Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic oligodendrogliomas.

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SUMMARY We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.

MRI is emerging as a promising modality for monitoring carotid atherosclerosis. Multiple MR contrast weightings are required for identification of plaque constituents. In this study, eight MR contrast weightings with proven potential for plaque characterization were used to image carotid endarterectomy specimens. A classification technique was developed to create a tissuespecific map by incorporating information from all MR contrast weightings. The classifier was validated by comparison with micro-CT (calcification only) and with matched histological slices registered to MR images using a nonlinear warping algorithm (other components). A pathologist who was blinded to the classifier results manually segmented digitized histological images. Atherosclerosis is a chronic and progressive disease that is characterized by the accumulation of lipids and fibrous tissue within the artery wall (1). Disruption of atherosclerotic plaques at the carotid bifurcation is believed to be the underlying cause of many embolic strokes; furthermore, the histological composition of carotid atheroma is related to a plaque's vulnerability to rupture (2,3). In general, unstable plaques are characterized by a thin, fibrous cap that separates a pool of extracellular lipid and necrosis from the lumen (4). If the integrity of the fibrous cap is compromised, the necrotic core is exposed to the bloodstream and thrombus formation may occur. Several factors may play a role in triggering plaque rupture, including the size and spatial distribution of various plaque components (5); however, the specific plaque components or mechanisms responsible for plaque rupture and/or erosion and subsequent clinical events have yet to be elucidated (4). Further knowledge regarding the explicit features that confer vulnerability to a lesion may come from studies that track changes in plaque composition over time.MR is a promising noninvasive technique for characterizing atherosclerotic plaque composition. Because of the complexity and variability of atherosclerotic lesions, it is necessary to employ several MR contrast weightings to adequately discriminate between plaque constituents. Ex vivo studies have demonstrated that T 2 -weighted contrast alone is inadequate for measuring the size of the lipid core (6), but a combination of proton density, partial T 2 , T 2 , and diffusion-weighted spin-echo sequences can provide a more accurate assessment of plaque microstructure (7). Multicontrast-weighted MR has also been shown to be necessary for characterizing plaque in vivo. In a series of patients undergoing carotid endarterectomy, no single MR contrast weighting was able to identify lipid-rich necrotic cores and intraplaque hemorrhage; rather, a review of proton density, T 1 , T 2 , and time-of-flight (TOF) contrast weightings was required (8). In a subsequent investigation, these same four contrast weightings provided enough information to successfully classify carotid plaques according to a modified American Heart Association classification scheme (9). These stu...

Retroviral envelopes are pathogenic glycoproteins which cause neuroinflammation, neurodegeneration, and endoplasmic reticulum stress responses. The human endogenous retrovirus (HERV-W) envelope protein, Syncytin-1, is highly expressed in CNS glia of individuals with multiple sclerosis (MS). In this study, we investigated the mechanisms by which Syncytin-1 mediated neuroimmune activation and oligodendrocytes damage. In brain tissue from individuals with MS, ASCT1, a receptor for Syncytin-1 and a neutral amino acid transporter, was selectively suppressed in astrocytes (p < 0.05). Syncytin-1 induced the expression of the endoplasmic reticulum stress sensor, old astrocyte specifically induced substance (OASIS), in cultured astrocytes, similar to findings in MS brains. Overexpression of OASIS in astrocytes increased inducible NO synthase expression but concurrently down-regulated ASCT1 (p < 0.01). Treatment of astrocytes with a NO donor enhanced expression of early growth response 1, with an ensuing reduction in ASCT1 expression (p < 0.05). Small-interfering RNA molecules targeting Syncytin-1 selectively down-regulated its expression, preventing the suppression of ASCT1 and the release of oligodendrocyte cytotoxins by astrocytes. A Syncytin-1-transgenic mouse expressing Syncytin-1 under the glial fibrillary acidic protein promoter demonstrated neuroinflammation, ASCT1 suppression, and diminished levels of myelin proteins in the corpus callosum, consistent with observations in CNS tissues from MS patients together with neurobehavioral abnormalities compared with wild-type littermates (p < 0.05). Thus, Syncytin-1 initiated an OASIS-mediated suppression of ASCT1 in astrocytes through the induction of inducible NO synthase with ensuing oligodendrocyte injury. These studies provide new insights into the role of HERV-mediated neuroinflammation and its contribution to an autoimmune disease.

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Synthetic aperture radar (SAR) images of moving ships often exhibit characteristic patterns associated with various wake phenomena. These features can be classified into three general categories which include (1) surface waves generated by the ship, (2) turbulent or vortex wakes, and (3) internal waves. In this paper an overview of the present status of SAR ship wake imaging is presented.

Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI.