545 research outputs found
Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs
The reference annotations made for a genome sequence provide the framework
for all subsequent analyses of the genome. Correct annotation is particularly
important when interpreting the results of RNA-seq experiments where short
sequence reads are mapped against the genome and assigned to genes according to
the annotation. Inconsistencies in annotations between the reference and the
experimental system can lead to incorrect interpretation of the effect on RNA
expression of an experimental treatment or mutation in the system under study.
Until recently, the genome-wide annotation of 3-prime untranslated regions
received less attention than coding regions and the delineation of intron/exon
boundaries. In this paper, data produced for samples in Human, Chicken and A.
thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing
technology from Helicos Biosciences which locates 3-prime polyadenylation sites
to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine
examples are illustrated where this combination of data allowed: (1) gene and
3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb);
(2) disentangling of gene expression in complex regions; (3) clearer
interpretation of small RNA expression and (4) identification of novel genes.
While the specific examples displayed here may become obsolete as genome
sequences and their annotations are refined, the principles laid out in this
paper will be of general use both to those annotating genomes and those seeking
to interpret existing publically available annotations in the context of their
own experimental dataComment: 44 pages, 9 figure
Mapping Exoplanets
The varied surfaces and atmospheres of planets make them interesting places
to live, explore, and study from afar. Unfortunately, the great distance to
exoplanets makes it impossible to resolve their disk with current or near-term
technology. It is still possible, however, to deduce spatial inhomogeneities in
exoplanets provided that different regions are visible at different
times---this can be due to rotation, orbital motion, and occultations by a
star, planet, or moon. Astronomers have so far constructed maps of thermal
emission and albedo for short period giant planets. These maps constrain
atmospheric dynamics and cloud patterns in exotic atmospheres. In the future,
exo-cartography could yield surface maps of terrestrial planets, hinting at the
geophysical and geochemical processes that shape them.Comment: Updated chapter for Handbook of Exoplanets, eds. Deeg & Belmonte. 17
pages, including 6 figures and 4 pages of reference
Detection of the pairwise kinematic Sunyaev-Zel'dovich effect with BOSS DR11 and the Atacama Cosmology Telescope
We present a new measurement of the kinematic Sunyaev-Zeldovich effect using
data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation
Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area,
we evaluate the mean pairwise baryon momentum associated with the positions of
50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A
non-zero signal arises from the large-scale motions of halos containing the
sample galaxies. The data fits an analytical signal model well, with the
optical depth to microwave photon scattering as a free parameter determining
the overall signal amplitude. We estimate the covariance matrix of the mean
pairwise momentum as a function of galaxy separation, using microwave sky
simulations, jackknife evaluation, and bootstrap estimates. The most
conservative simulation-based errors give signal-to-noise estimates between 3.6
and 4.1 for varying galaxy luminosity cuts. We discuss how the other error
determinations can lead to higher signal-to-noise values, and consider the
impact of several possible systematic errors. Estimates of the optical depth
from the average thermal Sunyaev-Zeldovich signal at the sample galaxy
positions are broadly consistent with those obtained from the mean pairwise
momentum signal.Comment: 15 pages, 8 figures, 2 table
Cold gas accretion in galaxies
Evidence for the accretion of cold gas in galaxies has been rapidly
accumulating in the past years. HI observations of galaxies and their
environment have brought to light new facts and phenomena which are evidence of
ongoing or recent accretion:
1) A large number of galaxies are accompanied by gas-rich dwarfs or are
surrounded by HI cloud complexes, tails and filaments. It may be regarded as
direct evidence of cold gas accretion in the local universe. It is probably the
same kind of phenomenon of material infall as the stellar streams observed in
the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI
have been found in nearby spiral galaxies. While a large fraction of this gas
is produced by galactic fountains, it is likely that a part of it is of
extragalactic origin. 3) Spirals are known to have extended and warped outer
layers of HI. It is not clear how these have formed, and how and for how long
the warps can be sustained. Gas infall has been proposed as the origin. 4) The
majority of galactic disks are lopsided in their morphology as well as in their
kinematics. Also here recent accretion has been advocated as a possible cause.
In our view, accretion takes place both through the arrival and merging of
gas-rich satellites and through gas infall from the intergalactic medium (IGM).
The infall may have observable effects on the disk such as bursts of star
formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold
gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates
needed to sustain the observed star formation (~1 Msol/yr), additional infall
of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages.
