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Find video protocols related to scientific articles indexed in Pubmed.
Asthma in patients with attention-deficit/hyperactivity disorder: A nationwide population-based study.
Ann Clin Psychiatry
PUBLISHED: 11-18-2014
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Asthma symptoms can interrupt daily activities, disturb sleep, and increase the risk of a child having an attention deficit or irritability, which also are symptoms of attention-deficit/hyperactivity disorder (ADHD). Previous studies have shown conflicting results regarding the association between ADHD and asthma. This study investigates the possible correlation between asthma and ADHD.
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Luminescence color switching of supramolecular assemblies of discrete molecular decanuclear gold(I) sulfido complexes.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-31-2014
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A series of discrete decanuclear gold(I) ?3-sulfido complexes with alkyl chains of various lengths on the aminodiphosphine ligands, [Au10{Ph2PN(CnH2n+1)PPh2}4(?3-S)4](ClO4)2, has been synthesized and characterized. These complexes have been shown to form supramolecular nanoaggregate assemblies upon solvent modulation. The photoluminescence (PL) colors of the nanoaggregates can be switched from green to yellow to red by varying the solvent systems from which they are formed. The PL color variation was investigated and correlated with the nanostructured morphological transformation from the spherical shape to the cube as observed by transmission electron microscopy and scanning electron microscopy. Such variations in PL colors have not been observed in their analogous complexes with short alkyl chains, suggesting that the long alkyl chains would play a key role in governing the supramolecular nanoaggregate assembly and the emission properties of the decanuclear gold(I) sulfido complexes. The long hydrophobic alkyl chains are believed to induce the formation of supramolecular nanoaggregate assemblies with different morphologies and packing densities under different solvent systems, leading to a change in the extent of Au(I)-Au(I) interactions, rigidity, and emission properties.
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Strong interaction effects and criticality of bosons in shaken optical lattices.
Phys. Rev. Lett.
PUBLISHED: 10-10-2014
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We study the quantum phase transitions and identify a tricritical point between a normal Bose superfluid, a superfluid that breaks additional Z_{2} Ising symmetry, and a Mott insulator in a recent shaken optical lattice experiment. We show that near the transition between normal and Z_{2} symmetry breaking superfluids, bosons can condense into a momentum state with high or even locally maximum kinetic energies due to the interaction effect. We present a general low-energy effective field theory that treats both the superfluid transition and the Ising transition in a uniform framework. Using the perturbative renormalization group method, we find that the critical behavior of the quantum phase transition belongs to a universality class different from that of a dilute Bose gas.
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Enhanced Electrocatalytic Activity of MoSx on TCNQ-Treated Electrode for Hydrogen Evolution Reaction.
ACS Appl Mater Interfaces
PUBLISHED: 10-10-2014
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Molybdenum sulfide has recently attracted much attention because of its low cost and excellent catalytical effects in the application of hydrogen evolution reaction (HER). To improve the HER efficiency, many researchers have extensively explored various avenues such as material modification, forming hybrid structures or modifying geometric morphology. In this work, we reported a significant enhancement in the electrocatalytic activity of the MoSx via growing on Tetracyanoquinodimethane (TCNQ) treated carbon cloth, where the MoSx was synthesized by thermolysis from the ammonium tetrathiomolybdate ((NH4)2MoS4) precursor at 170 °C. The pyridinic N- and graphitic N-like species on the surface of carbon cloth arising from the TCNQ treatment facilitate the formation of Mo(5+) and S2(2-) species in the MoSx, especially with S2(2-) serving as an active site for HER. In addition, the smaller particle size of the MoSx grown on TCNQ-treated carbon cloth reveals a high ratio of edge sites relative to basal plane sites, indicating the richer effective reaction sites and superior electrocatalytic characteristics. Hence, we reported a high hydrogen evolution rate for MoSx on TCNQ-treated carbon cloth of 6408 mL g(-1) cm(-2) h(-1) (286 mmol g(-1) cm(-2) h(-1)) at an overpotential of V = 0.2 V. This study provides the fundamental concepts useful in the design and preparation of transition metal dichalcogenide catalysts, beneficial in the development in clean energy.
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Human TLR10 is an anti-inflammatory pattern-recognition receptor.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-06-2014
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Toll-like receptor (TLR)10 is the only pattern-recognition receptor without known ligand specificity and biological function. We demonstrate that TLR10 is a modulatory receptor with mainly inhibitory effects. Blocking TLR10 by antagonistic antibodies enhanced proinflammatory cytokine production, including IL-1?, specifically after exposure to TLR2 ligands. Blocking TLR10 after stimulation of peripheral blood mononuclear cells with pam3CSK4 (Pam3Cys) led to production of 2,065 ± 106 pg/mL IL-1? (mean ± SEM) in comparison with 1,043 ± 51 pg/mL IL-1? after addition of nonspecific IgG antibodies. Several mechanisms mediate the modulatory effects of TLR10: on the one hand, cotransfection in human cell lines showed that TLR10 acts as an inhibitory receptor when forming heterodimers with TLR2; on the other hand, cross-linking experiments showed specific induction of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra, 16 ± 1.7 ng/mL, mean ± SEM). After cross-linking anti-TLR10 antibody, no production of IL-1? and other proinflammatory cytokines could be found. Furthermore, individuals bearing TLR10 polymorphisms displayed an increased capacity to produce IL-1?, TNF-?, and IL-6 upon ligation of TLR2, in a gene-dose-dependent manner. The modulatory effects of TLR10 are complex, involving at least several mechanisms: there is competition for ligands or for the formation of heterodimer receptors with TLR2, as well as PI3K/Akt-mediated induction of the anti-inflammatory cytokine IL-1Ra. Finally, transgenic mice expressing human TLR10 produced fewer cytokines when challenged with a TLR2 agonist. In conclusion, to our knowledge we demonstrate for the first time that TLR10 is a modulatory pattern-recognition receptor with mainly inhibitory properties.
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Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity.
Science
PUBLISHED: 09-27-2014
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Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naïve, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. ?-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans.
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mTOR- and HIF-1?-mediated aerobic glycolysis as metabolic basis for trained immunity.
Science
PUBLISHED: 09-27-2014
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Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent ?-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1? (hypoxia-inducible factor-1?) pathway. Inhibition of Akt, mTOR, or HIF-1? blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1? were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1? pathway represents the metabolic basis of trained immunity.
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Protective effects of garcinol on dimethylnitrosamine-induced liver fibrosis in rats.
Food Funct
PUBLISHED: 09-04-2014
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Garcinol, a polyisoprenylated benzophenone derivative, mainly isolated from Garcinia indica fruit rind, has been suggested to exhibit many biological benefits including antioxidative, anti-inflammatory, and anti-tumor activities. The aim of this study is to evaluate the protective effects of garcinol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. The administration of DMN for six consecutive weeks resulted in the decrease of body weights, the elevation of serum aminotransferases, as well as histological lesions in livers. However, oral administration of garcinol remarkably inhibited the elevation of aspartate transaminase (AST) and relieved liver damage induced by DMN. Furthermore, our results revealed that garcinol not only effectively reduced the accumulation of extracellular matrix (ECM) components but also inhibited the expression of ?-smooth muscle actin (?-SMA) in livers. The expression of transforming growth factor-?1 (TGF-?1) and the phosphorylation of Smad 2 and Smad 3 were also suppressed by garcinol supplementation. In conclusion, our current study suggested that garcinol exerted hepatoprotective and anti-fibrotic effects against DMN-induced liver injury in rats.
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Global analysis of human nonreceptor tyrosine kinase specificity using high-density Peptide microarrays.
J. Proteome Res.
PUBLISHED: 08-28-2014
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Protein kinases phosphorylate substrates in the context of specific phosphorylation site sequence motifs. The knowledge of the specific sequences that are recognized by kinases is useful for mapping sites of phosphorylation in protein substrates and facilitates the generation of model substrates to monitor kinase activity. Here, we have adapted a positional scanning peptide library method to a microarray format that is suitable for the rapid determination of phosphorylation site motifs for tyrosine kinases. Peptide mixtures were immobilized on glass slides through a layer of a tyrosine-free Y33F mutant avidin to facilitate the analysis of phosphorylation by radiolabel assay. A microarray analysis provided qualitatively similar results in comparison with the solution phase peptide library "macroarray" method. However, much smaller quantities of kinases were required to phosphorylate peptides on the microarrays, which thus enabled a proteome scale analysis of kinase specificity. We illustrated this capability by microarray profiling more than 80% of the human nonreceptor tyrosine kinases (NRTKs). Microarray results were used to generate a universal NRTK substrate set of 11 consensus peptides for in vitro kinase assays. Several substrates were highly specific for their cognate kinases, which should facilitate their incorporation into kinase-selective biosensors.
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Structure of RNA 3'-phosphate cyclase bound to substrate RNA.
