271 research outputs found
Star Formation Under the Outflow: The Discovery of a Non-Thermal Jet from OMC-2 FIR 3 and its Relationship to the Deeply Embedded FIR 4 Protostar
We carried out multiwavelength (0.7-5 cm), multiepoch (1994-2015) Very Large
Array (VLA) observations toward the region enclosing the bright far-IR sources
FIR 3 (HOPS 370) and FIR 4 (HOPS 108) in OMC-2. We report the detection of 10
radio sources, seven of them identified as young stellar objects. We image a
well-collimated radio jet with a thermal free-free core (VLA 11) associated
with the Class I intermediate-mass protostar HOPS 370. The jet presents several
knots (VLA 12N, 12C, 12S) of non-thermal radio emission (likely synchrotron
from shock-accelerated relativistic electrons) at distances of ~7,500-12,500 au
from the protostar, in a region where other shock tracers have been previously
identified. These knots are moving away from the HOPS 370 protostar at ~ 100
km/s. The Class 0 protostar HOPS 108, which itself is detected as an
independent, kinematically decoupled radio source, falls in the path of these
non-thermal radio knots. These results favor the previously proposed scenario
where the formation of HOPS 108 has been triggered by the impact of the HOPS
370 outflow with a dense clump. However, HOPS 108 presents a large proper
motion velocity of ~ 30 km/s, similar to that of other runaway stars in Orion,
whose origin would be puzzling within this scenario. Alternatively, an apparent
proper motion could result because of changes in the position of the centroid
of the source due to blending with nearby extended emission, variations in the
source shape, and /or opacity effects.Comment: 16 pages, 4 figures, accepted for publication in The Astrophysical
Journa
Disease-causing mutations in BEST1 gene are associated with altered sorting of bestrophin-1 protein
Doumanov, Jordan A. et al.Mutations in BEST1 gene, encoding the bestrophin-1 (Best1) protein are associated with macular dystrophies. Best1 is predominantly expressed in the retinal pigment epithelium (RPE), and is inserted in its basolateral membrane. We investigated the cellular localization in polarized MDCKII cells of disease-associated Best1 mutant proteins to study specific sorting motifs of Best1. Real-time PCR and western blots for endogenous expression of BEST1 in MDCK cells were performed. Best1 mutant constructs were generated using site-directed mutagenesis and transfected in MDCK cells. For protein sorting, confocal microscopy studies, biotinylation assays and statistical methods for quantification of mislocalization were used. Analysis of endogenous expression of BEST1 in MDCK cells revealed the presence of BEST1 transcript but no protein. Confocal microscopy and quantitative analyses indicate that transfected normal human Best1 displays a basolateral localization in MDCK cells, while cell sorting of several Best1 mutants (Y85H, Q96R, L100R, Y227N, Y227E) was altered. In contrast to constitutively active Y227E, constitutively inactive Y227F Best1 mutant localized basolaterally similar to the normal Best1 protein. Our data suggest that at least three basolateral sorting motifs might be implicated in proper Best1 basolateral localization. In addition, non-phosphorylated tyrosine 227 could play a role for basolateral delivery. © 2013 by the authors; licensee MDPI, Basel, Switzerland.This work was supported by Agence Nationale de la Recherche (Chaire d’Excellence to Shomi S.
Bhattacharya), Fondation Voir et Entendre (Young Investigator Grants to Christina Zeitz and Emeline
F. Nandrot), Centre National de la Recherche Scientifique (CNRS) and Fondation Bettencourt
Schueller (to Emeline F. Nandrot), Université Pierre et Marie Curie-Paris6 (Bonus Qualité Recherche
to Christina Zeitz), Foundation Fighting Blindness (grant number CD-CL-0808-0466-CHNO to
Isabelle Audo), Centre d’Investigation Clinique 503 recognized as a Foundation Fighting Blindness
Center (grant number C-CMM-0907-0428-INSERM04), Fundacion Progreso y Salud (to Shomi S.
Bhattacharya, Maria Luz Bellido Diaz, Abhay Krishna and Paloma Dominguez Gimenez), Instituto de
Salud Carlos III (grant number CM06/00183 to Maria Luz Bellido Diaz) and Bulgarian National
Science Fund (grant number DDVU 02/10). Additionally, the Institut de la Vision is funded by Institut
National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie-Paris 6, Centre
National de la Recherche Scientifique and Départment de Paris.Peer Reviewe
The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars IV. Unveiling the Embedded Intermediate-Mass Protostar and Disk within OMC2-FIR3/HOPS-370
We present ALMA (0.87~mm and 1.3~mm) and VLA (9~mm) observations toward the
candidate intermediate-mass protostar OMC2-FIR3 (HOPS-370;
L~314~L) at 0.1" (40~au) resolution for the continuum
emission and ~0.25" (100 au) resolution of nine molecular lines. The dust
continuum observed with ALMA at 0.87~mm and 1.3~mm resolve a near edge-on disk
toward HOPS-370 with an apparent radius of ~100 au. The VLA observations detect
both the disk in dust continuum and free-free emission extended along the jet
direction. The ALMA observations of molecular lines (HCO, SO, CHOH,
CO, CO, NS, and HCN) reveal rotation of the apparent disk
surrounding HOPS-370 orthogonal to the jet/outflow direction. We fit radiative
transfer models to both the dust continuum structure of the disk and molecular
line kinematics of the inner envelope and disk for the HCO, CHOH, NS,
and SO lines. The central protostar mass is determined to be 2.5 M_sun
with a disk radius of 94~au, when fit using combinations of the HCO,
CHOH, NS, and SO lines, consistent with an intermediate-mass protostar.
