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Showing papers by "Academia Sinica published in 2006"


Journal ArticleDOI
TL;DR: In this paper, the authors report on the relationship between hepatitis B viremia and progression to cirrhosis in chronic hepatitis B infection and show that progression to liver failure in hepatitis B-infected persons is correlated with the level of circulating virus.

1,366 citations


Journal ArticleDOI
TL;DR: Evidence is provided that miRNA controls Pi homeostasis by regulating the expression of a component of the proteolysis machinery in plants by suppressing the E2 transcript in transgenic Arabidopsis overexpressing miR399.
Abstract: In this study, we reveal a mechanism by which plants regulate inorganic phosphate (Pi) homeostasis to adapt to environmental changes in Pi availability. This mechanism involves the suppression of a ubiquitin-conjugating E2 enzyme by a specific microRNA, miR399. Upon Pi starvation, the miR399 is upregulated and its target gene, a ubiquitin-conjugating E2 enzyme, is downregulated in Arabidopsis thaliana. Accumulation of the E2 transcript is suppressed in transgenic Arabidopsis overexpressing miR399. Transgenic plants accumulated five to six times the normal Pi level in shoots and displayed Pi toxicity symptoms that were phenocopied by a loss-of-function E2 mutant. Pi toxicity was caused by increased Pi uptake and by translocation of Pi from roots to shoots and retention of Pi in the shoots. Moreover, unlike wild-type plants, in which Pi in old leaves was readily retranslocated to other developing young tissues, remobilization of Pi in miR399-overexpressing plants was impaired. These results provide evidence that miRNA controls Pi homeostasis by regulating the expression of a component of the proteolysis machinery in plants.

786 citations


Journal ArticleDOI
TL;DR: The data suggest that HLA-B*1502 could contribute to the pathogenesis ofCBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.
Abstract: The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associat

612 citations


Journal ArticleDOI
TL;DR: It is revealed that a previously identified Pi overaccumulator, pho2, is caused by a single nucleotide mutation resulting in early termination within the UBC24 gene, which provides important insight into the interaction between miR399 and U BC24 mRNA, but also supports their systemic function in Pi translocation and remobilization.
Abstract: We recently demonstrated that microRNA399 (miR399) controls inorganic phosphate (Pi) homeostasis by regulating the expression of UBC24 encoding a ubiquitin-conjugating E2 enzyme in Arabidopsis (Arabidopsis thaliana). Transgenic plants overexpressing miR399 accumulated excessive Pi in the shoots and displayed Pi toxic symptoms. In this study, we revealed that a previously identified Pi overaccumulator, pho2, is caused by a single nucleotide mutation resulting in early termination within the UBC24 gene. The level of full-length UBC24 mRNA was reduced and no UBC24 protein was detected in the pho2 mutant, whereas up-regulation of miR399 by Pi deficiency was not affected. Several characteristics of Pi toxicity in the pho2 mutant were similar to those in the miR399-overexpressing and UBC24 T-DNA knockout plants: both Pi uptake and translocation of Pi from roots to shoots increased and Pi remobilization within leaves was impaired. These phenotypes of the pho2 mutation could be rescued by introduction of a wild-type copy of UBC24. Kinetic analyses revealed that greater Pi uptake in the pho2 and miR399-overexpressing plants is due to increased Vmax. The transcript level of most PHT1 Pi transporter genes was not significantly altered, except PHT1;8 whose expression was enhanced in Pi-sufficient roots of pho2 and miR399-overexpressing compared with wild-type plants. In addition, changes in the expression of several organelle-specific Pi transporters were noticed, which may be associated with the redistribution of intracellular Pi under excess Pi. Furthermore, miR399 and UBC24 were colocalized in the vascular cylinder. This observation not only provides important insight into the interaction between miR399 and UBC24 mRNA, but also supports their systemic function in Pi translocation and remobilization.