RNA
PUBLISHED: 08-26-2014
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RNA 3'-phosphate cyclase (RtcA) catalyzes the ATP-dependent cyclization of a 3'-phosphate to form a 2',3'-cyclic phosphate at RNA termini. Cyclization proceeds through RtcA-AMP and RNA(3')pp(5')A covalent intermediates, which are analogous to intermediates formed during catalysis by the tRNA ligase RtcB. Here we present a crystal structure of Pyrococcus horikoshii RtcA in complex with a 3'-phosphate terminated RNA and adenosine in the AMP-binding pocket. Our data reveal that RtcA recognizes substrate RNA by ensuring that the terminal 3'-phosphate makes a large contribution to RNA binding. Furthermore, the RNA 3'-phosphate is poised for in-line attack on the P-N bond that links the phosphorous atom of AMP to N(?) of His307. Thus, we provide the first insights into RNA 3'-phosphate termini recognition and the mechanism of 3'-phosphate activation by an Rtc enzyme.
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Novel real-time temperature diagnosis of conventional hot-embossing process using an ultrasonic transducer.
Sensors (Basel)
PUBLISHED: 08-05-2014
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This paper presents an integrated high temperature ultrasonic transducer (HTUT) on a sensor insert and its application for real-time diagnostics of the conventional hot embossing process to fabricate V-cut patterns. The sensor was directly deposited onto the sensor insert of the hot embossing mold by using a sol-gel spray technique. It could operate at temperatures higher than 400 °C and uses an ultrasonic pulse-echo technique. The ultrasonic velocity could indicate the three statuses of the hot embossing process and also evaluate the replication of V-cut patterns on a plastic plate under various processing conditions. The progression of the process, including mold closure, plastic plate softening, cooling and plate detachment inside the mold, was clearly observed using ultrasound. For an ultrasonic velocity range from 2197.4 to 2435.9 m/s, the height of the V-cut pattern decreased from 23.0 to 3.2 µm linearly, with a ratio of -0.078 µm/(m/s). The incompleteness of the replication of the V-cut patterns could be indirectly observed by the ultrasonic signals. This study demonstrates the effectiveness of the ultrasonic sensors and technology for diagnosing the replicating condition of microstructures during the conventional hot embossing process.
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Prenatal ultrasonography and postnatal follow-up of a case of McKusick-Kaufman syndrome.
Taiwan J Obstet Gynecol
PUBLISHED: 07-15-2014
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McKusick-Kaufman syndrome (MKS) is a rare autosomal recessive syndrome characterized by hydrometrocolpos (HMC) and postaxial polydactyly (PAP). It is very difficult to diagnose MKS prenatally because of overlapping manifestations and associated anomalies with other syndromes. Herein, we present a case of MKS with prenatal ultrasound illustrating a fetal abdominal cystic mass.
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Prenatal sonographic diagnosis of single umbilical artery: Emphasis on the absent side and its relation to associated anomalies.
Taiwan J Obstet Gynecol
PUBLISHED: 07-15-2014
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To determine the absent side of a single umbilical artery (SUA) and to evaluate whether associated anomalies are related to the side of the missing artery in a Taiwanese population.
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Src family kinases and their role in hematological malignancies.
Leuk. Lymphoma
PUBLISHED: 06-06-2014
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Abstract The Src family protein tyrosine kinases (SFKs) are non-receptor intracellular kinases that have important roles in both hematopoiesis and leukemogenesis. The derangement of their expression or activation has been demonstrated to contribute to hematological malignancies. This review first examines the mechanisms of SFK overexpression and hyperactivation, emphasizing the dysregulation of the upstream modulators. Subsequently, the role of SFK upregulation in the initiation, progression and therapy resistance of many hematological malignancies will also be analysed. The presented evidence will endeavour to highlight the influence of SFK upregulation on an extensive number of hematological malignancies and the need to consider them as candidates in targeted anticancer therapy.
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Type 2 diabetes and antidiabetic medications in relation to dementia diagnosis.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 06-04-2014
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Type 2 diabetes (T2D) has been shown to increase dementia risk, but few studies evaluated the relationship between antidiabetic treatment and dementia.
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Smart sensors enable smart air conditioning control.
Sensors (Basel)
PUBLISHED: 05-26-2014
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In this study, mobile phones, wearable devices, temperature and human motion detectors are integrated as smart sensors for enabling smart air conditioning control. Smart sensors obtain feedback, especially occupants' information, from mobile phones and wearable devices placed on human body. The information can be used to adjust air conditioners in advance according to humans' intentions, in so-called intention causing control. Experimental results show that the indoor temperature can be controlled accurately with errors of less than ±0.1 °C. Rapid cool down can be achieved within 2 min to the optimized indoor capacity after occupants enter a room. It's also noted that within two-hour operation the total compressor output of the smart air conditioner is 48.4% less than that of the one using On-Off control. The smart air conditioner with wearable devices could detect the human temperature and activity during sleep to determine the sleeping state and adjusting the sleeping function flexibly. The sleeping function optimized by the smart air conditioner with wearable devices could reduce the energy consumption up to 46.9% and keep the human health. The presented smart air conditioner could provide a comfortable environment and achieve the goals of energy conservation and environmental protection.
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The interplay between central metabolism and innate immune responses.
Cytokine Growth Factor Rev.
PUBLISHED: 05-22-2014
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A growing body of recent studies bring into light an important cross-talk between immune response and metabolism not only at the level of the organism as a whole, but also at the level of the individual cells. Cellular bioenergetics functions not only as a power plant to fuel up the cells, but the intermediate metabolites are shown to play an important role to modulate cellular responses. It is especially the pathways through which a cell metabolizes glucose that have been recently shown to influence both innate and adaptive immune responses, with oxidative phosphorylation used by resting or tolerant cells, while aerobic glycolysis (also termed 'Warburg effect') fueling activated cells. In this review we will address how the center metabolism shifts upon activation in the innate immune cells and how the intermediate metabolites modulate the function of immune cells.
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Soft Tissue Infection Caused by Rapid Growing Mycobacterium following Medical Procedures: Two Case Reports and Literature Review.
Ann Dermatol
PUBLISHED: 04-30-2014
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Non-tubecrulosis mycobacterium infections were increasingly reported either pulmonary or extrapulmonary in the past decades. In Taiwan, we noticed several reports about the soft tissue infections caused by rapid growing mycobacterium such as Mycobacterium abscessus, Mycobacterium chelonae, on newspaper, magazines, or the multimedia. Most of them occurred after a plastic surgery, and medical or non-medical procedures. Here, we reported two cases of these infections following medical procedures. We also discussed common features and the clinical course of the disease, the characteristics of the infected site, and the treatment strategy. The literatures were also reviewed, and the necessity of the treatment guidelines was discussed.
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Serum adhesion molecules as outcome predictors in adult severe sepsis patients requiring mechanical ventilation in the emergency department.
Clin. Biochem.
PUBLISHED: 04-21-2014
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Serum adhesion molecules play a pivotal role in the pathogenesis of sepsis syndrome. This study aimed to evaluate the prognostic value of serum adhesion molecules in patients with severe sepsis and mechanical ventilation (MV) at the emergency department.
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Tanshinone IIA inhibits human gastric carcinoma AGS cell growth by decreasing BiP, TCTP, Mcl?1 and Bcl?xL and increasing Bax and CHOP protein expression.
Int. J. Mol. Med.
PUBLISHED: 04-01-2014
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Tanshinone IIA (Tan?IIA) is extracted from Danshen (Salviae Miltiorrhizae Radix) and is a natural anti?cancer agent, which possesses antitumor activity in a variety of human cancer cells. Tan?IIA can induce apoptosis and inhibit the proliferation of gastric cancer through different molecular mechanisms. However, the efficacy and molecular mechanism of Tan?IIA in gastric cancer have not been well studied. In the present study, the cytotoxicity of Tan?IIA in human gastric cancer AGS cells by 3?(4,5?dimethylthiazol?2?y1)?2,5?diphenyltetrazolium bromide assay was examined. The protein expression levels of B?cell lymphoma?extra large (Bcl?xL), Bcl?2?associated X protein (Bax), myeloid cell leukemia 1 protein (Mcl?1), translationally?controlled tumor protein (TCTP), binding immunoglobulin protein (BiP), calnexin, protein kinase-like endoplasmic reticulum kinase, eIF2?, activating transcription factor 4 (ATF4), inositol?requiring enzyme 1? (IRE1?), ATF6, caspase?12, caspase?9, caspase?3, C/EBP?homologous protein (CHOP) and ??actin in AGS cells were measured by western blot analysis. The results showed that Tan?IIA inhibited AGS cells in a time?and dose?dependent manner. AGS cells treated with Tan?IIA upregulated the protein expression of caspase?12, caspase?9, caspase?3, CHOP and Bax, but downregulated the protein expression of BiP, TCTP, Mcl?1 and Bcl?xL. These findings indicated that Tan?IIA inhibits the growth of human gastric cancer AGS cells. One of the molecular mechanisms may be through decreasing the protein expression of BiP to induce the activation of endoplasmic reticulum stress, followed by increasing the protein expression of caspase?12 to upregulate CHOP expression. The other may be through decreasing the protein expression of Mcl?1, Bcl?xL and TCTP, but increasing Bax, caspase?9 and caspase?3 to induce apoptosis. The chemotherapeutic potential of Tan?IIA for human gastric cancer warrants further study in the future.
