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Find video protocols related to scientific articles indexed in Pubmed.
Effective Passivation of Exfoliated Black Phosphorus Transistors against Ambient Degradation.
Nano Lett.
PUBLISHED: 11-08-2014
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Unencapsulated, exfoliated black phosphorus (BP) flakes are found to chemically degrade upon exposure to ambient conditions. Atomic force microscopy, electrostatic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy are employed to characterize the structure and chemistry of the degradation process, suggesting that O2 saturated H2O irreversibly reacts with BP to form oxidized phosphorus species. This interpretation is further supported by the observation that BP degradation occurs more rapidly on hydrophobic octadecyltrichlorosilane self-assembled monolayers and on H-Si(111) versus hydrophilic SiO2. For unencapsulated BP field-effect transistors, the ambient degradation causes large increases in threshold voltage after 6 h in ambient, followed by a ?10(3) decrease in FET current on/off ratio and mobility after 48 h. Atomic layer deposited AlOx overlayers effectively suppress ambient degradation, allowing encapsulated BP FETs to maintain high on/off ratios of ?10(3) and mobilities of ?100 cm(2) V(-1) s(-1) for over 2 weeks in ambient conditions. This work shows that the ambient degradation of BP can be managed effectively when the flakes are sufficiently passivated. In turn, our strategy for enhancing BP environmental stability will accelerate efforts to implement BP in electronic and optoelectronic applications.
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[The influence of the single different radiation dose and time on the microscopic structure and ultrastructure of Balb/c mice].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-25-2014
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To observe the influence of the single different radiation dose and time on the microscopic structure and ultrastructure of Balb/c Mice.
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The Two-pore channel (TPC) interactome unmasks isoform-specific roles for TPCs in endolysosomal morphology and cell pigmentation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-25-2014
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The two-pore channels (TPC1 and TPC2) belong to an ancient family of intracellular ion channels expressed in the endolysosomal system. Little is known about how regulatory inputs converge to modulate TPC activity, and proposed activation mechanisms are controversial. Here, we compiled a proteomic characterization of the human TPC interactome, which revealed that TPCs complex with many proteins involved in Ca(2+) homeostasis, trafficking, and membrane organization. Among these interactors, TPCs were resolved to scaffold Rab GTPases and regulate endomembrane dynamics in an isoform-specific manner. TPC2, but not TPC1, caused a proliferation of endolysosomal structures, dysregulating intracellular trafficking, and cellular pigmentation. These outcomes required both TPC2 and Rab activity, as well as their interactivity, because TPC2 mutants that were inactive, or rerouted away from their endogenous expression locale, or deficient in Rab binding, failed to replicate these outcomes. Nicotinic acid adenine dinucleotide phosphate (NAADP)-evoked Ca(2+) release was also impaired using either a Rab binding-defective TPC2 mutant or a Rab inhibitor. These data suggest a fundamental role for the ancient TPC complex in trafficking that holds relevance for lysosomal proliferative scenarios observed in disease.
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[Multiple factors quantitative analysis on middle ear function in primarily diagnosed patients with nasopharyngeal carcinoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 08-19-2014
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To explore the ways of quantitative and objective evaluation for analyzing the multiple influence factors on middle ear function in the patients with primarily diagnosed NPC, and to analyze the influence factors of middle ear function in the patients with primarily diagnosed nasopharyngeal carcinoma (NPC).
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Lipid-AuNPs@PDA nanohybrid for MRI/CT imaging and photothermal therapy of hepatocellular carcinoma.
ACS Appl Mater Interfaces
PUBLISHED: 08-12-2014
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Multifunctional theranostic nanoparticles represent an emerging agent with the potential to offer extremely sensitive diagnosis and targeted cancer therapy. Herein, we report the synthesis and characterization of a multifunctional theranostic agent (referred to as LA-LAPNHs) for targeted magnetic resonance imaging/computed X-ray tomography (MRI/CT) dual-mode imaging and photothermal therapy of hepatocellular carcinoma. The LA-LAPNHs were characterized as having a core-shell structure with the gold nanoparticles (AuNPs)@polydopamine (PDA) as the inner core, the indocyanine green (ICG), which is electrostatically absorbed onto the surface of PDA, as the photothermal therapeutic agent, and the lipids modified with gadolinium-1,4,7,10-tetraacetic acid and lactobionic acid (LA), which is self-assembled on the outer surface as the shell. The LA-LAPNHs could be selectively internalized into the hepatocellular cell line (HepG2 cells) but not into HeLa cells due to the specific recognition ability of LA to asialoglycoprotein receptor. Additionally, the dual-mode imaging ability of the LA-LAPNH aqueous solution was confirmed by enhanced MR and CT imaging showing a shorter T1 relaxation time and a higher Hounsfield unit value, respectively. In addition, the LA-LAPNHs showed significant photothermal cytotoxicity against liver cancer cells with near-infrared irradiation due to their strong absorbance in the region between 700 and 850 nm. In summary, this study demonstrates that LA-LAPNHs may be a promising candidate for targeted MR/CT dual-mode imaging and photothermal therapy of hepatocellular carcinoma.
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?-Methylacyl-CoA racemase (AMACR) serves as a prognostic biomarker for the early recurrence/metastasis of HCC.
J. Clin. Pathol.
PUBLISHED: 08-04-2014
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Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it is still lacking effective prognostic biomarkers so far. Previous results of the iTRAQ-based quantitative proteomics study (iTRAQ-2DLC-MS/MS) have shown that ?-methylacyl-CoA racemase (AMACR) might be a promising prognostic biomarker for the early recurrence/metastasis of hepatocellular carcinoma (HCC). Here a large-scale cohort clinical study was performed to evaluate its prognostic potential.
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The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity.
Nat Commun
PUBLISHED: 07-24-2014
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T-cell activation is critical for successful immune responses and is controlled at multiple levels. Although many changes of T-cell receptor-associated signalling molecules affect T-cell activation, the transcriptional mechanisms that control this process remain largely unknown. Here we find that T cell-specific deletion of the mediator subunit Med23 leads to hyperactivation of T cells and aged Med23-deficient mice exhibit an autoimmune syndrome. Med23 specifically and consistently promotes the transcription of multiple negative regulators of T-cell activation. In the absence of Med23, the T-cell activation threshold is lower, which results in enhanced antitumour T-cell function. Cumulatively, our data suggest that Med23 contributes to controlling T-cell activation at the transcriptional level and prevents the development of autoimmunity.
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Improved oxidative tolerance in suspension-cultured cells of C4 -pepctransgenic rice by H2 O2 and Ca(2+) under PEG-6000.
J Integr Plant Biol
PUBLISHED: 06-12-2014
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To understand the molecular responses of PC (Overexpressing the maize C4 -pepc gene, which encodes phosphoenolpyruvate carboxylase (PEPC)), to drought stress at cell level, we analyzed changes in the levels of signaling molecules (hydrogen peroxide (H2 O2 ), calcium ion (Ca(2+) ), and nitric oxide (NO)) in suspension-cultured PC and wild-type (WT) rice (Oryza sativa L.) cell under drought stress induced by 20% polyethylene glycol 6000 (PEG-6000). Results demonstrated that PC improved drought tolerance by enhancing antioxidant defense, retaining higher relative water content, survival percentages, and dry weight of cells. In addition, PEPC activity in PC under PEG treatment was strengthened by addition of H2 O2 inhibitor, dimethylthiourea (DMTU) and NO synthesis inhibitor, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), respectively, while that in PC was weakened by addition of free calcium chelator, ethylene glycol-bis(b-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA)?+?calcium channel outflow inhibitor, ruthenium red (RR)?+?plasma membrane channel blocker La(NO3 )3 , but EGTA?+?RR did not. Results also showed that NO and Ca(2+) was lying downstream of H2 O2 in drought-induced signaling. Calcium ion was also involved in the expression of C4 -pepc in PC. These results suggested that PC could improve oxidative tolerance in suspension-cultured cells and the acquisition of this tolerance required downregulation of H2 O2 and the entry of extracellular Ca(2+) into cells across the plasma membrane for regulation of PEPC activity and C4 -pepc expression.
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[Effects of autophagy on 5-fluorouracil cytotoxicity for gallbladder carcinoma GBC-SD cell].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-26-2014
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To explore the effects of autophagy on 5-fluorouracil (5-FU) cytotoxicity for gallbladder carcinoma GBC-SD cell and discuss a novel and promising strategy of autophagy inhibitor for increasing the clinical efficacy of 5-FU in the treatment of gallbladder carcinoma.
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Galectin-4 serves as a prognostic biomarker for the early recurrence / metastasis of hepatocellular carcinoma.
Cancer Sci.
