72 research outputs found
Evidence for an extended scattered disk
By telescopic tracking, we have established that the orbit of the
trans-neptunian object (2000 CR) has a perihelion of 44 AU, and
is thus outside the domain controlled by strong gravitational close encounters
with Neptune. Because this object is on a very large, eccentric orbit (with
semimajor axis 216 AU and eccentricity 0.8) this object must
have been placed on this orbit by a gravitational perturbation which is {\it
not} direct gravitational scattering off of any of the giant planets (on their
current orbits). The existence of this object may thus have profound cosmogonic
implications for our understanding of the formation of the outer Solar System.
We discuss some viable scenarios which could have produced it, including
long-term diffusive chaos and scattering off of other massive bodies in the
outer Solar System. This discovery implies that there must be a large
population of trans-neptunian objects in an `extended scattered disk' with
perihelia above the previously-discussed 38 AU boundary.Comment: 22 test pages, 4 figures, 2 tables. Submitted to Icarus, 26 March
200
Switching-On Survival and Repair Response Programs in Islet Transplants by Bone Marrow–Derived Vasculogenic Cells
OBJECTIVE—Vascular progenitors of bone marrow origin participate to neovascularization at sites of wound healing and transplantation. We hypothesized that the biological purpose of this bone marrow–derived vascular component is to contribute angiogenic and survival functions distinct from those provided by the local tissue-derived vasculature
Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells
We thank Anna-Lena Berg (AstraZeneca, Lund) and Cheryl Scudamore (MRC, Harwell, UK) for histological analysis, Julie Foster (Barts Cancer Institute, London) for CT scans, Johan Swinnen and Frank Claessens (Leuven University, Belgium) for discussion and AR-luciferase reporter plasmids, Florian Guillou (INRA, CNRS, Université de Tours, France) for the AMH-Cre mouse line and Laura Milne (MRC Centre for Reproductive Health, The University of Edinburgh) for technical support. We thank the members of the Cell Signalling group for critical input.International audienceThe organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interac
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