PDCD4 is a CSL associated protein with a transcription repressive function in cancer associated fibroblast activation.

The Notch/CSL pathway plays an important role in skin homeostasis and carcinogenesis. CSL, the key effector of canonical Notch signaling endowed with an intrinsic transcription repressive function, suppresses stromal fibroblast senescence and Cancer Associated Fibroblast (CAF) activation through direct down-modulation of key effector genes. Interacting proteins that participate with CSL in this context are as yet to be identified. We report here that Programmed Cell Death 4 (PDCD4), a nuclear/cytoplasmic shuttling protein with multiple functions, associates with CSL and plays a similar role in suppressing dermal fibroblast senescence and CAF activation. Like CSL, PDCD4 is down-regulated in stromal fibroblasts of premalignant skin actinic keratosis (AKs) lesions and squamous cell carcinoma (SCC). While devoid of intrinsic DNA binding capability, PDCD4 is present at CSL binding sites of CAF marker genes as well as canonical Notch/CSL targets and suppresses expression of these genes in a fibroblast-specific manner. Thus, we propose that PDCD4 is part of the CSL repressive complex involved in negative control of stromal fibroblasts conversion into CAFs

The Deep Lens Survey Transient Search I : Short Timescale and Astrometric Variability

We report on the methodology and first results from the Deep Lens Survey transient search. We utilize image subtraction on survey data to yield all sources of optical variability down to 24th magnitude. Images are analyzed immediately after acquisition, at the telescope and in near-real time, to allow for followup in the case of time-critical events. All classes of transients are posted to the web upon detection. Our observing strategy allows sensitivity to variability over several decades in timescale. The DLS is the first survey to classify and report all types of photometric and astrometric variability detected, including solar system objects, variable stars, supernovae, and short timescale phenomena. Three unusual optical transient events were detected, flaring on thousand-second timescales. All three events were seen in the B passband, suggesting blue color indices for the phenomena. One event (OT 20020115) is determined to be from a flaring Galactic dwarf star of spectral type dM4. From the remaining two events, we find an overall rate of \eta = 1.4 events deg-2 day-1 on thousand-second timescales, with a 95% confidence limit of \eta < 4.3. One of these events (OT 20010326) originated from a compact precursor in the field of galaxy cluster Abell 1836, and its nature is uncertain. For the second (OT 20030305) we find strong evidence for an extended extragalactic host. A dearth of such events in the R passband yields an upper 95% confidence limit on short timescale astronomical variability between 19.5 < R < 23.4 of \eta_R < 5.2. We report also on our ensemble of astrometrically variable objects, as well as an example of photometric variability with an undetected precursor.Comment: 24 pages, 12 figures, 3 tables. Accepted for publication in ApJ. Variability data available at http://dls.bell-labs.com/transients.htm

A spectropolarimetric view on the nature of the peculiar Type I SN 2005hk

We report two spectropolarimetric observations of SN 2005hk, which is a close copy of the "very peculiar" SN 2002cx, showing low peak luminosity, slow decline, high ionization near peak and an unusually low expansion velocity of only about 7,000 km s^-1. Further to the data presented by Chornock et al., (2006), at -4 days before maximum, we present data of this object taken on 9 November 2005 (near maximum) and 23 November (+ two weeks) that show the continuum and most of the spectral lines to be polarized at levels of about 0.2-0.3%. At both epochs the data corresponds to the Spectropolarimetric Type D1. The general low level of line polarization suggests that the line forming regions for most species observed in the spectrum have a similar shape to that of the photosphere, which deviates from a spherical symmetry by <10%. In comparison with spectropolarimetry of Type Ia and Core-collapse SNe at similar epochs, we find that the properties of SN 2005hk are most similar to those of Type Ia SNe. In particular, we find the low levels of continuum and line polarization to indicate that the explosion mechanism is approximately spherical, with homogeneous ejecta (unlike the chemically segregated ejecta of CCSNe). We discuss the possibility that SN 2005hk was the result of the pure deflagration of a white dwarf and note the issues concerning this interpretation.Comment: ApJ accepted, uses emulateapj, 16 pages, 10 figures, figures 3 and 4 update

Spectropolarimetry of the Type Ia SN 2007sr Two Months After Maximum Light

We present late time spectropolarimetric observations of SN 2007sr, obtained with the VLT telescope at ESO Paranal Observatory when the object was 63 days after maximum light. The late time spectrum displays strong line polarization in the CaII absorption features. SN 2007sr adds to the case of some normal Type Ia SNe that show high line polarization or repolarization at late times, a fact that might be connected with the presence of high velocity features at early times

The ULK3 Kinase Is Critical for Convergent Control of Cancer-Associated Fibroblast Activation by CSL and GLI.

The connection between signaling pathways activating cancer-associated fibroblasts (CAFs) remains to be determined. Metabolic alterations linked to autophagy have also been implicated in CAF activation. CSL/RBPJ, a transcriptional repressor that mediates Notch signaling, suppresses the gene expression program(s), leading to stromal senescence and CAF activation. Deregulated GLI signaling can also contribute to CAF conversion. Here, we report that compromised CSL function depends on GLI activation for conversion of human dermal fibroblasts into CAFs, separately from cellular senescence. Decreased CSL upregulates the expression of the ULK3 kinase, which binds and activates GLI2. Increased ULK3 also induces autophagy, which is unlinked from GLI and CAF activation. ULK3 upregulation occurs in the CAFs of several tumor types, and ULK3 silencing suppresses the tumor-enhancing properties of these cells. Thus, ULK3 links two key signaling pathways involved in CAF conversion and is an attractive target for stroma-focused anti-cancer intervention

Time Dilation from Spectral Feature Age Measurements of Type Ia Supernovae

We have developed a quantitative, empirical method for estimating the age of Type Ia supernovae (SNe Ia) from a single spectral epoch. The technique examines the goodness of fit of spectral features as a function of the temporal evolution of a large database of SNe Ia spectral features. When a SN Ia spectrum with good signal-to-noise ratio over the rest frame range 3800 to 6800 A is available, the precision of a spectral feature age (SFA) is (1-sigma) ~ 1.4 days. SFA estimates are made for two spectral epochs of SN 1996bj (z=0.574) to measure the rate of aging at high redshift. In the 10.05 days which elapsed between spectral observations, SN 1996bj aged 3.35 $\pm$ 3.2 days, consistent with the 6.38 days of aging expected in an expanding Universe and inconsistent with no time dilation at the 96.4 % confidence level. The precision to which individual features constrain the supernova age has implications for the source of inhomogeneities among SNe Ia.Comment: 14 pages (LaTex), 7 postscript figures to Appear in the Astronomical Journa