75 research outputs found
Functional transcriptome analysis in ARSACS KO cell model reveals a role of sacsin in autophagy
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurological disease caused by mutations in SACS, which encodes sacsin. The complex architecture of sacsin suggests that it could be a key player in cellular protein quality control system. Molecular chaperones that operate in protein folding/unfolding and assembly/disassembly patterns have been described as essential modulators of selectivity during the autophagy process. We performed RNA-sequencing analysis to generate a whole-genome molecular signature profile of sacsin knockout cells. Using data analysis of biological processes significantly disrupted due to loss of sacsin, we confirmed the presence of decreased mitochondrial function associated with increased oxidative stress, and also provided a demonstration of a defective autophagic pathway in sacsin-depleted cells. Western blotting assays revealed decreased expression of LC3 and increased levels of p62 even after treatment with the lysosomal inhibitor bafilomycin A1, indicating impairment of the autophagic flux. Moreover, we found reduced co-immunolocalization of the autophagosome marker LC3 with lysosomal and mitochondrial markers suggesting fusion inhibition of autophagic compartments and subsequent failed cargo degradation, in particular failed degradation of damaged mitochondria. Pharmacological up-regulation of autophagy restored correct autophagic flux in sacsin knockout cells. These results corroborate the hypothesis that sacsin may play a role in autophagy. Chemical manipulation of this pathway might represent a new target to alleviate clinical and pathological symptoms, delaying the processes of neurodegeneration in ARSACS
QUALIDADE DO COLOSTRO BOVINO E TRANSFERÊNCIA DE IMUNIDADE AOS BEZERROS RECÉM- NASCIDOS NA REGIÃO DE LAGES, SC
Colostrum samples were taken at the first milking from 74 cows in four farms. Serum samples were taken from their calves in the first 72 hours after birth. The levels of immunoglobulins in the colostrum and in the sera were analyzed by the Zinc Turbidity Test. In the colostrum a colostrometer (Schering-Plough Animal Health, United Kingdom) was also used to evaluate the immunoglobulin content. The results were statistically analyzed using InStat software (GraphPad Inc, USA). Immunoglobulin concentration in colostrum ranged from 2719.8 mg/100 mL to 8850.2 mg/100 mL (SD= ±1325.7), and in the sera of the calves from 281.94 mg/ml to 1163.4 mg/100 mL (SD=±238.25). There was no correlation among Ig concentration in the colostrum and serum (p=0.2123). The concentration varied widely among individual dam/calf pairs. Considering the limit of normality as one Standard Deviation below average, 18.92% of the calves had failure of passive transfer. A statistically significant (p=0.0156) difference was observed in the Ig concentration in the serum of calves from two farms, but not in the colostrum of the cows of these farms. There was also a difference (p=0.0121) between Ig concentration in the serum of calves born in winter (576.26 ± 225.28 mg/100 mL ) and in summer (776.4 ± 226,98 mg/100 mL ). This difference did not occur in colostrum. According to the colostrometer scale, colostrum samples were classified as good when they had a density between 1045 and 1090 (79.7% of the samples), regular when the density was between 1035 and 1045 (14.9% of the samples) and poor with densities below 1035 (5.4% of the samples).Foram coletadas amostras de colostro de 74 vacas Holandesas e mestiças Holandesas de quatro propriedades, e amostras de soro de seus bezerros nas primeiras 72 horas de vida. A quantidade de imunoglobulinas (Igs) no colostro e no soro foi analisada pelo teste de Turbidez do Sulfato de Zinco (TSZ) e no colostro também pelo colostrômetro. A concentração de Igs no colostro variou de 2719,8 mg/100 mL a 8850,2 mg/100 mL (s= ±1325,7), e no soro dos bezerros de 281,94 mg/ml a 1163,4 mg/100 mL (s=±238,25). Não houve correlação entre a concentração de imunoglobulinas no colostro e no soro (p=0,2123). Ocorreram variações individuais entre soros de diferentes bezerros e os colostros de suas mães. Considerando-se um desvio padrão abaixo da média como o limite de normalidade, 18,92% dos bezerros apresentaram falha de transferência de imunidade passiva. Ocorreu uma diferença significativa na concentração média de Igs no soro dos bezerros (teste t, p=0,0156) entre duas propriedades. Esta diferença não ocorreu na concentração de Igs no colostro (t test, p=0,5587). Houve também diferença significativa na concentração de Igs no soro entre bezerros nascidos no inverno (média=576,26 ± 225,28 mg/100 mL ) e no verão (média=776,4 ± 226,98 mg/100 mL ) ( t test, p=0,0121). Esta diferença não ocorreu no colostro. De acordo com a escala do colostrômetro, os colostros foram classificados como bons com densidade entre 1045 - 1090 (79,7% dos colostros analisados), regulares com densidade entre 1035 - 1045 (14,9% do total) e pobres com densidade entre 1000 - 1035 (5,4% do total)
