262 research outputs found
Hemochromatosis gene mutations may affect the survival of patients with myelodysplastic syndrome
The pre-main sequence binary HK Ori : Spectro-astrometry and EXPORT data
In this paper we present multi-epoch observations of the pre-main sequence
binary HK Ori. These data have been drawn from the EXPORT database and are
complemented by high quality spectro-astrometric data of the system. The
spectroscopic data appear to be very well represented by a combination of an A
dwarf star spectrum superposed on a (sub-)giant G-type spectrum. The radial
velocity of the system is consistent with previous determinations, and does not
reveal binary motion, as expected for a wide binary. The spectral, photometric
and polarimetric properties and variability of the system indicate that the
active object in the system is a T Tauri star with UX Ori characteristics. The
spectro-astrometry of HK Ori is sensitive down to milli-arcsecond scales and
confirms the speckle interferometric results from Leinert et al. The
spectro-astrometry allows with fair certainty the identification of the active
star within the binary, which we suggest to be a G-type T Tauri star based on
its spectral characteristics.Comment: MNRAS in press 8 pages 7 figure
The effects of linkage disequilibrium in large scale SNP datasets for MDR
<p>Abstract</p> <p>Background</p> <p>In the analysis of large-scale genomic datasets, an important consideration is the power of analytical methods to identify accurate predictive models of disease. When trying to assess sensitivity from such analytical methods, a confounding factor up to this point has been the presence of linkage disequilibrium (LD). In this study, we examined the effect of LD on the sensitivity of the Multifactor Dimensionality Reduction (MDR) software package.</p> <p>Results</p> <p>Four relative amounts of LD were simulated in multiple one- and two-locus scenarios for which the position of the functional SNP(s) within LD blocks varied. Simulated data was analyzed with MDR to determine the sensitivity of the method in different contexts, where the sensitivity of the method was gauged as the number of times out of 100 that the method identifies the correct one- or two-locus model as the best overall model. As the amount of LD increases, the sensitivity of MDR to detect the correct functional SNP drops but the sensitivity to detect the disease signal and find an indirect association increases.</p> <p>Conclusions</p> <p>Higher levels of LD begin to confound the MDR algorithm and lead to a drop in sensitivity with respect to the identification of a direct association; it does not, however, affect the ability to detect indirect association. Careful examination of the solution models generated by MDR reveals that MDR can identify loci in the correct LD block; though it is not always the functional SNP. As such, the results of MDR analysis in datasets with LD should be carefully examined to consider the underlying LD structure of the dataset.</p
Can Jupiters be found by monitoring Galactic Bulge microlensing events from northern sites?
In 1998 the EXPORT team monitored microlensing event lightcurves using a CCD
camera on the IAC 0.8m telescope on Tenerife to evaluate the prospect of using
northern telescopes to find microlens anomalies that reveal planets orbiting
the lens stars. The high airmass and more limited time available for
observations of Galactic Bulge sources makes a northern site less favourable
for microlensing planet searches. However, there are potentially a large number
of northern 1m class telescopes that could devote a few hours per night to
monitor ongoing microlensing events. Our IAC observations indicate that
accuracies sufficient to detect planets can be achieved despite the higher
airmass.Comment: 8 pages, 14 figures, 1 bbl file, based on EXPORT observations,
accepted by MNRA
A Triple Protostar System Formed via Fragmentation of a Gravitationally Unstable Disk
Binary and multiple star systems are a frequent outcome of the star formation
process, and as a result, almost half of all sun-like stars have at least one
companion star. Theoretical studies indicate that there are two main pathways
that can operate concurrently to form binary/multiple star systems: large scale
fragmentation of turbulent gas cores and filaments or smaller scale
fragmentation of a massive protostellar disk due to gravitational instability.
Observational evidence for turbulent fragmentation on scales of 1000~AU has
recently emerged. Previous evidence for disk fragmentation was limited to
inferences based on the separations of more-evolved pre-main sequence and
protostellar multiple systems. The triple protostar system L1448 IRS3B is an
ideal candidate to search for evidence of disk fragmentation. L1448 IRS3B is in
an early phase of the star formation process, likely less than 150,000 years in
age, and all protostars in the system are separated by 200~AU. Here we
report observations of dust and molecular gas emission that reveal a disk with
spiral structure surrounding the three protostars. Two protostars near the
center of the disk are separated by 61 AU, and a tertiary protostar is
coincident with a spiral arm in the outer disk at a 183 AU separation. The
inferred mass of the central pair of protostellar objects is 1 M,
while the disk surrounding the three protostars has a total mass of 0.30
M_{\sun}. The tertiary protostar itself has a minimum mass of 0.085
M. We demonstrate that the disk around L1448 IRS3B appears susceptible
to disk fragmentation at radii between 150~AU and 320~AU, overlapping with the
location of the tertiary protostar. This is consistent with models for a
protostellar disk that has recently undergone gravitational instability,
spawning one or two companion stars.Comment: Published in Nature on Oct. 27th. 24 pages, 8 figure
Task-Related Effects on the Temporal and Spatial Dynamics of Resting-State Functional Connectivity in the Default Network
