980 research outputs found

    Xenopus Drf1, a Regulator of Cdc7, Displays Checkpoint-dependent Accumulation on Chromatin during an S-phase Arrest

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    We have cloned a Xenopus Dbf4-related factor named Drf1 and characterized this protein by using Xenopus egg extracts. Drf1 forms an active complex with the kinase Cdc7. However, most of the Cdc7 in egg extracts is not associated with Drf1, which raises the possibility that some or all of the remaining Cdc7 is bound to another Dbf4-related protein. Immunodepletion of Drf1 does not prevent DNA replication in egg extracts. Consistent with this observation, Cdc45 can still associate with chromatin in Drf1-depleted extracts, albeit at significantly reduced levels. Nonetheless, Drf1 displays highly regulated binding to replicating chromatin. Treatment of egg extracts with aphidicolin results in a substantial accumulation of Drf1 on chromatin. This accumulation is blocked by addition of caffeine and by immunodepletion of either ATR or Claspin. These observations suggest that the increased binding of Drf1 to aphidicolin-treated chromatin is an active process that is mediated by a caffeine-sensitive checkpoint pathway containing ATR and Claspin. Abrogation of this pathway also leads to a large increase in the binding of Cdc45 to chromatin. This increase is substantially reduced in the absence of Drf1, which suggests that regulation of Drf1 might be involved in the suppression of Cdc45 loading during replication arrest. We also provide evidence that elimination of this checkpoint causes resumed initiation of DNA replication in both Xenopus tissue culture cells and egg extracts. Taken together, these observations argue that Drf1 is regulated by an intra-S-phase checkpoint mechanism that down-regulates the loading of Cdc45 onto chromatin containing DNA replication blocks

    Isotropic three-dimensional gap in the iron-arsenide superconductor LiFeAs from directional heat transport measurements

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    The thermal conductivity k of the iron-arsenide superconductor LiFeAs (Tc ~ 18K) was measured in single crystals at temperatures down to T~50mK and in magnetic fields up to H=17T, very close to the upper critical field Hc2~18T. For both directions of the heat current, parallel and perpendicular to the tetragonal c-axis, a negligible residual linear term k/T is found as T ->0, revealing that there are no zero-energy quasiparticles in the superconducting state. The increase in k with magnetic field is the same for both current directions and it follows closely the dependence expected for an isotropic superconducting gap. There is no evidence of multi-band character, whereby the gap would be different on different Fermi-surface sheets. These findings show that the superconducting gap in LiFeAs is isotropic in 3D, without nodes or deep minima anywhere on the Fermi surface. Comparison with other iron-pnictide superconductors suggests that a nodeless isotropic gap is a common feature at optimal doping (maximal Tc).Comment: 4 pages, 3 figure

    Does Reactance Against Cigarette Warning Labels Matter? Warning Label Responses and Downstream Smoking Cessation Amongst Adult Smokers in Australia, Canada, Mexico and the United States

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    Objective Some researchers have raised concerns that pictorial health warning labels (HWLs) on cigarette packages may lead to message rejection and reduced effectiveness of HWL messages. This study aimed to determine how state reactance (i.e., negative affect due to perceived manipulation) in response to both pictorial and text-only HWLs is associated with other types of HWL responses and with subsequent cessation attempts. Methods Survey data were collected every 4 months between September 2013 and 2014 from online panels of adult smokers in Australia, Canada, Mexico, and the US were analyzed. Participants with at least one wave of follow-up were included in the analysis (n = 4,072 smokers; 7,459 observations). Surveys assessed psychological and behavioral responses to HWLs (i.e., attention to HWLs, cognitive elaboration of risks due to HWLs, avoiding HWLs, and forgoing cigarettes because of HWLs) and cessation attempts. Participants then viewed specific HWLs from their countries and were queried about affective state reactance. Logistic and linear Generalized Estimating Equation (GEE) models regressed each of the psychological and behavioral HWL responses on reactance, while controlling for socio-demographic and smoking-related variables. Logistic GEE models also regressed having attempted to quit by the subsequent survey on reactance, each of the psychological and behavioral HWL responses (analyzed separately), adjustment variables. Data from all countries were initially pooled, with interactions between country and reactance assessed; when interactions were statistically significant, country-stratified models were estimated. Results Interactions between country and reactance were found in all models that regressed psychological and behavioral HWL responses on study variables. In the US, stronger reactance was associated with more frequent reading of HWLs and thinking about health risks. Smokers from all four countries with stronger reactance reported greater likelihood of avoiding warnings and forgoing cigarettes due to warnings, although the association appeared stronger in the US. Both stronger HWLs responses and reactance were positively associated with subsequent cessation attempts, with no significant interaction between country and reactance. Conclusions Reactance towards HWLs does not appear to interfere with quitting, which is consistent with its being an indicator of concern, not a systematic effort to avoid HWL message engagement

