280 research outputs found
High-speed WDM-PON using CW injection-locked Fabry-Pérot laser diodes
2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe
SUMO-Specific Protease 2 (SENP2) Is an Important Regulator of Fatty Acid Metabolism in Skeletal Muscle
Small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) that reverse protein modification by SUMO are involved in the control of numerous cellular processes, including transcription, cell division, and cancer development. However, the physiological function of SENPs in energy metabolism remains unclear. Here, we investigated the role of SENP2 in fatty acid metabolism in C2C12 myotubes and in vivo. In C2C12 myotubes, treatment with saturated fatty acids, like palmitate, led to nuclear factor-B-mediated increase in the expression of SENP2. This increase promoted the recruitment of peroxisome proliferator-activated receptor (PPAR) and PPAR, through desumoylation of PPARs, to the promoters of the genes involved in fatty acid oxidation (FAO), such as carnitine-palmitoyl transferase-1 (CPT1b) and long-chain acyl-CoA synthetase 1 (ACSL1). In addition, SENP2 overexpression substantially increased FAO in C2C12 myotubes. Consistent with the cell culture system, muscle-specific SENP2 overexpression led to a marked increase in the mRNA levels of CPT1b and ACSL1 and thereby in FAO in the skeletal muscle, which ultimately alleviated high-fat diet-induced obesity and insulin resistance. Collectively, these data identify SENP2 as an important regulator of fatty acid metabolism in skeletal muscle and further implicate that muscle SENP2 could be a novel therapeutic target for the treatment of obesity-linked metabolic disorders.11116Ysciescopu
Reordering Hierarchical Tree Based on Bilateral Symmetric Distance
BACKGROUND: In microarray data analysis, hierarchical clustering (HC) is often used to group samples or genes according to their gene expression profiles to study their associations. In a typical HC, nested clustering structures can be quickly identified in a tree. The relationship between objects is lost, however, because clusters rather than individual objects are compared. This results in a tree that is hard to interpret. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes an ordering method, HC-SYM, which minimizes bilateral symmetric distance of two adjacent clusters in a tree so that similar objects in the clusters are located in the cluster boundaries. The performance of HC-SYM was evaluated by both supervised and unsupervised approaches and compared favourably with other ordering methods. CONCLUSIONS/SIGNIFICANCE: The intuitive relationship between objects and flexibility of the HC-SYM method can be very helpful in the exploratory analysis of not only microarray data but also similar high-dimensional data
Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken
Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio
Combination treatment with doxorubicin and gamitrinib synergistically augments anticancer activity through enhanced activation of Bim
Background: A common approach to cancer therapy in clinical practice is the combination of several drugs to boost the anticancer activity of available drugs while suppressing their unwanted side effects. In this regard, we examined the efficacy of combination treatment with the widely-used genotoxic drug doxorubicin and the mitochondriotoxic Hsp90 inhibitor gamitrinib to exploit disparate stress signaling pathways for cancer therapy.Methods: The cytotoxicity of the drugs as single agents or in combination against several cancer cell types was analyzed by MTT assay and the synergism of the drug combination was evaluated by calculating the combination index. To understand the molecular mechanism of the drug synergism, stress signaling pathways were analyzed after drug combination. Two xenograft models with breast and prostate cancer cells were used to evaluate anticancer activity of the drug combination in vivo. Cardiotoxicity was assessed by tissue histology and serum creatine phosphokinase concentration.Results: Gamitrinib sensitized various human cancer cells to doxorubicin treatment, and combination treatment with the two drugs synergistically increased apoptosis. The cytotoxicity of the drug combination involved activation and mitochondrial accumulation of the proapoptotic Bcl-2 family member Bim. Activation of Bim was associated with increased expression of the proapoptotic transcription factor C/EBP-homologous protein and enhanced activation of the stress kinase c-Jun N-terminal kinase. Combined drug treatment with doxorubicin and gamitrinib dramatically reduced in vivo tumor growth in prostate and breast xenograft models without increasing cardiotoxicity.Conclusions: The drug combination showed synergistic anticancer activities toward various cancer cells without aggravating the cardiotoxic side effects of doxorubicin, suggesting that the full therapeutic potential of doxorubicin can be unleashed through combination with gamitrinib.open
Stretchable and wearable colorimetric patches based on thermoresponsive plasmonic microgels embedded in a hydrogel film
Stimuli-responsive colorimetric sensors are promising for various industrial and medical applications due to the capability of simple, fast, and inexpensive visualization of external stimuli. Here we demonstrate a thermoresponsive, smart colorimetric patch based on a thermoresponsive plasmonic microgel embedded in a stretchable hydrogel film. To achieve a fast and efficient thermoresponsive color change, raspberry-shaped plasmonic microgels were fabricated by decorating gold nanoparticles (AuNPs) on poly(N-isopropylacrylamide) (PNIPAM) microgels, which exhibit reversible and strain-insensitive color shifts (between red and grayish violet) in response to a temperature change. The smart colorimetric patch containing a plasmonic microgels exhibits a significant extinction peak shift (176 nm) in a short time (1 s), with a temperature-sensing resolution of 0.2 degrees C. Moreover, the transition temperature of the plasmonic microgel can be finely tuned by additives and comonomers, so that the exquisite temperature visualization can be conducted over a wide temperature range of 25-40 degrees C by assembling plasmonic microgel films with different transition temperatures into an array patch. For proof-of-concept demonstrations, a freestanding smart colorimetric patch was utilized as a spatial temperature scanner and a colorimetric thermometer for a thermoresponsive actuator, which is potentially applicable in smart, wearable sensors and soft robotics