559 citations


Journal ArticleDOI
TL;DR: To validate the results of the prioritization, 1569 SNPs from the SNP500Cancer database are analyzed and it is shown that SNPs with a high predicted risk exhibit low allele frequencies for the minor alleles, consistent with a well-known finding that a strong selective pressure exists for functional polymorphisms.
Abstract: Single nucleotide polymorphism (SNP) prioritization based on the phenotypic risk is essential for association studies. Assessment of the risk requires access to a variety of heterogeneous biological databases and analytical tools. FASTSNP (function analysis and selection tool for single nucleotide polymorphisms) is a web server that allows users to efficiently identify and prioritize high-risk SNPs according to their phenotypic risks and putative functional effects. A unique feature of FASTSNP is that the functional effect information used for SNP prioritization is always up-to-date, because FASTSNP extracts the information from 11 external web servers at query time using a team of web wrapper agents. Moreover, FASTSNP is extendable by simply deploying more Web wrapper agents. To validate the results of our prioritization, we analyzed 1569 SNPs from the SNP500Cancer database. The results show that SNPs with a high predicted risk exhibit low allele frequencies for the minor alleles, consistent with a well-known finding that a strong selective pressure exists for functional polymorphisms. We have been using FASTSNP for 2 years and FASTSNP enables us to discover a novel promoter polymorphism. FASTSNP is available at http://fastsnp.ibms.sinica.edu.tw.

526 citations


Journal ArticleDOI
TL;DR: In this article, Liu et al. investigated SERS on ordered Ag nanoparticle arrays with an interparticle gap above 75 nm and showed that significant near-field interaction occurs when the gap between the nanorods reaches half the value of their diameter.
Abstract: Raman spectroscopy, which is based on the inelastic scattering of photons by chemical entities, has been successfully utilized for the investigation of adsorbed molecules on surfaces, although the low cross section limits its applications. Surface-enhanced Raman scattering (SERS) has drawn a lot of attention since its discovery in 1974, primarily because it can greatly enhance the normally weak Raman signal and thereby facilitate the convenient identification of the vibrational signatures of molecules in chemical and biological systems. Recently, the observation of single-molecule Raman scattering has further enhanced the Raman detection sensitivity limit and widened the scope of SERS for sensor applications. Although SERS effects can be achieved simply by exploiting the electromagnetic resonance properties of roughened surfaces or nanoparticles of Au or Ag, the fabrication of reliable SERS substrates with uniformly high enhancement factors remains the focus of much research. Spraying Au or Ag colloids on a substrate leads to an extremely high SERS signal at some local ‘hot-junctions’; however, it is not easy to achieve a reliable, stable, and uniform SERS signal spanning a wide dynamical range using this method. Van Duyne and coworkers have used nanosphere lithography, while Liu and Lee exploited soft lithography, in order to fabricate Ag nanoparticle arrays with high SERS activity and improved uniformity. Kall and co-workers have shown theoretically that the effective Raman cross section of a molecule placed between two metal nanoparticles can be enhanced by more than 12 orders of magnitude. Such enhancement is likely to be related to the ‘hot-junctions’ observed in some SERS experiments. Several theoretical groups have also investigated field enhancement for SERS from metal nanoparticle arrays. Specifically, Garcia–Vidal and Pendry proposed that very localized plasmon modes, created by strong electromagnetic coupling between two adjacent metallic objects, dominate the SERS response in an array of nanostructures. The interparticle-coupling-induced enhancement was attributed to the broadening of the plasmon resonance peak because the probability of the resonance covering both the excitation wavelength and the Raman peak increases with its width. They calculated the average enhancement factor over the surfaces of an array of infinitely long Ag nanorods with semicircular cross sections, and showed that significant near-field interaction occurs between adjacent nanorods when the gap between the nanorods reaches half the value of their diameter. Other groups have studied the dependence of the enhancement factor on the gap between adjacent nanoparticles on a SERS active substrate. For example, Gunnarsson et al. investigated SERS on ordered Ag nanoparticle arrays with an interparticle gap above 75 nm. Lee and co-workers were able to achieve the temperature-controlled variation of interparticle gaps between Ag nanoparticles embedded in a polymer membrane. Wei et al. performed SERS on self-organized Au nanoparticle arrays with narrow interparticle gaps, although they have not carried out a detailed investigation of the dependence of the SERS signal on the interparticle gap. Sauer et al. investigated SERS from nanowire arrays embedded in an alumina matrix with interparticle gaps of ∼ 110 nm, but no gap-related enhancement was observed in their experiment. These theoretical and experimental studies indicate that the precise control of gaps between nanostructures on a SERS-active substrate in the sub-10 nm regime, which is extremely difficult to obtain by existing nanofabrication methods, is likely to be critical for the fabrication of substrates with uniformly high enhancement factors, and for understanding collective surface plasmons existing inside the gaps. C O M M U N IC A IO N S

