BACKGROUND AND PURPOSE:Investigation of the anatomy, patency, and blood flow of arterial and venous vessels in small animal models of cerebral ischemia, venous thrombosis, or vasospasm is of major interest. However, due to their small caliber, in vivo examination of these vessels is technically challenging. Using micro-CT, we compared the feasibility of in vivo DSA and CTA of the murine cerebrovasculature using an intra-arterial route of contrast administration.MATERIALS AND METHODS:The ECA was catheterized in 5 C57BL/6J mice. During intra-arterial injection of an iodized contrast agent (30 μL/1 sec), DSA of the intra- and extracranial vessels was performed in mice breathing room air and repeated in hypoxic/hypercapnic mice. Micro-CTA was performed within 20 seconds of intra-arterial contrast injection (220 μL/20 sec). Image quality of both methods was compared. Radiation dose measurements were performed with thermoluminescence dosimeters.RESULTS:Both methods provided high-resolution images of the murine cerebrovasculature, with the smallest identifiable vessel calibers of ≤50 μm. Due to its high temporal resolution of 30 fps, DSA allowed identification of anastomoses between the ICA and ECA by detection of retrograde flow within the superficial temporal artery. Micro-CTA during intra-arterial contrast injection resulted in a reduced injection volume and a higher contrast-to-noise ratio (19.0 ± 1.0) compared with DSA (10.0 ± 1.8) or micro-CTA when using an intravenous injection route (1.3 ± 0.4).CONCLUSIONS:DSA of the murine cerebrovasculature is feasible using micro-CT and allows precise and repeated measurements of the vessel caliber, and changes of the vessel caliber, while providing relevant information on blood flow in vivo.

BACKGROUND Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity. METHODOLOGY/PRINCIPAL FINDINGS We identified three novel ASM splice variants in human cells, termed ASM-5,-6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models. CONCLUSIONS/SIGNIFICANCE These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity.

A search for a Higgs boson in the four-lepton decay channel H→ZZ, with each Z boson decaying to an electron or muon pair, is reported. The search covers Higgs boson mass hypotheses in the range of 110<m_{H}<600  GeV. The analysis uses data corresponding to an integrated luminosity of 4.7  fb^{-1} recorded by the CMS detector in pp collisions at sqrt[s]=7  TeV from the LHC. Seventy-two events are observed with four-lepton invariant mass m_{4ℓ}>100  GeV (with 13 below 160 GeV), while 67.1±6.0 (9.5±1.3) events are expected from background. The four-lepton mass distribution is consistent with the expectation of standard model background production of ZZ pairs. Upper limits at 95% confidence level exclude the standard model Higgs boson in the ranges of 134-158 GeV, 180-305 GeV, and 340-465 GeV. Small excesses of events are observed around masses of 119, 126, and 320 GeV, making the observed limits weaker than expected in the absence of a signal.