447 research outputs found
The Switch from NF-YAl to NF-YAs Isoform Impairs Myotubes Formation
NF-YA, the regulatory subunit of the trimeric transcription factor (TF) NF-Y, is regulated by alternative splicing (AS) generating two major isoforms, "long" (NF-YAl) and "short" (NF-YAs). Muscle cells express NF-YAl. We ablated exon 3 in mouse C2C12 cells by a four-guide CRISPR/Cas9n strategy, obtaining clones expressing exclusively NF-YAs (C2-YAl-KO). C2-YAl-KO cells grow normally, but are unable to differentiate. Myogenin and-to a lesser extent, MyoD- levels are substantially lower in C2-YAl-KO, before and after differentiation. Expression of the fusogenic Myomaker and Myomixer genes, crucial for the early phases of the process, is not induced. Myomaker and Myomixer promoters are bound by MyoD and Myogenin, and Myogenin overexpression induces their expression in C2-YAl-KO. NF-Y inactivation reduces MyoD and Myogenin, but not directly: the Myogenin promoter is CCAAT-less, and the canonical CCAAT of the MyoD promoter is not bound by NF-Y in vivo. We propose that NF-YAl, but not NF-YAs, maintains muscle commitment by indirectly regulating Myogenin and MyoD expression in C2C12 cells. These experiments are the first genetic evidence that the two NF-YA isoforms have functionally distinct roles
Relativistic effects and two-body currents in using out-of-plane detection
Measurements of the reaction were performed
using an 800-MeV polarized electron beam at the MIT-Bates Linear Accelerator
and with the out-of-plane magnetic spectrometers (OOPS). The
longitudinal-transverse, and , and the
transverse-transverse, , interference responses at a missing momentum
of 210 MeV/c were simultaneously extracted in the dip region at Q=0.15
(GeV/c). On comparison to models of deuteron electrodisintegration, the
data clearly reveal strong effects of relativity and final-state interactions,
and the importance of the two-body meson-exchange currents and isobar
configurations. We demonstrate that these effects can be disentangled and
studied by extracting the interference response functions using the novel
out-of-plane technique.Comment: 4 pages, 4 figures, and submitted to PRL for publicatio
A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region
The coincidence cross-section and the interference structure function, R_LT,
were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and
central momentum transfer of q=400 MeV/c. The measurement was at an opening
angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to
65 MeV. The R_LT structure function is found to be consistent with zero for E_m
> 50 MeV, confirming an earlier study which indicated that R_L vanishes in this
region. The integrated strengths of the p- and s-shell are compared with a
Distorted Wave Impulse Approximation calculation. The s-shell strength and
shape are compared with a Hartree Fock-Random Phase Approximation calculation.
The DWIA calculation overestimates the cross sections for p- and s-shell proton
knockout as expected, but surprisingly agrees with the extracted R_LT value for
both shells. The HF-RPA calculation describes the data more consistently, which
may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.
Dysregulation of NFâY splicing drives metabolic rewiring and aggressiveness in colon cancer
NF-Y is an evolutionarily conserved transcription factor that binds specifically to the CCAAT
elements of eukaryotic genes, most of which frequently deregulated in cancer. NF-YA, the
regulatory subunit of the NF-Y complex, has two isoforms generated by alternative splicing,
NF-YAl and NF-YAs, which differ in the transactivation domain.
Transcriptomic data from The Cancer Genome Atlas (TCGA) database highlighted a
significant increase in the expression of NF-YAs at the expense of NF-YAl in colorectal cancer
(CRC), compared to healthy tissues. Despite this, high NF-YAl levels predict lower patientsâ
survival and distinguish the mesenchymal molecular subtype CMS4, which is characterized by
the worst prognosis.