473 citations


Journal ArticleDOI
TL;DR: The early views of the Moon manifested in mythology and art throughout the world were primarily tied to lunar and terrestrial cycles and the relationships between the Sun and the Moon as mentioned in this paper, and many of these early views were associated with the violent or catastrophic events in which the Moon was expunged from the Earth.
Abstract: As with all science, our continually developing concepts of lunar evolution are firmly tied to both new types of observations and the integration of these observations to the known pool of data. This process invigorates the intellectual foundation on which old models are tested and new concepts are built. Just as the application of new observational tools to lunar science in 1610 (Galileo’s telescope) and 1840 (photography) yielded breakthroughs concerning the true nature of the lunar surface, the computational and technological advances highlighted by the Apollo and post-Apollo missions and associated scientific investigations provided a new view of the thermal and magmatic evolution of the Moon. ### 1.1. Pre-Apollo view of the thermal and magmatic evolution of the Moon Many of the early views of the Moon manifested in mythology and art throughout the world were primarily tied to lunar and terrestrial cycles and the relationships between the Sun and the Moon. Prophetically, myths involving the lunar deities Mwuetsi from Zimbabwe and Coyolxauhqui from Mexico told of rather violent or catastrophic events in which the Moon was expunged from the Earth. Numerous ancient scientific observations were made about the nature of the Moon ranging from those uncovered in early Neolithic sites that correctly identified mare Crisium and mare Humorum to the insights made by Greek philosophers such as Anaxagoras (ca. 500-428 B.C.) and Democritus (ca. 460-370 B.C.), who attached terrestrial analogues to its character (stone, mountains). With the advent of the telescope (1610) and photography (1840) as scientific tools for lunar exploration, semiquantitative data could be collected that would provide an intellectual foundation for scientific interpretation. Initially, modern terrestrial geological analogs were extended to the Moon (lunar highlands, volcanic craters, seas). Combined with the rigors of computational modeling, these observational data were extended to predict the original thermal state of the Moon and its thermal and magmatic history. Its proximity to the Earth …

437 citations


Journal ArticleDOI
TL;DR: It is demonstrated that arsenic trioxide-induced sumoylation of PML correlates with a change of endogenous Daxx partitioning from GR-regulated gene promoter to PODs and a relief of DAXx repression on GR target gene expression, which provides mechanistic insights into DaxX in SUMO-dependent transcriptional control and subnuclear compartmentalization.

421 citations


Journal ArticleDOI
TL;DR: In this article, the enhancement of the thermal conductivity of water in the presence of copper (Cu) using the chemical reduction method is presented, which is the first time that chemical reduction for synthesis of nanofluids containing Cu nanoparticles in water is reported.

391 citations


Journal ArticleDOI
TL;DR: In this article, a strategy for the synthesis of multifunctional mesoporous silica nanoparticles is presented, which simultaneously possess magnetic, luminescent, and porous properties.
Abstract: We demonstrate a strategy for the synthesis of multifunctional mesoporous silica nanoparticles. These uniform tumblerlike nanocomposites, which simultaneously possess magnetic, luminescent, and porous properties, have great potential in biomedical applications.

333 citations



Journal ArticleDOI
26 Jul 2006-Polymer
TL;DR: In this paper, multi-wall carbon nanotubes (CNT) were coated with protonated polyaniline (PANI) in situ during the polymerization of aniline.