PUBLISHED: 04-09-2014
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Galectin-4 is a multifunctional lectin found at both intracellular and extracellular sites. It could serve as a tumor suppressor intracellularly and promote tumor metastases extracellularly during colorectal cancer development. However, galectin-4 expression and its prognostic value for patients with hepatocellular carcinoma (HCC) have not been well investigated. Here we report that galectin-4 was significantly downregulated in early recurrent/metastatic HCC patients, when compared to non-recurrent/metastatic HCC patients. Low expression of gelectin-4 was well associated with larger tumor size, microvascular invasion, malignant differentiation, more advanced TNM stage, and poor prognosis. Cancer cell migration and invasion could be significantly reduced through overexpression of galectin-4, but upregulated by knocking down of galectin-4 in vitro. Moreover, the serum galectin-4 level could be significantly elevated solely by hepatitis B virus infection. Combined with clinicopathological features, the higher serologic level of galectin-4 was well associated with more aggressive characteristics of HCC. Taken together, galectin-4 expression closely associates with HCC progression and might have potential use as a prognostic biomarker for HCC patients.
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Efficacy and safety of potassium-titanyl- phosphate laser vaporization for clinically non-muscle invasive bladder cancer.
Urol J
PUBLISHED: 03-06-2014
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Although transurethral resection of the bladder tumor (TURBT) is still regarded as thegold standard for the treatment of clinical non-muscle invasive bladder cancer, alternative surgical options remain investigating. Our aim was to evaluate the efficacy and safety of potassium- titanyl-phosphate (KTP) laser for the treatment of primary, clinically non-muscle invasive bladder cancer compared with standard transurethral resection of bladder tumor.
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Reaction analysis and visualization of ReaxFF molecular dynamics simulations.
J. Mol. Graph. Model.
PUBLISHED: 03-02-2014
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ReaxFF MD (Reactive Force Field Molecular Dynamics) is a promising method for investigating complex chemical reactions in relatively larger scale molecular systems. The existing analysis tools for ReaxFF MD lack the capability of capturing chemical reactions directly by analyzing the simulation trajectory, which is critical in exploring reaction mechanisms. This paper presents the algorithms, implementation strategies, features, and applications of VARxMD, a tool for Visualization and Analysis of Reactive Molecular Dynamics. VARxMD is dedicated to detailed chemical reaction analysis and visualization from the trajectories obtained in ReaxFF MD simulations. The interrelationships among the atoms, bonds, fragments, species and reactions are analyzed directly from the three-dimensional (3D) coordinates and bond orders of the atoms in a trajectory, which are accomplished by determination of atomic connectivity for recognizing connected molecular fragments, perception of bond types in the connected fragments for molecules or radicals, indexing of all these molecules or radicals (chemical species) based on their 3D coordinates and recognition of bond breaking or forming in the chemical species for reactions. Consequently, detailed chemical reactions taking place between two sampled frames can be generated automatically. VARxMD is the first tool specialized for reaction analysis and visualization in ReaxFF MD simulations. Applications of VARxMD in ReaxFF MD simulations of coal and HDPE (high-density polyethylene) pyrolysis show that VARxMD provides the capabilities in exploring the reaction mechanism in large systems with complex chemical reactions involved that are difficult to access manually.
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Coronin 1 regulates cognition and behavior through modulation of cAMP/protein kinase A signaling.
PLoS Biol.
PUBLISHED: 03-01-2014
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Cognitive and behavioral disorders are thought to be a result of neuronal dysfunction, but the underlying molecular defects remain largely unknown. An important signaling pathway involved in the regulation of neuronal function is the cyclic AMP/Protein kinase A pathway. We here show an essential role for coronin 1, which is encoded in a genomic region associated with neurobehavioral dysfunction, in the modulation of cyclic AMP/PKA signaling. We found that coronin 1 is specifically expressed in excitatory but not inhibitory neurons and that coronin 1 deficiency results in loss of excitatory synapses and severe neurobehavioral disabilities, including reduced anxiety, social deficits, increased aggression, and learning defects. Electrophysiological analysis of excitatory synaptic transmission in amygdala revealed that coronin 1 was essential for cyclic-AMP-protein kinase A-dependent presynaptic plasticity. We further show that upon cell surface stimulation, coronin 1 interacted with the G protein subtype G?s to stimulate the cAMP/PKA pathway. The absence of coronin 1 or expression of coronin 1 mutants unable to interact with G?s resulted in a marked reduction in cAMP signaling. Strikingly, synaptic plasticity and behavioral defects of coronin 1-deficient mice were restored by in vivo infusion of a membrane-permeable cAMP analogue. Together these results identify coronin 1 as being important for cognition and behavior through its activity in promoting cAMP/PKA-dependent synaptic plasticity and may open novel avenues for the dissection of signal transduction pathways involved in neurobehavioral processes.
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Coexpression within Integrated Mitochondrial Pathways Reveals Different Networks in Normal and Chemically Treated Transcriptomes.
Int J Genomics
PUBLISHED: 02-22-2014
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As energy producers, mitochondria play a pivotal role in multiple cellular processes. Although several lines of evidence suggest that differential expression of mitochondrial respiratory complexes (MRCs) has a significant impact on mitochondrial function, the role of integrated MRCs in the whole coexpression network has yet to be revealed. In this study, we construct coexpression networks based on microarray datasets from different tissues and chemical treatments to explore the role of integrated MRCs in the coexpression network and the effects of different chemicals on the mitochondrial network. By grouping MRCs as one seed target, the hypergeometric distribution allowed us to identify genes that are significantly coexpress with whole MRCs. Coexpression among 46 MRC genes (approximately 78% of MRC genes tested) was significant in the normal tissue transcriptome dataset. These MRC genes are coexpressed with genes involved in the categories "muscle system process," "metabolic process," and "neurodegenerative disease pathways," whereas, in the chemically treated tissues, coexpression of these genes mostly disappeared. These results indicate that chemical stimuli alter the normal coexpression network of MRC genes. Taken together, the datasets obtained from the different coexpression networks are informative about mitochondrial biogenesis and should contribute to understanding the side effects of drugs on mitochondrial function.
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Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) from glucose with elevated 3-hydroxyvalerate fraction via combined citramalate and threonine pathway in Escherichia coli.
Appl. Microbiol. Biotechnol.
PUBLISHED: 01-15-2014
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The biosynthesis of polyhydroxyalkanoate copolymers in Escherichia coli from unrelated carbon sources becomes attractive nowadays. We previously developed a poly(hydroxybutyrate-co-hydroxyvalerte) (PHBV) biosynthetic pathway from an unrelated carbon source via threonine metabolic route in E. coli (Chen et al., Appl Environ Microbiol 77:4886-4893, 2011). In our study, a citramalate pathway was introduced in recombinant E. coli by cloning a cimA gene from Leptospira interrogans. By blocking the pyruvate and the propionyl-CoA catabolism and replacing the ?-ketothiolase gene, the PHBV with 11.5 mol% 3HV fraction was synthesized. Further, the combination of citramalate pathway with the threonine biosynthesis pathway improved the 3HV fraction in PHBV copolymer to 25.4 mol% in recombinant E. coli.
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Quantitative proteomics analysis of early recurrence/metastasis of huge hepatocellular carcinoma following radical resection.
Proteome Sci
PUBLISHED: 01-01-2014
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Hepatic resection is the preferred treatment for huge hepatocellular carcinoma (>10 cm in diameter; H-HCC). However, the patients with H-HCC suffer from poor prognosis due to the early recurrence/metastasis. The underlying mechanism of H-HCC's early recurrence/metastasis is currently not well understood.
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An amphioxus RAG1-like DNA fragment encodes a functional central domain of vertebrate core RAG1.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-24-2013
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The highly diversified repertoire of antigen receptors in the vertebrate immune system is generated via proteins encoded by the recombination activating genes (RAGs) RAG1 and RAG2 by a process known as variable, diversity, and joining [V(D)J] gene recombination. Based on the study of vertebrate RAG proteins, many hypotheses have been proposed regarding the origin and evolution of RAG. This issue remains unresolved, leaving a significant gap in our understanding of the evolution of adaptive immunity. Here, we show that the amphioxus genome contains an ancient RAG1-like DNA fragment (bfRAG1L) that encodes a virus-related protein that is much shorter than vertebrate RAG1 and harbors a region homologous to the central domain of core RAG1 (cRAG1). bfRAG1L also contains an unexpected retroviral type II nuclease active site motif, DXN(D/E)XK, and is capable of degrading both DNA and RNA. Moreover, bfRAG1L shares important functional properties with the central domain of cRAG1, including interaction with RAG2 and localization to the nucleus. Remarkably, the reconstitution of bfRAG1L into a cRAG1-like protein yielded an enzyme capable of recognizing recombination signal sequences and performing V(D)J recombination in the presence of mouse RAG2. Moreover, this reconstituted cRAG1-like protein could mediate the assembly of antigen receptor genes in RAG1-deficient mice. Together, our results demonstrate that amphioxus bfRAG1L encodes a protein that is functionally equivalent to the central domain of cRAG1 and is well prepared for further evolution to mediate V(D)J recombination. Thus, our findings provide unique insights into the evolutionary origin of RAG1.
