236 research outputs found
Important cardiac transcription factor genes are accompanied by bidirectional long non-coding RNAs
BackgroundHeart development is a relatively fragile process in which many transcription factor genes show dose-sensitive characteristics such as haploinsufficiency and lower penetrance. Despite efforts to unravel the genetic mechanism for overcoming the fragility under normal conditions, our understanding still remains in its infancy. Recent studies on the regulatory mechanisms governing gene expression in mammals have revealed that long non-coding RNAs (lncRNAs) are important modulators at the transcriptional and translational levels. Based on the hypothesis that lncRNAs also play important roles in mouse heart development, we attempted to comprehensively identify lncRNAs by comparing the embryonic and adult mouse heart and brain.ResultsWe have identified spliced lncRNAs that are expressed during development and found that lncRNAs that are expressed in the heart but not in the brain are located close to genes that are important for heart development. Furthermore, we found that many important cardiac transcription factor genes are located in close proximity to lncRNAs. Importantly, many of the lncRNAs are divergently transcribed from the promoter of these genes. Since the lncRNA divergently transcribed from Tbx5 is highly evolutionarily conserved, we focused on and analyzed the transcript. We found that this lncRNA exhibits a different expression pattern than that of Tbx5, and knockdown of this lncRNA leads to embryonic lethality.ConclusionThese results suggest that spliced lncRNAs, particularly bidirectional lncRNAs, are essential regulators of mouse heart development, potentially through the regulation of neighboring transcription factor genes
Reptilian Heart Development And The Molecular Basis Of Cardiac Chamber Evolution
The emergence of terrestrial life witnessed the need for more sophisticated circulatory systems. This has evolved in birds, mammals and crocodilians into complete septation of the heart into left and right sides, allowing separate pulmonary and systemic circulatory systems, a key requirement for the evolution of endothermy(1-3). However, the evolution of the amniote heart is poorly understood. Reptilian hearts have been the subject of debate in the context of the evolution of cardiac septation: do they possess a single ventricular chamber or two incompletely septated ventricles(4-7)? Here we examine heart development in the red-eared slider turtle, Trachemys scripta elegans (a chelonian), and the green anole, Anolis carolinensis (a squamate), focusing on gene expression in the developing ventricles. Both reptiles initially form a ventricular chamber that homogenously expresses the T-box transcription factor gene Tbx5. In contrast, in birds and mammals, Tbx5 is restricted to left ventricle precursors(8,9). In later stages, Tbx5 expression in the turtle (but not anole) heart is gradually restricted to a distinct left ventricle, forming a left-right gradient. This suggests that Tbx5 expression was refined during evolution to pattern the ventricles. In support of this hypothesis, we show that loss of Tbx5 in the mouse ventricle results in a single chamber lacking distinct identity, indicating a requirement for Tbx5 in septation. Importantly, misexpression of Tbx5 throughout the developing myocardium to mimic the reptilian expression pattern also results in a single mispatterned ventricular chamber lacking septation. Thus ventricular septation is established by a steep and correctly positioned Tbx5 gradient. Our findings provide a molecular mechanism for the evolution of the amniote ventricle, and support the concept that altered expression of developmental regulators is a key mechanism of vertebrate evolution
SALL4 Expression in Gonocytes and Spermatogonial Clones of Postnatal Mouse Testes
The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC). In adults, SSCs reside within the population of undifferentiated spermatogonia (Aundiff) that expands clonally from single cells (Asingle) to form pairs (Apaired) and chains of 4, 8 and 16 Aaligned spermatogonia. Although stem cell activity is thought to reside in the population of Asingle spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4) is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0) and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in Asingle, Apaired and Aaligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of Aundiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1) SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2) SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3) SALL4 co-staining with GFRα1 and cKIT reveals distinct subpopulations of Aundiff spermatogonia that merit further investigation. © 2013 Gassei, Orwig
Measurement of radon concentrations at Super-Kamiokande
Radioactivity from radon is a major background for observing solar neutrinos
at Super-Kamiokande. In this paper, we describe the measurement of radon
concentrations at Super-Kamiokande, the method of radon reduction, and the
radon monitoring system. The measurement shows that the current low-energy
event rate between 5.0 MeV and 6.5 MeV implies a radon concentration in the
Super-Kamiokande water of less than 1.4 mBq/m.Comment: 11 pages, 4 figure
Observation of the east-west anisotropy of the atmospheric neutrino flux
The east-west anisotropy, caused by the deflection of primary cosmic rays in
the Earth's magnetic field, is observed for the first time in the flux of
atmospheric neutrinos. Using a 45 kt-year exposure of the
Super-Kamiokande detector, 552 e-like and 633 mu-like horizontally-going
events are selected in the momentum range between 400 and 3000 MeV/c.
The azimuthal distribution of e-like and mu-like events agrees with the
expectation from atmospheric neutrino flux calculations that account for the
geomagnetic field, verifying that the geomagnetic field effects in the
production of atmospheric neutrinos in the GeV energy range are well
understood.Comment: 8 pages,3 figures revtex, submitted to PR
Study of Non-Standard Neutrino Interactions with Atmospheric Neutrino Data in Super-Kamiokande I and II
In this paper we study non-standard neutrino interactions as an example of
physics beyond the standard model using atmospheric neutrino data collected
during the Super-Kamiokande I(1996-2001) and II(2003-2005) periods. We focus on
flavor-changing-neutral-currents (FCNC), which allow neutrino flavor
transitions via neutral current interactions, and effects which violate lepton
non-universality (NU) and give rise to different neutral-current
interaction-amplitudes for different neutrino flavors. We obtain a limit on the
FCNC coupling parameter, varepsilon_{mu tau}, |varepsilon_{mu tau}|<1.1 x
10^{-2} at 90%C.L. and various constraints on other FCNC parameters as a
function of the NU coupling, varepsilon_{e e}. We find no evidence of
non-standard neutrino interactions in the Super-Kamiokande atmospheric data.Comment: 12 Pages, 14 figures. To be submitted to Phys. Rev.
Search for Dark Matter WIMPs using Upward Through-going Muons in Super-Kamiokande
We present the results of indirect searches for Weakly Interacting Massive
Particles (WIMPs) with 1679.6 live days of data from the Super-Kamiokande
detector using neutrino-induced upward through-going muons. The search is
performed by looking for an excess of high energy muon neutrinos from WIMP
annihilations in the Sun, the core of the Earth, and the Galactic Center, as
compared to the number expected from the atmospheric neutrino background. No
statistically significant excess was seen. We calculate flux limits in various
angular cones around each of the above celestial objects. We obtain
conservative model-independent upper limits on WIMP-nucleon cross-section as a
function of WIMP mass and compare these results with the corresponding results
from direct dark matter detection experiments.Comment: 10 pages, 14 figures, Submitted to Phys. Rev.
Search for Differences in Oscillation Parameters for Atmospheric Neutrinos and Antineutrinos at Super-Kamiokande
We present a search for differences in the oscillations of antineutrinos and
neutrinos in the Super-Kamiokande -I, -II, and -III atmospheric neutrino
sample. Under a two-flavor disappearance model with separate mixing parameters
between neutrinos and antineutrinos, we find no evidence for a difference in
oscillation parameters. Best fit antineutrino mixing is found to be at (dm2bar,
sin2 2 thetabar) = (2.0x10^-3 eV^2, 1.0) and is consistent with the overall
Super-K measurement.Comment: 6 pages, 4 figures. Figure update
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