Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B.

BackgroundUBE4B is an E3/E4 ubiquitin ligase whose gene is located in chromosome 1p36.22. We analyzed the associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and with tumor prognostic features and histology.MethodsWe evaluated the association of UBE4B gene expression with neuroblastoma patient outcomes using the R2 Platform. We screened neuroblastoma tumor samples for UBE4B protein expression using immunohistochemistry. FISH for UBE4B and 1p36 deletion was performed on tumor samples. We then evaluated UBE4B expression for associations with prognostic factors and with levels of phosphorylated ERK in neuroblastoma tumors and cell lines.ResultsLow UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression was associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels were associated with high-risk features. UBE4B protein levels were also associated with levels of phosphorylated ERK.ConclusionsWe have demonstrated associations between UBE4B gene expression and neuroblastoma patient outcomes and prognostic features. Reduced UBE4B protein expression in neuroblastoma tumors was associated with high-risk features, a lack of differentiation, and with ERK activation. These results suggest UBE4B may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions and that UBE4B expression may mediate neuroblastoma differentiation

Biochemical Characterization of a Filtered Synaptoneurosome Preparation from Guinea Pig Cerebral Cortex: Cyclic Adenosine 3’:5’-Monophosphate-generating Systems, Receptors, and Enzymes

A particulate preparation was obtained by low speed centrifugation of guinea pig cerebral cortical homogenates prepared with a Krebs-Henseleit buffer. Light microscopic examination, using a reflected light differential interference contrast system, reveals the presence of intact neurons, axonal fragments, glial cells, and erythrocytes along with an abundance of small spherical entities (diameter about 1.1 μm) and snowman-shaped entities (diameter of larger sphere about 1.1 μm, diameter of attached smaller sphere about 0.6 μm). Many unattached smaller spherical entities are also present (diameter about 0.6 μm). Pressure filtration through 5 or l0-μm Millipore filters, followed by low speed centrifugation and resuspension, removes most of the larger entities to afford a suspension composed mainly of the small spherical and snowman-shaped entities. Electron microscopic examination reveals the presence of many synaptosomes with attached resealed postsynaptic entities. It is proposed that these correspond to the snowman-shaped entities to be termed synaptoneurosomes. Accumulations of cyclic AMP elicited by 2-chloroadenosine and histamine, and by combinations of 2-chloroadenosine, histamine, norepinephrine, and forskolin, are lower in filtered than in unfiltered preparations, whereas accumulations elicited by forskolin are unchanged. Levels of adenylate cyclase are reduced by filtration, whereas levels of phosphodiesterase are unchanged. Filtration reduces levels of markers for whole cells and endothelial cells, whereas neuronal markers such as acetylcholinesterase activity and norepinephrine uptake are increased. Levels of S-100 protein, a marker for glial cells, are not significantly decreased. There is no apparent change in the density of many receptors or ion channels. Levels of A1-adenosine and H1-histamine receptors are increased, whereas levels of so-called peripheral benzodiazepine-binding sites are decreased

Order statistics for d-dimensional diffusion processes

We present results for the ordered sequence of first passage times of arrival of N random walkers at a boundary in Euclidean spaces of d dimensions

Assessing the efficiency of mother-to-child HIV prevention in low- and middle-income countries using data envelopment analysis

AIDS is one of the most significant health care problems worldwide. Due to the difficulty and costs involved in treating HIV, preventing infection is of paramount importance in controlling the AIDS epidemic. The main purpose of this paper is to explore the potential of using Data Envelopment Analysis (DEA) to establish international comparisons on the efficiency of implementation of HIV prevention programmes. To do this we use data from 52 low- and middle-income countries regarding the prevention of mother-to-child transmission of HIV. Our results indicate that there is a remarkable variation in the efficiency of prevention services across nations, suggesting that a better use of resources could lead to more and improved services, and ultimately, prevent the infection of thousands of children. These results also demonstrate the potential strategic role of DEA for the efficient and effective planning of scarce resources to fight the epidemic

CD44 modulates Smad1 activation in the BMP-7 signaling pathway

Bone morphogenetic protein 7 (BMP-7) regulates cellular metabolism in embryonic and adult tissues. Signal transduction occurs through the activation of intracellular Smad proteins. In this paper, using a yeast two-hybrid screen, Smad1 was found to interact with the cytoplasmic domain of CD44, a receptor for the extracellular matrix macromolecule hyaluronan. Coimmunoprecipitation experiments confirmed the interaction of Smad1 with full-length CD44—interactions that did not occur when CD44 receptors truncated within the cytoplasmic domain were tested. Chondrocytes overexpressing a truncated CD44 on a background of endogenous full-length CD44 no longer exhibited Smad1 nuclear translocation upon BMP-7 stimulation. Further, pretreatment of chondrocytes with Streptomyces hyaluronidase to disrupt extracellular hyaluronan–cell interactions inhibited BMP-7–mediated Smad1 phosphorylation, nuclear translocation of Smad1 or Smad4, and SBE4–luciferase reporter activation. These results support a functional link between the BMP signaling cascade and CD44. Thus, changes in hyaluronan–cell interactions may serve as a means to modulate cellular responsiveness to BMP

Development of a food composition database to monitor changes in packaged foods and beverages

In order to monitor nutritional changes in the US food supply and assess potential impact on individual dietary intake, an approach was developed to enhance existing standard food composition tables with time-varying product- and brand-specific information for barcoded packaged foods. A “Crosswalk” was formed between barcoded products and USDA foodcodes in a time-specific manner, such that sales-weighted average nutritional profiles were generated for each foodcode based on corresponding products (275,000–350,000 per 2-year cycle). This Crosswalk-enhanced food composition table was applied to dietary intake data from the National Health and Nutrition Examination Survey (cycles 2007–2008, 2009–2010, and 2011–2012). Total energy density of foods consumed by Americans from stores/vending was stable over time and differed by <5 kcal/100 g using the Crosswalk-enhanced vs standard database. However, changes in the energy density of food groups were found utilizing the Crosswalk that were not detected using the standard database. Likewise, significant declines in energy intake from beverages among children (288 ± 7.3 to 258 ± 6.8 kcal/d) were found using the Crosswalk-enhanced database but were non-significant using the standard database. The Crosswalk approach can potentially augment national nutrition surveys by utilizing commercial food purchase and nutrient databases to capture changes in the nutrient content of packaged foods

Hazardous materials management using a Cradle-to-Grave Tracking and Information System (CGTIS)

Hazardous materials management includes interactions among materials, personnel, facilities, hazards, and processes of various groups within a DOE site`s environmental, safety & health (ES&H) and line organizations. Although each group is charged with addressing a particular aspect of these properties and interactions, the information it requires must be gathered into a coherent set of common data for accurate and consistent hazardous material management and regulatory reporting. It is these common data requirements which the Cradle-to-Grave Tracking and Information System (CGTIS) is designed to satisfy. CGTIS collects information at the point at which a process begins or a material enters a facility, and maintains that information, for hazards management and regulatory reporting, throughout the entire life-cycle by providing direct on-line links to a site`s multitude of data bases to bring information together into one common data model