Recent evidence points to two potentially fundamental aspects of the default network (DN), which have been relatively understudied. One is the temporal nature of the functional interactions among nodes of the network in the resting-state, usually assumed to be static. The second is possible influences of previous brain states on the spatial patterns (i.e., the brain regions involved) of functional connectivity (FC) in the DN at rest. The goal of the current study was to investigate modulations in both the spatial and temporal domains. We compared the resting-state FC of the DN in two runs that were separated by a 45 minute interval containing cognitive task execution. We used partial least squares (PLS), which allowed us to identify FC spatiotemporal patterns in the two runs and to determine differences between them. Our results revealed two primary modes of FC, assessed using a posterior cingulate seed β a robust correlation among DN regions that is stable both spatially and temporally, and a second pattern that is reduced in spatial extent and more variable temporally after cognitive tasks, showing switching between connectivity with certain DN regions and connectivity with other areas, including some task-related regions. Therefore, the DN seems to exhibit two simultaneous FC dynamics at rest. The first is spatially invariant and insensitive to previous brain states, suggesting that the DN maintains some temporally stable functional connections. The second dynamic is more variable and is seen more strongly when the resting-state follows a period of task execution, suggesting an after-effect of the cognitive activity engaged during task that carries over into resting-state periods
Cell-free H-cluster Synthesis and [FeFe] Hydrogenase Activation: All Five CO and CNβ Ligands Derive from Tyrosine
[FeFe] hydrogenases are promising catalysts for producing hydrogen as a sustainable fuel and chemical feedstock, and they also serve as paradigms for biomimetic hydrogen-evolving compounds. Hydrogen formation is catalyzed by the H-cluster, a unique iron-based cofactor requiring three carbon monoxide (CO) and two cyanide (CNβ) ligands as well as a dithiolate bridge. Three accessory proteins (HydE, HydF, and HydG) are presumably responsible for assembling and installing the H-cluster, yet their precise roles and the biosynthetic pathway have yet to be fully defined. In this report, we describe effective cell-free methods for investigating H-cluster synthesis and [FeFe] hydrogenase activation. Combining isotopic labeling with FTIR spectroscopy, we conclusively show that each of the CO and CNβ ligands derive respectively from the carboxylate and amino substituents of tyrosine. Such in vitro systems with reconstituted pathways comprise a versatile approach for studying biosynthetic mechanisms, and this work marks a significant step towards an understanding of both the protein-protein interactions and complex reactions required for H-cluster assembly and hydrogenase maturation
Voltage-Gated Ion Channel Dysfunction Precedes Cardiomyopathy Development in the Dystrophic Heart
Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is associated with severe cardiac complications including cardiomyopathy and cardiac arrhythmias. Recent research suggests that impaired voltage-gated ion channels in dystrophic cardiomyocytes accompany cardiac pathology. It is, however, unknown if the ion channel defects are primary effects of dystrophic gene mutations, or secondary effects of the developing cardiac pathology.To address this question, we first investigated sodium channel impairments in cardiomyocytes derived from dystrophic neonatal mice prior to cardiomyopahty development, by using the whole cell patch clamp technique. Besides the most common model for DMD, the dystrophin-deficient mdx mouse, we also used mice additionally carrying an utrophin mutation. In neonatal cardiomyocytes, dystrophin-deficiency generated a 25% reduction in sodium current density. In addition, extra utrophin-deficiency significantly altered sodium channel gating parameters. Moreover, also calcium channel inactivation was considerably reduced in dystrophic neonatal cardiomyocytes, suggesting that ion channel abnormalities are universal primary effects of dystrophic gene mutations. To assess developmental changes, we also studied sodium channel impairments in cardiomyocytes derived from dystrophic adult mice, and compared them with the respective abnormalities in dystrophic neonatal cells. Here, we found a much stronger sodium current reduction in adult cardiomyocytes. The described sodium channel impairments slowed the upstroke of the action potential in adult cardiomyocytes, and only in dystrophic adult mice, the QRS interval of the electrocardiogram was prolonged.Ion channel impairments precede pathology development in the dystrophic heart, and may thus be considered potential cardiomyopathy triggers
ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma
<p>Abstract</p> <p>Background</p> <p>Cancer cells display widespread changes in DNA methylation that may lead to genetic instability by global hypomethylation and aberrant silencing of tumor suppressor genes by focal hypermethylation. In turn, altered DNA methylation patterns have been used to identify putative tumor suppressor genes.</p> <p>Methods</p> <p>In a methylation screening approach, we identified <it>ECRG4 </it>as a differentially methylated gene. We analyzed different cancer cells for <it>ECRG4 </it>promoter methylation by COBRA and bisulfite sequencing. Gene expression analysis was carried out by semi-quantitative RT-PCR. The <it>ECRG4 </it>coding region was cloned and transfected into colorectal carcinoma cells. Cell growth was assessed by MTT and BrdU assays. ECRG4 localization was analyzed by fluorescence microscopy and Western blotting after transfection of an <it>ECRG4-eGFP </it>fusion gene.</p> <p>Results</p> <p>We found a high frequency of <it>ECRG4 </it>promoter methylation in various cancer cell lines. Remarkably, aberrant methylation of <it>ECRG4 </it>was also found in primary human tumor tissues, including samples from colorectal carcinoma and from malignant gliomas. <it>ECRG4 </it>hypermethylation associated strongly with transcriptional silencing and its expression could be re-activated <it>in vitro </it>by demethylating treatment with 5-aza-2'-deoxycytidine. Overexpression of <it>ECRG4 </it>in colorectal carcinoma cells led to a significant decrease in cell growth. In transfected cells, ECRG4 protein was detectable within the Golgi secretion machinery as well as in the culture medium.</p> <p>Conclusions</p> <p><it>ECRG4 </it>is silenced via promoter hypermethylation in different types of human cancer cells. Its gene product may act as inhibitor of cell proliferation in colorectal carcinoma cells and may play a role as extracellular signaling molecule.</p
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