    Does Reactance Against Cigarette Warning Labels Matter? Warning Label Responses and Downstream Smoking Cessation Amongst Adult Smokers in Australia, Canada, Mexico and the United States

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    Objective Some researchers have raised concerns that pictorial health warning labels (HWLs) on cigarette packages may lead to message rejection and reduced effectiveness of HWL messages. This study aimed to determine how state reactance (i.e., negative affect due to perceived manipulation) in response to both pictorial and text-only HWLs is associated with other types of HWL responses and with subsequent cessation attempts. Methods Survey data were collected every 4 months between September 2013 and 2014 from online panels of adult smokers in Australia, Canada, Mexico, and the US were analyzed. Participants with at least one wave of follow-up were included in the analysis (n = 4,072 smokers; 7,459 observations). Surveys assessed psychological and behavioral responses to HWLs (i.e., attention to HWLs, cognitive elaboration of risks due to HWLs, avoiding HWLs, and forgoing cigarettes because of HWLs) and cessation attempts. Participants then viewed specific HWLs from their countries and were queried about affective state reactance. Logistic and linear Generalized Estimating Equation (GEE) models regressed each of the psychological and behavioral HWL responses on reactance, while controlling for socio-demographic and smoking-related variables. Logistic GEE models also regressed having attempted to quit by the subsequent survey on reactance, each of the psychological and behavioral HWL responses (analyzed separately), adjustment variables. Data from all countries were initially pooled, with interactions between country and reactance assessed; when interactions were statistically significant, country-stratified models were estimated. Results Interactions between country and reactance were found in all models that regressed psychological and behavioral HWL responses on study variables. In the US, stronger reactance was associated with more frequent reading of HWLs and thinking about health risks. Smokers from all four countries with stronger reactance reported greater likelihood of avoiding warnings and forgoing cigarettes due to warnings, although the association appeared stronger in the US. Both stronger HWLs responses and reactance were positively associated with subsequent cessation attempts, with no significant interaction between country and reactance. Conclusions Reactance towards HWLs does not appear to interfere with quitting, which is consistent with its being an indicator of concern, not a systematic effort to avoid HWL message engagement

    The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM

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    The activation of ATR-ATRIP in response to double-stranded DNA breaks (DSBs) depends upon ATM in human cells and Xenopus egg extracts. One important aspect of this dependency involves regulation of TopBP1 by ATM. In Xenopus egg extracts, ATM associates with TopBP1 and thereupon phosphorylates it on S1131. This phosphorylation enhances the capacity of TopBP1 to activate the ATR-ATRIP complex. We show that TopBP1 also interacts with the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. This interaction involves the Nbs1 subunit of the complex. ATM can no longer interact with TopBP1 in Nbs1-depleted egg extracts, which suggests that the MRN complex helps to bridge ATM and TopBP1 together. The association between TopBP1 and Nbs1 involves the first pair of BRCT repeats in TopBP1. In addition, the two tandem BRCT repeats of Nbs1 are required for this binding. Functional studies with mutated forms of TopBP1 and Nbs1 suggested that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. These findings suggest that the MRN complex is a crucial mediator in the process whereby ATM promotes the TopBP1-dependent activation of ATR-ATRIP in response to DSBs

    Orbital-Dependent Polaron Formation in the Relativistic Mott Insulator Sr\u3csub\u3e2\u3c/sub\u3eIrO\u3csub\u3e4\u3c/sub\u3e

