756 research outputs found

    Identification of a new cAMP response element-binding factor by southwestern blotting.

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    We have identified in mammalian cells a novel cyclic AMP response element (CRE)-binding protein of molecular mass 47 kDa. This protein was not recognized by either the CREB-327/341 or c-Jun antisera, and its tissue distribution did not overlap with those of the CREB and Jun families. For example, hepatoma and placental tissue did not contain the 47-kDa DNA-binding protein, but did contain the CREB isoforms. On the other hand, S49 lymphoma cells contained a high level of the 47-kDa DNA-binding protein but did not contain a 47-kDa Jun-related protein which was found in normal liver and hepatoma. This new 47-kDa factor bound to the CRE in the dephosphorylated form, and phosphorylation of the protein by the catalytic subunit of protein kinase A completely abolished its DNA-binding activity. The isoforms of the CREB-327/341 family, on the other hand, bound to DNA in the phosphorylated form, and alkaline phosphatase treatment reduced significantly their interaction with CRE sequence. This reverse effect of phosphorylation/dephosphorylation on the DNA-binding property of this new 47-kDa protein in particular distinguishes it from other known CREB factors and suggests that the protein might play a unique role in the regulation of cAMP-mediated transcription

    A List of Bright Interferometric Calibrators measured at the ESO VLTI

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    In a previous publication (Richichi & Percheron 2005) we described a program of observations of candidate calibrator stars at the ESO Very Large Telescope Interferometer (VLTI), and presented the main results from a statistical point of view. In the present paper, we concentrate on establishing a new homogeneous group of bright interferometric calibrators, based entirely on publicly available K-band VLTI observations carried out with the VINCI instrument up to July 2004. For this, we have defined a number of selection criteria for the quality and volume of the observations, and we have accordingly selected a list of 17 primary and 47 secondary calibrators. We have developed an approach to a robust global fit for the angular diameters using the whole volume of quality-controlled data, largely independent of a priori assumptions. Our results have been compared with direct measurements, and indirect estimates based on spectrophotometric methods, and general agreement is found within the combined uncertainties. The stars in our list cover the range K=-2.9 to +3.0 mag in brightness, and 1.3 to 20.5 milliarcseconds in uniform-disk diameter. The relative accuracy of the angular diameter values is on average 0.4% and 2% for the primary and secondary calibrators respectively. Our calibrators are well suited for interferometric observations in the near-infrared on baselines between ~20m and ~200m, and their accuracy is superior, at least for the primary calibrators, to other similar catalogues. Therefore, the present list of calibrators has the potential to lead to significantly improved interferometric scientific results

    Neural network parametrization of the lepton energy spectrum in semileptonic B meson decays

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    We construct a parametrization of the lepton energy spectrum in inclusive semileptonic decays of B mesons, based on the available experimental information: moments of the spectrum with cuts, their errors and their correlations, together with kinematical constraints. The result is obtained in the form of a Monte Carlo sample of neural networks trained on replicas of the experimental data, which represents the probability density in the space of lepton energy spectra. This parametrization is then used to extract the b quark mass m_b^{1S} in a way that theoretical uncertainties are minimized, for which the value m_b^{1S}=4.84 \pm 0.14^{exp}\pm 0.05^{th} GeV is obtained.Comment: 32 pages, 22 figures, JHEP3 class. v4 version accepted for publication in JHE

    Hipparcos red stars in the HpV_{T2} and VI_C systems

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    For Hipparcos M, S, and C spectral type stars, we provide calibrated instantaneous (epoch) Cousins VIV-I color indices using newly derived HpVT2HpV_{T2} photometry. Three new sets of ground-based Cousins VIVI data have been obtained for more than 170 carbon and red M giants. These datasets in combination with the published sources of VIVI photometry served to obtain the calibration curves linking Hipparcos/Tycho HpVT2Hp-V_{T2} with the Cousins VIV-I index. In total, 321 carbon stars and 4464 M- and S-type stars have new VIV-I indices. The standard error of the mean VIV-I is about 0.1 mag or better down to Hp9Hp\approx9 although it deteriorates rapidly at fainter magnitudes. These VIV-I indices can be used to verify the published Hipparcos VIV-I color indices. Thus, we have identified a handful of new cases where, instead of the real target, a random field star has been observed. A considerable fraction of the DMSA/C and DMSA/V solutions for red stars appear not to be warranted. Most likely such spurious solutions may originate from usage of a heavily biased color in the astrometric processing.Comment: 10 figures, 1 electronic table, accepted in A&

    Rotational velocities of the giants in symbiotic stars: III. Evidence of fast rotation in S-type symbiotics

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    We have measured the projected rotational velocities (vsini) in a number of symbiotic stars and M giants using high resolution spectroscopic observations. On the basis of our measurements and data from the literature, we compare the rotation of mass-donors in symbiotics with vsini of field giants and find that: (1) the K giants in S-type symbiotics rotate at vsini>4.5 km/s, which is 2-4 times faster than the field K giants; (2) the M giants in S-type symbiotics rotate on average 1.5 times faster than the field M giants. Statistical tests show that these differences are highly significant: p-value < 0.001 in the spectral type bins K2III-K5III, M0III-M6III, and M2III-M5III; (3) our new observations of D'-type symbiotics also confirm that they are fast rotators. As a result of the rapid rotation, the cool giants in symbiotics should have 3-30 times larger mass loss rates. Our results suggest also that bipolar ejections in symbiotics seem to happen in objects where the mass donors rotate faster than the orbital period. All spectra used in our series of papers can be obtained upon request from the authors.Comment: MNRAS (accepted), 7 pages, 5 figure