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Congenital urethral polyps in the pediatric population.
Can J Urol
PUBLISHED: 10-17-2013
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Congenital urethral polyps are a rare entity. Most commonly, they present as benign posterior urethral growths in the pediatric male patient. However, reports of urethral polyps in female patients or even those with an anterior urethral location can also be found in the literature. Patients can present with a spectrum of symptoms including dysuria, hematuria, and obstructive type urinary complaints. Diagnosis in these cases includes a combination of medical imaging (e.g. ultrasound, fluoroscopic, CT or MRI), direct endoscopic visualization, and final surgical pathology. Treatment involves surgical removal either via an endoscopic or open approach.
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Laparoendoscopic Single-Site Surgery with a Single Channel Versus Conventional Laparoscopic Varicocele Ligation: A Prospective Randomized Study.
J. Endourol.
PUBLISHED: 10-17-2013
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Abstract Purpose: The objective of this study was to evaluate the safety and feasibility of single channel laparoscopy in the treatment of patients with varicocele. Patients and Methods: Ninety patients with clinically palpable varicoceles were randomly assigned to receive laparoendoscopic single-site with a single channel varicocele ligation (LESS[sc]-VL) (n=45) or conventional transperitoneal laparoscopic varicocele ligation (CTL-VL) (n=45). Patient characteristics, perioperative details, total procedural cost, time to return to work, visual analogue scale (VAS) pain score, semen parameters, and cosmetic results were recorded. Results: There were no differences in operative time (P=0.102), postoperative hospitalization time (P=0.130), total cost (P=0.112), or postoperative complications (P>0.05) between the two groups. Time to return to normal activities was shorter in the LESS(sc)-VL group than that in the CTL-VL group (P=0.018). The mean of all semen parameters were improved statistically 3 months after ligation (P<0.001). The VAS incision pain score was significantly lower 6 and 24 hours after surgery in patients who underwent LESS(sc)-VL(P<0.05). Patients who underwent LESS(sc)-VL had a better cosmetic result, reflected by both the verbal response scale and the numeric scale (P=0.008 and P=0.005, respectively). Conclusions: LESS(sc)-VL is a safe and effective minimally invasive surgical alternative for varicocelectomy. Compared with CTL-VL, LESS(sc)-VL may decrease postoperative pain and hide the surgical incision better within the umbilicus.
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Cu-NHC-TEMPO catalyzed aerobic oxidation of primary alcohols to aldehydes.
J. Org. Chem.
PUBLISHED: 08-27-2013
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Imidazolium salts bearing TEMPO groups react with commercially available copper powder affording Cu-NHC complexes. The in situ generated Cu-NHC-TEMPO complexes are quite efficient catalysts for aerobic oxidation of primary alcohols into aldehydes. The catalyst is easily available, and various primary alcohols were selectively converted to aldehydes in excellent yields.
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A novel aptasensor for the ultra-sensitive detection of adenosine triphosphate via aptamer/quantum dot based resonance energy transfer.
Analyst
PUBLISHED: 07-01-2013
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We designed a novel aptamer based biosensor (aptasensor) for ultrasensitive detection of adenosine triphosphate (ATP) through resonance energy transfer (RET). The ATP aptamer was modified with Cy3 at the 3 end, and a green quantum dot (525) was attached to the 5 end of its complementary sequence respectively. The ATP aptamer and its complementary sequence could assemble into a duplex structure in the absence of target ATP, and then decrease the distance between the quantum dot and Cy3 which could produce significant RET signal. Upon ATP binding, the ATP aptamer could dissociate with its complementary sequence and then increase the distance between the quantum dot and Cy3 which would significantly decrease the RET signal. Therefore, the ATP detection could be easily achieved through detection of the fluorescence intensity ratio between 525 nm and 560 nm. The results show that the emission fluorescence intensity ratio of 525/560 is linearly related to the logarithmic concentration of ATP. The linear range of this aptasensor is from 0.1 nM to 1 ?M, and the detection limit is lower down to 0.01 nM. Excellent selectivity of this aptasensor for ATP has been demonstrated through the detection of thymidine triphosphate (TTP), cytidine triphosphate (CTP), guanosine triphosphate (GTP) and adenosine diphosphate (ADP) respectively as control. The method we described here could easily detect ATP with excellent selectivity, linearity and sensitivity down to the nanomolar range, as well as avoid photobleaching.
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Copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagents.
Org. Lett.
PUBLISHED: 06-21-2013
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The copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagent are described. Various amides and carboxylic acids were methylated affording N-substituted amides and esters. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.
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Parathyroid hormone (PTH)/PTH-related peptide type 1 receptor (PPR) signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH.
J. Biol. Chem.
PUBLISHED: 06-02-2013
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Parathyroid hormone (PTH) is the only Food and Drug Administration-approved anabolic agent to treat osteoporosis; however, the cellular targets of PTH action in bone remain controversial. PTH modulates bone turnover by binding to the PTH/PTH-related peptide (PTHrP) type 1 receptor (PPR), a G-protein-coupled receptor highly expressed in bone and kidneys. Osteocytes, the most abundant cells in adult bone, also express PPR. However, the physiological relevance of PPR signaling in osteocytes remains to be elucidated. Toward this goal, we generated mice with PPR deletion in osteocytes (Ocy-PPRKO). Skeletal analysis of these mice revealed a significant increase in bone mineral density and trabecular and cortical bone parameters. Osteoblast activities were reduced in these animals, as demonstrated by decreased collagen type I ?1 mRNA and receptor activator of NF-?B ligand (RANKL) expression. Importantly, when subjected to an anabolic or catabolic PTH regimen, Ocy-PPRKO animals demonstrated blunted skeletal responses. PTH failed to suppress SOST/Sclerostin or induce RANKL expression in Ocy-PPRKO animals compared with controls. In vitro, osteoclastogenesis was significantly impaired in Ocy-PPRKO upon PTH administration, indicating that osteocytes control osteoclast formation through a PPR-mediated mechanism. Taken together, these data indicate that PPR signaling in osteocytes is required for bone remodeling, and receptor signaling in osteocytes is needed for anabolic and catabolic skeletal responses.
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Increased expression of mitotic arrest deficient-like 1 (MAD1L1) is associated with poor prognosis and insensitive to Taxol treatment in breast cancer.
Breast Cancer Res. Treat.
PUBLISHED: 05-23-2013
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Aneuploidy is a characteristic of human cancers, and recent studies have suggested that defects of mitotic checkpoints play a role in carcinogenesis. Mitotic Arrest Deficient-Like 1 (MAD1L1), whose altered expression is associated with chromosomal instability, is a checkpoint gene. We examined MAD1L1 protein expression from 461 breast cancer tissues and patients normal breast tissues by tissue microarray to study the correlation between the MAD1L1 expression and the clinicopathological features. MAD1L1 protein expression was significantly increased in the nuclei of cancer cells (28.4 %) compared with that in normal mammary cells (2.2 %), and was correlated with Her-2 status, cancer subtypes, p53 status, and age. High level of MAD1L1 expression in nuclei was associated with worse OS (p = 0.018). Furthermore, patients with high level of MAD1L1 expression (in nuclei) and undergone Taxol chemotherapy treatment have shorter overall survival than ones without Taxol treatment in this study (p = 0.026). In conclusion, our data demonstrated a significant correlation between nuclear expression of MAD1L1 protein and adverse prognosis in breast cancer. MAD1L1 might be used as a prognostic biomarker for breast cancer and expression of MAD1L1 in nuclei is also a predict biomarker of contraindication to pacilitaxel treatment in breast cancer.
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Unique clinicopathological features of metaplastic breast carcinoma compared with invasive ductal carcinoma and poor prognostic indicators.
World J Surg Oncol
PUBLISHED: 05-12-2013
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Metaplastic breast carcinoma is a rare aggressive malignant neoplasm. The purposes of this study are to review the pathologic features and clinical outcomes of metaplastic breast carcinoma compared to invasive ductal carcinoma and to evaluate the prognosis of metaplastic breast carcinoma.
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The nucleation site selection of vapour-liquid-solid nanowires.
J Phys Condens Matter
PUBLISHED: 05-03-2013
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Adopting twinning superlattice nanowires and III-V nanowires with [112¯] sidewalls, whose cross-sections are irregular hexagons, the precise catalyst droplet surface area variation for the calculation of the nuclei formation enthalpy are obtained for possible nucleation positions at the nanowire growth front. Regular nanowires with hexagonal cross-section are also calculated. The nucleation site selection rules are drawn from the fact that the favorable site corresponds to a smaller nucleation barrier, which is not deducible from the spherical-cap shaped droplet approximation. The influence of droplet volume and nanowire geometry on the nucleation site selection should also be taken into consideration when calculations of the nanowire nucleation properties are involved.