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Validation of Malay Version of Snaith-Hamilton Pleasure Scale: Comparison between Depressed Patients and Healthy Subjects at an Out-Patient Clinic in Malaysia.
Malays J Med Sci
PUBLISHED: 03-21-2014
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The Snaith-Hamilton Pleasure Scale (SHAPS) is a self-assessment scale designed to evaluate anhedonia in various psychiatric disorders. In order to facilitate its use in Malaysian settings, our current study aimed to examine the validity of a Malay-translated version of the SHAPS (SHAPS-M).
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Synthesis, characterization, and luminescence studies of discrete polynuclear gold(I) sulfido and selenido complexes with intramolecular aurophilic contacts.
Inorg Chem
PUBLISHED: 03-12-2014
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The synthesis, characterization, and photophysical and photochemical properties of a family of high-nuclearity gold(I) chalcogenides, specifically, the gold(I) sulfido and selenido complexes containing different bridging diphosphine ligands with nuclearities of ten ([Au10{?-Ph2PN(R)PPh2}4(?3-E)4](2+)) and six ([Au6{?-Ph2PN(R)PPh2}3(?3-E)2](2+)), are reported. The X-ray crystal structures of the complex cations of Au10 and Au6 are found to be propeller-like structures and distorted cubane structures, respectively, with the presence of short intramolecular gold···gold distances. The complexes show intense green and/or orange phosphorescence upon photoexcitation in the solid state and in solution at ambient and low temperature. The emission properties are found to be strongly dependent on the nuclearities and the chalcogenido ligands, but are rather insensitive to the substituents on the bis(diphenylphosphino)amines. The emissions are tentatively assigned to originate from the excited states derived from the phosphine-centered intraligand (IL) transition or metal-centered (ds/dp) mixed with ligand-to-metal-metal charge transfer (LMMCT) (E?Au) transition. The photochemical properties of the complexes were also studied by transient absorption spectroscopy.
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Innate immune memory: towards a better understanding of host defense mechanisms.
Curr. Opin. Immunol.
PUBLISHED: 02-06-2014
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Innate immunity is classically defined as unable to build up immunological memory. Recently however, the assumption of the lack of immunological memory within innate immune responses has been reconsidered. Plants and invertebrates lacking adaptive immune system can be protected against secondary infections. It has been shown that mammals can build cross-protection to secondary infections independently of T-lymphocytes and B-lymphocytes. Moreover, recent studies have demonstrated that innate immune cells such as NK cells and monocytes can display adaptive characteristics, a novel concept for which the term trained immunity has been proposed. Several mechanisms are involved in mediating innate immune memory, among which epigenetic histone modifications and modulation of recognition receptors on the surface of innate immune cells are likely to play a central role.
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Convergent evolution in European and Rroma populations reveals pressure exerted by plague on Toll-like receptors.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-03-2014
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Recent historical periods in Europe have been characterized by severe epidemic events such as plague, smallpox, or influenza that shaped the immune system of modern populations. This study aims to identify signals of convergent evolution of the immune system, based on the peculiar demographic history in which two populations with different genetic ancestry, Europeans and Rroma (Gypsies), have lived in the same geographic area and have been exposed to similar environments, including infections, during the last millennium. We identified several genes under evolutionary pressure in European/Romanian and Rroma/Gipsy populations, but not in a Northwest Indian population, the geographic origin of the Rroma. Genes in the immune system were highly represented among those under strong evolutionary pressures in Europeans, and infections are likely to have played an important role. For example, Toll-like receptor 1 (TLR1)/TLR6/TLR10 gene cluster showed a strong signal of adaptive selection. Their gene products are functional receptors for Yersinia pestis, the agent of plague, as shown by overexpression studies showing induction of proinflammatory cytokines such as TNF, IL-1?, and IL-6 as one possible infection that may have exerted evolutionary pressures. Immunogenetic analysis showed that TLR1, TLR6, and TLR10 single-nucleotide polymorphisms modulate Y. pestis-induced cytokine responses. Other infections may also have played an important role. Thus, reconstruction of evolutionary history of European populations has identified several immune pathways, among them TLR1/TLR6/TLR10, as being shaped by convergent evolution in two human populations with different origins under the same infectious environment.
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A tRNA splicing operon: Archease endows RtcB with dual GTP/ATP cofactor specificity and accelerates RNA ligation.
Nucleic Acids Res.
PUBLISHED: 01-16-2014
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Archease is a 16-kDa protein that is conserved in all three domains of life. In diverse bacteria and archaea, the genes encoding Archease and the tRNA ligase RtcB are localized into an operon. Here we provide a rationale for this operon organization by showing that Archease and RtcB from Pyrococcus horikoshii function in tandem, with Archease altering the catalytic properties of the RNA ligase. RtcB catalyzes the GTP and Mn(II)-dependent joining of either 2',3'-cyclic phosphate or 3'-phosphate termini to 5'-hydroxyl termini. We find that catalytic concentrations of Archease are sufficient to activate RtcB, and that Archease accelerates both the RNA 3'-P guanylylation and ligation steps. In addition, we show that Archease can alter the NTP specificity of RtcB such that ATP, dGTP or ITP is used efficiently. Moreover, RtcB variants that have inactivating substitutions in the guanine-binding pocket can be rescued by the addition of Archease. We also present a 1.4 Å-resolution crystal structure of P. horikoshii Archease that reveals a metal-binding site consisting of conserved carboxylates located at the protein tip. Substitution of the Archease metal-binding residues drastically reduced Archease-dependent activation of RtcB. Thus, evolution has sought to co-express archease and rtcB by creating a tRNA splicing operon.
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Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2,3-dioxygenase promotes breast cancer progression.
Breast Cancer Res.
PUBLISHED: 01-14-2014
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Expression of indoleamine 2,3-dioxygenase (IDO) in primary breast cancer increases tumor growth and metastasis. However, the clinical significance of stromal IDO and the regulation of stromal IDO are unclear.
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Acrylamide-induced apoptosis in rat primary astrocytes and human astrocytoma cell lines.
Toxicol In Vitro
PUBLISHED: 01-09-2014
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This study aimed to evaluate the acrylamide (ACR)-induced apoptotic effects on rat primary astrocytes and three human astrocytoma-derived cell lines (U-1240 MG, U-87 MG, and U-251 MG). As determined through the MTT assay, treatment with 1 and 2 mM ACR for 24-72 h resulted in decreased cell viability in all cells. Decreases in cell viability could be blocked in all cells with the exception of U-251 MG cells by Z-DEVD FMK. ACR-induced dose-dependent apoptotic effects were also demonstrated by increases in the sub-G1 phase cell population in all cells. The decreased expressions of pro-caspase 3, 8, and 9 and the interruption of the mitochondrial membrane potential were observed in all cells. Exposure to 2 mM ACR for 48 h resulted in increased Bax/Bcl-2 ratios in primary astrocytes and U-87 MG cells, whereas the overexpression of Bcl-2 was observed in U-1240 MG and U-251 MG cells. The ACR-induced increases in the levels of p53 and pp53 in primary astrocytes could be attenuated by caffeine. These results suggest the existence of a common apoptotic pathway among all cell types and that U-87 MG cells may be a suitable substitute in vitro model for primary astrocytes in future studies on ACR-induced neurotoxicity.
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Antidiabetic Effects of Carassius auratus Complex Formula in High Fat Diet Combined Streptozotocin-Induced Diabetic Mice.
Evid Based Complement Alternat Med
PUBLISHED: 01-08-2014
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Carassius auratus complex formula, including Carassius auratus, Rhizoma dioscoreae, Lycium chinense, and Rehmannia glutinosa Libosch, is a combination prescription of traditional Chinese medicine, which has always been used to treat diabetes mellitus in ancient China. In this study, we provided experimental evidence for the use of Carassius auratus complex formula in the treatment of high fat diet combined streptozotocin- (STZ-) induced type 2 diabetes. Carassius auratus complex formula aqueous extract was prepared and the effects of it on blood glucose, serum insulin, adipose tissue weight, oral glucose tolerance test (OGTT), total cholesterol, and triglyceride (TG) levels in mice were measured. Moreover, adiponectin, TG synthesis related gene expressions, and the inhibitory effect of aldose reductase (AR) were performed to evaluate its antidiabetic effects. After the 8-week treatment, blood glucose, insulin levels, and adipose tissue weight were significantly decreased. OGTT and HOMA-IR index showed improved glucose tolerance. It could also lower plasma TG, TC, and liver TG levels. Furthermore, Carassius auratus complex formula could inhibit the activity of AR and restore adiponectin expression in serum. Based on these findings, it is suggested that Carassius auratus complex formula possesses potent anti-diabetic effects on high fat diet combined STZ-induced diabetic mice.
