24 research outputs found
Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2.
CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis
A unique Valanginian paleoenvironment at an iron ore deposit near ZengĆvĂĄrkony (Mecsek Mts, South Hungary), and a possible genetic model
Abstract
The spatially restricted Early Valanginian iron ore (limonite) and manganese deposit at ZengĂ”vĂĄrkony (Mecsek Mts, southern Hungary) contains a rich, strongly limonitized, remarkably large-sized (specimens are 30â70% larger than those at their type localities) brachiopod-dominated (mainly Lacunosella and Nucleata) megafauna and a diverse crustacean microfauna, which indicates a shallow, nutrient-rich environment possibly linked to an uplifted block, and/or a hydrothermal vent
Immersed boundary-finite element model of fluid-structure interaction in the aortic root
It has long been recognized that aortic root elasticity helps to ensure
efficient aortic valve closure, but our understanding of the functional
importance of the elasticity and geometry of the aortic root continues to
evolve as increasingly detailed in vivo imaging data become available. Herein,
we describe fluid-structure interaction models of the aortic root, including
the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the
sinotubular junction, that employ a version of Peskin's immersed boundary (IB)
method with a finite element (FE) description of the structural elasticity. We
develop both an idealized model of the root with three-fold symmetry of the
aortic sinuses and valve leaflets, and a more realistic model that accounts for
the differences in the sizes of the left, right, and noncoronary sinuses and
corresponding valve cusps. As in earlier work, we use fiber-based models of the
valve leaflets, but this study extends earlier IB models of the aortic root by
employing incompressible hyperelastic models of the mechanics of the sinuses
and ascending aorta using a constitutive law fit to experimental data from
human aortic root tissue. In vivo pressure loading is accounted for by a
backwards displacement method that determines the unloaded configurations of
the root models. Our models yield realistic cardiac output at physiological
pressures, with low transvalvular pressure differences during forward flow,
minimal regurgitation during valve closure, and realistic pressure loads when
the valve is closed during diastole. Further, results from high-resolution
computations demonstrate that IB models of the aortic valve are able to produce
essentially grid-converged dynamics at practical grid spacings for the
high-Reynolds number flows of the aortic root
Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy
We review HB stars in a broad astrophysical context, including both variable
and non-variable stars. A reassessment of the Oosterhoff dichotomy is
presented, which provides unprecedented detail regarding its origin and
systematics. We show that the Oosterhoff dichotomy and the distribution of
globular clusters (GCs) in the HB morphology-metallicity plane both exclude,
with high statistical significance, the possibility that the Galactic halo may
have formed from the accretion of dwarf galaxies resembling present-day Milky
Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the
second-parameter problem is presented. A technique is proposed to estimate the
HB types of extragalactic GCs on the basis of integrated far-UV photometry. The
relationship between the absolute V magnitude of the HB at the RR Lyrae level
and metallicity, as obtained on the basis of trigonometric parallax
measurements for the star RR Lyrae, is also revisited, giving a distance
modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are
studied. Finally, the conductive opacities used in evolutionary calculations of
low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and
Space Scienc
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Gaia Early Data Release 3: Gaia photometric science alerts
Context. Since July 2014, the Gaia mission has been engaged in a high-spatial-resolution, time-resolved, precise, accurate astrometric, and photometric survey of the entire sky. Aims. We present the Gaia Science Alerts project, which has been in operation since 1 June 2016. We describe the system which has been developed to enable the discovery and publication of transient photometric events as seen by Gaia. Methods. We outline the data handling, timings, and performances, and we describe the transient detection algorithms and filtering procedures needed to manage the high false alarm rate. We identify two classes of events: (1) sources which are new to Gaia and (2) Gaia sources which have undergone a significant brightening or fading. Validation of the Gaia transit astrometry and photometry was performed, followed by testing of the source environment to minimise contamination from Solar System objects, bright stars, and fainter near-neighbours. Results. We show that the Gaia Science Alerts project suffers from very low contamination, that is there are very few false-positives. We find that the external completeness for supernovae, CE = 0.46, is dominated by the Gaia scanning law and the requirement of detections from both fields-of-view. Where we have two or more scans the internal completeness is CI = 0.79 at 3 arcsec or larger from the centres of galaxies, but it drops closer in, especially within 1 arcsec. Conclusions. The per-Transit photometry for Gaia transients is precise to 1% at G = 13, and 3% at G = 19. The per-Transit astrometry is accurate to 55 mas when compared to Gaia DR2. The Gaia Science Alerts project is one of the most homogeneous and productive transient surveys in operation, and it is the only survey which covers the whole sky at high spatial resolution (subarcsecond), including the Galactic plane and bulge. © S. T. Hodgkin et al. 2021
Tracheal intubation in traumatic brain injury
Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. Results: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79â1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65â1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. Conclusion: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. Clinical trial registration: NCT02210221
Informed consent procedures in patients with an acute inability to provide informed consent
Purpose: Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedur
C/EBPbeta couples dopamine signalling to substance P precursor gene expression in striatal neurones.
Dopamine-induced changes in striatal gene expression are thought to play an important role in drug addiction and compulsive behaviour. In this study we report that dopamine induces the expression of the transcription factor CCAAT/Enhancer Binding Protein beta (C/EBP)-beta in primary cultures of striatal neurones. We identified the preprotachykinin-A (PPT-A) gene coding for substance P and neurokinin-A as a potential target gene of C/EBPbeta. We demonstrated that C/EBPbeta physically interacts with an element of the PPT-A promoter, thereby facilitating substance P precursor gene transcription. The regulation of PPT-A gene by C/EBPbeta could subserve many important physiological processes involving substance P, such as nociception, neurogenic inflammation and addiction. Given that substance P is known to increase dopamine signalling in the striatum and, in turn, dopamine increases substance P expression in medium spiny neurones, our results implicate C/EBPbeta in a positive feedback loop, changes of which might contribute to the development of drug addiction