Development of surface plasmon resonance-based sensor for detection of silver nanoparticles in food and the environment
Silver nanoparticles are recognized as effective antimicrobial agents and have been implemented in various consumer products including washing machines, refrigerators, clothing, medical devices, and food packaging. Alongside the silver nanoparticles benefits, their novel properties have raised concerns about possible adverse effects on biological systems. To protect consumer’s health and the environment, efficient monitoring of silver nanoparticles needs to be established. Here, we present the development of human metallothionein (MT) based surface plasmon resonance (SPR) sensor for rapid detection of nanosilver. Incorporation of human metallothionein 1A to the sensor surface enables screening for potentially biologically active silver nanoparticles at parts per billion sensitivity. Other protein ligands were also tested for binding capacity of the nanosilver and were found to be inferior to the metallothionein. The biosensor has been characterized in terms of selectivity and sensitivity towards different types of silver nanoparticles and applied in measurements of real-life samples—such as fresh vegetables and river water. Our findings suggest that human MT1-based SPR sensor has the potential to be utilized as a routine screening method for silver nanoparticles, that can provide rapid and automated analysis dedicated to environmental and food safety monitoring
The VEGF -634G>C promoter polymorphism is associated with risk of gastric cancer
<p>Abstract</p> <p>Background</p> <p>Both TGF-β1 and VEGF play a critic role in the multiple-step process of tumorgenesis of gastric cancer. Single nucleotide polymorphisms (SNPs) of the <it>TGFB1 </it>and <it>VEGF </it>genes have been associated with risk and progression of many cancers. In this study, we investigated the association between potentially functional SNPs of these two genes and risk of gastric cancer in a US population.</p> <p>Methods</p> <p>The risk associated with genotypes and haplotypes of four <it>TGFB1 </it>SNPs and four <it>VEGF </it>SNPs were determined by multivariate logistic regression analysis in 171 patients with gastric cancer and 353 cancer-free controls frequency-matched by age, sex and ethnicity.</p> <p>Results</p> <p>Compared with the <it>VEGF</it>-634GG genotype, the -634CG genotype and the combined -634CG+CC genotypes were associated with a significantly elevated risk of gastric cancer (adjusted OR = 1.88, 95% CI = 1.24-2.86 and adjusted OR = 1.56, 95% CI = 1.07-2.27, respectively). However, none of other <it>TGFB1 </it>and <it>VEGF </it>SNPs was associated with risk of gastric cancer.</p> <p>Conclusion</p> <p>Our data suggested that the <it>VEGF</it>-634G>C SNP may be a marker for susceptibility to gastric cancer, and this finding needs to be validated in larger studies.</p
Structural Characterization of Mesoporous Silica Nanofibers Synthesized Within Porous Alumina Membranes
Mesoporous silica nanofibers were synthesized within the pores of the anodic aluminum oxide template using a simple sol–gel method. Transmission electron microscopy investigation indicated that the concentration of the structure-directing agent (EO20PO70EO20) had a significant impact on the mesostructure of mesoporous silica nanofibers. Samples with alignment of nanochannels along the axis of mesoporous silica nanofibers could be formed under the P123 concentration of 0.15 mg/mL. When the P123 concentration increased to 0.3 mg/mL, samples with a circular lamellar mesostructure could be obtained. The mechanism for the effect of the P123 concentration on the mesostructure of mesoporous silica nanofibres was proposed and discussed
Fine-Scale Mapping of Natural Variation in Fly Fecundity Identifies Neuronal Domain of Expression and Function of an Aquaporin
To gain insight into the molecular genetic basis of standing variation in fitness related traits, we identify a novel factor that regulates the molecular and physiological basis of natural variation in female Drosophila melanogaster fecundity. Genetic variation in female fecundity in flies derived from a wild orchard population is heritable and largely independent of other measured life history traits. We map a portion of this variation to a single QTL and then use deficiency mapping to further refine this QTL to 5 candidate genes. Ubiquitous expression of RNAi against only one of these genes, an aquaporin encoded by Drip, reduces fecundity. Within our mapping population Drip mRNA level in the head, but not other tissues, is positively correlated with fecundity. We localize Drip expression to a small population of corazonin producing neurons located in the dorsolateral posterior compartments of the protocerebrum. Expression of Drip–RNAi using both the pan-neuronal ELAV-Gal4 and the Crz-Gal4 drivers reduces fecundity. Low-fecundity RILs have decreased Crz expression and increased expression of pale, the enzyme encoding the rate-limiting step in the production of dopamine, a modulator of insect life histories. Taken together these data suggest that natural variation in Drip expression in the corazonin producing neurons contributes to standing variation in fitness by altering the concentration of two neurohormones
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