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Colitis-accelerated colorectal cancer and metabolic dysregulation in a mouse model.
Carcinogenesis
PUBLISHED: 04-24-2013
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The connection between inflammation and colorectal cancer (CRC) has been well recognized, and numerous related molecular mechanisms have been uncovered. To gain further insight, we used BALB/c mice treated with azoxymethane (AOM) and dextran sulfate sodium salt (DSS) to establish a colitis-associated CRC model recapitulating tubulovillous adenoma with high-grade dysplasia at week 14. We evaluated the mice in four groups: a control group fed a standard diet; a group given DSS, in which we observed no tumor or dysplasia; a group given AOM, in which we observed few dysplastic foci despite repeated administrations of the carcinogen and a group given both AOM and DSS, in which our observations agreed with those of other studies that found accelerated colorectal carcinogenesis following DSS-induced colitis. We examined the messenger RNA and micro RNA (miRNA) expression profiles of the four groups. In colitis-associated CRC, we observed the dysregulation of many pathways, including the upregulation of Wnt signaling and CRC pathways and the downregulation of apoptosis. Also, most differentially expressed genes were significantly enriched in metabolic rather than immune/inflammation pathways/processes. Additionally, we demonstrated that the expression of several important miRNAs involved in both the inflammatory response and metabolism was dramatically altered during colitis-associated CRC. Gene network analysis and gene profile analysis confirmed a close relationship between metabolic and inflammatory genes in colitis-associated CRC. Thus, our study may provide a framework for identifying metabolic genes as targets of novel molecular-based therapies against CRC.
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A modified laparoendoscopic single-site renal cyst decortication: single-channel retroperitoneal laparoscopic decortication of simple renal cyst.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 04-18-2013
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Laparoscopic renal cyst decortication often uses three-port incisions or single-port incision with three or four channels (laparoendoscopic single-site surgery). This article introduces a modified laparoendoscopic single-site surgery for the treatment of simple renal cysts: single-channel retroperitoneal laparoscopic decortication (SCRL) of a simple renal cyst.
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Int7G24A polymorphism (rs334354) and cancer risk.
Arch Med Sci
PUBLISHED: 03-22-2013
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The transforming growth factor ? (TGF-?) signaling system plays an important role in carcinogenesis. Alteration of TGF-? receptors is a potential mechanism in the development and progression of human cancers. Several studies have investigated the association between TGFBR1 gene Int7G24A and cancer risk, but the results are still inconclusive, so a meta-analysis is needed to verify the association.
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GreenLight HPS 120-W laser vaporization versus transurethral resection of the prostate for treatment of benign prostatic hyperplasia: a prospective randomized trial.
J Xray Sci Technol
PUBLISHED: 03-20-2013
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The most recent advance in laser treatment of benign prostatic hyperplasia (BPH) is the introduction of a high-performance system (HPS) 120-W laser. The HPS laser beam at a wavelength of 532~nm is highly absorbed by oxyhemoglobin in the tissue and maintains focus with negligible divergence up to 3 mm from the fiber and with limited divergence at 5 mm. This study is designed to evaluate the three-year clinical efficacy and safety of photoselective vaporization of the prostate (PVP, n=100 cases) with GreenLight HPS laser compared with transurethral resection of the prostate (TURP, n=100 cases) for treatment of BPH. The results showed that the mean operating time, catheterization time and admission time were significantly shorter in the PVP group, respectively. There were dramatic improvements in International Prostate Symptom Score (IPSS), quality of life (Qol), maximum flow rate (Qmax) and postvoid residual (PVR) compared with preoperative values and the degree of improvements was comparable in both groups. The intraoperative complications were lower in PVP group. In summary, PVP is an effective technique in patients with BPH, when compared to TURP, producing equivalent improvements in IPSS, Qmax, Qol and PVR with the advantages of markedly reduced catheterization time, admission time and adverse events.
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Changes in nutrient ratios and phytoplankton community structure caused by hydropower development in the Maotiao River, China.
Environ Geochem Health
PUBLISHED: 02-19-2013
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Reservoirs created for hydropower production have become an important feature impacting a river. Understanding the effects of river impoundment on the downstream environment is critical to decision-making for water resource protection. The changes caused by impoundment are changes in water quality and the resulting effect on the phytoplankton community structure. The impacts caused by a series of reservoirs along a river are still not well understood. In this study, we conducted an investigation of five reservoirs along the Maotiao River, China. We found that a series of impoundments plays a role in decreasing the phytoplankton biomass in downstream reservoirs. Within the studied area, nitrogen is not a limiting factor for phytoplankton growth. The ratio of silicon to phosphorus (Si:P) can become a major factor in the regulation of phytoplankton community structure. The Si:P ratio increased from upstream to downstream reservoirs, causing a concurrent increase in the percentage of Bacillariophyta, particularly during the winter. In addition, our results indicate that the creation of dams eliminates Si limitation downstream.
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Low ING4 protein expression detected by paraffin-section immunohistochemistry is associated with poor prognosis in untreated patients with gastrointestinal stromal tumors.
Gastric Cancer
PUBLISHED: 02-19-2013
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Inhibitor of growth 4 (ING4) has deserved attention as a tumor suppressor gene in many malignant tumors. In our study, we investigated ING4 immunoexpression in gastrointestinal stromal tumors (GISTs) and its prognostic value.
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Characterization of a flatworm inositol (1,4,5) trisphosphate receptor (IP?R) reveals a role in reproductive physiology.
Cell Calcium
PUBLISHED: 01-22-2013
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Inositol 1,4,5-trisphosphate receptors (IP?Rs) are intracellular Ca²? channels that elevate cytoplasmic Ca²? in response to the second messenger IP3. Here, we describe the identification and in vivo functional characterization of the planarian IP?R, the first intracellular Ca²? channel to be defined in flatworms. A single IP?R gene in Dugesia japonica encoded a 2666 amino acid protein (Dj.IP?R) that shared well conserved structural features with vertebrate IP?R counterparts. Expression of an NH?-terminal Dj.IP?R region (amino acid residues 223-585) recovered high affinity ³H-IP? binding (0.9±0.1 nM) which was abolished by a single point mutation of an arginine residue (R495L) important for IP? coordination. In situ hybridization revealed that Dj.IP?R mRNA was most strongly expressed in the pharynx and optical nerve system as well as the reproductive system in sexualized planarians. Consistent with this observed tissue distribution, in vivo RNAi of Dj.IP?R resulted in a decreased egg-laying behavior suggesting Dj.IP?R plays an upstream role in planarian reproductive physiology.
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Promoter hypermethylation of ARID1A gene is responsible for its low mRNA expression in many invasive breast cancers.
PLoS ONE
PUBLISHED: 01-21-2013
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ARID1A (AT-rich interactive domain 1A) has recently been identified as a tumor suppressor gene. Its mRNA expression is significantly low in many breast cancers; this is often associated with more aggressive phenotypes. However, the underlying molecular mechanism for its low expression has not been fully understood. This study was undertaken to evaluate the contribution of gene copy number variation, mutations, promoter methylation and histone modification to ARID1As low expression. 38 pairs of breast invasive ductal carcinomas and their normal breast tissue counterparts from the same patients were randomly selected for gene expression and copy number variation detection. Promoter methylation and histone modification levels were evaluated by MeDIP-qPCR and ChIP-qPCR, respectively. PCR product Sanger sequencing was carried out to detect the exon mutation rate. Twenty-two out of 38 invasive ductal carcinomas in the study (57.9%) revealed ARID1A mRNA low expression by realtime RT-PCR. The relative promoter methylation level was, significantly higher in ARID1A mRNA low expression group compared with its high expression group (p<0.001). In the low expression group, nineteen out of 22 invasive ductal carcinomas (86.4%) exhibited ARID1A promoter hypermthylation. In addition, the promoter hypermethylation was accompanied with repressive histone modification (H3K27Me3). Although five out of 38 invasive ductal carcinomas (13.2%) exhibited loss of ARID1A gene copy number by realtime PCR and nine exon novel mutations are seen from eight out of 33 invasive ductal carcinomas (24.2%), there was no statistically significant difference in both ARID1A mRNA low and high expression groups (p=0.25,and p=0.68, respectively). We demonstrate that promoter hypermethylation was the main culprit for ARID1A mRNA low expression in invasive ductal carcinomas. The influence of mutation and copy number variation on the expression were statistically insignificant at mRNA level, and were, therefore, not considered the main causes for ARID1A mRNA low expression in invasive breast cancer.
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Characteristics and Function of Sulfur Dioxygenase in Echiuran Worm Urechis unicinctus.
