bicarbonate transporter that is present not only in photo- and auto-trophic bacteria, but also in a diverse range of nonautotrophic microorganisms. Since the two systems rarely coexist in a species but are interchangeable, we investigated what advantages the one system might have over the other. Using the genus Staphylococcus as a model, we deleted the CA gene can in Staphylococcus car-nosus and mpsABC genes in Staphylococcus aureus. Deletion of the respective gene in one or the other species led to growth inhibition that could only be reversed by CO2 supplementation. While the S. carnosus Δcan mutant could be fully complemented with mpsABC,the S. aureus ΔmpsABC mutant was only partially complemented by can, suggesting that MpsAB outperforms CA. Interestingly, we provide evidence that mucus biofilm formation such as that involving polysaccharide intercellular adhesin (PIA) impedes the diffusion of CO2 into cells, making MpsAB more advantageous in biofilm-producing strains or species. Coexpression of MpsAB and CA does not confer any growth benefits, even under stress conditions. In conclusion, the distribution of MpsAB or CA in bacteria does not appear to be random as expression of bicarbonate transporters provides an advantage where diffusion of CO2 is impeded. IMPORTANCE CO2 and bicarbonate are required for carboxylation reactions in central metabolismandbiosynthesisofsmallmoleculesinallbacteria.Thisisachievedbytwo different systems for dissolved inorganic carbon supply (DICS): these are the membrane potential-generating system (MpsAB) and the carbonic anhydrase (CA), but both rarely coexist in a given species. Here, we compared both systems and demonstrate that the distribution of MpsAB and/or CA within the phylum Firmicutes is apparently not random. The bicarbonate transporter MpsAB has an advantage in species where CO2 diffusion is hampered—for instance, in mucus- and biofilm-forming bacteria. However, coexpression of MpsAB and CA does not confer any growth benefits, even under stress conditions. Given the clinical relevance of Staphylococcus in the medical environment, such findings contribute to the understanding of bacterial metabolism and thus are crucial for exploration of potential targets for antimicrobials. The knowledge gained here as exemplified by staphylococcal species could be extended to other pathogenic bacteria.Fil: Fan, Sook Ha. Eberhard Karls Universität Tübingen.; AlemaniaFil: Matsuo, Miki. Eberhard Karls Universität Tübingen.; AlemaniaFil: Huang, Lili. Eberhard Karls Universität Tübingen.; AlemaniaFil: Tribelli, Paula Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Götz, Friedrich. Eberhard Karls Universität Tübingen.; Alemani