Stellar Properties of z ~ 8 Galaxies in the Reionization Lensing Cluster Survey
Measurements of stellar properties of galaxies when the universe was less
than one billion years old yield some of the only observational constraints of
the onset of star formation. We present here the inclusion of
\textit{Spitzer}/IRAC imaging in the spectral energy distribution fitting of
the seven highest-redshift galaxy candidates selected from the \emph{Hubble
Space Telescope} imaging of the Reionization Lensing Cluster Survey (RELICS).
We find that for 6/8 \textit{HST}-selected sources, the
solutions are still strongly preferred over 1-2 solutions after the
inclusion of \textit{Spitzer} fluxes, and two prefer a solution,
which we defer to a later analysis. We find a wide range of intrinsic stellar
masses ( -- ), star formation
rates (0.2-14 ), and ages (30-600 Myr) among our sample.
Of particular interest is Abell1763-1434, which shows evidence of an evolved
stellar population at , implying its first generation of star formation
occurred just Myr after the Big Bang. SPT0615-JD, a spatially resolved
candidate, remains at its high redshift, supported by deep
\textit{Spitzer}/IRAC data, and also shows some evidence for an evolved stellar
population. Even with the lensed, bright apparent magnitudes of these candidates (H = 26.1-27.8 AB mag), only the \textit{James Webb Space
Telescope} will be able further confirm the presence of evolved stellar
populations early in the universe.Comment: 8 pages, 3 figures, 2 table
Reactive oxygen species derived from NOX3 and NOX5 drive differentiation of human oligodendrocytes
Reactive oxygen species (ROS) are signaling molecules that mediate stress response, apoptosis, DNA damage, gene expression and differentiation. We report here that differentiation of oligodendrocytes (OLs), the myelin forming cells in the CNS, is driven by ROS. To dissect the OL differentiation pathway, we used the cell line MO3-13, which display the molecular and cellular features of OL precursors. These cells exposed 1–4 days to low levels of H2O2 or to the protein kinase C (PKC) activator, phorbol-12-Myristate-13-Acetate (PMA) increased the expression of specific OL differentiation markers: the specific nuclear factor Olig-2, and Myelin Basic Protein (MBP), which was processed and accumulated selectively in membranes. The induction of differentiation genes was associated with the activation of ERK1-2 and phosphorylation of the nuclear cAMP responsive element binding protein 1 (CREB). PKC mediates ROS-induced differentiation because PKC depletion or bis-indolyl-maleimide (BIM), a PKC inhibitor, reversed the induction of differentiation markers by H2O2. H2O2 and PMA increased the expression of membrane-bound NADPH oxidases, NOX3 and NOX5. Selective depletion of these proteins inhibited differentiation induced by PMA. Furthermore, NOX5 silencing down regulated NOX3 mRNA levels, suggesting that ROS produced by NOX5 up-regulate NOX3 expression. These data unravel an elaborate network of ROS-generating enzymes (NOX5 to NOX3) activated by PKC and necessary for differentiation of OLs. Furthermore, NOX3 and NOX5, as inducers of OL differentiation, represent novel targets for therapies of demyelinating diseases, including multiple sclerosis, associated with impairment of OL differentiation
RELICS: Strong Lens Models for Five Galaxy Clusters From the Reionization Lensing Cluster Survey
Strong gravitational lensing by galaxy clusters magnifies background
galaxies, enhancing our ability to discover statistically significant samples
of galaxies at z>6, in order to constrain the high-redshift galaxy luminosity
functions. Here, we present the first five lens models out of the Reionization
Lensing Cluster Survey (RELICS) Hubble Treasury Program, based on new HST
WFC3/IR and ACS imaging of the clusters RXC J0142.9+4438, Abell 2537, Abell
2163, RXC J2211.7-0349, and ACT-CLJ0102-49151. The derived lensing
magnification is essential for estimating the intrinsic properties of
high-redshift galaxy candidates, and properly accounting for the survey volume.