PLoS ONE
PUBLISHED: 01-01-2013
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Sulfide is a common toxin to animals and is abundant in coastal and aquatic sediments. Sulfur dioxygenase (SDO) is thought to be the key enzyme involved in sulfide oxidation in some organisms. The echiuran worm, Urechis unicinctus, inhabits coastal sediment and tolerates high concentrations of sulfide. The SDO is presumably important for sulfide tolerance in U. unicinctus.
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P16 and p53 play distinct roles in different subtypes of breast cancer.
PLoS ONE
PUBLISHED: 01-01-2013
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Breast cancers are heterogeneous and complex diseases, and subtypes of breast cancers may involve unique molecular mechanisms. The p16(INK4a) and p53 pathways are two of the major pathways involved in control of the cell cycle. They also play key roles in tumorigenesis. However, whether the roles of these pathways differ in the subtypes of breast cancer is unclear. Therefore, p16 and p53 expression were investigated in different breast cancer subtypes to ascertain their contributions to these cancers. A total of 400 cases of non-invasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), including the major molecular subtypes luminal-A, luminal-B, Her-2, and triple-negative subtypes, and 50 cases of normal controls were compared. Luminal-A cancers expressed the lowest level of p16 among the subtypes in DCIS, and the level of p16 expression was up-regulated in the luminal-A of IDC (P<0.008). Triple-negative breast cancers were characterized by a correlation of p53 overexpression with a high level of p16 expression. Luminal lesion types with high p16 expression in DCIS were found to be more likely to develop into aggressive breast cancers, possibly promoted by p53 dysfunction. Taken together, the present study suggest that p16 expression in luminal-A breast cancers is associated with their progression from DCIS to IDC, and both p53 and p16 expressions are important for the development of triple-negative breast cancers in DCIS and IDC.
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Downregulation of the transcription factor KLF4 is required for the lineage commitment of T cells.
Cell Res.
PUBLISHED: 11-22-2011
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The roles of the reprogramming factors Oct4, Sox2, c-Myc and Klf4 in early T cell development are incompletely defined. Here, we show that Klf4 is the only reprogramming factor whose expression is downregulated when early thymic progenitors (ETPs) differentiate into T cells. Enforced expression of Klf4 in uncommitted progenitors severely impaired T cell development mainly at the DN2-to-DN3 transition when T cell lineage commitment occurs and affected the transcription of a variety of genes with crucial functions in early T cell development, including genes involved in microenvironmental signaling (IL-7R?), Notch target genes (Deltex1), and essential T cell lineage regulatory or inhibitory genes (Bcl11a, SpiB, and Id1). The survival of thymocytes and the rearrangement at the Tcrb locus were impaired in the presence of enforced Klf4 expression. The defects in the DN1-to-DN2 and DN2-to-DN3 transitions in Klf4 transgenic mice could not be rescued by the introduction of a TCR transgene, but was partially rescued by restoring the expression of IL-7R?. Thus, our data indicate that the downregulation of Klf4 is a prerequisite for T cell lineage commitment.
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Synthesis of ruthenium(II) complexes of tetradentate bis(N-pyridylimidazolylidenyl)methane and their reactivities towards N- donors.
Dalton Trans
PUBLISHED: 11-03-2011
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A family of hexa-coordinated ruthenium(II) complexes of bis(N-pyridylimidazolylidenyl)methane (L) were prepared and structurally characterized. Carbene transfer reactions of [Ru(p-cymene)Cl(2)](2), [Ru(CO)(2)Cl(2)](n) and RuHCl(CO)(PPh(3))(3) with silver-NHC complexes in situ generated from [H(2)L](PF(6))(2) and Ag(2)O afforded [RuL(CH(3)CN)(2)](PF(6))(2) (1), [Ru(2)L(p-cymene)(2)Cl(2)](PF(6))(2) (2), [RuL(CO)(2)](PF(6))(2) (3) and [RuL(PPh(3))(2)](PF(6))(2) (4), respectively. The reactions of 1 towards several N- and P-donors were studied. The treatment of 1 with 1,10-phenanthroline resulted in the substitution of one pyridine and one acetonitrile molecule affording [RuL(phen)(CH(3)CN)](PF(6))(2) (5) as a mixture of two isomers. Reaction of 1,2-bis(diphenylphosphino)ethane (dppe) and 1 gave [RuL(dppe)(CH(3)CN)(2)](PF(6))(2) (7), in which two pyridines were substituted by a dppe ligand trans to two NHC groups. In contrast, reactions of 1 with ethane-1,2-diamine, propane-1,3-diamine and 3,5-dimethyl-1H-pyrazole led to the substitution of acetonitrile and subsequent N-H addition of the C?N bond of the coordinated acetonitrile yielding [RuL(ethane-1,2-diamine)(N-(2-aminoethyl)acetimidamide)](PF(6))(2) (8), [RuL(propane-1,3-diamine)(N-(3-aminopropyl)acetimidamide)](PF(6))(2) (9) and RuL(1-(3,5-dimethyl-1H-pyrazol-1-yl)ethanimine)(CH(3)CN)](PF(6))(2) (10), respectively.
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Screening for prostate cancer: the current evidence and guidelines controversy.
Can J Urol
PUBLISHED: 10-25-2011
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Prostate cancer presents a global public health dilemma. While screening with prostate specific antigen (PSA) has led to more men diagnosed with prostate cancer than in previous years, the potential for negative effects from over-diagnosis and treatment cannot be ignored.
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Urolithiasis location and size and the association with microhematuria and stone-related symptoms.
J. Endourol.
PUBLISHED: 09-01-2011
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To conduct a study to assess the association between calculus location and size and the incidence of both microhematuria and symptoms of urolithiasis in a urology office environment.
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[Analysis with the logistic regression mode to the audiologic and vestibular functions in Menieres disease].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 08-04-2011
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To investigate the clinical features, characteristic of cochlear and vestibular dysfunction in Menieres disease (MD) by using the multiple factor Logistic regression analysis.
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Pharmacology for common urologic diseases: 2011 review for the primary care physician.
Can J Urol
PUBLISHED: 04-20-2011
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Coordination of care between the urologist and primary care physician is critical to effective treatment of a variety of urologic conditions. Medical therapies for benign prostatic hyperplasia, erectile dysfunction, hypogonadism, overactive bladder, and prostate cancer are widely available and a basic understanding of the pathophysiology of these disease states as well as the pharmacology of existing treatment options are necessary to avoid complications and maximize efficacy associated with patient outcomes. Important regulatory decisions have been made concerning the approval and lack of approval of several important urologic medications. Major advances have been made in the therapy of castrate resistant prostate cancer as well as hormonal related skeletal events secondary to advanced carcinoma of the prostate. We provide a 2011 update of the available medications for treatment of several common urologic diseases.
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MCP-1 upregulates amylin expression in murine pancreatic ? cells through ERK/JNK-AP1 and NF-?B related signaling pathways independent of CCR2.
PLoS ONE
PUBLISHED: 04-01-2011
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Amylin is the most abundant component of islet amyloid implicated in the development of type 2 diabetes. Plasma amylin levels are elevated in individuals with obesity and insulin resistance. Monocyte chemoattractant protein-1 (MCP-1, CCL2) is involved in insulin resistance of obesity and type 2 diabetes. We investigated the effect of MCP-1 on amylin expression and the underlying mechanisms with murine pancreatic ?-cell line MIN6 and pancreatic islets.
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LKB1 regulates TCR-mediated PLC?1 activation and thymocyte positive selection.
EMBO J.
PUBLISHED: 03-14-2011
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The serine/threonine kinase LKB1 is a tumour suppressor that regulates cell growth, polarity, and proliferation in many different cell types. We previously demonstrated that LKB1 controls thymocyte survival via regulation of AMPK activation. In this study, we show that LKB1 was also involved in thymocyte positive selection through regulation of T cell receptor (TCR) signalling. Both Lck-Cre- and CD4-Cre-mediated deletion of LKB1 impaired the generation of mature CD4 and CD8 single positive (SP) thymocytes that might have resulted from the attenuated tyrosine phosphorylation of phospholipase C-? 1 (PLC?1) in the absence of LKB1. We found that LKB1 was directly phosphorylated by Lck at tyrosine residues 36, 261, and 365 and predominately interacted with LAT and PLC?1 following TCR stimulation. Loss of LKB1 led to impaired recruitment of PLC?1 to the LAT signalosome. Correlatively, LKB1-deficient thymocytes failed to upregulate lineage-specifying factors, and to differentiate into SP thymocytes even if their impaired survival was rescued. These observations indicated that LKB1 is a critical component involved in TCR signalling, and our studies provide novel insights into the mechanisms of LKB1-mediated thymocyte development.
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Do silver alloy-coated catheters increase risk of urethral strictures after robotic-assisted laparoscopic radical prostatectomy?
