1,495 research outputs found
Scattered light mapping of protoplanetary disks
High-contrast scattered light observations have revealed the surface
morphology of several dozens of protoplanetary disks at optical and
near-infrared wavelengths. Inclined disks offer the opportunity to measure part
of the phase function of the dust grains that reside in the disk surface which
is essential for our understanding of protoplanetary dust properties and the
early stages of planet formation. We aim to construct a method which takes into
account how the flaring shape of the scattering surface of an (optically thick)
protoplanetary disk projects onto the image plane of the observer. This allows
us to map physical quantities (scattering radius and scattering angle) onto
scattered light images and retrieve stellar irradiation corrected (r^2-scaled)
images and dust phase functions. We apply the method on archival polarized
intensity images of the protoplanetary disk around HD 100546 that were obtained
with VLT/SPHERE in R'-band and VLT/NACO in H- and Ks-band. The brightest side
of the r^2-scaled R'-band polarized intensity image of HD 100546 changes from
the far to the near side of the disk when a flaring instead of a geometrically
flat disk surface is used for the r^2-scaling. The decrease in polarized
surface brightness in the scattering angle range of ~40-70 deg is likely a
result of the dust phase function and degree of polarization which peak in
different scattering angle regimes. The derived phase functions show part of a
forward scattering peak which indicates that large, aggregate dust grains
dominate the scattering opacity in the disk surface. Projection effects of a
protoplanetary disk surface need to be taken into account to correctly
interpret scattered light images. Applying the correct scaling for the
correction of stellar irradiation is crucial for the interpretation of the
images and the derivation of the dust properties in the disk surface layer.Comment: Accepted for publication in A&A, 6 pages, 3 figure
Glucose restriction induces cell death in parental but not in homeodomain-interacting protein kinase 2-depleted RKO colon cancer cells: molecular mechanisms and implications for tumor therapy.
Tumor cell tolerance to nutrient deprivation can be an important factor for tumor progression, and may depend on deregulation of both oncogenes and oncosuppressor proteins. Homeodomain-interacting protein kinase 2 (HIPK2) is an oncosuppressor that, following its activation by several cellular stress, induces cancer cell death via p53-dependent or -independent pathways. Here, we used genetically matched human RKO colon cancer cells harboring wt-HIPK2 (HIPK2(+/+)) or stable HIPK2 siRNA interference (siHIPK2) to investigate in vitro whether HIPK2 influenced cell death in glucose restriction. We found that glucose starvation induced cell death, mainly due to c-Jun NH2-terminal kinase activation, in HIPK2(+/+)cells compared with siHIPK2 cells that did not die. (1)H-nuclear magnetic resonance quantitative metabolic analyses showed a marked glycolytic activation in siHIPK2 cells. However, treatment with glycolysis inhibitor 2-deoxy-D-glucose induced cell death only in HIPK2(+/+) cells but not in siHIPK2 cells. Similarly, siGlut-1 interference did not re-establish siHIPK2 cell death under glucose restriction, whereas marked cell death was reached only after zinc supplementation, a condition known to reactivate misfolded p53 and inhibit the pseudohypoxic phenotype in this setting. Further siHIPK2 cell death was reached with zinc in combination with autophagy inhibitor. We propose that the metabolic changes acquired by cells after HIPK2 silencing may contribute to induce resistance to cell death in glucose restriction condition, and therefore be directly relevant for tumor progression. Moreover, elimination of such a tolerance might serve as a new strategy for cancer therapy
Organic molecules in the protoplanetary disk of DG Tau revealed by ALMA
Planets form in protoplanetary disks and inherit their chemical compositions.
