2,520 research outputs found
Automated detection of ncRNAs in the draft genome sequence of a colonial tunicate: the carpet sea squirt Didemnum vexillum
Statistics D. vexillum draft genome. (PDF 485 kb
The radial arrangement of the human chromosome 7 in the lymphocyte cell nucleus is associated with chromosomal band gene density
This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer-Verlag 2008.In the nuclei of human lymphocytes, chromosome territories are distributed according to the average gene density of each chromosome. However, chromosomes are very heterogeneous in size and base composition, and can contain both very gene-dense and very gene-poor regions. Thus, a precise analysis of chromosome organisation in the nuclei should consider also the distribution of DNA belonging to the chromosomal bands in each chromosome. To improve our understanding of the chromatin organisation, we localised chromosome 7 DNA regions, endowed with different gene densities, in the nuclei of human lymphocytes. Our results showed that this chromosome in cell nuclei is arranged radially with the gene-dense/GC-richest regions exposed towards the nuclear interior and the gene-poorest/GC-poorest ones located at the nuclear periphery. Moreover, we found that chromatin fibres from the 7p22.3 and the 7q22.1 bands are not confined to the territory of the bulk of this chromosome, protruding towards the inner part of the nucleus. Overall, our work demonstrates the radial arrangement of the territory of chromosome 7 in the lymphocyte nucleus and confirms that human genes occupy specific radial positions, presumably to enhance intra- and inter-chromosomal interaction among loci displaying a similar expression pattern, and/or similar replication timing
Perturbations and non-Gaussianities in three-form inflationary magnetogenesis
We reconsider magnetogenesis in the context of three-form inflation, and its
backreaction. In particular, we focus on first order perturbation theory during
inflation and subsequent radiation era: we discuss the consistency of the
perturbative approach, and elaborate on the possible non-Gaussian signatures of
the model.Comment: 29 pages and 8 figure
Angular momentum-Large-scale structure alignments in LCDM models and the SDSS
We study the alignments between the angular momentum of individual objects
and the large-scale structure in cosmological numerical simulations and real
data from the Sloan Digital Sky Survey, Data Release 6. To this end we measure
anisotropies in the two point cross-correlation function around simulated halos
and observed galaxies, studying separately the 1- and 2-halo regimes. The
alignment of the angular momentum of dark-matter haloes in LCDM simulations is
found to be dependent on scale and halo mass. At large distances (2-halo
regime), the spins of high mass haloes are preferentially oriented in the
direction perpendicular to the distribution of matter; lower mass systems show
a weaker trend that may even reverse to show an angular momentum in the plane
of the matter distribution. In the 1-halo term regime, the angular momentum is
aligned in the direction perpendicular to the matter distribution; the effect
is stronger than for the 1-halo term and increases for higher mass systems.
On the observational side, we focus our study on galaxies in the Sloan
Digital Sky Survey, Data Release 6 (SDSS-DR6) with elongated apparent shapes,
and study alignments with respect to the major semi-axis. We find an excess of
structure in the direction of the major semi-axis for all samples; the red
sample shows the highest alignment (2.7+-0.08%) and indicates that the angular
momentum of flattened spheroidals tends to be perpendicular to the large-scale
structure. (Abridged)Comment: 10 pages, 6 figures, accepted for publication in MNRAS; the
definitive version is available at www.blackwell-synergy.co
Dihydroceramide desaturase functions as an inducer and rectifier of apoptosis : effect of retinol derivatives, antioxidants and phenolic compounds
Dihydroceramide desaturase (Degs1) catalyses the introduction of 4,5-trans double bond into dihydroceramide to form ceramide. We show here that Degs1 is polyubiquitinated in response to retinol derivatives, phenolic compounds or anti-oxidants in HEK293T cells. The functional predominance of native versus polyubiquitinated forms of Degs1 appears to govern cytotoxicity. Therefore, 4-HPR or celecoxib appear to stimulate the de novo ceramide pathway (with the exception of C24:0 ceramide), using native Degs1, and thereby promote PARP cleavage and LC3B-I/II processing (autophagy/apoptosis). The ubiquitin-proteasomal degradation of Degs1 is positively linked to cell survival via XBP-1s and results in a concomitant increase in dihydroceramides and a decrease in C24:0 ceramide levels. However, in the case of 4-HPR or celecoxib, the native form of Degs1 functionally predominates, such that the apoptotic programme is sustained. In contrast, 4-HPA or AM404 do not produce apoptotic ceramide, using native Degs1, but do promote a rectifier function to induce ubiquitin-proteasomal degradation of Degs1 and are not cytotoxic. Therefore, Degs1 appears to function both as an ‘inducer’ and ‘rectifier’ of apoptosis in response to chemical cellular stress, the dynamic balance for which is dependent on the nature of chemical stress, thereby determining cytotoxicity. The de novo synthesis of ceramide or the ubiquitin-proteasomal degradation of Degs1 in response to anti-oxidants, retinol derivatives and phenolic compounds appear to involve sensors, and for rectifier function, this might be Degs1 itself
Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: Efficacy and safety results from a randomized open-label study
Denosumab has been shown to reduce new vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis. In subjects who were treatment-naive or previously treated with alendronate, denosumab was associated with greater gains in bone mineral density (BMD) and decreases in bone turnover markers when compared with alendronate-treated subjects. This trial was designed to compare the efficacy and safety of denosumab with risedronate over 12 months in postmenopausal women who transitioned from daily or weekly alendronate treatment and were considered to be suboptimally adherent to therapy. In this randomized, open-label study, postmenopausal women aged ≥55 years received denosumab 60 mg subcutaneously every 6 months or risedronate 150 mg orally every month for 12 months. Endpoints included percentage change from baseline in total hip BMD (primary endpoint), femoral neck, and lumbar spine BMD at month 12, and percentage change from baseline in sCTX-1 at months 1 and 6. Safety was also assessed. A total of 870 subjects were randomized (435, risedronate; 435, denosumab) who had a mean (SD) age of 67.7 (6.9) years, mean (SD) BMD T-scores of -1.6 (0.9), -1.9 (0.7), and -2.2 (1.2) at the total hip, femoral neck, and lumbar spine, respectively, and median sCTX-1 of 0.3 ng/mL at baseline. At month 12, denosumab significantly increased BMD compared with risedronate at the total hip (2.0% vs 0.5%), femoral neck (1.4% vs 0%), and lumbar spine (3.4% vs 1.1%; p<0.0001 at all sites). Denosumab significantly decreased sCTX-1 compared with risedronate at month 1 (median change from baseline of -78% vs -17%; p<0.0001) and month 6 (-61% vs -23%; p<0.0001). Overall and serious adverse events were similar between groups. In postmenopausal women who were suboptimally adherent to alendronate therapy, transitioning to denosumab was well tolerated and more effective than risedronate in increasing BMD and reducing bone turnover
Homotopy Invariants and Time Evolution in (2+1)-Dimensional Gravity
We establish the relation between the ISO(2,1) homotopy invariants and the
polygon representation of (2+1)-dimensional gravity. The polygon closure
conditions, together with the SO(2,1) cycle conditions, are equivalent to the
ISO(2,1) cycle conditions for the representa- tions of the fundamental group in
ISO(2,1). Also, the symplectic structure on the space of invariants is closely
related to that of the polygon representation. We choose one of the polygon
variables as internal time and compute the Hamiltonian, then perform the
Hamilton-Jacobi transformation explicitly. We make contact with other authors'
results for g = 1 and g = 2 (N = 0).Comment: 34 pages, Mexico preprint ICN-UNAM-93-1
Dense matter with eXTP
In this White Paper we present the potential of the Enhanced X-ray Timing and
Polarimetry (eXTP) mission for determining the nature of dense matter; neutron
star cores host an extreme density regime which cannot be replicated in a
terrestrial laboratory. The tightest statistical constraints on the dense
matter equation of state will come from pulse profile modelling of
accretion-powered pulsars, burst oscillation sources, and rotation-powered
pulsars. Additional constraints will derive from spin measurements, burst
spectra, and properties of the accretion flows in the vicinity of the neutron
star. Under development by an international Consortium led by the Institute of
High Energy Physics of the Chinese Academy of Science, the eXTP mission is
expected to be launched in the mid 2020s.Comment: Accepted for publication on Sci. China Phys. Mech. Astron. (2019
Diabetes and Clinical Outcome in Patients With Metastatic Colorectal Cancer: CALGB 80405 (Alliance)
Background
Diabetes is a prognostic factor for some malignancies, but its association with outcome in patients with advanced or metastatic colorectal cancer (CRC) is less clear.
Methods
This cohort study was nested within a randomized trial of first-line chemotherapy and bevacizumab and/or cetuximab for advanced or metastatic CRC. Patients were enrolled at 508 community and academic centers throughout the National Clinical Trials Network. The primary exposure was physician-documented diabetes at the time of enrollment. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS) and adverse events. Tests of statistical significance were two-sided.
Results
Among 2326 patients, 378 (16.3%) had diabetes. The median follow-up time was 6.0 years. We observed 1973 OS events and 2173 PFS events. The median time to an OS event was 22.7 months among those with diabetes and 27.1 months among those without diabetes (HR = 1.27, 95% CI = 1.13 to 1.44; P < .001). The median time to a PFS event was 9.7 months among those with diabetes and 10.8 months among those without diabetes (HR = 1.16, 95% CI = 1.03 to 1.30; P = .02). Patients with diabetes were more likely to experience no less than grade 3 hypertension (8.1% vs 4.4%; P = .054) but were not more likely to experience other adverse events, including neuropathy.
Conclusions
Diabetes is associated with an increased risk of mortality and tumor progression in patients with advanced or metastatic CRC. Patients with diabetes tolerate first-line treatment with chemotherapy and monoclonal antibodies similarly to patients without diabetes
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