Urology
PUBLISHED: 02-24-2011
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To evaluate whether the use of silver-coated catheters increased the risk of developing urethral stricture disease after robotic-assisted laparoscopic radical prostatectomy (RALP). Recently, silver alloy-coated Foley catheters have been shown to decrease the risk of catheter-associated urinary tract infections. Other than the increased cost, no disadvantages to the use of these catheters have been reported.
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Migration and homeostasis of naive T cells depends on coronin 1-mediated prosurvival signals and not on coronin 1-dependent filamentous actin modulation.
J. Immunol.
PUBLISHED: 02-21-2011
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Coronins are WD repeat-containing proteins highly conserved in the eukaryotic kingdom implicated in the regulation of F-actin. Mammalian coronin 1, one of the most conserved isoforms expressed in leukocytes, regulates survival of T cells, which has been suggested to be due to its role in preventing F-actin-induced apoptosis. In this study, we come to a different conclusion. We show that coronin 1 does not modulate F-actin and that induction of F-actin failed to induce apoptosis. Instead, coronin 1 was required for providing prosurvival signals, in the absence of which T cells rapidly underwent apoptosis. These results argue against a role for coronin 1 in F-actin-mediated T cell apoptosis and establish coronin 1 as an essential regulator of the balance between prosurvival and proapoptotic signals in naive T cells.
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Upregulation of pancreatic derived factor (FAM3B) expression in pancreatic ?-cells by MCP-1 (CCL2).
Mol. Cell. Endocrinol.
PUBLISHED: 01-11-2011
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Pancreatic derived factor (PANDER, FAM3B) is a peptide mainly synthesized and secreted by pancreatic ?-cells. PANDER is proposed to be involved in regulation of ?-cell function under physiological conditions and impairment of ?-cell function under pathological conditions. MCP-1 (CCL2) is expressed by normal pancreatic islets and has been implicated in inflammation related pancreatic disorders. We examined the effect of MCP-1 on PANDER expression by using murine pancreatic ?-cell line MIN6 and pancreatic islets. We found that MCP-1 induced PANDER mRNA transcription and protein synthesis in MIN6 cells and islets. By using calcium chelator (EGTA); inhibitors for PKC (Go6976), MEK1/2 (PD98059) or c-Jun-N-terminal kinase (JNK) (SP600125); c-Jun dominant-negative construct; PANDER promoter luciferase constructs; and islets isolated from Fos knockout mice; we demonstrated that MCP-1 induced PANDER gene expression in ?-cells through Ca(2+)-ERK1/2-AP-1 and PKC-JNK-AP-1 signaling pathways. Our findings suggest a new link between the endocrine and immune systems and provide useful information for further investigating the physiological functions of PANDER and its involvement in inflammation-related pancreatic disorders.
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p300-mediated acetylation stabilizes the Th-inducing POK factor.
J. Immunol.
PUBLISHED: 09-01-2010
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The lineage-specifying factor Th-inducing POK (ThPOK) directs the intrathymic differentiation of CD4 T cells. Although the regulation of ThPOK at the transcription level has been extensively studied, specific posttranslational modifications regulating the activity of ThPOK have not been addressed. In this paper, we show that ThPOK is an unstable protein that is more readily degraded in CD8 T cells compared with CD4 T cells. Among the various proteins that bind ThPOK, acetyltransferase p300 specifically promotes the acetylation of ThPOK at K210, K216, and K339, outcompeting ubiquitination, thereby stabilizing the protein. In CD4 T cells, attenuation of p300-mediated acetylation promotes the degradation of ThPOK. In contrast, mutation of lysines 210, 216, and 339 to arginines stabilizes ThPOK and enhances its ability to suppress the expression of CD8 molecule and cytotoxic effectors in CD8 T cells. Our results reveal an essential role of p300-mediated acetylation in regulating the stability of ThPOK and suggest that such regulation may play a part in CD4/CD8 lineage differentiation.
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Using nitrogen isotopic approach to identify nitrate sources in waters of Tianjin, China.
Bull Environ Contam Toxicol
PUBLISHED: 07-22-2010
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To understand the nitrogen sources and fate in the surface water of Tianjin, the concentrations of nitrogen and ?¹?N-NO?? were analyzed in different types of waters. Mostly, NO?? was the dominant species of DIN (Dissolved Inorganic Nitrogen), although NH?+ was the main species in certain samples, such as sewage. The ?¹?N-NO?? values ranged from -5.5 to +28.6‰. The water chemical and isotopic results suggested that domestic sewage and agricultural activities were the two main sources of nitrate in surface waters. In addition, the nitrogen isotopic compositions were significantly influenced by nitrification, ammonia volatilization and denitrification.
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Interferon regulatory factor 4 regulates thymocyte differentiation by repressing Runx3 expression.
Eur. J. Immunol.
PUBLISHED: 04-10-2010
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The transcription factor interferon regulatory factor 4 (IRF4) was originally found to be preferentially expressed in lymphoid cells and to be required for the function, differentiation, and homeostasis of both mature T and B lymphocytes. Recent studies have indicated that IRF4 is also involved in early B-cell development. However, the role of IRF4 in intrathymic T-cell development remains unknown. In this study, we show that IRF4 is upregulated in TCR-signaled thymocytes and is predominantly expressed in CD4 single-positive (SP), but not in CD8 SP, cells. T-cell-specific overexpression of IRF4 impaired the generation and maturation of CD8 SP thymocytes. Further analysis revealed that IRF4 selectively bound to the distal promoter region of Runx3 and repressed its transcription, probably through the deacetylation of histones H3 and H4 in intermediate CD4(+) CD8(low) cells and CD4 SP thymocytes. Similar to the effect of Runx3 deficiency, transgenic expression of IRF4 led not only to an aberrantly high expression of CD4 surface molecules on intermediate CD4(+) CD8(low) cells and CD8 SP thymocytes, but also impaired CD8(+) T-cell function. Taken together, our data suggest that IRF4 plays an important role in the regulation of Runx3 expression and CD4(+) /CD8(+) thymocyte differentiation.
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Assessment of the sources of nitrate in the Changjiang River, China using a nitrogen and oxygen isotopic approach.
Environ. Sci. Technol.
PUBLISHED: 02-04-2010
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The Changjiang River is the largest freshwater river in China. Here, the sources and variability in nitrate of the Changjiang River are assessed for the first time using dual isotopic approach. Water samples were collected once in August 2006 from the main channel of the Changjiang and its major tributaries. The concentrations and isotopic composition of nitrate were then analyzed for the waters in the Changjiang River. The delta(15)N and delta(18)O of NO(3)(-) ranges from 7.3 per thousand to 12.9 per thousand and 2.4 per thousand to 11.2 per thousand in the Changjiang River waters, respectively. The ranges of isotopic compositions of nitrate suggested that nitrification (including "modified fertilizer") and urban sewage effluent are the major sources of nitrate in the Changjiang River. The high delta(18)O-NO(3)(-) values were observed in the water of the upper reaches, indicated that the current drought might be one important reason for shifting of isotopes in the special sampling period. In addition, there was a strong positive relationship between delta(15)N-NO(3)(-) and delta(18)O-NO(3)(-), which indicated that denitrification added to the enrichment of heavy isotopes of nitrate.
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Design and analysis of a dispersion flattened and highly nonlinear photonic crystal fiber with ultralow confinement loss.
Appl Opt
PUBLISHED: 01-22-2010
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We present a novel and robust design for a photonic crystal fiber with flattened dispersion, a highly nonlinear coefficient, and low confinement loss for its dual concentric core structure. The proposed fiber has a modest number of design parameters. Analysis results show that the proposed eight-ring photonic crystal fiber is obtained with a nonlinear coefficient greater than 33 W(-1) km(-1) and a near-zero dispersion slope of -7.828 x 10(-4) ps/nm(2)/km at 1550 nm. Ultraflat dispersion with a value between -1.380 and +0.9860 ps/nm/km and a superlow-order confinement loss of 10(-4) dB/km are simultaneously obtained ranging from 1400 to 1625 nm. For practical fabrication, the influence of random imperfections of airhole diameters on dispersion and nonlinearity is discussed to verify the robustness of our design.
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The serine/threonine kinase LKB1 controls thymocyte survival through regulation of AMPK activation and Bcl-XL expression.
Cell Res.
PUBLISHED: 12-22-2009
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LKB1 is a serine/threonine kinase that directly activates the energy sensor AMP-activated protein kinase (AMPK) in response to bioenergetic stress, and mainly acts as a tumor suppressor that controls cell polarity and proliferation. Although LKB1 is expressed in multiple tissues including the thymus and the spleen, its roles in T-cell development and function remain unknown. Here, we show that T-cell-specific deletion of LKB1 resulted in reduced survival of double-positive (DP) thymocytes and impaired generation of both CD4 and CD8 single-positive thymocytes. Disruption of LKB1 not only prevented the activation of AMPK but also impaired the expression of anti-apoptotic protein Bcl-XL. Importantly, ectopic expression of either Bcl-XL or the constitutively active AMPK mutant significantly rescued DP thymocytes from LKB1 deficiency-induced cell death. Moreover, ectopic expression of the constitutively active AMPK mutant was found to restore the expression of Bcl-XL in LKB1-deficient DP thymocytes. These findings identify LKB1 as a critical factor for the survival of DP thymocytes through regulation of AMPK activation and Bcl-XL expression.