It is thus crucial to map the distribution and investigate the formation of
simple organics, such as formaldehyde and methanol, in protoplanetary disks. We
analyze ALMA observations of the nearby disk-jet system around the T Tauri star
DG Tau in the o-HCO and CHOH E,
A transitions at an unprecedented resolution of ,
i.e., au at a distance of 121 pc. The HCO emission originates from
a rotating ring extending from au with a peak at au, i.e., at
the edge of the 1.3mm dust continuum. CHOH emission is not detected down to
an r.m.s. of 3 mJy/beam in the 0.162 km/s channel. Assuming an ortho-to-para
ratio of 1.8-2.8 the ring- and disk-height-averaged HCO column density is
cm, while that of CHOH is
cm. In the inner au no o-HCO emission
is detected with an upper limit on its beam-averaged column density of
cm. The HCO ring in the disk of DG Tau is
located beyond the CO iceline (R au). This suggests that the
HCO abundance is enhanced in the outer disk due to formation on grain
surfaces by the hydrogenation of CO ice. The emission peak at the edge of the
mm dust continuum may be due to enhanced desorption of HCO in the gas phase
caused by increased UV penetration and/or temperature inversion. The
CHOH/HCO abundance ratio is , in agreement with disk chemistry
models. The inner edge of the HCO ring coincides with the radius where the
polarization of the dust continuum changes orientation, hinting at a tight link
between the HCO chemistry and the dust properties in the outer disk and at
the possible presence of substructures in the dust distribution.Comment: 8 pages, 6 figures, accepted for publication on A&A Letter
Constraining the mass of the planet(s) sculpting a disk cavity. The intriguing case of 2MASS J16042165-2130284
The large cavities observed in the dust and gas distributions of transition
disks may be explained by planet-disk interactions. At ~145 pc, 2MASS
J16042165-2130284 (J1604) is a 5-12 Myr old transitional disk with different
gap sizes in the mm- and m-sized dust distributions (outer edges at ~79
and at ~63 au, respectively). Its CO emission shows a ~30 au cavity.
This radial structure suggests that giant planets are sculpting this disk. We
aim to constrain the masses and locations of plausible giant planets around
J1604. We observed J1604 with the Spectro-Polarimetric High-contrast Exoplanet
REsearch (SPHERE) at the Very Large Telescope (VLT), in IRDIFS\_EXT,
pupil-stabilized mode, obtaining YJH- band images with the integral field
spectrograph (IFS) and K1K2-band images with the Infra-Red Dual-beam Imager and
Spectrograph (IRDIS). The dataset was processed exploiting the angular
differential imaging (ADI) technique with high-contrast algorithms. Our
observations reach a contrast of ~12 mag from 0.15" to 0.80"
(~22 to 115 au), but no planet candidate is detected. The disk is directly
imaged in scattered light at all bands from Y to K, and it shows a red color.
This indicates that the dust particles in the disk surface are mainly
m-sized grains. We confirm the sharp dip/decrement in
scattered light in agreement with polarized light observations. Comparing our
images with a radiative transfer model we argue that the southern side of the
disk is most likely the nearest. This work represents the deepest search yet
for companions around J1604. We reach a mass sensitivity of from ~22 to ~115 au according to a hot start scenario. We propose
that a brown dwarf orbiting inside of ~15 au and additional Jovian planets at
larger radii could account for the observed properties of J1604 while
explaining our lack of detection.Comment: 10 pages, 7 Figures. Accepted for publication in A&A . Abridged
abstrac
P62/sqstm1/keap1/nrf2 axis reduces cancer cells death-sensitivity in response to zn(Ii)–curcumin complex
The hyperactivation of nuclear factor erythroid 2 p45-related factor 2 (NRF2), frequently found in many tumor types, can be responsible for cancer resistance to therapies and poor patient prognosis. Curcumin has been shown to activate NRF2 that has cytotprotective or protumorigenic roles according to tumor stage. The present study aimed at investigating whether the zinc–curcumin Zn(II)–curc compound, which we previously showed to display anticancer effects through multiple mechanisms, could induce NRF2 activation and to explore the underlying molecular mechanisms. Biochemical studies showed that Zn(II)–curc treatment increased the NRF2 protein levels along with its targets, heme oxygenase-1 (HO-1) and p62/SQSTM1, while markedly reduced the levels of Keap1 (Kelch-like ECH-associated protein 1), the NRF2 inhibitor, in the cancer cell lines analyzed. The silencing of either NRF2 or p62/SQSTM1 with specific siRNA demonstrated the crosstalk between the two molecules and that the knockdown of either molecule increased the cancer cell sensitivity to Zn(II)–curc-induced cell death. This suggests that the crosstalk between p62/SQSTM1 and NRF2 could be therapeutically exploited to increase cancer patient response to therapies