    Development of a set of patient reported outcome measures for patients with benign liver tumours and cysts:patient focus groups and systematic review

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    BACKGROUND: Patient reported outcome measures (PROMs) may be useful for patients with benign liver tumours and cysts (BLTC) to evaluate the impact of treatment and/or guide shared decision making. Yet, a set of PROMs relevant to patients with BLTC is currently unavailable. In this study, we selected a PROMs set for patients with BLTC. METHODS: Potentially relevant patient reported outcomes (PROs) were selected by psychologist-researchers based on keywords used or suggested by participants of two virtual focus groups meetings consisting of thirteen female BLTC patients with a median age of 50 years. Subsequently, patients were asked to report their most relevant PROs. PROMs identified by systematic literature review and computerized adaptive tests (CATs) in the Patient-Reported Outcomes Measurement Information System (PROMIS) were considered in selecting the final PROMs set to assess relevant outcomes. RESULTS: The most important PROs were: insecurity/anxiety (11/12 patients), pain (9/12 patients), fatigue (8/12 patients), and limitations in daily life (5/12 patients). The literature review included 23 studies, which used various generic and disease-specific PROMs, often not measuring (all) relevant PROs. The final selected PROMs set included numerical rating scales for pain, two questions on overall health and quality of life and four PROMIS CATs. CONCLUSIONS: A PROMs set generically and efficiently measuring outcomes relevant for patients with BLTC was developed and may be used in future research and clinical practice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41687-022-00531-1

    An absolutely calibrated effective temperature scale from the InfraRed Flux Method

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    Various effective temperature scales have been proposed over the years. Despite much work and the high internal precision usually achieved, systematic differences of order 100 K (or more) among various scales are still present. We present an investigation based on the Infrared Flux Method aimed at assessing the source of such discrepancies and pin down their origin. We break the impasse among different scales by using a large set of solar twins, stars which are spectroscopically and photometrically identical to the Sun, to set the absolute zero point of the effective temperature scale to within few degrees. Our newly calibrated, accurate and precise temperature scale applies to dwarfs and subgiants, from super-solar metallicities to the most metal-poor stars currently known. At solar metallicities our results validate spectroscopic effective temperature scales, whereas for [Fe/H]<-2.5 our temperatures are roughly 100 K hotter than those determined from model fits to the Balmer lines and 200 K hotter than those obtained from the excitation equilibrium of Fe lines. Empirical bolometric corrections and useful relations linking photometric indices to effective temperatures and angular diameters have been derived. Our results take full advantage of the high accuracy reached in absolute calibration in recent years and are further validated by interferometric angular diameters and space based spectrophotometry over a wide range of effective temperatures and metallicities.Comment: Accepted for publication in Astronomy and Astrophysics. Landscape table available online at http://www.mpa-garching.mpg.de/~luca/IRFM

    PP2A is activated by cytochrome c upon formation of a diffuse encounter complex with SET/TAF-Iß

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    Intrinsic protein flexibility is of overwhelming relevance for intermolecular recognition and adaptability of highly dynamic ensemble of complexes, and the phenomenon is essential for the understanding of numerous biological processes. These conformational ensembles—encounter complexes—lack a unique organization, which prevents the determination of well-defined high resolution structures. This is the case for complexes involving the oncoprotein SET/template-activating factor-Iß (SET/TAF-Iß), a histone chaperone whose functions and interactions are significantly affected by its intrinsic structural plasticity. Besides its role in chromatin remodeling, SET/TAF-Iß is an inhibitor of protein phosphatase 2A (PP2A), which is a key phosphatase counteracting transcription and signaling events controlling the activity of DNA damage response (DDR) mediators. During DDR, SET/TAF-Iß is sequestered by cytochrome c (Cc) upon migration of the hemeprotein from mitochondria to the cell nucleus. Here, we report that the nuclear SET/TAF-Iß:Cc polyconformational ensemble is able to activate PP2A. In particular, the N-end folded, globular region of SET/TAF-Iß (a.k.a. SET/TAF-Iß ¿C)—which exhibits an unexpected, intrinsically highly dynamic behavior—is sufficient to be recognized by Cc in a diffuse encounter manner. Cc-mediated blocking of PP2A inhibition is deciphered using an integrated structural and computational approach, combining small-angle X-ray scattering, electron paramagnetic resonance, nuclear magnetic resonance, calorimetry and molecular dynamics simulations

    BRCA2 diffuses as oligomeric clusters with RAD51 and changes mobility after DNA damage in live cells

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    Genome maintenance by homologous recombination depends on coordinating many proteins in time and space to assemble at DNA break sites. To understand this process, we followed the mobility of BRCA2, a critical recombination mediator, in live cells at the single-molecule level using both single-particle tracking and fluorescence correlation spectroscopy. BRCA2-GFP and -YFP were compared to distinguish diffusion from fluorophore behavior. Diffusive behavior of fluorescent RAD51 and RAD54 was determined for comparison. All fluorescent proteins were expressed from endogenous loci. We found that nuclear BRCA2 existed in oligomeric clusters, and exhibited heterogeneous mobility. DNA damage increased BRCA2 transient binding, presumably including binding to damaged sites. Despite its very different size, RAD51 displayed mobility similar to BRCA2, which indicates physical interaction between these proteins both before and after induction of DNA damage. We propose that BRCA2-mediated sequestration of nuclear RAD51 serves to prevent inappropriate DNA interactions and that all RAD51 is delivered to DNA damage sites in association with BRCA2
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