585 research outputs found
Asymmetrical distribution of non-conserved regulatory sequences at PHOX2B is reflected at the ENCODE loci and illuminates a possible genome-wide trend
<p>Abstract</p> <p>Background</p> <p>Transcriptional regulatory elements are central to development and interspecific phenotypic variation. Current regulatory element prediction tools rely heavily upon conservation for prediction of putative elements. Recent <it>in vitro </it>observations from the ENCODE project combined with <it>in vivo </it>analyses at the zebrafish <it>phox2b </it>locus suggests that a significant fraction of regulatory elements may fall below commonly applied metrics of conservation. We propose to explore these observations <it>in vivo </it>at the human <it>PHOX2B </it>locus, and also evaluate the potential evidence for genome-wide applicability of these observations through a novel analysis of extant data.</p> <p>Results</p> <p>Transposon-based transgenic analysis utilizing a tiling path proximal to human <it>PHOX2B </it>in zebrafish recapitulates the observations at the zebrafish <it>phox2b </it>locus of both conserved and non-conserved regulatory elements. Analysis of human sequences conserved with previously identified zebrafish <it>phox2b </it>regulatory elements demonstrates that the orthologous sequences exhibit overlapping regulatory control. Additionally, analysis of non-conserved sequences scattered over 135 kb 5' to <it>PHOX2B</it>, provides evidence of non-conserved regulatory elements positively biased with close proximity to the gene. Furthermore, we provide a novel analysis of data from the ENCODE project, finding a non-uniform distribution of regulatory elements consistent with our <it>in vivo </it>observations at <it>PHOX2B</it>. These observations remain largely unchanged when one accounts for the sequence repeat content of the assayed intervals, when the intervals are sub-classified by biological role (developmental versus non-developmental), or by gene density (gene desert versus non-gene desert).</p> <p>Conclusion</p> <p>While regulatory elements frequently display evidence of evolutionary conservation, a fraction appears to be undetected by current metrics of conservation. <it>In vivo </it>observations at the <it>PHOX2B </it>locus, supported by our analyses of <it>in vitro </it>data from the ENCODE project, suggest that the risk of excluding non-conserved sequences in a search for regulatory elements may decrease as distance from the gene increases. Our data combined with the ENCODE data suggests that this may represent a genome wide trend.</p
Identification of RNA binding motif proteins essential for cardiovascular development
Background
We recently identified Rbm24 as a novel gene expressed during mouse cardiac development. Due to its tightly restricted and persistent expression from formation of the cardiac crescent onwards and later in forming vasculature we posited it to be a key player in cardiogenesis with additional roles in vasculogenesis and angiogenesis.
Results
To determine the role of this gene in cardiac development, we have identified its zebrafish orthologs (rbm24a and rbm24b), and functionally evaluated them during zebrafish embryogenesis. Consistent with our underlying hypothesis, reduction in expression of either ortholog through injection of morpholino antisense oligonucleotides results in cardiogenic defects including cardiac looping and reduced circulation, leading to increasing pericardial edema over time. Additionally, morphant embryos for either ortholog display incompletely overlapping defects in the forming vasculature of the dorsal aorta (DA), posterior caudal vein (PCV) and caudal vein (CV) which are the first blood vessels to form in the embryo. Vasculogenesis and early angiogenesis in the trunk were similarly compromised in rbm24 morphant embryos at 48 hours post fertilization (hpf). Subsequent vascular maintenance was impaired in both rbm24 morphants with substantial vessel degradation noted at 72 hpf.
Conclusion
Taken collectively, our functional data support the hypothesis that rbm24a and rbm24b are key developmental cardiac genes with unequal roles in cardiovascular formation
Identification of RNA binding motif proteins essential for cardiovascular development
Background: We recently identified Rbm24 as a novel gene expressed during mouse cardiac development. Due to its tightly restricted and persistent expression from formation of the cardiac crescent onwards and later in forming vasculature we posited it to be a key player in cardiogenesis with additional roles in vasculogenesis and angiogenesis. Results: To determine the role of this gene in cardiac development, we have identified its zebrafish orthologs (rbm24a and rbm24b), and functionally evaluated them during zebrafish embryogenesis. Consistent with our underlying hypothesis, reduction in expression of either ortholog through injection of morpholino antisense oligonucleotides results in cardiogenic defects including cardiac looping and reduced circulation, leading to increasing pericardial edema over time. Additionally, morphant embryos for either ortholog display incompletely overlapping defects in the forming vasculature of the dorsal aorta (DA), posterior caudal vein (PCV) and caudal vein (CV) which are the first blood vessels to form in the embryo. Vasculogenesis and early angiogenesis in the trunk were similarly compromised in rbm24 morphant embryos at 48 hours post fertilization (hpf). Subsequent vascular maintenance was impaired in both rbm24 morphants with substantial vessel degradation noted at 72 hpf. Conclusion: Taken collectively, our functional data support the hypothesis that rbm24a and rbm24b are key developmental cardiac genes with unequal roles in cardiovascular formation
Associations with photoreceptor thickness measures in the UK Biobank.
Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness
Event-by-event fluctuations in Mean and Mean in sqrt(s_NN) = 130 GeV Au+Au Collisions
Distributions of event-by-event fluctuations of the mean transverse momentum
and mean transverse energy near mid-rapidity have been measured in Au+Au
collisions at sqrt(s_NN) = 130 GeV at RHIC. By comparing the distributions to
what is expected for statistically independent particle emission, the magnitude
of non-statistical fluctuations in mean transverse momentum is determined to be
consistent with zero. Also, no significant non-random fluctuations in mean
transverse energy are observed. By constructing a fluctuation model with two
event classes that preserve the mean and variance of the semi-inclusive p_T or
e_T spectra, we exclude a region of fluctuations in sqrt(s_NN) = 130 GeV Au+Au
collisions.Comment: 10 pages, RevTeX 3, 7 figures, 4 tables, 307 authors, submitted to
Phys. Rev. C on 22 March 2002. Plain text data tables for the points plotted
in figures for this and previous PHENIX publications are (will be made)
publicly available at
http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
Measurement of the mid-rapidity transverse energy distribution from GeV Au+Au collisions at RHIC
The first measurement of energy produced transverse to the beam direction at
RHIC is presented. The mid-rapidity transverse energy density per participating
nucleon rises steadily with the number of participants, closely paralleling the
rise in charged-particle density, such that E_T / N_ch remains relatively
constant as a function of centrality. The energy density calculated via
Bjorken's prescription for the 2% most central Au+Au collisions at
sqrt(s_NN)=130 GeV is at least epsilon_Bj = 4.6 GeV/fm^3 which is a factor of
1.6 larger than found at sqrt(s_NN)=17.2 GeV (Pb+Pb at CERN).Comment: 307 authors, 6 pages, 4 figures, 1 table, submitted to PRL 4/18/2001;
revised version submitted to PRL 5/24/200
Measurements of double-helicity asymmetries in inclusive production in longitudinally polarized collisions at GeV
We report the double helicity asymmetry, , in inclusive
production at forward rapidity as a function of transverse momentum
and rapidity . The data analyzed were taken during
GeV longitudinally polarized collisions at the Relativistic Heavy Ion
Collider (RHIC) in the 2013 run using the PHENIX detector. At this collision
energy, particles are predominantly produced through gluon-gluon
scatterings, thus is sensitive to the gluon polarization
inside the proton. We measured by detecting the decay
daughter muon pairs within the PHENIX muon spectrometers in the
rapidity range . In this kinematic range, we measured the
to be ~(stat)~~(syst). The
can be expressed to be proportional to the product of the
gluon polarization distributions at two distinct ranges of Bjorken : one at
moderate range where recent RHIC data of jet and
double helicity spin asymmetries have shown evidence for significant gluon
polarization, and the other one covering the poorly known small- region . Thus our new results could be used to further
constrain the gluon polarization for .Comment: 335 authors, 10 pages, 4 figures, 3 tables, 2013 data. Version
accepted for publication by Phys. Rev. D. Plain text data tables for the
points plotted in figures for this and previous PHENIX publications are (or
will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Nuclear dependence of the transverse-single-spin asymmetry for forward neutron production in polarized collisions at GeV
During 2015 the Relativistic Heavy Ion Collider (RHIC) provided collisions of
transversely polarized protons with Au and Al nuclei for the first time,
enabling the exploration of transverse-single-spin asymmetries with heavy
nuclei. Large single-spin asymmetries in very forward neutron production have
been previously observed in transversely polarized collisions at
RHIC, and the existing theoretical framework that was successful in describing
the single-spin asymmetry in collisions predicts only a moderate
atomic-mass-number () dependence. In contrast, the asymmetries observed at
RHIC in collisions showed a surprisingly strong dependence in
inclusive forward neutron production. The observed asymmetry in Al
collisions is much smaller, while the asymmetry in Au collisions is a
factor of three larger in absolute value and of opposite sign. The interplay of
different neutron production mechanisms is discussed as a possible explanation
of the observed dependence.Comment: 315 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for
publication in Phys. Rev. Lett. Plain text data tables for the points plotted
in figures for this and previous PHENIX publications are (or will be)
publicly available at http://www.phenix.bnl.gov/papers.htm
J/psi suppression at forward rapidity in Au+Au collisions at sqrt(s_NN)=39 and 62.4 GeV
We present measurements of the J/psi invariant yields in sqrt(s_NN)=39 and
62.4 GeV Au+Au collisions at forward rapidity (1.2<|y|<2.2). Invariant yields
are presented as a function of both collision centrality and transverse
momentum. Nuclear modifications are obtained for central relative to peripheral
Au+Au collisions (R_CP) and for various centrality selections in Au+Au relative
to scaled p+p cross sections obtained from other measurements (R_AA). The
observed suppression patterns at 39 and 62.4 GeV are quite similar to those
previously measured at 200 GeV. This similar suppression presents a challenge
to theoretical models that contain various competing mechanisms with different
energy dependencies, some of which cause suppression and others enhancement.Comment: 365 authors, 10 pages, 11 figures, 4 tables. Submitted to Phys. Rev.
C. Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
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