Full-resolution version available at
http://www.astron.nl/~oosterlo/accretionRevie
FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells
Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours
The influence of parents and the home environment on preschoolers' physical activity behaviours: A qualitative investigation of childcare providers' perspectives
<p>Abstract</p> <p>Background</p> <p>Physical activity offers numerous physiological and psychological benefits for young children; however, many preschool-aged children are not engaging in sufficient activity. The home environment, inclusive of parent role modeling, has been identified as influencing preschoolers' physical activity. This study sought to examine childcare providers' perspectives of the importance of parents and the home environment for supporting the physical activity behaviours of preschool-aged children (aged 2.5-5 years) attending childcare.</p> <p>Methods</p> <p>A heterogeneous sample of childcare providers (<it>n </it>= 84; response rate 39%) working at childcare facilities in London, Ontario participated. Thirteen semi-structured focus groups were conducted in London centres between February 2009 and February 2010. Focus groups were audio recorded and transcribed verbatim and inductive content analysis was used to code and classify themes. A number of strategies were used to verify the trustworthiness of the data.</p> <p>Results</p> <p>Childcare providers acknowledged their reliance on parents/guardians to create a home environment that complements the positive physical activity messaging children may receive in childcare. Moreover, childcare staff highlighted the need for positive parent role modeling and parent support to encourage active healthy lifestyles among young children.</p> <p>Conclusion</p> <p>This study's findings highlight the need for increased parent-caregiver partnering in terms of communication and cooperation in service of promoting appropriate amounts of physical activity among London preschoolers.</p
Epidemic Microclusters of Blood-Culture Proven Sepsis in Very-Low-Birth Weight Infants: Experience of the German Neonatal Network
INTRODUCTION: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. METHODS: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. RESULTS: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. DISCUSSION: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care
Effectiveness of temozolomide for primary glioblastoma multiforme in routine clinical practice
Temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiforme since 2005. To assess the effectiveness of temozolomide in routine clinical practice, we conducted an observational study at Maastricht University Medical Centre (MUMC). Data of patients receiving radiotherapy and temozolomide between January 2005 and January 2008 were retrieved from a clinical database (radiochemotherapy group), as were data of patients in a historical control group from the period before 2005 treated with radiotherapy only (radiotherapy group). The primary endpoint was overall survival. A total of 125 patients with GBM were selected to form the study cohort. Median survival benefit was 4 months: the median overall survival was 12 months (95% CI, 9.7–14.3) in the group with radiochemotherapy with temozolomide, versus 8 months (95% CI, 5.3–10.7) in the group with only radiotherapy. Progression-free survival was 7 months (95% CI, 5.5–8.5) in the radiochemotherapy group and 4 months (95% CI, 2.9-5.1) in the group with only radiotherapy. The two-year survival rate was 18% with radiochemotherapy with temozolomide against 4% with radiotherapy alone. Concomitant treatment with radiotherapy and temozolomide followed by adjuvant temozolomide resulted in grade III or IV haematological toxic effects in 9% of patients. The addition of temozolomide to radiotherapy in routine clinical practice for newly diagnosed glioblastoma resulted in a clinically meaningful survival benefit with minimal haematological toxicity, which confirms the experience of previous trials and justifies the continued use of temozolomide in routine clinical practice
A chemical survey of exoplanets with ARIEL
Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio
P73 regulates cisplatin-induced apoptosis in ovarian cancer cells via a calcium/calpain-dependent mechanism
P73 is important in drug-induced apoptosis in some cancer cells, yet its role in the regulation of chemosensitivity in ovarian cancer (OVCA) is poorly understood. Furthermore, if and how the deregulation of p73-mediated apoptosis confers resistance to cisplatin (CDDP) treatment is unclear. Here we demonstrate that TAp73α over-expression enhanced CDDP-induced PARP cleavage and apoptosis in both chemosensitive (OV2008 and A2780s) and their resistant counterparts (C13* and A2780cp) and another chemoresistant OVCA cells (Hey); in contrast, the effect of ΔNp73α over-expression was variable. P73α downregulation attenuated CDDP-induced PUMA and NOXA upregulation and apoptosis in OV2008 cells. CDDP decreased p73α steady-state protein levels in OV2008, but not in C13*, although the mRNA expression was identical. CDDP-induced p73α downregulation was mediated by a calpain-dependent pathway. CDDP induced calpain activation and enhanced its cytoplasmic interaction and co-localization with p73α in OV2008, but not C13* cells. CDDP increased the intracellular calcium concentration ([Ca2+]i) in OV2008 but not C13* whereas cyclopiazonic acid (CPA), a Ca2+-ATPase inhibitor, caused this response and calpain activation, p73α processing and apoptosis in both cell types. CDDP-induced [Ca2+]i increase in OV2008 cells was not effected by the elimination of extracellular Ca2+, but this was attenuated by the depletion of internal Ca2+ store, indicating that mobilization of intracellular Ca2+] stores was potentially involved. These findings demonstrate that p73α and its regulation by the Ca2+-mediated calpain pathway are involved in CDDP-induced apoptosis in OVCA cells and that dysregulation of Ca2+/calpain/p73 signaling may in part be the pathophysiology of CDDP resistance. Understanding the cellular and molecular mechanisms of chemoresistance will direct the development of effective strategies for the treatment of chemoresistant OVCA
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