Through the analysis of 3D cellular models, we demonstrated that altered expression of genes
related to extracellular matrix and epithelial-mesenchymal transition sustains enhanced
migratory and invasive behavior of NF-YAl-transduced cells. Moreover, the integration of
metabolomics, bioenergetics and transcriptional analyses demonstrated a direct role for NFYAl
in metabolic flexibility of cancer cells that adjust their metabolism in response to
environmental changes to potentiate migration. The zebrafish xenograft model confirmed the
metastatic potential triggered by NF-YAl in CRC cells.
Altogether, our data highlight the transcriptional role of NF-YAl in CRC aggressiveness and
suggest splice-switching strategies to hinder NF-YAl-induced metastatic dissemination
Precise 3D track reconstruction algorithm for the ICARUS T600 liquid argon time projection chamber detector
Liquid Argon Time Projection Chamber (LAr TPC) detectors offer charged
particle imaging capability with remarkable spatial resolution. Precise event
reconstruction procedures are critical in order to fully exploit the potential
of this technology. In this paper we present a new, general approach of
three-dimensional reconstruction for the LAr TPC with a practical application
to track reconstruction. The efficiency of the method is evaluated on a sample
of simulated tracks. We present also the application of the method to the
analysis of real data tracks collected during the ICARUS T600 detector
operation with the CNGS neutrino beam.Comment: Submitted to Advances in High Energy Physic
Measurement of the Transverse-Longitudinal Cross Sections in the p (e,e'p)pi0 Reaction in the Delta Region
Accurate measurements of the p(e,e?p)pi0 reaction were performed at
Q^2=0.127(GeV/c)^2 in the Delta resonance energy region. The experiments at the
MIT-Bates Linear Accelerator used an 820 MeV polarized electron beam with the
out of plane magnetic spectrometer system (OOPS). In this paper we report the
first simultaneous determination of both the TL and TL? (``fifth" or polarized)
cross sections at low Q^{2} where the pion cloud contribution dominates the
quadrupole amplitudes (E2 and C2). The real and imaginary parts of the
transverse-longitudinal cross section provide both a sensitive determination of
the Coulomb quadrupole amplitude and a test of reaction calculations.
Comparisons with model calculations are presented. The empirical MAID
calculation gives the best overall agreement with this accurate data. The
parameters of this model for the values of the resonant multipoles are
|M_{1+}(I=3/2)|= (40.9 \pm 0.3)10^{-3}/m_pi, CMR= C2/M1= -6.5 \pm 0.3%,
EMR=E2/M1=-2.2 \pm 0.9%, where the errors are due to the experimental
uncertainties.Comment: 10 pages, 3 figures, minor corrections and addition
Search for anomalies in the {\nu}e appearance from a {\nu}{\mu} beam
We report an updated result from the ICARUS experiment on the search for
{\nu}{\mu} ->{\nu}e anomalies with the CNGS beam, produced at CERN with an
average energy of 20 GeV and travelling 730 km to the Gran Sasso Laboratory.
The present analysis is based on a total sample of 1995 events of CNGS neutrino
interactions, which corresponds to an almost doubled sample with respect to the
previously published result. Four clear {\nu}e events have been visually
identified over the full sample, compared with an expectation of 6.4 +- 0.9
events from conventional sources. The result is compatible with the absence of
additional anomalous contributions. At 90% and 99% confidence levels the limits
to possible oscillated events are 3.7 and 8.3 respectively. The corresponding
limit to oscillation probability becomes consequently 3.4 x 10-3 and 7.6 x 10-3
respectively. The present result confirms, with an improved sensitivity, the
early result already published by the ICARUS collaboration
Performance Of A Liquid Argon Time Projection Chamber Exposed To The WANF Neutrino Beam
We present the results of the first exposure of a Liquid Argon TPC to a
multi-GeV neutrino beam. The data have been collected with a 50 liters
ICARUS-like chamber located between the CHORUS and NOMAD experiments at the
CERN West Area Neutrino Facility (WANF). We discuss both the instrumental
performance of the detector and its capability to identify and reconstruct low
multiplicity neutrino interactions.Comment: 14 pages, 12 figures. Submitted for publication to Physical Review
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