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Prediction of the repeat domain structures and impact of parkinsonism-associated variations on structure and function of all functional domains of leucine-rich repeat kinase 2 (LRRK2).
Hum. Mutat.
PUBLISHED: 01-08-2014
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Genetic variations of leucine-rich repeat kinase 2 (LRRK2) are the major cause of dominantly inherited Parkinson disease (PD). LRRK2 protein contains seven predicted domains: a tandem Ras-like GTPase (ROC) domain and C-terminal of Roc (COR) domain, a protein kinase domain, and four repeat domains. PD-causative variations arise in all domains, suggesting that aberrant functioning of any domain can contribute to neurotoxic mechanisms of LRRK2. Determination of the three-dimensional structure of LRRK2 is one of the best avenues to decipher its neurotoxic mechanism. However, with the exception of the Roc domain, the three-dimensional structures of the functional domains of LRRK2 have yet to be determined. Based on the known three-dimensional structures of repeat domains of other proteins, the tandem Roc-COR domains of the Chlorobium tepidum Rab family protein, and the kinase domain of the Dictyostelium discoideum Roco4 protein, we predicted (1) the motifs essential for protein-protein interactions in all domains, (2) the motifs critical for catalysis and substrate recognition in the tandem Roc-COR and kinase domains, and (3) the effects of some PD-associated missense variations on the neurotoxic action of LRRK2. Results of our analysis provide a conceptual framework for future investigation into the regulation and the neurotoxic mechanism of LRRK2.
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Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia.
Nat Commun
PUBLISHED: 01-07-2014
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Candidaemia is the fourth most common cause of bloodstream infection, with a high mortality rate of up to 40%. Identification of host genetic factors that confer susceptibility to candidaemia may aid in designing adjunctive immunotherapeutic strategies. Here we hypothesize that variation in immune genes may predispose to candidaemia. We analyse 118,989 single-nucleotide polymorphisms (SNPs) across 186 loci known to be associated with immune-mediated diseases in the largest candidaemia cohort to date of 217 patients of European ancestry and a group of 11,920 controls. We validate the significant associations by comparison with a disease-matched control group. We observe significant association between candidaemia and SNPs in the CD58 (P = 1.97 × 10(-11); odds ratio (OR) = 4.68), LCE4A-C1orf68 (P = 1.98 × 10(-10); OR = 4.25) and TAGAP (P = 1.84 × 10(-8); OR = 2.96) loci. Individuals carrying two or more risk alleles have an increased risk for candidaemia of 19.4-fold compared with individuals carrying no risk allele. We identify three novel genetic risk factors for candidaemia, which we subsequently validate for their role in antifungal host defence.
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Long-term immunogenicity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques.
PLoS ONE
PUBLISHED: 01-01-2014
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Enterovirus 71 (EV71) has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac) based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt) was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-? and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.
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Quiescent and proliferative fibroblasts exhibit differential p300 HAT activation through control of 5-methoxytryptophan production.
PLoS ONE
PUBLISHED: 01-01-2014
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Quiescent fibroblasts possess unique genetic program and exhibit high metabolic activity distinct from proliferative fibroblasts. In response to inflammatory stimulation, quiescent fibroblasts are more active in expressing cyclooxygenase-2 and other proinflammatory genes than proliferative fibroblasts. The underlying transcriptional mechanism is unclear. Here we show that phorbol 12-myristate 13-acetate (PMA) and cytokines increased p300 histone acetyltransferase activity to a higher magnitude (> 2 fold) in quiescent fibroblasts than in proliferative fibroblasts. Binding of p300 to cyclooxygenase-2 promoter was reduced in proliferative fibroblasts. By ultrahigh-performance liquid chromatography coupled with a quadrupole time of flight mass spectrometer and enzyme-immunoassay, we found that production of 5-methoxytryptophan was 2-3 folds higher in proliferative fibroblasts than that in quiescent fibroblasts. Addition of 5-methoxytryptophan and its metabolic precursor, 5-hydroxytryptophan, to quiescent fibroblasts suppressed PMA-induced p300 histone acetyltransferase activity and cyclooxygenase-2 expression to the level of proliferative fibroblasts. Silencing of tryptophan hydroxylase-1 or hydroxyindole O-methyltransferase in proliferative fibroblasts with siRNA resulted in elevation of PMA-induced p300 histone acetyltransferase activity to the level of that in quiescent fibroblasts, which was rescued by addition of 5-hydroxytryptophan or 5-methoxytryptophan. Our findings indicate that robust inflammatory gene expression in quiescent fibroblasts vs. proliferative fibroblasts is attributed to uncontrolled p300 histone acetyltransferase activation due to deficiency of 5-methoxytryptophan production. 5-methoxytryptophan thus is a potential valuable lead compound for new anti-inflammatory drug development.
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Novel structural features in Candida albicans hyphal glucan provide a basis for differential innate immune recognition of hyphae versus yeast.
J. Biol. Chem.
PUBLISHED: 12-16-2013
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The innate immune system differentially recognizes Candida albicans yeast and hyphae. It is not clear how the innate immune system effectively discriminates between yeast and hyphal forms of C. albicans. Glucans are major components of the fungal cell wall and key fungal pathogen-associated molecular patterns. C. albicans yeast glucan has been characterized; however, little is known about glucan structure in C. albicans hyphae. Using an extraction procedure which minimizes degradation of the native structure, we extracted glucans from C. albicans hyphal cell walls. 1H-NMR data analysis revealed that, when compared to reference (1-3,1-6) beta-linked glucans and C. albicans yeast glucan, hyphal glucan has a unique cyclical or closed chain structure which is not found in yeast glucan. GC/MS analyses showed high abundance of 3- and 6-linked glucose units when compared to yeast beta-glucan. In addition, to the expected (1-3), (1-6) and 3,6 linkages, we also identified a 2,3 linkage which has not been reported previously in C. albicans. Hyphal glucan induced robust immune responses in human peripheral blood mononuclear cells and macrophages via a Dectin-1-dependent mechanism. In contrast, C. albicans yeast glucan was a much less potent stimulus. We also demonstrated the capacity of C. albicans hyphal glucan, but not yeast glucan, to induce IL-1beta processing and secretion. This finding provides important evidence for understanding the immune discrimination between colonization and invasion at the mucosal level. When taken together, these data provide a structural basis for differential innate immune recognition of C. albicans yeast versus hyphae.
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Efficient continuous-duty Bitter-type electromagnets for cold atom experiments.
Rev Sci Instrum
PUBLISHED: 11-05-2013
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We present the design, construction, and characterization of Bitter-type electromagnets which can generate high magnetic fields under continuous operation with efficient heat removal for cold atom experiments. The electromagnets are constructed from a stack of alternating layers consisting of copper arcs and insulating polyester spacers. Efficient cooling of the copper is achieved via parallel rectangular water cooling channels between copper layers with low resistance to flow; a high ratio of the water-cooled surface area to the volume of copper ensures a short length scale (~1 mm) to extract dissipated heat. High copper fraction per layer ensures high magnetic field generated per unit energy dissipated. The ensemble is highly scalable and compressed to create a watertight seal without epoxy. From our measurements, a peak field of 770 G is generated 14 mm away from a single electromagnet with a current of 400 A and a total power dissipation of 1.6 kW. With cooling water flowing at 3.8 l/min, the coil temperature only increases by 7 °C under continuous operation.
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The challenges of classical swine fever control: Modified live and E2 subunit vaccines.
Virus Res.
PUBLISHED: 09-11-2013
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Classical swine fever (CSF) is an economically important, highly contagious disease of swine worldwide. CSF is caused by classical swine fever virus (CSFV), and domestic pigs and wild boars are its only natural hosts. The two main strategies used to control CSF epidemic are systematic prophylactic vaccination and a non-vaccination stamping-out policy. This review compares the protective efficacy of the routinely used modified live vaccine (MLV) and E2 subunit vaccines and summarizes the factors that influence the efficacy of the vaccines and the challenges that both vaccines face to CSF control. Although MLV provide earlier and more complete protection than E2 subunit vaccines, it has the drawback of not allowing differentiation between infected and vaccinated animals (DIVA). The marker vaccine of E2 protein with companion discriminatory test to detect antibodies against E(rns) allows DIVA and is a promising strategy for future control and eradication of CSF. Maternal derived antibody (MDA) is the critical factor in impairing the efficacy of both MLV and E2 subunit vaccines, so the well-designed vaccination programs of sows and piglets should be considered together. Because of the antigen variation among various genotypes of CSFV, antibodies raised by either MLV or subunit vaccine neutralize genotypically homologous strains better than heterologous ones. However, although this is not a major concern for MLV as the induced immune responses can protect pigs against the challenge of various genotypes of CSFVs, it is critical for E2 subunit vaccines. It is thus necessary to evaluate whether the E2 subunit vaccine can completely protect against the current prevalent strains in the field. An ideal new generation of vaccine should be able to maintain the high protective efficiency of MLV and overcome the problem of antigenic variations while allowing for DIVA.