DZ Cha: a bona fide photoevaporating disc
DZ Cha is a weak-lined T Tauri star (WTTS) surrounded by a bright
protoplanetary disc with evidence of inner disc clearing. Its narrow \Ha line
and infrared spectral energy distribution suggest that DZ Cha may be a
photoevaporating disc. We aim to analyse the DZ Cha star + disc system to
identify the mechanism driving the evolution of this object. We have analysed
three epochs of high resolution optical spectroscopy, photometry from the UV up
to the sub-mm regime, infrared spectroscopy, and J-band imaging polarimetry
observations of DZ Cha. Combining our analysis with previous studies we find no
signatures of accretion in the \Ha line profile in nine epochs covering a
time baseline of years. The optical spectra are dominated by
chromospheric emission lines, but they also show emission from the forbidden
lines [SII] 4068 and [OI] 6300 that indicate a disc outflow. The
polarized images reveal a dust depleted cavity of au in radius and two
spiral-like features, and we derive a disc dust mass limit of
M_\mathrm{dust}
80 \MJup) companions are detected down to 0\farcs07 ( au,
projected). The negligible accretion rate, small cavity, and forbidden line
emission strongly suggests that DZ Cha is currently at the initial stages of
disc clearing by photoevaporation. At this point the inner disc has drained and
the inner wall of the truncated outer disc is directly exposed to the stellar
radiation. We argue that other mechanisms like planet formation or binarity
cannot explain the observed properties of DZ Cha. The scarcity of objects like
this one is in line with the dispersal timescale ( yr) predicted
by this theory. DZ Cha is therefore an ideal target to study the initial stages
of photoevaporation.Comment: A&A in press, language corrections include
Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial
Background:We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases.Methods:This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m 2, 5-FU to 550 mg m 2 per day and L-OHP to 15 mg m 2 per day.Results:Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.Conclusion:Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases. © 2010 Cancer Research UK All rights reserved
Targeting COX-2/PGE(2) pathway in HIPK2 knockdown cancer cells: impact on dendritic cell maturation.
production after HIPK2 depletion and how to modulate it./VEGF production. At translational level, while conditioned media of both siRNA control and HIPK2 depleted cells inhibited DCs maturation, conditioned media of only zinc-treated HIPK2 depleted cells efficiently restored DCs maturation, seen as the expression of co-stimulatory molecules CD80 and CD86, cytokine IL-10 release, and STAT3 phosphorylation./VEGF production; and 3) zinc treatment of HIPK2 depleted cells restored DCs maturation
Baricitinib therapy response in rheumatoid arthritis patients associates to STAT1 phosphorylation in monocytes
Baricitinib is a Janus kinase (JAK) 1 and 2 inhibitor approved for treating rheumatoid arthritis (RA). The JAK/STAT system is essential in the intracellular signaling of different cytokines and in the activation process of the monocyte lineage. This study verifies the effects of baricitinib on STAT phosphorylation in monocytes of RA patients and evaluates the correlation between STAT phosphorylation and response to therapy. We evaluated the disease activity of patients (DAS28CRP) at baseline (T0) and after 4 and 12 weeks (T1-T3) of treatment with baricitinib, dividing them into responders (n = 7) and non-responders (n = 7) based on the reduction of DAS28CRP between T0 and T1 of at least 1.2 points. Through flow cytometry, STAT1 phosphorylation was analyzed at T0/T1/T3 in monocytes, at basal conditions and after IL2, IFN alpha, and IL6 stimulation. We showed that monocyte frequency decreased from T0 to T1 only in responders. Regarding the phosphorylation of STAT1, we observed a tendency for higher basal pSTAT1 in monocytes of non-responder patients and, after 4 weeks, a significant reduction of cytokine-induced pSTAT1 in monocytes of responders compared with non-responders. The single IFN alpha stimulation only partially recapitulated the differences in STAT1 phosphorylation between the two patient subgroups. Finally, responders showed an increased IFN signature at baseline compared with non-responders. These results may suggest that monocyte frequency and STAT1 phosphorylation in circulating monocytes could represent early markers of response to baricitinib therapy
- …