Journal ArticleDOI
TL;DR: It is demonstrated that these conflicting angiosperm phylogenies are most probably linked to the transitional sites at all codon positions, especially at the third one where the strong base-composition bias and saturation effect take place.
Abstract: Whether the Amborella/Amborella-Nymphaeales or the grass lineage diverged first within the angiosperms has recently been debated. Central to this issue has been focused on the artifacts that might result from sampling only grasses within the monocots. We therefore sequenced the entire chloroplast genome (cpDNA) of Phalaenopsis aphrodite, Taiwan moth orchid. The cpDNA is a circular molecule of 148,964 bp with a comparatively short single-copy region (11,543 bp) due to the unusual loss and truncation/scattered deletion of certain ndh subunits. An open reading frame, orf91, located in the complementary strand of the rrn23 was reported for the first time. A comparison of nucleotide substitutions between P. aphrodite and the grasses indicates that only the plastid expression genes have a strong positive correlation between nonsynonymous (K a ) and synonymous (f s ) substitutions per site, providing evidence for a generation time effect, mainly across these genes. Among the intron-containing protein-coding genes of the sampled monocots, the K s of the genes are significantly correlated to transitional substitutions of their introns. We compiled a concatenated 61 protein-coding gene alignment for the available 20 cpDNAs of vascular plants and analyzed the data set using Bayesian inference, maximum parsimony, and neighbor-joining (NJ) methods. The analyses yielded robust support for the Amborella/Amborella-Nymphaeales-basal hypothesis and for the orchid and grasses together being a monophyletic group nested within the remaining angiosperms. However, the NJ analysis using K a , the first two codon positions, or amino acid sequences, respectively, supports the monocots-basal hypothesis. We demonstrated that these conflicting angiosperm phylogenies are most probably linked to the transitional sites at all codon positions, especially at the third one where the strong base-composition bias and saturation effect take place.

Journal ArticleDOI
TL;DR: This study showed a long-term beneficial effect on CVD mortality and medical expenditure associated with a switch from regular salt to potassium-enriched salt in a group of elderly veterans.

Journal ArticleDOI
10 Mar 2006-Science
TL;DR: The highly sensitive H atom Rydberg tagging time-of-flight method is used to conduct a crossed molecular beam scattering study of the F + H2 → HF + H reaction with full quantum-state resolution, finding pronounced forward-scattered HF products in the v′ = 2 vibrational state.
Abstract: Reaction resonances, or transiently stabilized transition-state structures, have proven highly challenging to capture experimentally. Here, we used the highly sensitive H atom Rydberg tagging time-of-flight method to conduct a crossed molecular beam scattering study of the F + H2 --> HF + H reaction with full quantum-state resolution. Pronounced forward-scattered HF products in the v' = 2 vibrational state were clearly observed at a collision energy of 0.52 kcal/mol; this was attributed to both the ground and the first excited Feshbach resonances trapped in the peculiar HF(v' = 3)-H' vibrationally adiabatic potential, with substantial enhancement by constructive interference between the two resonances.

Journal ArticleDOI
TL;DR: The use of a microreactor approach to the fabrication of a self-organized photosensitive gold nanoparticle chain encapsulated in a dielectric nanowire shows the potential of using gold nanopeapodded silica nanowires as wavelength-controlled optical nanoswitches.
Abstract: Noble-metal nanoparticles embedded in dielectric matrices are considered to have practical applications in ultrafast all-optical switching devices owing to their enhanced third-order nonlinear susceptibility, especially near the surface-plasmon-resonance (SPR) frequency. Here we present the use of a microreactor approach to the fabrication of a self-organized photosensitive gold nanoparticle chain encapsulated in a dielectric nanowire. Such a hybrid nanowire shows pronounced SPR absorption. More remarkably, a strong wavelength-dependent and reversible photoresponse has been demonstrated in a two-terminal device using an ensemble of gold nanopeapodded silica nanowires under light illumination, whereas no photoresponse was observed for the plain silica nanowires. These results show the potential of using gold nanopeapodded silica nanowires as wavelength-controlled optical nanoswitches. The microreactor approach can be applied to the preparation of a range of hybrid metal-dielectric one-dimensional nanostructures that can be used as functional building blocks for nanoscale waveguiding devices, sensors and optoelectronics.