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Activation of Src family tyrosine kinases by ferric ions.
Biochim. Biophys. Acta
PUBLISHED: 09-06-2013
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The Src-family tyrosine kinases (SFKs) are oncogenic enzymes that contribute to the initiation and progression of many types of cancer. In normal cells, SFKs are kept in an inactive state mainly by phosphorylation of a consensus regulatory tyrosine near the C-terminus (Tyr(530) in the SFK c-Src). As recent data indicate that tyrosine modification enhances binding of metal ions, the hypothesis that SFKs might be regulated by metal ions was investigated. The c-Src C-terminal peptide bound two Fe(3+) ions with affinities at pH4.0 of 33 and 252?M, and phosphorylation increased the affinities at least 10-fold to 1.4 and 23?M, as measured by absorbance spectroscopy. The corresponding phosphorylated peptide from the SFK Lyn bound two Fe(3+) ions with much higher affinities (1.2pM and 160nM) than the Src C-terminal peptide. Furthermore, when Lyn or Hck kinases, which had been stabilised in the inactive state by phosphorylation of the C-terminal regulatory tyrosine, were incubated with Fe(3+) ions, a significant enhancement of kinase activity was observed. In contrast Lyn or Hck kinases in the unphosphorylated active state were significantly inhibited by Fe(3+) ions. These results suggest that Fe(3+) ions can regulate SFK activity by binding to the phosphorylated C-terminal regulatory tyrosine.
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Impairment of thymocyte function via induction of apoptosis by areca nut extract.
J Immunotoxicol
PUBLISHED: 08-12-2013
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Abstract Areca quid (AQ) chewing is a popular oral habit, especially in Southeast Asia cultures, in which children may be engaged in the addictive habit early in their lives. Extracts of areca nuts, the main component of AQ, have been shown to affect the functionality of T-cells. However, the potential influence of ANE on the development of T-cells is unknown. This study, therefore, investigated the impact of areca nut extracts (ANE) on thymocytes and the potential mechanisms of action. Mice administered intraperitoneally with ANE at 1, 5, or 25?mg/kg daily for 5 days showed significant dose-dependent reductions in thymocyte viability. A marked decrease in the total number of thymocytes and the proportion of thymic CD4(+)CD8(+) cells was observed in the 25?mg ANE/kg-treated mice, whereas the proportion of CD4 and CD8 single positive and CD4(-)CD8(-) cells was significantly increased. Further examination on the functionality of thymocytes showed that ANE suppress IL-2 production both ex vivo and in vitro. These results suggest that ANE may attenuate the development and functionality of thymic T-cells. ANE also directly induced apoptosis in thymic T-cells through activation of casapase-3 and apoptosis inducing factor (AIF). Collectively, the data suggested that the thymus is a sensitive target to ANE. Early exposure to ANE may interfere with the development and functionality of thymic T-cells.
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Prenatal diagnosis of fetal omphalocele by ultrasound: a comparison of two centuries.
Taiwan J Obstet Gynecol
PUBLISHED: 08-07-2013
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An omphalocele, a fetal abdominal defect, is a very important congenital anomaly. Prenatal diagnosis of fetal omphalocele is crucial to clinical management.
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Nodal regulates energy metabolism in glioma cells by inducing expression of hypoxia-inducible factor 1?.
Neuro-oncology
PUBLISHED: 08-01-2013
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A shift in glucose metabolism from oxidative phosphorylation to anaerobic glycolysis is the biochemical hallmark of malignant cancer cells.
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From cosmology to cold atoms: observation of Sakharov oscillations in a quenched atomic superfluid.
Science
PUBLISHED: 08-01-2013
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Predicting the dynamics of many-body systems far from equilibrium is a challenging theoretical problem. A long-predicted phenomenon in hydrodynamic nonequilibrium systems is the occurrence of Sakharov oscillations, which manifest in the anisotropy of the cosmic microwave background and the large-scale correlations of galaxies. Here, we report the observation of Sakharov oscillations in the density fluctuations of a quenched atomic superfluid through a systematic study in both space and time domains and with tunable interaction strengths. Our work suggests a different approach to the study of nonequilibrium dynamics of quantum many-body systems and the exploration of their analogs in cosmology and astrophysics.
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Cationic solid lipid nanoparticles with cholesterol-mediated surface layer for transporting saquinavir to the brain.
Biotechnol. Prog.
PUBLISHED: 05-27-2013
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Cholesterol-mediated cationic solid lipid nanoparticles (CSLNs) were formulated with esterquat 1 (EQ 1) and stearylamine as positively charged external layers on hydrophobic internal cores of cacao butter. These CSLNs were employed to deliver saquinavir (SQV) to the brain. The permeability of SQV across the blood-brain barrier (BBB) using SQV-loaded CSLNs (SQV-CSLNs) was estimated with an in vitro model of a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes. The results revealed that the average diameter of SQV-CSLNs diminished when the weight percentage of cholesterol and EQ 1 increased. The morphological images indicated a uniform size of SQV-CSLNs with compact lipid structure. In addition, an increasing weight percentage of cholesterol and EQ 1 enhanced the zeta potential of SQV-CSLNs. The fluorescent staining demonstrated that HBMECs could internalize SQV-CSLNs. An increase in the weight percentage of cholesterol and EQ 1 also promoted the uptake of SQV-CSLNs by HBMECs. Moreover, a high content of cholesterol and EQ 1 in SQV-CSLNs increased the BBB permeability of SQV. The cholesterol-mediated SQV-CSLNs can be an efficacious drug delivery system for brain-targeting delivery of antiviral agents. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 2013.
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The prognostic significance of metaplastic carcinoma of the breast (MCB)--a case controlled comparison study with infiltrating ductal carcinoma.
Breast
PUBLISHED: 05-10-2013
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Metaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast cancer with an incidence of less than 0.1%-0.5%. Due to its rarity, the clinical characteristics and prognostic significance of MCB compared with other common breast cancers (like infiltrating ductal carcinoma [IDC], and infiltrating lobular carcinoma [ILC]) are not clear, and controversial among different reports.
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Disrupting the CXCL12/CXCR4 axis disturbs the characteristics of glioblastoma stem-like cells of rat RG2 glioblastoma.
Cancer Cell Int.
PUBLISHED: 05-07-2013
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Glioblastoma stem-like cells (GSC) have been shown to promote tumor growth, tumor-associated neovascularization, therapeutic resistance, and metastasis. CXCR4 receptors have been found involved in the proliferation, metastasis, angiogenesis, and drug-resistant characteristics of glioblastoma. However, the role of CXCR4 in modulating the stem-like cell properties of rat glioblastoma remains ambiguous.
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Prevalence of Gastroesophageal Reflux Disease in Major Depressive Disorder: A Population-Based Study.
Psychosomatics
PUBLISHED: 04-27-2013
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Gastroesophageal reflux disease (GERD) is a common physical disease among psychiatric patients. We conducted this study to investigate the prevalence and risk of GERD in patients with major depressive disorder (MDD) in Taiwan.
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Runx1-deficient afferents impair visceral nociception, exacerbating dextran sodium sulfate-induced colitis.
Brain Behav. Immun.
PUBLISHED: 04-17-2013
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Colitis is a group of inflammatory and auto-immune disorders that affect the tissue lining of the gastrointestinal (GI) system. Studies of chemically-induced animal models of colitis have indicated that nociceptive afferents or neuropeptides have differing effects on GI inflammation. However, the molecular mechanisms involved in visceral pain and the role of visceral sensory afferents involved in the modulation of colitis remains unclear. A previous study demonstrated that Runx1, a Runt domain transcription factor, is restricted to nociceptors. In these neurons, Runx1 regulates the expression of numerous ion channels and receptors, controlling the lamina-specific innervation patterns of nociceptive afferents in the spinal cord. Moreover, mice that lack Runx1 exhibit specific defects in thermal and neuropathic pain. To examine the function of Runx1 in visceral nociception, we employed double-transgenic mice (WntCre: Runx1(F)(/)(F)), in which the expression of Runx1 was specifically disrupted in the sensory neurons. To determine the role of Runx1 in visceral pain sensation, the WntCre: Runx1(F)(/)(F) mice and their control littermates (Runx1(F)(/)(F)) were treated using dextran sodium sulfate (DSS) to induce colitis. The results indicated that disrupted Runx1 in the sensory afferents resulted in: (1) impairment of the visceral pain sensation in murine DSS-induced colitis; (2) exacerbating the phenotypes in murine DSS-induced colitis; (3) a differential effect on the production of pro- and anti-inflammatory cytokines in the colon tissues isolated from mice treated using DSS and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and (4) alteration of the distribution of lymphocytes and mast cells in mucosa. These results show that the function of Runx1 in sensory afferents is vital for modulating visceral pain and the neuro-immune axis.