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    We use optical spectroscopy to investigate the electron-phonon interaction in Sr2IrO4, a well-known 5d transition metal oxide with spin-orbit entangled states. The temperature evolution in the optical spectra is well described by the Fröhlich polaron model, indicating a large electron-phonon interaction. We further find that electrons in different orbitals selectively couple with different phonon modes. While Jeff = 3/2 holes do not seem to couple with any phonons, Jeff = 1/2 and 3z2−r2 electrons mainly couple with in-plane and out-of-plane Ir-O bending modes, respectively. The symmetries of the orbitals and phonons are consistent with our observations

    Regeneration Ecology of Chrysopogon aucheri and Cymbopogon jwarancusa in Grasslands of Upland Balochistan , Pakistan

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    Field experiments were conducted to investigate the seed attributes, movements and fates of dispersal units, and seedling establishment of Chrysopogon aucheri and Cymbopogon jwarancusa in a representative grassland ecosystem in upland Balochistan, Pakistan. Cymbopogon jwarancusa had more filled and viable caryopses than Chrysopogon aucheri. Seeds (spikelets) of both species had similar morphological features. Chrysopogon aucheri had one dispersal unit, a triplet spikelet. Cymbopogon jwarancusa had four types of dispersal units: a paired spikelet, a partial raceme, an entire raceme, and a partial inflorescence comprised of two racemes. Paired spikelets and partial racemes of Cymbopogon jwarancusa had greater mean dispersal distances (94 and 101 cm) from the edge of the basal crown of marked plants to the ground surface than triplet spikelets of Chrysopogon aucheri (79 cm). Spikelets of Cymbopogon jwarancusa and Chrysopogon aucheri moved mean distances of 26 and 32 cm, respectively, on the ground surface before becoming trapped in a microhabitat. The mean angle of dispersal for both species was toward the northeast, according to the prevailing wind direction. An ant (Tica verona) was the only detected seed (spikelet) predator for Chrysopogon aucheri. Both species had a weakly persistent soil seed bank, with higher amounts of seeds found under plant canopies compared to open interspaces. The recruitment of Chrysopogon aucheri and Cymbopogon jwarancusa seedlings from the natural seed bank was monitored in seven different microhabitats under natural and above-normal precipitation regimes . Above-normal precipitation increased seedling recruitment for both species in all microhabitats. Cymbopogon jwarancusa had higher seedling densities than Chrysopogon auchfiri. Seedling survival and tiller development for both species were greatest in the gravel microhabitat in the natural precipitation treatment. Monsoon rains in late July enhanced emergence of both species from recently dispersed seeds but emerged seedlings did not survive to the end of the growing season. The field studies indicate that Cymbopogon jwarancusa has a greater regeneration potential than Chrysopogon aucheri in this grassland ecosystem in upland Balochistan. It may be difficult to increase the composition of Chrysopogon aucheri, the more desirable species in these grasslands, when using management techniques that rely on natural regeneration

    Akabane viral encephalitis in calves in South Korea

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    This work was supported by the Brain Korea 21 Project and the Ministry of Agriculture and Forestry (399002-3), Republic of Korea

    Transdifferentiation-inducing HCCR-1 oncogene

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    <p>Abstract</p> <p>Background</p> <p>Cell transdifferentiation is characterized by loss of some phenotypes along with acquisition of new phenotypes in differentiated cells. The differentiated state of a given cell is not irreversible. It depends on the up- and downregulation exerted by specific molecules.</p> <p>Results</p> <p>We report here that <it>HCCR-1</it>, previously shown to play an oncogenic role in human cancers, induces epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) in human and mouse, respectively. The stem cell factor receptor CD117/c-Kit was induced in this transdifferentiated (EMT) sarcoma tissues. This MET occurring in <it>HCCR-1 </it>transfected cells is reminiscent of the transdifferentiation process during nephrogenesis. Indeed, expression of <it>HCCR-1 </it>was observed during the embryonic development of the kidney. This suggests that <it>HCCR-1 </it>might be involved in the transdifferentiation process of cancer stem cell.</p> <p>Conclusions</p> <p>Therefore, we propose that <it>HCCR-1 </it>may be a regulatory factor that stimulates morphogenesis of epithelia or mesenchyme during neoplastic transformation.</p
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