Modeling of the dust continuum and spectral energy distribution (SED) yields a
disk mass of 0.035~M (inferred dust+gas) and a dust disk radius of
62~au, thus the dust disk may have a smaller radius than the gas disk, similar
to Class II disks. In order to explain the observed luminosity with the
measured protostar mass, HOPS-370 must be accreting at a rate between 1.7 and
3.210~M~yr.Comment: Accepted to ApJ; 51 pages, 12 Figures, 7 Table
Stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau in cellular and mouse models of tauopathies
Synapses represent an important target of Alzheimer disease (AD), and alterations of their excitability are among the earliest changes associated with AD development. Synaptic activation has been shown to be protective in models of AD, and deep brain stimulation (DBS), a surgical strategy that modulates neuronal activity to treat neurological and psychiatric disorders, produced positive effects in AD patients. However, the molecular mechanisms underlying the protective role(s) of brain stimulation are still elusive. We have previously demonstrated that induction of synaptic activity exerts protection in mouse models of AD and frontotemporal dementia (FTD) by enhancing the macroautophagy/autophagy flux and lysosomal degradation of pathological MAPT/Tau. We now provide evidence that TFEB (transcription factor EB), a master regulator of lysosomal biogenesis and autophagy, is a key mediator of this cellular response. In cultured primary neurons from FTD-transgenic mice, synaptic stimulation inhibits MTORC1 signaling, thus promoting nuclear translocation of TFEB, which, in turn, induces clearance of MAPT/Tau oligomers. Conversely, synaptic activation fails to promote clearance of toxic MAPT/Tau in neurons expressing constitutively active RRAG GTPases, which sequester TFEB in the cytosol, or upon TFEB depletion. Activation of TFEB is also confirmed in vivo in DBS-stimulated AD mice. We also demonstrate that DBS reduces pathological MAPT/Tau and promotes neuroprotection in Parkinson disease patients with tauopathy. Altogether our findings indicate that stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau. This mechanism, underlying the protective effect of DBS, provides encouraging support for the use of synaptic stimulation as a therapeutic treatment against tauopathies.This work was supported by the ELKARTEK [KK-2020/00034]; Spanish Ministry of Science and Innovation [PID2019-109724RB-I00]; CIBERNED [CB06/0005/0076]; T.V. is supported by AIRC, IG 2017 #20661, and Italian Ministery of University and Research grant [PRIN2020CLZ5XWTV]
Revised Architecture and Two New Super-Earths in the HD 134606 Planetary System
Multi-planet systems exhibit a diversity of architectures that diverge from
the solar system and contribute to the topic of exoplanet demographics. Radial
velocity (RV) surveys form a crucial component of exoplanet surveys, as their
long observational baselines allow searches for more distant planetary orbits.
This work provides a significantly revised architecture for the multi-planet
system HD 134606 using both HARPS and UCLES RVs. We confirm the presence of
previously reported planets b, c, and d with periods
, , and
days, and masses , , and
Earth masses respectively, with the planet d orbit significantly
revised to over double that originally reported. We report two newly detected
super-Earths, e and f, with periods and
days, and masses and
Earth masses, respectively. In addition, we identify a
linear trend in the RV time series, and the cause of this acceleration is
deemed to be a newly detected sub-stellar companion at large separation. HD
134606 now displays four low mass planets in a compact region near the star,
one gas giant further out in the Habitable Zone, an additional massive
companion in the outer regime, and a low mass M dwarf stellar companion at
large separation, making it an intriguing target for system formation/evolution
studies. The location of planet d in the Habitable Zone proves to be an
exciting candidate for future space-based direct imaging missions, whereas
continued RV observations of this system are recommended for understanding the
nature of the massive, long period companion.Comment: 23 pages, 10 figures, 4 tables, accepted for publication in the
Astronomical Journa
The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. I. Identifying and Characterizing the Protostellar Content of the OMC-2 FIR4 and OMC-2 FIR3 Regions
We present ALMA (0.87~mm) and VLA (9~mm) observations toward OMC2-FIR4 and
OMC2-FIR3 within the Orion integral-shaped filament that are thought to be the
nearest regions of intermediate mass star formation. We characterize the
continuum sources within these regions on 40~AU (0\farcs1) scales and
associated molecular line emission at a factor of 30 better resolution
than previous observations at similar wavelengths. We identify six compact
continuum sources within OMC2-FIR4, four in OMC2-FIR3, and one additional
source just outside OMC2-FIR4. This continuum emission is tracing the inner
envelope and/or disk emission on less than 100~AU scales. HOPS-108 is the only
protostar in OMC2-FIR4 that exhibits emission from high-excitation transitions
of complex organic molecules (e.g., methanol and other lines) coincident with
the continuum emission. HOPS-370 in OMC2-FIR3 with L~~360~\lsun, also
exhibits emission from high-excitation methanol and other lines. The methanol