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SEASON OF BIRTH IN OBSESSIVE-COMPULSIVE DISORDER.
Depress Anxiety
PUBLISHED: 04-10-2013
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Effects of season of birth (SOB) have been documented in numerous neuropsychiatric disorders. To date, few studies have evaluated this issue in obsessive-compulsive disorder (OCD). The aim of this study was to investigate the birth seasonality in OCD.
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Prenatal diagnosis of fetal congenital cystic adenomatoid malformation of the lung using three-dimensional ultrasound: comparison between the 20th and 21st centuries.
Taiwan J Obstet Gynecol
PUBLISHED: 04-04-2013
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Congenital cystic adenomatoid malformation of the lung (CCAML) is one of the most common lung lesions diagnosed prenatally. In order to compare the trends and improvements of prenatal diagnosis of CCAML, we herein retrospectively reviewed our cases of fetal CCAML detected by three-dimensional ultrasound (3-D US) between two centuries.
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Using Akaike information criterion and minimum mean square error mode in compensating for ultrasonographic errors for estimation of fetal weight by new operators.
Taiwan J Obstet Gynecol
PUBLISHED: 04-04-2013
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The accuracy of ultrasound (US) measurements is operator dependent. In order to decrease the operator-dependent errors in estimated fetal weight (EFW), a model selection analysis was undertaken to select significant compensation weighting factors on ultrasonographic parameters to support artificial neural network (ANN), and thus to enhance the accuracy of fetal weight estimation.
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Sann-Joong-Kuey-Jian-Tang inhibits hepatocellular carcinoma Hep-G2 cell proliferation by increasing TNF-?, Caspase-8, Caspase- 3 and Bax but by decreasing TCTP and Mcl-1 expression in vitro.
Mol Med Rep
PUBLISHED: 03-04-2013
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Hepatic cancer remains a challenging disease and there is a need to identify new treatments. Sann-Joong-Kuey-Jian-Tang (SJKJT), a traditional medicinal prescription, has been used to treat lymphadenopathy and exhibits cytotoxic activity in many types of human cancer cells. Our previous studies revealed that SJKJT is capable of inhibiting colon cancer colo 205 cells by inducing autophagy and apoptosis. However, the effects and molecular mechanisms of SJKJT in human hepatocellular carcinoma have not been clearly elucidated. In the present study we evaluated the effects of SJKJT in human hepatic cellular carcinoma Hep-G2 cells. The cytotoxicity of SJKJT in Hep-G2 cells was measured by MTT assay. The cell cycles were analyzed by fluorescence?activated cell sorting (FACS). The protein expression of translationally controlled tumor protein (TCTP), Mcl-1, Fas, TNF-?, Caspase-8, Caspase-3 and Bax in Hep-G2 cells treated with SJKJT was evaluated by western blotting. The protein expression of Caspase-3 was also detected by immunofluorescence staining. The results showed that SJKJT inhibits Hep-G2 cells in a time- and dose?dependent manner. During SJKJT treatment for 48 and 72 h, the half-maximum inhibitory concentration (IC50) was 1.48 and 0.94 mg/ml, respectively. The FACS results revealed that increased doses of SJKJT were capable of increasing the percentage of cells in the sub-G1 phase. Immunofluorescence staining showed that Hep-G2 treated with SJKJT had increased expression of Caspase-3. The western blot results showed that the protein expression of Fas, TNF-?, Caspase-8, Caspase- 3 and Bax was upregulated, but that of TCTP and Mcl-1 was downregulated in Hep-G2 cells treated with SJKJT. In conclusion, these findings indicated that SJKJT inhibits Hep-G2 cells. One of the molecular mechanisms responsible for this may be the increased Fas, TNF-?, Caspase-8, Caspase- 3 and Bax expression; another mechanism may be via decreasing TCTP and Mcl-1 expression in order to induce apoptosis.
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Sann-Joong-Kuey-Jian-Tang decreases the protein expression of Mcl?1 and TCTP and increases that of TNF-? and Bax in BxPC?3 pancreatic carcinoma cells.
Int. J. Mol. Med.
PUBLISHED: 02-19-2013
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Sann-Joong-Kuey-Jian-Tang (SJKJT), a traditional Chinese medicinal prescription, has been used for the treatment of lymphadenopathy and solid tumors, and has shown therapeutic potential in several human malignant tumor cell lines. However, the efficacy and molecular mechanisms of action of SJKJT in human pancreatic cancer have not yet been elucidated. In the present study, we evaluated the cytotoxic effects of SJKJT on BxPC-3 human pancreatic carcinoma cells by MTT assay. The protein expression levels of myeloid cell leukemia 1 protein (Mcl-1), translationally controlled tumor protein (TCTP), tumor necrosis factor-? (TNF??), caspase-8, caspase-3, Bax and Bcl-2 family in the BxPC-3 cells were measured by western blot analysis. The cell cycle was analyzed by flow cytometry. The protein expression of caspase-3 was also detected by immunocytochemistry (ICC). The results revealed that SJKJT inhibited the proliferation of BxPC-3 cells in a time- and dose-dependent manner. The protein expression levels of TNF-?, caspase-8, caspase-3 and Bax increased in the BxPC-3 cells treated with SJKJT; however, the levels of Mcl-1, TCTP and Bcl-xL decreased. The results also demonstrated that SJKJT increased the percentage of BxPC-3 cells in the sub-G1 phase. In addition, ICC staining indicated that the protein expression of caspase-3 was upregulated in the BxPC-3 cells treated with SJKJT. These findings indicate that SJKJT inhibits the proliferation of BxPC-3 cells through the extrinsic and intrinsic pathway, inducing apoptosis in vitro. Our study, using BxPC-3 human pancreatic cancer cells, demonstrates that SJKJT has potential as a chemotherapeutic agent for the treatment of pancreatic cancer. Further sutdies are warranted to fully elucidate its mechanisms of action.
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A truncated fragment of Src protein kinase generated by calpain-mediated cleavage is a mediator of neuronal death in excitotoxicity.
J. Biol. Chem.
PUBLISHED: 02-11-2013
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Excitotoxicity resulting from overstimulation of glutamate receptors is a major cause of neuronal death in cerebral ischemic stroke. The overstimulated ionotropic glutamate receptors exert their neurotoxic effects in part by overactivation of calpains, which induce neuronal death by catalyzing limited proteolysis of specific cellular proteins. Here, we report that in cultured cortical neurons and in vivo in a rat model of focal ischemic stroke, the tyrosine kinase Src is cleaved by calpains at a site in the N-terminal unique domain. This generates a truncated Src fragment of ~52 kDa, which we localized predominantly to the cytosol. A cell membrane-permeable fusion peptide derived from the unique domain of Src prevents calpain from cleaving Src in neurons and protects against excitotoxic neuronal death. To explore the role of the truncated Src fragment in neuronal death, we expressed a recombinant truncated Src fragment in cultured neurons and examined how it affects neuronal survival. Expression of this fragment, which lacks the myristoylation motif and unique domain, was sufficient to induce neuronal death. Furthermore, inactivation of the prosurvival kinase Akt is a key step in its neurotoxic signaling pathway. Because Src maintains neuronal survival, our results implicate calpain cleavage as a molecular switch converting Src from a promoter of cell survival to a mediator of neuronal death in excitotoxicity. Besides unveiling a new pathological action of Src, our discovery of the neurotoxic action of the truncated Src fragment suggests new therapeutic strategies with the potential to minimize brain damage in ischemic stroke.
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Prenatal diagnosis of fetal gastroschisis using three-dimensional ultrasound: comparison between the 20th and 21st centuries.
Taiwan J Obstet Gynecol
PUBLISHED: 01-31-2013
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In order to compare the trends and improvements of prenatal diagnosis of gastroschisis, we herein retrospectively reviewed our cases of fetal gastroschisis detected by three-dimensional ultrasound (3D US) between the two centuries.
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Birth seasonality in schizophrenia: effects of gender and income status.
Psychiatry Clin. Neurosci.
PUBLISHED: 01-25-2013
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The aim of this study was to examine the correlations of birth seasonality in schizophrenia, considering influences of gender and income status.
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Cluster of differentiation 24 expression is an independent prognostic factor of adverse outcome in cervical carcinoma.