We report on new spectroscopic redshifts of multiply imaged lensed galaxies
behind these clusters, which are used as constraints, and detail our strategy
to reduce systematic uncertainties due to lack of spectroscopic information. In
addition, we quantify the uncertainty on the lensing magnification due to
statistical and systematic errors related to the lens modeling process, and
find that in all but one cluster, the magnification is constrained to better
than 20% in at least 80% of the field of view, including statistical and
systematic uncertainties. The five clusters presented in this paper span the
range of masses and redshifts of the clusters in the RELICS program. We find
that they exhibit similar strong lensing efficiencies to the clusters targeted
by the Hubble Frontier Fields within the WFC3/IR field of view. Outputs of the
lens models are made available to the community through the Mikulski Archive
for Space TelescopesComment: Accepted to Ap
RELICS: High-Resolution Constraints on the Inner Mass Distribution of the z=0.83 Merging Cluster RXJ0152.7-1357 from strong lensing
Strong gravitational lensing (SL) is a powerful means to map the distribution
of dark matter. In this work, we perform a SL analysis of the prominent X-ray
cluster RXJ0152.7-1357 (z=0.83, also known as CL 0152.7-1357) in \textit{Hubble
Space Telescope} images, taken in the framework of the Reionization Lensing
Cluster Survey (RELICS). On top of a previously known galaxy multiply
imaged by RXJ0152.7-1357, for which we identify an additional multiple image,
guided by a light-traces-mass approach we identify seven new sets of multiply
imaged background sources lensed by this cluster, spanning the redshift range
[1.79-3.93]. A total of 25 multiple images are seen over a small area of ~0.4
, allowing us to put relatively high-resolution constraints on the
inner matter distribution. Although modestly massive, the high degree of
substructure together with its very elongated shape make RXJ0152.7-1357 a very
efficient lens for its size. This cluster also comprises the third-largest
sample of z~6-7 candidates in the RELICS survey. Finally, we present a
comparison of our resulting mass distribution and magnification estimates with
those from a Lenstool model. These models are made publicly available through
the MAST archive.Comment: 15 Pages, 7 Figures, 4 Tables Accepted for publication in Ap
Vocal fold mobility alteration reversed after thyroidectomy
The involvement of the inferior or recurrent laryngeal nerve (RLN) in mobility derangement of the vocal folds occurs more frequently due to thyroid malignancy invasion. Although uncommon, the same derangement, which is caused by benign thyroid entities, is also described and reverts to normality after a thyroidectomy in up to 89% of cases. In these cases, the pathogenesis of the vocal cord mobility disturbance is attributed to the direct compression of the RLN by massive thyroid enlargement. The authors describe three cases of patients presenting unilateral vocal cord palsy, which, before surgery, was diagnosed by laryngoscopy concomitantly with large and compressive goiter. Vocal fold mobility became normal after the thyroidectomy in all three cases. Therefore, it is noteworthy that these alterations may present reversibility after appropriate surgical treatment. An early surgical approach is recommended to reduce the nerve injury as much as possible; to preserve the integrity of both RLNs since the nerve function will be restored in some patient
RELICS: Properties of z>5.5 Galaxies Inferred from Spitzer and Hubble Imaging Including A Candidate z~6.8 Strong [OIII] Emitter
