Mitosis-independent survivin gene expression in vivo and regulation by p53

Survivin is an essential mitotic gene, and this has been speculated to reflect its primary function in development and cancer. Here, we generated a knock-in transgenic mouse (SVVp-GFP) in which a green fluorescent protein (GFP) reporter gene was placed under the control of the survivin promoter that regulates transcription at mitosis. The expression of endogenous survivin was widespread in mouse tissues during development and shortly after birth. In contrast, GFP reactivity was undetectable in transgenic mouse embryos, and was largely limited postnatally to mitotic cells in the testes. Double transgenic mice generated in the tumor-prone Min/+ background exhibited intestinal adenomas that strongly expressed endogenous survivin, but only isolated GFP-positive cells. Conversely, dysplastic adenomas (16%) stained intensely for GFP, and revealed focal reactivity for mutant, but not wild-type, p53. The expression of GFP was increased by approximately 10-fold in p53(-/-) as opposed to p53(+/+) HCT116 colorectal cancer cells, and reintroduction of p53 in p53(-/-) cells abolished GFP expression. Therefore, the mitotic transcription of the survivin gene is highly restricted in vivo, and unexpectedly negatively regulated by p53. Contrary to a commonly held view, the dominant function(s) of survivin in development and tumor ontogeny are largely cell cycle-independent

Survivin as a global target of intrinsic tumor suppression networks

Despite the constant exposure to genomic insults that may lead to malignancy, cancer is surprisingly a relatively rare occurrence, and this is largely credited to an elaborate network of endogenous tumor suppression. Many effectors of tumor suppression have been identified, and their functions when activated in damaged cells have in large part been elucidated. What is less clear is whether there are common target gene(s) of tumor suppression, whose expression must be ablated in order to block transformation and preserve cellular homeostasis. Fresh experimental evidence suggests that silencing of the mitotic regulator and cell death inhibitor, survivin, is a universal requirement for successful tumor suppression in humans

Thermal Infrared Observations of Asteroid (99942) Apophis with Herschel

The near-Earth asteroid (99942) Apophis is a potentially hazardous asteroid. We obtained far-infrared observations of this asteroid with the Herschel Space Observatory's PACS instrument at 70, 100, and 160 micron. These were taken at two epochs in January and March 2013 during a close Earth encounter. These first thermal measurements of Apophis were taken at similar phase angles before and after opposition. We performed a detailed thermophysical model analysis by using the spin and shape model recently derived from applying a 2-period Fourier series method to a large sample of well-calibrated photometric observations. We find that the tumbling asteroid Apophis has an elongated shape with a mean diameter of 375$^{+14}_{-10}$ m (of an equal volume sphere) and a geometric V-band albedo of 0.30$^{+0.05}_{-0.06}$. We find a thermal inertia in the range 250-800 Jm$^{-2}$s$^{-0.5}$K$^{-1}$ (best solution at 600 Jm$^{-2}$s$^{-0.5}$K$^{-1}$), which can be explained by a mixture of low conductivity fine regolith with larger rocks and boulders of high thermal inertia on the surface. The thermal inertia, and other similarities with (25143) Itokawa indicate that Apophis might also have a rubble-pile structure. If we combine the new size value with the assumption of an Itokawa-like density and porosity we estimate a mass between 4.4 and 6.2 10$^{10}$ kg which is more than 2-3 times larger than previous estimates. We expect that the newly derived properties will influence impact scenario studies and influence the long-term orbit predictions of Apophis.Comment: Accepted for publication in Astronomy & Astrophysics, 21 pages, 8 figures, 2 table

Survivin at a glance

Survivin (also known as BIRC5) is an evolutionarily conserved eukaryotic protein that is essential for cell division and can inhibit cell death. Normally it is only expressed in actively proliferating cells, but is upregulated in most, if not all cancers; consequently, it has received significant attention as a potential oncotherapeutic target. In this Cell Science at a Glance article and accompanying poster, we summarise our knowledge of survivin 21 years on from its initial discovery. We describe the structure, expression and function of survivin, highlight its interactome and conclude by describing anti-survivin strategies being trialled

CEA Bolometer Arrays: the First Year in Space

The CEA/LETI and CEA/SAp started the development of far-infrared filled bolometer arrays for space applications over a decade ago. The unique design of these detectors makes possible the assembling of large focal planes comprising thousands of bolometers running at 300 mK with very low power dissipation. Ten arrays of 16x16 pixels were thoroughly tested on the ground, and integrated in the Herschel/PACS instrument before launch in May 2009. These detectors have been successfully commissioned and are now operating in their nominal environment at the second Lagrangian point of the Earth-Sun system. In this paper we briefly explain the functioning of CEA bolometer arrays, and we present the properties of the detectors focusing on their noise characteristics, the effect of cosmic rays on the signal, the repeatability of the measurements, and the stability of the system

The XMM-LSS survey: the Class 1 cluster sample over the extended 11 deg2^2 and its spatial distribution

This paper presents 52 X-ray bright galaxy clusters selected within the 11 deg$^2$ XMM-LSS survey. 51 of them have spectroscopic redshifts ($0.05<z<1.06$), one is identified at $z_{\rm phot}=1.9$, and all together make the high-purity "Class 1" (C1) cluster sample of the XMM-LSS, the highest density sample of X-ray selected clusters with a monitored selection function. Their X-ray fluxes, averaged gas temperatures (median $T_X=2$ keV), luminosities (median $L_{X,500}=5\times10^{43}$ ergs/s) and total mass estimates (median $5\times10^{13} h^{-1} M_{\odot}$) are measured, adapting to the specific signal-to-noise regime of XMM-LSS observations. The redshift distribution of clusters shows a deficit of sources when compared to the cosmological expectations, regardless of whether WMAP-9 or Planck-2013 CMB parameters are assumed. This lack of sources is particularly noticeable at $0.4 \lesssim z \lesssim 0.9$. However, after quantifying uncertainties due to small number statistics and sample variance we are not able to put firm (i.e. $>3 \sigma$) constraints on the presence of a large void in the cluster distribution. We work out alternative hypotheses and demonstrate that a negative redshift evolution in the normalization of the $L_{X}-T_X$ relation (with respect to a self-similar evolution) is a plausible explanation for the observed deficit. We confirm this evolutionary trend by directly studying how C1 clusters populate the $L_{X}-T_X-z$ space, properly accounting for selection biases. We point out that a systematically evolving, unresolved, central component in clusters and groups (AGN contamination or cool core) can impact the classification as extended sources and be partly responsible for the observed redshift distribution.[abridged]Comment: 33 pages, 21 figures, 3 tables ; accepted for publication in MNRA