emission toward these two protostars is indicative of temperatures high enough
to thermally evaporate methanol from icy dust grains; overall these protostars
have characteristics similar to hot corinos. We do not identify a clear outflow
from HOPS-108 in \twco, but find evidence of interaction between the
outflow/jet from HOPS-370 and the OMC2-FIR4 region. The multitude of
observational constraints indicate that HOPS-108 is likely a low to
intermediate-mass protostar in its main mass accretion phase and it is the most
luminous protostar in OMC2-FIR4. The high resolution data presented here are
essential for disentangling the embedded protostars from their surrounding
dusty environments and characterizing them
a retrospective multicenter study
Funding This study was supported in part by a grant from the French government through the « Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). Prof. Ignacio Martin-Loeches has been supported by SFI (Science Foundation Ireland), Grant number 20/COV/0038. The funders of the study had no role in the study design, data collection, analysis or interpretation, writing of the report or deci sion to submit for publication.BACKGROUND: Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox's proportional hazard models with adjustment on pre-specified confounders. RESULTS: Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17-1.31) at day 2, 0.95 (0.63-1.42) at day 7, 1.48 (1.01-2.16) at day 14 and 1.94 (1.09-3.46) at day 21. CONCLUSIONS: No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.publishersversionpublishe
Perceptions of parents on satisfaction with care in the pediatric intensive care unit: the EMPATHIC study
Abstract:
PURPOSE: To identify parental perceptions on pediatric intensive care-related satisfaction items within the framework of developing a Dutch pediatric intensive care unit (PICU) satisfaction instrument.
METHODS: Prospective cohort study in tertiary PICUs at seven university medical centers in The Netherlands.
PARTICIPANTS: Parents of 1,042 children discharged from a PICU.
RESULTS: A 78-item questionnaire was sent to 1,042 parents and completed by 559 (54%). Seventeen satisfaction items were rated with mean scores or =1.65, and thus considered of limited value. The empirical structure of the items was in agreement with the theoretically formulated domains: Information, Care a
A qualitative study exploring the experiences of parents of children admitted to seven Dutch pediatric intensive care units
Purpose: To explore parents' experiences during the admission of their children to a pediatric intensive care unit (PICU). Method: Qualitative method using in-depth interviews. Thematic analysis was applied to capture parents' experiences. Thirty-nine mothers and 25 fathers of 41 children admitted to seven of the eight PICUs in university medical centers in The Netherlands were interviewed. Results: Parents were interviewed within 1 month after their child's discharge from a PICU. Thematic analysis identified 1,514 quotations that were coded into 63 subthemes. The subthemes were categorized into six major themes: attitude of the professionals; coordination of care; emotional intensity; information management; environmental factors; parent participation. Most themes had an overarching relationship representing the array of experiences encountered by parents when their child was staying in a PICU. The theme of emotional intensity was in particular associated with all the other themes. Conclusions: The findings provided a range of themes and subthemes describing the complexity of the parental experiences of a PICU admission. The subthemes presen
A Dominant Negative ERβ Splice Variant Determines the Effectiveness of Early or Late Estrogen Therapy after Ovariectomy in Rats
The molecular mechanisms for the discrepancy in outcome of initiating estrogen therapy (ET) around peri-menopause or several years after menopause in women are unknown. We hypothesize that the level of expression of a dominant negative estrogen receptor (ER) β variant, ERβ2, may be a key factor determining the effectiveness of ET in post-menopausal women. We tested this hypothesis in ovariectomized nine month-old (an age when irregular estrous cycles occur) female Sprague Dawley rats. Estradiol treatment was initiated either 6 days (Early ET, analogous to 4 months post-menopause in humans), or 180 days (Late ET, analogous to 11 years post-menopause in humans) after ovariectomy. Although ERβ2 expression increased in all OVX rats, neurogenic and neuroprotective responses to estradiol differed in Early and Late ET. Early ET reduced ERβ2 expression in both hippocampus and white blood cells, increased the hippocampal cell proliferation as assessed by Ki-67 expression, and improved mobility in the forced swim test. Late ET resulted in either no or modest effects on these parameters. There was a close correlation between the degree of ERβ2 expression and the preservation of neural effects by ET after OVX in rats, supporting the hypothesis that persistent elevated levels of ERβ2 are a molecular basis for the diminished effectiveness of ET in late post-menopausal women. The correlation between the expression of ERβ2 in circulating white blood cells and brain cells suggests that ERβ2 expression in peripheral blood cells may be an easily accessible marker to predict the effective window for ET in the brain
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