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Znhit1 causes cell cycle arrest and down-regulates CDK6 expression.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-28-2009
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Cyclin-dependent kinase 6 (CDK6) is the key element of the D-type cyclin holoenzymes which has been found to function in the regulation of G1-phase of the cell cycle and is presumed to play important roles in T cell function. In this study, Znhit1, a member of a new zinc finger protein family defined by a conserved Zf-HIT domain, induced arrest in the G1-phase of the cell cycle in NIH/3T3 cells. Of the G1 cell cycle factors examined, the expression of CDK6 was found to be strongly down-regulated by Znhit1 via transcriptional repression. This effect may have correlations with the decreased acetylation level of histone H4 in the CDK6 promoter region. In addition, considering that CDK6 expression predominates in T cells, the negative regulatory role of Znhit1 in TCR-induced T cell proliferation was validated using transgenic mice. These findings identified Znhit1 as a CDK6 regulator that plays an important role in cell proliferation.
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c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2.
Cell Res.
PUBLISHED: 04-25-2009
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T cells are derived from progenitor thymocytes, of which only a minority receive the appropriate TCR signal, undergo positive selection and mature. Owing to the very short lifespan of thymocytes, the prerequisite for positive selection is survival. TCR signal-induced Bcl-2 expression is believed to play a dominant role in the survival of positively selecting thymocytes, but how Bcl-2 is directly regulated is unknown. Here we report that the immediate early gene (IEG) c-Fos can stimulate the expression of Bcl-2, depending on a specific AP-1-binding site in the Bcl-2 promoter. In c-Fos transgenic (Fos-Tg) mice, c-Fos binds to this site and promotes the expression of Bcl-2. As a result, Fos-Tg thymocytes exhibited enhanced survival, and more mature single-positive (SP) thymocytes were generated, even on a unique TCR background. The TCR repertoire remained normal in Fos-Tg mice. Our results identified c-Fos as the mediator of the stimulatory effect of TCR signaling on Bcl-2 expression. Therefore, c-Fos, as an IEG, because of its early response ability, can quickly rescue the survival of short-lived thymocytes during positive selection. Our results provide novel insight into the mechanism regulating the survival of positively selecting thymocytes.
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Regulation of T cell development and activation by creatine kinase B.
PLoS ONE
PUBLISHED: 03-04-2009
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Creatine kinase catalyzes the reversible transfer of the N-phosphoryl group from phosphocreatine to ADP to generate ATP and plays a key role in highly energy-demanding processes such as muscle contraction and flagellar motility; however, its role in signal transduction (which frequently involves ATP-consuming phosphorylation) and consequent cell-fate decisions remains largely unknown. Here we report that creatine kinase B was significantly up-regulated during the differentiation of double-positive thymocytes into single-positive thymocytes. Ectopic expression of creatine kinase B led to increased ATP level and enhanced phosphorylation of the TCR signaling proteins. Consequentially, transgenic expression of creatine kinase B promoted the expression of Nur77 and Bim proteins and the cell death of TCR signaled thymocyte. In addition, the activation, proliferation and cytokine secretion of T cells were also enhanced by the expression of creatine kinase B transgene. In contrast, treatment of T cells with specific creatine kinase inhibitor or creatine kinase B shRNA resulted in severely impaired T cell activation. Taken together, our results indicate that creatine kinase B plays an unexpected role in modulating TCR-mediated signaling and critically regulates thymocyte selection and T cell activation.
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Robotic-assistance does not enhance standard laparoscopic technique for right-sided donor nephrectomy.
JSLS
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To examine donor and recipient outcomes after right-sided robotic-assisted laparoscopic donor nephrectomy (RALDN) compared with standard laparoscopic donor nephrectomy (LDN) and to determine whether robotic-assistance enhances LDN.
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A piezo motor based on a new principle with high output force, rigidity and integrity: the Tuna Drive.
Rev Sci Instrum
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We present a linear piezoelectric motor as simple as one piezoelectric scanner tube (PST) spring-clamping a central shaft at both ends with roughly equal clamping forces. The clamping points are aligned with ±X electrodes at one end and ±Y electrodes at the other end. Thus, the ±X (or ±Y) push-pull motions of the PST can cause the push-pull motions of the clamping points on the shaft (called push-pull rubbing), which reduces the total dynamic friction force at one (or the other) end of the PST. This new piezo motor advances one step by fast push-pull rubbing at one end while slowly retracting the PST followed by fast push-pull rubbing at the other end while slowly elongating the PST. Apart from the obvious advantages of simplicity, rigidity, integrity, etc., we will also show that this motor can produce a large output force, which we believe is because of the huge drop of the clamping friction force when the push-pull rubbing occurs.
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Myelopoiesis is regulated by osteocytes through Gs?-dependent signaling.
Blood
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Hematopoietic progenitors are regulated in their respective niches by cells of the bone marrow microenvironment. The bone marrow microenvironment is composed of a variety of cell types, and the relative contribution of each of these cells for hematopoietic lineage maintenance has remained largely unclear. Osteocytes, the most abundant yet least understood cells in bone, are thought to initiate adaptive bone remodeling responses via osteoblasts and osteoclasts. Here we report that these cells regulate hematopoiesis, constraining myelopoiesis through a Gs?-mediated mechanism that affects G-CSF production. Mice lacking Gs? in osteocytes showed a dramatic increase in myeloid cells in bone marrow, spleen, and peripheral blood. This hematopoietic phenomenon was neither intrinsic to the hematopoietic cells nor dependent on osteoblasts but was a consequence of an altered bone marrow microenvironment imposed by Gs? deficiency in osteocytes. Conditioned media from osteocyte-enriched bone explants significantly increased myeloid colony formation in vitro, which was blocked by G-CSF–neutralizing antibody, indicating a critical role of osteocyte-derived G-CSF in the myeloid expansion.
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The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss.
Cancer Res.
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Somatic mutation of the tumor suppressor gene LKB1 occurs frequently in lung cancer where it causes tumor progression and metastasis, but the underlying mechanisms remain mainly unknown. Here, we show that the oncogene NEDD9 is an important downstream mediator of lung cancer progression evoked by LKB1 loss. In de novo mouse models, RNAi-mediated silencing of Nedd9 inhibited lung tumor progression, whereas ectopic NEDD9 expression accelerated this process. Mechanistically, LKB1 negatively regulated NEDD9 transcription by promoting cytosolic translocation of CRTC1 from the nucleus. Notably, ectopic expression of either NEDD9 or CRTC1 partially reversed the inhibitory function of LKB1 on metastasis of lung cancer cells. In clinical specimens, elevated expression of NEDD9 was associated with malignant progression and metastasis. Collectively, our results decipher the mechanism through which LKB1 deficiency promotes lung cancer progression and metastasis, and provide a mechanistic rationale for therapeutic attack of these processes.
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Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1.
Proc. Natl. Acad. Sci. U.S.A.
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T cells play a critical role in tumor immunosurveillance by eliminating newly transformed somatic cells. However, tumor cell variants can escape from immunological control after immunoediting, leading to tumor progression. Whether and how T cells respond to tumor growth remain unclear. Here, we found that tumor-infiltrating T cells exhibited persistently up-regulated expression of the activator protein 1 (AP-1) subunit c-Fos during tumor progression. The ectopic expression of c-Fos in T cells exacerbated tumor growth, whereas the T-cell-specific deletion of c-Fos reduced tumor malignancy. This unexpected immunosuppressive effect of c-Fos was mediated through the induced expression of immune inhibitory receptor programmed death 1 (PD-1) via the direct binding of c-Fos to the AP-1-binding site in the Pdcd1 (gene encoding PD-1) promoter. A knock-in mutation of this binding site abrogated PD-1 induction, augmented antitumor T-cell function and repressed tumor growth. Taken together, these findings indicate that T-cell c-Fos subsequently induces PD-1 expression in response to tumor progression and that disrupting such induction is essential for repression of tumor growth.
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The dual-effects of LaCl? on the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells.