Int. J. Gynecol. Cancer
PUBLISHED: 01-16-2013
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Cluster of differentiation (CD) 24 is a cell adhesion molecule that has been implicated in tumor invasion and metastasis of various solid tumors. The aim of this study was to explore the expression patterns of CD24 as a predictive marker for long-term survival in cervical carcinomas.
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Tanshinone IIA inhibits the growth of pancreatic cancer BxPC?3 cells by decreasing protein expression of TCTP, MCL?1 and Bcl?xL.
Mol Med Rep
PUBLISHED: 01-15-2013
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Pancreatic cancer remains a challenging disease worldwide. Tanshinone IIA (Tan?IIA) is one of the active constituents of Danshen (Radix Salviae miltiorrhizae). Tan?IIA has been hypothesized to inhibit numerous human cancer cells by various molecular mechanisms. However, the efficacy and molecular mechanism of Tan?IIA action in pancreatic cancer has not been well studied. In the present study, the cytotoxicity of Tan?IIA in human pancreatic cancer BxPC?3 cells was evaluated by MTT assay. Cell cycle analysis of BxPC?3 cells treated with Tan?IIA was performed by flow cytometry (FACS). Protein expression levels of TCTP, Mcl?1, Bcl?xL, Bax and Caspase?3 in BxPC?3 cells were measured by western blot analysis. The results revealed that Tan?IIA inhibited BxPC?3 cells in a time? and dose?dependent manner. FACS analysis demonstrated that Tan?IIA increases the rate of sub?G1 phase. BxPC?3 cells treated with Tan?IIA were identified to upregulate protein expression of Bax and Caspase?3 and downregulate expression of TCTP, Mcl?1 and Bcl?xL. These results indicate that Tan?IIA may inhibit BxPC?3 human pancreatic cancer cells through the induction of apoptosis by decreasing protein expression of TCTP, Mcl?1 and Bcl?xL and increasing Bax expression in vitro. The chemotherapeutic potential of Tan?IIA for human pancreatic cancer warrants further study.
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A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates.
Arch. Virol.
PUBLISHED: 01-10-2013
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We have previously demonstrated that vaccination with a subunit dengue vaccine containing a consensus envelope domain III with aluminum phosphate elicits neutralizing antibodies against all four serotypes of dengue virus in mice. In this study, we evaluated the immunogenicity of the subunit dengue vaccine in non-human primates. After vaccination, monkeys that received the subunit vaccine with aluminum phosphate developed a significantly strong and long-lasting antibody response. A specific T cell response with cytokine production was also induced, and this correlated with the antibody response. Additionally, neutralizing antibodies against serotype 2 were detected in two of three monkeys. The increase in serotype-2-specific antibody titers and avidity observed in these two monkeys suggested that a serotype-2-biased antibody response occurs. These data provide evidence that a protective neutralizing antibody response was successfully elicited in non-human primates by the dengue subunit vaccine with aluminum phosphate adjuvant.
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Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans.
Nat Commun
PUBLISHED: 01-10-2013
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Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. Here by integrating transcriptional analysis and functional genomics, we identified Candida-specific host defence mechanisms in humans. Candida induced significant expression of genes from the type I interferon pathway in human peripheral blood mononuclear cells. This unexpectedly prominent role of type I interferon pathway in anti-Candida host defence was supported by additional evidence. Polymorphisms in type I interferon genes modulated Candida-induced cytokine production and were correlated with susceptibility to systemic candidiasis. In in vitro experiments, type I interferons skewed Candida-induced inflammation from a Th17 response towards a Th1 response. Patients with chronic mucocutaneous candidiasis displayed defective expression of genes in the type I interferon pathway. These findings indicate that the type I interferon pathway is a main signature of Candida-induced inflammation and has a crucial role in anti-Candida host defence in humans.
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Phyto-power dietary supplement potently inhibits dimethylnitrosamine-induced liver fibrosis in rats.
Food Funct
PUBLISHED: 01-08-2013
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Curcumin has been extensively studied for its therapeutic effects in a variety of disorders. Fermented soy consumption is associated with a low incidence rate of chronic diseases in many Asian countries. The aim of this study was to investigate the potential underlying mechanisms of the effect of a phyto-power dietary supplement on liver fibrosis. Sprague-Dawley rats were intraperitoneally injected with dimethylnitrosamine (DMN; 10 mg kg(-1)) three times a week for four consecutive weeks. A phyto-power dietary supplement (50 or 100 mg kg(-1)) was administered by oral gavage daily for four weeks. Liver morphology, function, and fibrotic status were examined in DMN induced hepatic fibrogenesis. However, a phyto-power dietary supplement alleviated liver damage as indicated by histopathological examination of the ?-smooth muscle actin (?-SMA) and collagen I, accompanied by the concomitant reduction of transforming growth factor-?1 (TGF-?1) and matrix metalloproteinase 2 (MMP2). These data indicate that the phyto-power dietary supplement may inhibit the TGF-?1/Smad signaling and relieve liver damage in experimental fibrosis.
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Guided differentiation of induced pluripotent stem cells into neuronal lineage in alginate-chitosan-gelatin hydrogels with surface neuron growth factor.
Colloids Surf B Biointerfaces
PUBLISHED: 01-01-2013
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The understanding of differentiating induced pluripotent stem (iPS) cells in porous biomaterials is a critical challenge in recent biotechnological development. This study presents the investigation on the differentiation of iPS cells toward neurons in biomedical scaffolds containing alginate, chitosan, and gelatin with grafted neuron growth factor (NGF). Alginate-chitosan-gelatin scaffolds were prepared by particulate leaching method using polystyrene (PS) microspheres as porogen. In addition, the neuronal differentiation of iPS cells in the constructs was identified by immunochemical staining. The morphological studies demonstrated that an increase in the concentration of PS microspheres from 0.5 to 0.75 g/mL improved the pore regularity in alginate-chitosan-gelatin hydrogels. The effect of composition on the differentiation of iPS cells into neuronal lineage was in the order where alginate:chitosan:gelatin=1:1:3>2:1:2>1:1:1. Moreover, an increase in the concentration of NGF promoted the neuronal production from iPS cells in cultivated constructs. Alginate-chitosan-gelatin scaffolds with surface NGF can guide the differentiation of iPS cells for regenerating neurons.
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Propagule pressure and colony social organization are associated with the successful invasion and rapid range expansion of fire ants in China.
Mol. Ecol.
PUBLISHED: 12-19-2011
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We characterized patterns of genetic variation in populations of the fire ant Solenopsis invicta in China using mitochondrial DNA sequences and nuclear microsatellite loci to test predictions as to how propagule pressure and subsequent dispersal following establishment jointly shape the invasion success of this ant in this recently invaded area. Fire ants in Wuchuan (Guangdong Province) are genetically differentiated from those found in other large infested areas of China. The immediate source of ants in Wuchuan appears to be somewhere near Texas, which ranks first among the southern USA infested states in the exportation of goods to China. Most colonies from spatially distant, outlying areas in China are genetically similar to one another and appear to share a common source (Wuchuan, Guangdong Province), suggesting that long-distance jump dispersal has been a prevalent means of recent spread of fire ants in China. Furthermore, most colonies at outlier sites are of the polygyne social form (featuring multiple egg-laying queens per nest), reinforcing the important role of this social form in the successful invasion of new areas and subsequent range expansion following invasion. Several analyses consistently revealed characteristic signatures of genetic bottlenecks for S. invicta populations in China. The results of this study highlight the invasive potential of this pest ant, suggest that the magnitude of international trade may serve as a predictor of propagule pressure and indicate that rates and patterns of subsequent range expansion are partly determined by the interplay between species traits and the trade and transportation networks.
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Pivotal role of ADP-ribosylation factor 6 in Toll-like receptor 9-mediated immune signaling.
J. Biol. Chem.
PUBLISHED: 12-14-2011
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CpG oligodeoxynucleotide (CpG ODN) cellular uptake into endosomes, the rate-limiting step of Toll-like receptor 9 (TLR9) signaling, is critical in eliciting innate immune responses. ADP-ribosylation factor 6 (ARF6) is a member of the Ras superfamily, which is critical to a wide variety of cellular events including endocytosis. Here, we found that inhibition of ARF6 by dominant mutants and siRNA impaired CpG ODN-mediated responses, whereas cells expressing the constitutively active ARF6 mutant enhanced CpG ODN-induced cytokine production. Inhibition of ARF6 impaired TLR9 trafficking into endolysosomes, thereby inhibiting proceed functional cleavage of TLR9. Additional studies showed that CpG ODN uptake was increased in ARF6-activated cells but impaired in ARF6-defective cells. Furthermore, cells pretreated with CpG ODN but not GpC ODN had increased CpG ODN uptake due to CpG ODN-induced ARF6 activity. Further studies with ARF6-defective and ARF6-activated cells demonstrated that class III phosphatidylinositol 3-kinases (PI3K) was required for downstream ARF6 regulation of CpG ODN uptake. Together, our findings demonstrate that a novel class III PI3K-ARF6 axis pathway mediates TLR9 signaling by regulating the cellular uptake of CpG ODN.