Journal ArticleDOI
TL;DR: This study provides information on the domain structure partition of SARS-CoV N protein and insights into the differing roles of structured and disordered regions in coronavirus nucleocapsid proteins.
Abstract: The SARS-CoV nucleocapsid (N) protein is a major antigen in severe acute respiratory syndrome. It binds to the viral RNA genome and forms the ribonucleoprotein core. The SARS-CoV N protein has also been suggested to be involved in other important functions in the viral life cycle. Here we show that the N protein consists of two non-interacting structural domains, the N-terminal RNA-binding domain (RBD) (residues 45-181) and the C-terminal dimerization domain (residues 248-365) (DD), surrounded by flexible linkers. The C-terminal domain exists exclusively as a dimer in solution. The flexible linkers are intrinsically disordered and represent potential interaction sites with other protein and protein-RNA partners. Bioinformatics reveal that other coronavirus N proteins could share the same modular organization. This study provides information on the domain structure partition of SARS-CoV N protein and insights into the differing roles of structured and disordered regions in coronavirus nucleocapsid proteins.

Journal ArticleDOI
TL;DR: It is suggested that JEV NS5 is an IFN antagonist and that it may play a role in blocking IFN-stimulated Jak-Stat signaling via activation of PTPs during JEV infection.
Abstract: Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes severe human disease, has been shown to block the interferon (IFN)-induced Janus kinase signal transducer and activation of transcription (Jak-Stat) signaling cascade by preventing Tyk2 tyrosine phosphorylation and Stat activation. In this study, we demonstrate that expression of the JEV nonstructural protein NS5 readily blocked IFN-stimulated Jak-Stat signaling events such as Stat1 nuclear translocation and tyrosine phosphorylation of Tyk2 and Stat1. The region of JEV NS5 responsible for Stat1 suppression was identified using various deletion clones. Deletion of 83 N-terminal residues of JEV NS5, but not the 143 C-terminal residues, abolished its ability to block IFN-stimulated Stat1 activation. The role of JEV NS5 as an IFN antagonist was further demonstrated by its ability to block the induction of interferon-stimulated genes and the antiviral effect of IFN-α against the IFN-sensitive encephalomyocarditis virus, which appears to replicate and kill cells that express NS5 even with alpha IFN treatment. Furthermore, the molecular mechanism responsible for IFN antagonism by NS5 probably involves protein tyrosine phosphatases (PTPs), as the IFN-blocking events in both JEV-infected and NS5-expressing cells were reversed by sodium orthovanadate, a broad-spectrum inhibitor of PTPs. We suggest that JEV NS5 is an IFN antagonist and that it may play a role in blocking IFN-stimulated Jak-Stat signaling via activation of PTPs during JEV infection.

Journal ArticleDOI
S. S. Adler1, S. Afanasiev2, Christine Angela Aidala1, N. N. Ajitanand3  +341 moreInstitutions (43)
TL;DR: The PHENIX experiment as mentioned in this paper measured midrapidity of electrons as a function of centrality in Au+Au collisions at [FORMULA: SEE TEXT] and removed contributions from photon conversions and from light hadron decays, mainly Dalitz decays of pi0 and eta mesons.
Abstract: The PHENIX experiment has measured midrapidity ([FORMULA: SEE TEXT]) transverse momentum spectra ([FORMULA: SEE TEXT]) of electrons as a function of centrality in Au+Au collisions at [FORMULA: SEE TEXT]. Contributions from photon conversions and from light hadron decays, mainly Dalitz decays of pi0 and eta mesons, were removed. The resulting nonphotonic electron spectra are primarily due to the semileptonic decays of hadrons carrying heavy quarks. Nuclear modification factors were determined by comparison to nonphotonic electrons in p+p collisions. A significant suppression of electrons at high pT is observed in central Au+Au collisions, indicating substantial energy loss of heavy quarks.