Biol Trace Elem Res
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A series of experimental methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, alkaline phosphatase (ALP) activity measurement, alizarin red S stain and measurement, quantitative real-time reverse transcriptase polymerase chain reaction, and Western blot analysis were employed to assess the effects of LaCl? on the proliferation, osteogenic differentiation, and mineralization of a murine preosteoblast cell line MC3T3-E1 at cell and molecular levels. The results indicated that LaCl? had dual effects on the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. First, LaCl? promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells at lower concentrations, then had no effects and further turned to inhibit the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells with increasing concentrations. The expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), ALP, bone sialoprotein (BSP), collagen I (Col I), and osteocalcin (OCN) genes was upregulated in the presence of 0.0001 and 0.1 ?M LaCl?, but these genes were downregulated in the MC3T3-E1 cells treated with 1,000 ?M LaCl?. In addition, the expression of BMP2, Runx2, and OCN proteins was promoted by LaCl? at the concentration of 0.0001 ?M, but these proteins were downregulated after 1,000 ?M LaCl? treatment. The results suggest that LaCl? likely up- or downregulates the expression of Runx2, which subsequently up- or downregulates osteoblasts marker genes Col I and BMP2 at early stages and ALP and OCN at later stages of differentiation, thus causes to promote or inhibit the proliferation, osteogenic differentiation and mineralization of MC3T3-E1 cells. The results will be helpful for understanding the mechanisms of bone metabolism and application of lanthanum-based compounds in the future.
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Recombinatorial biases and convergent recombination determine interindividual TCR? sharing in murine thymocytes.
J. Immunol.
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Overlap of TCR repertoires among individuals provides the molecular basis for public T cell responses. By deep-sequencing the TCR? repertoires of CD4+CD8+ thymocytes from three individual mice, we observed that a substantial degree of TCR? overlap, comprising ?10-15% of all unique amino acid sequences and ?5-10% of all unique nucleotide sequences across any two individuals, is already present at this early stage of T cell development. The majority of TCR? sharing between individual thymocyte repertoires could be attributed to the process of convergent recombination, with additional contributions likely arising from recombinatorial biases; the role of selection during intrathymic development was negligible. These results indicate that the process of TCR gene recombination is the major determinant of clonotype sharing between individuals.
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Epigenetic silencing of CD8 genes by ThPOK-mediated deacetylation during CD4 T cell differentiation.
J. Immunol.
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Intrathymic CD4/CD8 differentiation is a process that establishes the mutually exclusive expression profiles of the CD4 and CD8 T cell lineage. The RUNX3-mediated silencing of CD4 in CD8 lineage cells has been well documented; however, it is unclear how CD8 is silenced during CD4 lineage differentiation. In this study, we report that, by directly binding the CD8 locus, ThPOK works as a negative regulator that mediates the deacetylation of Cd8 genes and repositions the CD8 alleles close to heterochromatin during the development of the CD4 lineage. The ectopic expression of ThPOK resulted in increased recruitment of histone deacetylases at Cd8 loci; the enhanced deacetylation of Cd8 genes eventually led to impaired Cd8 transcription. In the absence of ThPOK, the enhanced acetylation and transcription of Cd8 genes were observed. The results of these studies showed that Cd8 loci are the direct targets of ThPOK, and, more importantly, they provide new insights into CD8 silencing during CD4 lineage commitment.
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Quercetin, a flavonoid with anti-inflammatory activity, suppresses the development of abdominal aortic aneurysms in mice.
Eur. J. Pharmacol.
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Inflammation has been implicated as a contributing factor in the development of abdominal aortic aneurysms (AAA). Quercetin, a natural flavonoid with anti-inflammatory properties, is known for its beneficial effects on vascular disease. In this study, we examined the effects of quercetin to inflammatory cell infiltration, subsequent expression of cytokines and activation of proteases on the expansion of experimental AAA. Aneurysms were induced by abluminal application of calcium chloride in C57/BL6 mice. Quercetin (60 mg/kg) was administered once daily by gavage beginning 2 weeks before AAA induction and continuing for 8 weeks. Mice treated with quercetin exhibited a 32.7% reduction in aortic size compared with vehicle-treated controls. Prevention of AAA was associated with preservation of medial structure, as well as a relative reduction in macrophage and CD3(+) T cell infiltration in aortic tissue, inflammatory cytokines release and nuclear factor ?B activation. Quercetin also reduced the expression of matrix metalloproteinase (MMP)-2, MMP-9, cathepsin B, and cathepsin K in aortic tissue. In addition, quercetin treatment increased tissue inhibitors of metalloproteinases (TIMP)-1 gene expression. These data indicate that quercetin may be useful for the prevention and treatment of AAA via blocking the inflammatory response and inhibiting the proteases involved in the pathogenesis of this disease.
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Erythropoietin attenuates cardiopulmonary bypass-induced renal inflammatory injury by inhibiting nuclear factor-?B p65 expression.
Eur. J. Pharmacol.
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Acute renal injury is one of the most frequent complications after cardiopulmonary bypass (CPB). This study was designed to evaluate the potential protective effect of erythropoietin (EPO) on CPB-induced renal injury in a rat model. Male Sprague-Dawley rats were randomly divided into three groups, sham-operated group (sham), control CPB group (control), erythropoietin CPB group (EPO). Blood samples were collected at the beginning, at the end of CPB, and at 0.5, 1, 2 and 24 h post-operation, and the kidneys were harvested 24 h postoperatively and observed by optical microscopy. Levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were assayed. Tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) and interleukin-6(IL-6) levels in the renal tissues were evaluated by the method of enzyme linked immunosorbent assay (ELISA). Protein and mRNA levels of nuclear factor kappa B p65 (NF-?B p65), intercellular adhesion molecule-1 (ICAM-1) were also determined using western blot and real-time PCR respectively. Serum Cr and BUN levels as well as TNF-?, IL-1? and IL-6 levels in renal tissues in control group were significantly higher than those in the sham group. However, the levels of above biomarkers were markedly decreased in EPO group when comparing with control group. Furthermore, NF-?B p65, ICAM-1 protein and mRNA expression were significantly down-regulated in EPO group comparing with control group. In addition, microscopic examinations revealed that histological injury was alleviated when treated with EPO. The results indicated that EPO potently protected against CPB-induced acute renal injury and inhibited expression of NF-?B p65 and inflammatory response.
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MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene.
J. Biol. Chem.
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High glycolysis, well known as "Warburg effect," is frequently observed in a variety of cancers. Whether the deregulation of miRNAs contributes to the Warburg effect remains largely unknown. Because miRNA regulates gene expression at both mRNA and protein levels, we constructed a gene functional association network, which allows us to detect the gene activity instead of gene expression, to integratively analyze the microarray data for gene expression and miRNA expression profiling and identify glycolysis-related gene-miRNA pairs deregulated in cancer. Hexokinase 2 (HK2), coding for the first rate-limiting enzyme of glycolysis, is among the top list of genes predicted and potentially regulated by multiple miRNAs including miR-143. Interestingly, miR-143 expression was inversely associated with HK2 protein level but not mRNA level in human lung cancer samples. miR-143, down-regulated by mammalian target of rapamycin activation, reduces glucose metabolism and inhibits cancer cell proliferation and tumor formation through targeting HK2. Collectively, we have not only established a novel methodology for gene-miRNA pair prediction but also identified miR-143 as an essential regulator of cancer glycolysis via targeting HK2.
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The impact of financial interest in intensity-modulated radiation therapy on the utilization of radiation therapy for treatment of newly diagnosed prostate cancer: a single center experience.
ISRN Urol
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Objective. As recent participants in an integrated prostate cancer (PCa) care center, we sought to evaluate whether financial investment in an intensity-modulated radiation therapy (IMRT) center resulted in an increased utilization of radiation therapy in our patients with newly diagnosed PCa. Materials & Methods. Following institutional review board approval, we retrospectively reviewed the records of all consecutive patients who were diagnosed with prostate cancer in the 12 months prior to and after investment in IMRT. Primary treatment modalities included active surveillance (AS), brachytherapy (BT), radiation therapy (XRT), radical prostatectomy (RP), and androgen deprivation therapy (ADT). Treatment data were available for all patients and were compared between the two groups. Results. A total of 344 patients with newly diagnosed PCa were evaluated over the designated time period. The pre-investment group totaled 198 patients, while 146 patients constituted the post-investment group. Among all patients evaluated, there was a similar rate in the use of XRT (20.71% versus 20.55%, P = 1.000) pre- and post-investment in IMRT. Conclusions. Financial interest in IMRT by urologists does not impact overall utilization rates among patients with newly diagnosed PCa at our center.
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Identification and characterization of a novel thermostable pyrethroid-hydrolyzing enzyme isolated through metagenomic approach.
Microb. Cell Fact.
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Pyrethroid pesticides are broad-spectrum pest control agents in agricultural production. Both agricultural and residential usage is continuing to grow, leading to the development of insecticide resistance in the pest and toxic effects on a number of nontarget organisms. Thus, it is necessary to hunt suitable enzymes including hydrolases for degrading pesticide residues, which is an efficient "green" solution to biodegrade polluting chemicals. Although many pyrethroid esterases have consistently been purified and characterized from various resources including metagenomes and organisms, the thermostable pyrethroid esterases have not been reported up to the present.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.