No abstract

These findings may prove useful in providing additional stability when using an all-inside technique in a difficult case, or in a patient with poor bone stock, and may also be useful as an alternative to more commonly used tibial tunnel soft tissue fixation techniques.

We report 850μm dust polarization observations of a low-mass (∼12 M e ) starless core in the ρ Ophiuchus cloud, Ophiuchus C, made with the POL-2 instrument on the James Clerk Maxwell Telescope (JCMT) as part of the JCMT B-fields In STar-forming Region Observations survey. We detect an ordered magnetic field projected on the plane of the sky in the starless core. The magnetic field across the ∼0.1pc core shows a predominant northeastsouthwest orientation centering between ∼40°and ∼100°, indicating that the field in the core is well aligned with the magnetic field in lower-density regions of the cloud probed by near-infrared observations and also the cloudscale magnetic field traced by Planck observations. The polarization percentage (P) decreases with increasing total intensity (I), with a power-law index of −1.03±0.05. We estimate the plane-of-sky field strength (B pos ) using modified Davis-Chandrasekhar-Fermi methods based on structure function (SF), autocorrelation function (ACF), and unsharp masking (UM) analyses. We find that the estimates from the SF, ACF, and UM methods yield strengths of 103±46 μG, 136±69 μG, and 213±115 μG, respectively. Our calculations suggest that the Ophiuchus C core is near magnetically critical or slightly magnetically supercritical (i.e., unstable to collapse). The total magnetic energy calculated from the SF method is comparable to the turbulent energy in Ophiuchus C, while the ACF method and the UM method only set upper limits for the total magnetic energy because of large uncertainties.

BackgroundRb1 is the most frequently mutated gene in the pediatric cancer retinoblastoma, and its loss causes E2F transcription factors to induce proliferation related genes. However, high E2F levels following pRB loss also induce apoptosis-promoting genes as a safeguard mechanism to suppress emergent tumors. Although p53 accumulation and apoptosis induction is believed to be a primary mechanism to eliminate cells with excess E2F activity, p53 deletion doesn’t suppress RB/E2F induced apoptosis in vivo in the retina. This prompted us to test the PTEN/PI3K/AKT signaling pathway on RB/E2F apoptosis suppression in vivo, to ascertain if the PI3K pathway may provide a potential avenue for retinoblastoma therapy.MethodsWe developed a mouse model in which Rb1 and Pten were conditionally deleted from retinal progenitor cells using Chx10-Cre, whereas Rbl1 (p107) was constitutively deleted. Pathway components were also tested individually by in vivo electroporation into newborn retinas for an effect on apoptosis and tumor initiation. Mouse retinal tissues were analyzed by immunohistochemistry (IHC) for proliferation, apoptosis, and pathway activation. ShRNAs were used in vitro to assess effects on apoptosis and gene expression.ResultsCo-deleting Pten with Rb1 and Rbl1 in mouse retinal progenitor cells (RPCs) causes fully penetrant bilateral retinoblastomas by 30 days and strongly suppresses Rb/E2F-induced apoptosis. In vivo electroporation of constitutively active (ca)-Pik3ca, ca-Akt, or dominant-negative (dn)-Foxo1 into apoptosis prone newborn murine retina with deleted Rb/p107 eliminate Rb/E2F induced apoptosis and induce retinoblastoma emergence. Retinal deletion of Pten activates p-AKT and p-FOXO1 signaling in incipient retinoblastoma. An unbiased shRNA screen focusing on Akt phosphorylation targets identified FOXOs as critical mediators of Rb/E2F induced apoptosis and expression of Bim and p73 pro-apoptotic genes.ConclusionsThese data indicate that we defined a key molecular trigger involving E2F/FOXO functioning to control retinal progenitor cell homeostasis and retinoblastoma tumor initiation. We anticipate that our findings could provide contextual understanding of the proliferation of other progenitor cells, considering the high frequency of co-altered signaling from RB/E2F and PTEN/PI3K/AKT pathways in a wide variety of normal and malignant settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0360-y) contains supplementary material, which is available to authorized users.

BackgroundMetastatic colon cancer is one of the leading causes of cancer-related death worldwide, with disease progression and metastatic spread being closely associated with angiogenesis. We investigated whether an antiangiogenic gene transfer approach using the Sleeping Beauty (SB) transposon system could be used to inhibit growth of colorectal tumors metastatic to the liver.ResultsLiver CT26 tumor-bearing mice were hydrodynamically injected with different doses of a plasmid containing a transposon encoding an angiostatin-endostatin fusion gene (Statin AE) along with varying amounts of SB transposase-encoding plasmid. Animals that were injected with a low dose (10 μg) of Statin AE transposon plasmid showed a significant decrease in tumor formation only when co-injected with SB transposase-encoding plasmid, while for animals injected with a higher dose (25 μg) of Statin AE transposon, co-injection of SB transposase-encoding plasmid did not significantly affect tumor load. For animals injected with 10 μg Statin AE transposon plasmid, the number of tumor nodules was inversely proportional to the amount of co-injected SB plasmid. Suppression of metastases was further evident in histological analyses, in which untreated animals showed higher levels of tumor cell proliferation and tumor vascularization than animals treated with low dose transposon plasmid.ConclusionThese results demonstrate that hepatic colorectal metastases can be reduced using antiangiogenic transposons, and provide evidence for the importance of the transposition process in mediating suppression of these tumors.