236 research outputs found
Vida, enfermedad y muerte en dos pueblos finlandeses durante 1751-1850
X Congreso Nacional de Paleopatología. Univesidad Autónoma de Madrid, septiembre de 200
Un caso de betatalasemia en un niño de una necrópolis tebana del Imperio Nuevo. La etiopatogenia de la cribra orbitalia a revisión
X Congreso Nacional de Paleopatología. Univesidad Autónoma de Madrid, septiembre de 200
Paleopatología en la tumba del gobernador egipcio Monthemhat: los resultados definitivos
X Congreso Nacional de Paleopatología. Univesidad Autónoma de Madrid, septiembre de 200
IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.
The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D:IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer's Disease, notably apolipoprotein-e. Lastly, using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 as a target of IRF3 that is relevant across various neuroinflammatory disorders. Together, our results identify IRF3 as an important regulator of LPS-mediated neuroinflammatory responses and highlight IRF3 as a central regulator of disease-specific gene activation in different neuroinflammatory diseases
Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis.
Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS-/-) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS-/- mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS-/- livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease
Quantum Backaction on kg-Scale Mirrors: Observation of Radiation Pressure Noise in the Advanced Virgo Detector
The quantum radiation pressure and the quantum shot noise in laser-interferometric gravitational wave detectors constitute a macroscopic manifestation of the Heisenberg inequality. If quantum shot noise can be easily observed, the observation of quantum radiation pressure noise has been elusive, so far, due to the technical noise competing with quantum effects. Here, we discuss the evidence of quantum radiation pressure noise in the Advanced Virgo gravitational wave detector. In our experiment, we inject squeezed vacuum states of light into the interferometer in order to manipulate the quantum backaction on the 42 kg mirrors and observe the corresponding quantum noise driven displacement at frequencies between 30 and 70 Hz. The experimental data, obtained in various interferometer configurations, is tested against the Advanced Virgo detector quantum noise model which confirmed the measured magnitude of quantum radiation pressure noise
Virgo Detector Characterization and Data Quality during the O3 run
The Advanced Virgo detector has contributed with its data to the rapid growth
of the number of detected gravitational-wave signals in the past few years,
alongside the two LIGO instruments. First, during the last month of the
Observation Run 2 (O2) in August 2017 (with, most notably, the compact binary
mergers GW170814 and GW170817) and then during the full Observation Run 3 (O3):
an 11 months data taking period, between April 2019 and March 2020, that led to
the addition of about 80 events to the catalog of transient gravitational-wave
sources maintained by LIGO, Virgo and KAGRA. These discoveries and the manifold
exploitation of the detected waveforms require an accurate characterization of
the quality of the data, such as continuous study and monitoring of the
detector noise. These activities, collectively named {\em detector
characterization} or {\em DetChar}, span the whole workflow of the Virgo data,
from the instrument front-end to the final analysis. They are described in
details in the following article, with a focus on the associated tools, the
results achieved by the Virgo DetChar group during the O3 run and the main
prospects for future data-taking periods with an improved detector.Comment: 86 pages, 33 figures. This paper has been divided into two articles
which supercede it and have been posted to arXiv on October 2022. Please use
these new preprints as references: arXiv:2210.15634 (tools and methods) and
arXiv:2210.15633 (results from the O3 run
Virgo Detector Characterization and Data Quality: results from the O3 run
The Advanced Virgo detector has contributed with its data to the rapid growth
of the number of detected gravitational-wave (GW) signals in the past few
years, alongside the two Advanced LIGO instruments. First during the last month
of the Observation Run 2 (O2) in August 2017 (with, most notably, the compact
binary mergers GW170814 and GW170817), and then during the full Observation Run
3 (O3): an 11-months data taking period, between April 2019 and March 2020,
that led to the addition of about 80 events to the catalog of transient GW
sources maintained by LIGO, Virgo and now KAGRA. These discoveries and the
manifold exploitation of the detected waveforms require an accurate
characterization of the quality of the data, such as continuous study and
monitoring of the detector noise sources. These activities, collectively named
{\em detector characterization and data quality} or {\em DetChar}, span the
whole workflow of the Virgo data, from the instrument front-end hardware to the
final analyses. They are described in details in the following article, with a
focus on the results achieved by the Virgo DetChar group during the O3 run.
Concurrently, a companion article describes the tools that have been used by
the Virgo DetChar group to perform this work.Comment: 57 pages, 18 figures. To be submitted to Class. and Quantum Grav.
This is the "Results" part of preprint arXiv:2205.01555 [gr-qc] which has
been split into two companion articles: one about the tools and methods, the
other about the analyses of the O3 Virgo dat
Virgo Detector Characterization and Data Quality: tools
Detector characterization and data quality studies -- collectively referred
to as {\em DetChar} activities in this article -- are paramount to the
scientific exploitation of the joint dataset collected by the LIGO-Virgo-KAGRA
global network of ground-based gravitational-wave (GW) detectors. They take
place during each phase of the operation of the instruments (upgrade, tuning
and optimization, data taking), are required at all steps of the dataflow (from
data acquisition to the final list of GW events) and operate at various
latencies (from near real-time to vet the public alerts to offline analyses).
This work requires a wide set of tools which have been developed over the years
to fulfill the requirements of the various DetChar studies: data access and
bookkeeping; global monitoring of the instruments and of the different steps of
the data processing; studies of the global properties of the noise at the
detector outputs; identification and follow-up of noise peculiar features
(whether they be transient or continuously present in the data); quick
processing of the public alerts. The present article reviews all the tools used
by the Virgo DetChar group during the third LIGO-Virgo Observation Run (O3,
from April 2019 to March 2020), mainly to analyse the Virgo data acquired at
EGO. Concurrently, a companion article focuses on the results achieved by the
DetChar group during the O3 run using these tools.Comment: 44 pages, 16 figures. To be submitted to Class. and Quantum Grav.
This is the "Tools" part of preprint arXiv:2205.01555 [gr-qc] which has been
split into two companion articles: one about the tools and methods, the other
about the analyses of the O3 Virgo dat
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