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Basaloid follicular hamartoma: a case report and review of the literature.
Kaohsiung J. Med. Sci.
PUBLISHED: 12-11-2011
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Basaloid follicular hamartoma (BFH) is a rare, benign, skin adnexal tumor. Several clinical patterns have been reported, but they all share the same histopathological features. BFH may be hereditary or nonhereditary and can be accompanied by systemic diseases. Microscopic examination of BFH shows branching cords and anastomosing strands of basaloid cells in a loose, fibrous stroma. The most important pathological differential diagnosis is infundibulocystic basal cell carcinoma. These two lesions must be differentiated carefully based on clinical presentation and histopathological picture, and even molecular studies may be needed. We present a report of a 78-year-old woman with a solitary, asymptomatic, slow-growing skin tumor on her left scalp. No associated systemic disorders were found. On the basis of an excisional biopsy performed on the tumor, a pathological diagnosis of sporadic BFH was made.
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Modeling exotic highly pathogenic avian influenza virus entrance risk through air passenger violations.
Risk Anal.
PUBLISHED: 12-09-2011
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The highly pathogenic avian influenza virus (HPAIV) is able to survive in poultry products and could be carried into a country by air travelers. An assessment model was constructed to estimate the probability of the exotic viable HPAIV entering Taiwan from two neighboring areas through poultry products carried illegally by air passengers at Taiwans main airports. The entrance risk was evaluated based on HPAIV-related factors (the prevalence and the incubation period of HPAIV; the manufacturing process of poultry products; and the distribution-storage-transportation factor event) and the passenger event. Distribution functions were adopted to simulate the probabilities of each HPAIV factor. The odds of passengers being intercepted with illegal poultry products were estimated by logistic regression. The Monte Carlo simulation established that the risk caused by HPAIV-related factors from area A was lower than area B, whereas the entrance risk by the passenger event from area A was similar to area B. Sensitivity analysis showed that the incubation period of HPAIV and the interception of passenger violations were major determinants. Although the result showed viable HPAIV was unlikely to enter Taiwan through meat illegally carried by air passengers, this low probability could be caused by incomplete animal disease data and modeling uncertainties. Considering the negative socioeconomic impacts of HPAIV outbreaks, strengthening airport quarantine measures is still necessary. This assessment provides a profile of HPAIV entrance risk through air travelers arriving from endemic areas and a feasible direction for quarantine and public health measures.
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The correlation between TWIST, E-cadherin, and beta-catenin in human bladder cancer.
J BUON
PUBLISHED: 11-24-2011
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Epithelial-to-mesenchymal transition (EMT)- related factors are known to contribute to the invasion and migration of multiple cancers. However, the expression levels of and the relationship between TWIST, E-cadherin, and beta-catenin in bladder cancer are not yet known. Therefore, this study investigated the relationship between TWIST, E-cadherin, and beta-catenin in tissue specimens and cell lines of bladder cancer.
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P16INK4A overexpression predicts lymph node metastasis in cervical carcinomas.
J. Clin. Pathol.
PUBLISHED: 10-19-2011
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The p16(INK4A) protein (p16) is a cyclin-dependent kinase inhibitor that arrests the cell cycle in the G1 phase.
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Resveratrol modulates MED28 (Magicin/EG-1) expression and inhibits epidermal growth factor (EGF)-induced migration in MDA-MB-231 human breast cancer cells.
J. Agric. Food Chem.
PUBLISHED: 10-17-2011
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Resveratrol and pterostilbene exhibit diverse biological activities. MED28, a subunit of the mammalian Mediator complex for transcription, was also identified as magicin, an actin cytoskeleton Grb2-associated protein, and as endothelial-derived gene (EG-1). Several tumors exhibit aberrant MED28 expression, whereas the underlying mechanism is unclear. Triple-negative breast cancers, often expressing epidermal growth factor (EGF) receptor (EGFR), are associated with metastasis and poor survival. The objective of this study is to compare the effect of resveratrol and pterostilbene and to investigate the role of MED28 in EGFR-overexpressing MDA-MB-231 breast cancer cells. Pretreatment of resveratrol, but not pterostlbene, suppressed EGF-mediated migration and expression of MED28 and matrix metalloproteinase (MMP)-9 in MDA-MB-231 cells. Moreover, overexpression of MED28 increased migration, and the addition of EGF further enhanced migration. Our data indicate that resveratrol modulates the effect of MED28 on cellular migration, presumably through the EGFR/phosphatidylinositol 3-kinase (PI3K) signaling pathway, in breast cancer cells.
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Tanshinone IIA potentiates the efficacy of 5-FU in Colo205 colon cancer cells in vivo through downregulation of P-gp and LC3-II.
Exp Ther Med
PUBLISHED: 09-18-2011
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Traditional Chinese herbal medicines are widely accepted as an option for the treatment of colorectal cancers. Danshen (Salviae miltiorrhizae Radix) is widely prescribed in traditional Chinese medicine for cardiovascular diseases. Tanshinone IIA (Tan-IIA) is extracted from Danshen. Our previous studies have shown that Tan-IIA induces apoptosis in Colo205 human colon cancer cells in vitro and in vivo. In the present study, we investigated the efficacy of Tan-IIA and 5-fluorouracil (5-FU) in a Colo205 cell xenograft model. For in vivo studies, SCID mice were engrafted with Colo205 cells and from day 10 onwards were randomly divided into 3 groups and treated with 5-FU plus Tan-IIA, 5-FU plus corn oil, and the vehicle alone. At the end of a 4-week dosing schedule, the SCID mice were sacrificed and xenograft tumors were dissected for protein western blot analysis. Our results showed that the Colo205 xenograft model co-treated with Tan-IIA plus 5-FU caused a reduction in the xenograft tumor volumes and decreased P-glycoprotein (P-gp) and microtubule-associated protein light chain 3 (LC3)-II expression compared to 5-FU alone. Based on these observations, it may be possible to develop Tan-IIA plus 5-FU as therapeutic agents for human colon cancer.
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Proteomic analysis of gemcitabine-induced drug resistance in pancreatic cancer cells.
Mol Biosyst
PUBLISHED: 09-06-2011
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Currently, the most effective agent against pancreatic cancer is gemcitabine (GEM), which inhibits tumor growth by interfering with DNA replication and blocking DNA synthesis. However, GEM-induced drug resistance in pancreatic cancer compromises the therapeutic efficacy of GEM. To investigate the molecular mechanisms associated with GEM-induced resistance, 2D-DIGE and MALDI-TOF mass spectrometry were performed to compare the proteomic alterations of a panel of differential GEM-resistant PANC-1 cells with GEM-sensitive pancreatic cells. The proteomic results demonstrated that 33 proteins were differentially expressed between GEM-sensitive and GEM-resistant pancreatic cells. Of these, 22 proteins were shown to be resistance-specific and dose-dependent in the regulation of GEM. Proteomic analysis also revealed that proteins involved in biosynthesis and detoxification are significantly over-expressed in GEM-resistant PANC-1 cells. In contrast, proteins involved in vascular transport, bimolecular decomposition, and calcium-dependent signal regulation are significantly over-expressed in GEM-sensitive PANC-1 cells. Notably, both protein-protein interaction of the identified proteins with bioinformatic analysis and immunoblotting results showed that the GEM-induced pancreatic cell resistance might interplay with tumor suppressor protein p53. Our approach has been shown here to be useful for confidently detecting pancreatic proteins with differential resistance to GEM. Such proteins may be functionally involved in the mechanism of chemotherapy-induced resistance.
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Association of the ADRA1A gene and the severity of metabolic abnormalities in patients with schizophrenia.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 08-08-2011
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Patients with schizophrenia have a higher risk of developing metabolic abnormalities and their associated diseases. Some studies found that the accumulative number of metabolic syndrome components was associated with the severity of metabolic abnormalities. The purpose of this study was to examine the roles of the ADRA1A, ADRA2A, ADRB3, and 5HT2A genes in the risk of having more severe metabolic abnormalities among patients with schizophrenia. We studied a sample of 232 chronic inpatients with schizophrenia (120 males and 112 females) to explore the associations between the four candidate genes and the severity of metabolic syndrome by accumulative number of the components. Four single nucleotide polymorphisms in the candidate genes were genotyped, including the Arg347Cys in ADRA1A, the C1291G in ADRA2A, the Try64Arg in ADRB3, and the T102C in 5HT2A. An association between the accumulative number of metabolic syndrome components and the ADRA1A gene was found after adjusting age, sex, and other related variables (p-value=0.036). Presence of the Arg347 allele in the ADRA1A gene is a risk factor for having more severe metabolic abnormalities. These findings suggest a medical attention of closely monitoring metabolic risks for schizophrenia patients with high-risk genotypes.
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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.