We present constraints on the physical properties (including stellar mass,
age, and star formation rate) of 207 galaxy candidates
from the Reionization Lensing Cluster Survey (RELICS) and companion
Spitzer-RELICS surveys. We measure photometry using T-PHOT and perform spectral
energy distribution fitting using EAY and BAGPIPES. Of the 207 candidates
for which we could successfully measure Spitzer fluxes, 23 were demoted to
likely low redshift (). Among the remaining high redshift candidates, we
find intrinsic stellar masses between and
, and rest-frame UV absolute magnitudes between
and mag. While our sample is mostly comprised of
galaxies, there are a number of brighter objects in the
sample, extending to . The galaxies in our sample span
approximately four orders of magnitude in stellar mass and star-formation
rates, and exhibit ages ranging from maximally young to maximally old. We
highlight 11 galaxies which have detections in Spitzer/IRAC imaging and
redshift estimates , several of which show evidence for some
combination of evolved stellar populations, large contributions of nebular
emission lines, and/or dust. Among these is PLCKG287+32-2013, one of the
brightest candidates known (AB mag 24.9) with a Spitzer 3.6m flux
excess suggesting strong [OIII] + H- emission (1000\AA\ rest-frame
equivalent width). We discuss the possible uses and limits of our sample and
present a public catalog of Hubble 0.4--1.6m + Spitzer 3.6m and
4.5m photometry along with physical property estimates for all 207 objects
in the sample. Because of their apparent brightnesses, high redshifts, and
variety of stellar populations, these objects are excellent targets for
follow-up with James Webb Space Telescope.Comment: 20 pages, 9 figure
A Candidate Galaxy Strongly Lensed into a Spatially Resolved Arc
The most distant galaxies known are at z~10-11, observed 400-500 Myr after
the Big Bang. The few z~10-11 candidates discovered to date have been
exceptionally small- barely resolved, if at all, by the Hubble Space Telescope.
Here we present the discovery of SPT0615-JD, a fortuitous z~10
(z_phot=9.9+/-0.6) galaxy candidate stretched into an arc over ~2.5" by the
effects of strong gravitational lensing. Discovered in the Reionization Lensing
Cluster Survey (RELICS) Hubble Treasury program and companion S-RELICS Spitzer
program, this candidate has a lensed H-band magnitude of 25.7+/-0.1 AB mag.
With a magnification of \mu~4-7 estimated from our lens models, the de-lensed
intrinsic magnitude is 27.6+/-0.3 AB mag, and the half-light radius is r_e<0.8
kpc, both consistent with other z>9 candidates. The inferred stellar mass (log
[M* /M_Sun]=9.7^{+0.7}_{-0.5}) and star formation rate (\log [SFR/M_Sun
yr^{-1}]=1.3^{+0.2}_{-0.3}) indicate that this candidate is a typical
star-forming galaxy on the z>6 SFR-M* relation. We note that three independent
lens models predict two counterimages, at least one of which should be of a
similar magnitude to the arc, but these counterimages are not yet detected.
Counterimages would not be expected if the arc were at lower redshift. However,
the only spectral energy distributions capable of fitting the Hubble and
Spitzer photometry well at lower redshifts require unphysical combinations of
z~2 galaxy properties. The unprecedented lensed size of this z~10 candidate
offers the potential for the James Webb Space Telescope to study the geometric
and kinematic properties of a galaxy observed 500 Myr after the Big Bang.Comment: 7 pages, 4 figures. Submitted to ApJ Letter
- …