Journal ArticleDOI
S. S. Adler1, S. Afanasiev2, Christine Angela Aidala1, N. N. Ajitanand3  +340 moreInstitutions (43)
TL;DR: Azimuthal correlations of jet-induced high-p(T) charged hadron pairs are studied at midrapidity in Au+Au collisions at sqrt[s(NN)]=200 GeV in this article.
Abstract: Azimuthal correlations of jet-induced high-p(T) charged hadron pairs are studied at midrapidity in Au+Au collisions at sqrt[s(NN)]=200 GeV. The distribution of jet-associated partner hadrons (1.0

Journal ArticleDOI
TL;DR: This study provides the first comprehensive structural analysis of the infectious vaccinia virus IMV, showing that it contains 75 viral proteins, including structural proteins, enzymes, transcription factors, and predicted viral proteins not known to be expressed or present in the IMV.
Abstract: Vaccinia virus is a large enveloped poxvirus with more than 200 genes in its genome. Although many poxvirus genomes have been sequenced, knowledge of the host and viral protein components of the virions remains incomplete. In this study, we used gel-free liquid chromatography and tandem mass spectroscopy to identify the viral and host proteins in purified vaccinia intracellular mature virions (IMV). Analysis of the proteins in the IMV showed that it contains 75 viral proteins, including structural proteins, enzymes, transcription factors, and predicted viral proteins not known to be expressed or present in the IMV. We also determined the relative abundances of the individual protein components in the IMV. Finally, 23 IMV-associated host proteins were also identified. This study provides the first comprehensive structural analysis of the infectious vaccinia virus IMV.

Journal ArticleDOI
Yee-yung Charng1, Hsiang-chin Liu1, Nai-yu Liu1, Fu-Chiun Hsu1, Swee-Suak Ko1 
TL;DR: Analysis of the function of a novel Hsp, heat-stress-associated 32-kD protein (Hsa32), which is highly conserved in land plants but absent in most other organisms, suggests that Hsa32 is required not for induction but rather maintenance of acquired thermotolerance, a feature that could be important to plants.
Abstract: Plants and animals share similar mechanisms in the heat shock (HS) response, such as synthesis of the conserved HS proteins (Hsps). However, because plants are confined to a growing environment, in general they require unique features to cope with heat stress. Here, we report on the analysis of the function of a novel Hsp, heat-stress-associated 32-kD protein (Hsa32), which is highly conserved in land plants but absent in most other organisms. The gene responds to HS at the transcriptional level in moss (Physcomitrella patens), Arabidopsis (Arabidopsis thaliana), and rice (Oryza sativa). Like other Hsps, Hsa32 protein accumulates greatly in Arabidopsis seedlings after HS treatment. Disruption of Hsa32 by T-DNA insertion does not affect growth and development under normal conditions. However, the acquired thermotolerance in the knockout line was compromised following a long recovery period (>24 h) after acclimation HS treatment, when a severe HS challenge killed the mutant but not the wild-type plants, but no significant difference was observed if they were challenged within a short recovery period. Quantitative hypocotyl elongation assay also revealed that thermotolerance decayed faster in the absence of Hsa32 after a long recovery. Similar results were obtained in Arabidopsis transgenic plants with Hsa32 expression suppressed by RNA interference. Microarray analysis of the knockout mutant indicates that only the expression of Hsa32 was significantly altered in HS response. Taken together, our results suggest that Hsa32 is required not for induction but rather maintenance of acquired thermotolerance, a feature that could be important to plants.

Journal ArticleDOI
TL;DR: It is reported that HCV infection causes production of reactive oxygen species (ROS) and lowering of mitochondrial transmembrane potential (ΔΨm) in in vitro HCV-infected cell cultures, and ROS, along with the previously identified NO, are identified as the primary inducers of DSBs and mitochondrial damage in HCV -infected cells.
Abstract: Hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinomas and non-Hodgkin's B-cell lymphomas. Previously, we reported that HCV infection causes cellular DNA damage and mutations, which are mediated by nitric oxide (NO). NO often damages mitochondria, leading to induction of double-stranded DNA breaks (DSBs) and accumulation of oxidative DNA damage. Here we report that HCV infection causes production of reactive oxygen species (ROS) and lowering of mitochondrial transmembrane potential (DeltaPsi(m)) in in vitro HCV-infected cell cultures. The changes in membrane potential could be inhibited by BCL-2. Furthermore, an inhibitor of ROS production, antioxidant N-acetyl-L-cysteine (NAC), or an inhibitor of NO, 1,400W, prevented the alterations of DeltaPsi(m). The HCV-induced DSB was also abolished by a combination of NO and ROS inhibitors. These results indicated that the mitochondrial damage and DSBs in HCV-infected cells were mediated by both NO and ROS. Among the HCV proteins, core, E1, and NS3 are potent ROS inducers: their expression led to DNA damage and activation of STAT3. Correspondingly, core-protein-transgenic mice showed elevated levels of lipid peroxidation and oxidatively damaged DNA. These HCV studies thus identified ROS, along with the previously identified NO, as the primary inducers of DSBs and mitochondrial damage in HCV-infected cells.

Journal ArticleDOI
TL;DR: Evidence is provided that HIB prevents aberrant Hh signaling posterior to the morphogenic furrow, which is essential for normal eye development, and inactivating HIB results in Ci accumulation and enhanced pathway activity.

Journal ArticleDOI
TL;DR: In this article, the authors use mean plant-eater hypsodonty (molarcrown height) of late NeogenemammallocalitiestomaplateMiocene and Pliocenepalaeoprecipitation on the Eurasian continent and, with higher temporal resolution, in Europe.

Journal ArticleDOI
TL;DR: XBP1 was activated during flaviviral infection, as evidenced by XBP1 mRNA splicing and protein expression, as well as induction of the downstream genes ERdj4, EDEM1, and p58(IPK) in Japanese encephalitis virus and dengue virus serotype 2-infected cells.
Abstract: The unfolded protein response (UPR) is a coordinated change in gene expression triggered by perturbations in functions of the endoplasmic reticulum (ER). XBP1, a key transcription factor of the UPR, is activated by an IRE1-mediated splicing event, which results in a frameshift and encodes a protein with transcriptional activity. Here, we report that XBP1 was activated during flaviviral infection, as evidenced by XBP1 mRNA splicing and protein expression, as well as induction of the downstream genes ERdj4, EDEM1, and p58(IPK) in Japanese encephalitis virus (JEV)- and dengue virus serotype 2 (DEN-2)-infected cells. Reporter systems based on IRE1-mediated XBP1 splicing were established, and several flaviviral proteins associated with the ER, including glycoproteins and small hydrophobic membrane-anchored proteins, were found to trigger the splicing event. Notably, nonstructural protein NS2B-3 of DEN-2, but not of JEV, was a potent inducer of XBP1 splicing through an unclear mechanism(s). Reduction of XBP1 by a small interfering RNA had no effect on cells' susceptibility to the two viruses but exacerbated the flavivirus-induced cytopathic effects. Overall, flaviviruses trigger the XBP1 signaling pathway and take advantage of this cellular response to alleviate virus-induced cytotoxicity.

Journal ArticleDOI
TL;DR: Wu et al. as mentioned in this paper investigated the attenuation of Pd with the hypocentral distance R in southern California as a function of magnitude M, and obtained the following relationship: log (Pd )= � 3.463 + 0.729 � M � 1.374 ± 0.305.
Abstract: [1] Pd is the peak amplitude of displacement in the first three seconds after the arrival of the P wave. We investigated the attenuation of Pd with the hypocentral distance R in southern California as a function of magnitude M, and obtained the following relationship: log (Pd )= � 3.463 + 0.729 � M � 1.374 � log (R) ± 0.305. Given an earthquake location determined by the P-wave arrival times at stations close to the epicenter, this relationship can be used to define a so-called ‘‘Pd magnitude’’ of earthquakes. Our result shows that for earthquakes in southern California the Pd magnitudes agree with the catalog magnitudes with a standard deviation of 0.18 for events less than magnitude 6.5. Therefore, Pd is a robust measurement for estimating the magnitudes of earthquakes and has practical application in earthquake early warning systems. Citation: Wu, Y.-M., and L. Zhao (2006), Magnitude estimation using the first three seconds P-wave amplitude in earthquake early warning, Geophys. Res. Lett., 33, L16312, doi:10.1029/2006GL026871.

Journal ArticleDOI
TL;DR: Using the Submillimeter Array (SMA), the first high angular resolution measurements of the linear polarization of Sagittarius A* at submillimeter wavelengths and the first detection of intraday variability in its linear polarization were made in this article.
Abstract: Using the Submillimeter Array, we have made the first high angular resolution measurements of the linear polarization of Sagittarius A* at submillimeter wavelengths and the first detection of intraday variability in its linear polarization We detected linear polarization at 340 GHz (880 μm) at several epochs At the typical resolution of 14 × 22, the expected contamination from the surrounding (partially polarized) dust emission is negligible We found that both the polarization fraction and the position angle are variable, with the polarization fraction dropping from 85% to 23% over 3 days This is the first significant measurement of variability in the linear polarization fraction in this source We also found variability in the polarization and total intensity within single nights, although the relationship between the two is not clear from these data The simultaneous 332 and 342 GHz position angles are the same, setting a 1 σ rotation measure (RM) upper limit of 7 × 105 rad m-2 From position angle variations and comparison of quiescent position angles observed here and at 230 GHz, we infer that the RM is a few times 105 rad m-2, a factor of a few below our direct detection limit A generalized model of the RM produced in the accretion flow suggests that the accretion rate at small radii must be low, below 10-6-10-7 M☉ yr-1 depending on the radial density and temperature profiles, but in all cases below the gas capture rate inferred from X-ray observations

Journal ArticleDOI
TL;DR: It is shown that the heterodimeric transcriptional elongation factor FACT (facilitates chromatin transcription) is functionally linked to DNA synthesis and supported a model in which the concerted action of helicase and chromatin‐modifying activities promotes chromosome replication.
Abstract: Chromatin is suppressive in nature to cellular enzymes that metabolize DNA, mainly due to the inherent inaccessibility of the DNA template. Despite extensive understanding of the involvement of chromatin-modifying factors in transcription, roles of related activities in DNA replication remain largely elusive. Here, we show that the heterodimeric transcriptional elongation factor FACT (facilitates chromatin transcription) is functionally linked to DNA synthesis. Its involvement in DNA replication is partly mediated by the stable association with the replicative helicase complex, MCM, and further by the coexistence with MCM on replication origin. Furthermore, relying on its nucleosome-reorganizing activity, FACT can facilitate chromatin unwinding by the MCM complex, which is otherwise inert on the nucleosomal template. As a consequence, the physical and functional interaction between FACT and MCM is an important determinant in the proper initiation of DNA replication and S phase in vivo. Together, our findings identify FACT as an integral and conserved component of the endogenous replication machinery, and support a model in which the concerted action of helicase and chromatin-modifying activities promotes chromosome replication.

Journal ArticleDOI
TL;DR: The Majorana nature of neutrinos may only be experimentally verified via lepton-number violating processes involving charged leptons as discussed by the authors, which is the only way to verify the Majorana neutrino nature.
Abstract: The Majorana nature of neutrinos may only be experimentally verified via lepton-number violating processes involving charged leptons. We explore the Delta L=2 like-sign dilepton production at hadron colliders to search for signals of Majorana neutrinos. We find significant sensitivity for resonant production of a Majorana neutrino in the mass range of 10-80 GeV at the current run of the Tevatron with 2 fb(-1) integrated luminosity and in the range of 10-400 GeV at the CERN LHC with 100 fb(-1).