Effects of Aging and Anatomic Location on Gene Expression in Human Retina

Objective: To determine the effects of age and topographic location on gene expression in human neural retina. Methods: Macular and peripheral neural retina RNA was isolated from human donor eyes for DNA microarray and quantitative RT-PCR analyses. Results: Total RNA integrity from human donors was preserved. Hierarchical clustering analysis demonstrates that the gene expression profiles of young, old, macula, and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young, or old retina were identified, including inhibitors of Wnt Signaling Pathway (DKK1, FZD10, and SFRP2) which are preferably expressed in the periphery. Conclusion: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases

Analysis and Exploitation of Musician Social Networks for Recommendation and Discovery

This paper presents an extensive analysis of a sample of a social network of musicians. The network sample is first analyzed using standard complex network techniques to verify that it has similar properties to other web-derived complex networks. Content-based pairwise dissimilarity values between the musical data associated with the network sample are computed, and the relationship between those content-based distances and distances from network theory explored. Following this exploration, hybrid graphs and distance measures are constructed, and used to examine the community structure of the artist network. Finally, results of these investigations are presented and considered in the light of recommendation and discovery applications with these hybrid measures as their basis

Interaction between Family History of Alcoholism and Locus of Control in the Opioid Regulation of Impulsive Responding under the Influence of Alcohol

Naltrexone (NTX) is an opioid antagonist indicated for the treatment of alcoholism, which is not universally effective. Thus, identifying individual predictors of NTX’s behavioral effects is critical to optimizing its therapeutic use. Moreover, given the high rate of relapse during treatment for alcoholism, understanding NTX’s behavioral effects when combined with moderate ethanol intake is important. Our previous study of abstinent alcoholics and control subjects showed that a more internal Locus of Control score predicted increased impulsive choice on NTX (Mitchell et al., 2007). Here we tested whether this predictive relationship remains in the context of moderate alcohol intake

Dark Matter implications of the Fermi-LAT measurement of anisotropies in the diffuse gamma-ray background: status report

For the first time, the Fermi-LAT measured the angular power spectrum (APS) of anisotropies in the diffuse gamma-ray background. The data is found to be broadly compatible with a model with contributions from the point sources in the 1-year catalog, the galactic diffuse background, and the extragalactic isotropic emission; however deviations are present at both large and small angular scales. In this study, we complement the model with a contribution from Dark Matter (DM) whose distribution is modeled exploiting the results of the most recent N-body simulations, considering the contribution of extragalactic halos and subhalos (from Millennium-II) and of galactic substructures (from Aquarius). With the use of the Fermi Science Tools, these simulations serve as templates to produce mock gamma-ray count maps for DM gamma-ray emission, both in the case of an annihilating and a decaying DM candidate. The APS will then be computed and compared with the Fermi-LAT results to derive constraints on the DM particle physics properties. The possible systematic due to an imperfect model of the galactic foreground is also studied and taken into account properly. The present paper reports on the status of the project.Comment: Proceeding for the RICAP2011 conferenc

Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network

Previously, we found that distinct brain areas predict individual selection bias in decisions between small immediate (“Now”) and larger delayed rewards (“Later”). Furthermore, such selection bias can be manipulated by endogenous opioid blockade. To test whether blocking endogenous opioids with Naltrexone (NTX) alters brain activity during decision-making in areas predicting individual bias, we compared fMRI BOLD signal correlated with Now versus Later decision-making after acute administration of NTX (50 mg) or placebo. We tested abstinent alcoholics and control subjects in a double-blind two-session design. We defined regions of interest (ROI) centered on activation peaks predicting Now versus Later selection bias. NTX administration significantly increased BOLD signal during decision-making in the right lateral orbital gyrus ROI, an area where enhanced activity during decision-making predicts Later bias. Exploratory analyses identified additional loci where BOLD signal during decision-making was enhanced (left orbitofrontal cortex, left inferior temporal gyrus, and cerebellum) or reduced (right superior temporal pole) by NTX. Additional analyses identified sites, including the right lateral orbital gyrus, in which NTX effects on BOLD signal predicted NTX effects on selection bias. These data agree with opioid receptor expression in human frontal and temporal cortices, and suggest possible mechanisms of NTX’s therapeutic effects

Activity of immunoproteasome inhibitor ONX-0914 in acute lymphoblastic leukemia expressing MLL–AF4 fusion protein

Proteasome inhibitors bortezomib and carfilzomib are approved for the treatment of multiple myeloma and mantle cell lymphoma and have demonstrated clinical efficacy for the treatment of acute lymphoblastic leukemia (ALL). The t(4;11)(q21;q23) chromosomal translocation that leads to the expression of MLL–AF4 fusion protein and confers a poor prognosis, is the major cause of infant ALL. This translocation sensitizes tumor cells to proteasome inhibitors, but toxicities of bortezomib and carfilzomib may limit their use in pediatric patients. Many of these toxicities are caused by on-target inhibition of proteasomes in non-lymphoid tissues (e.g., heart muscle, gut, testicles). We found that MLL–AF4 cells express high levels of lymphoid tissue-specific immunoproteasomes and are sensitive to pharmacologically relevant concentrations of specific immunoproteasome inhibitor ONX-0914, even in the presence of stromal cells. Inhibition of multiple active sites of the immunoproteasomes was required to achieve cytotoxicity against ALL. ONX-0914, an inhibitor of LMP7 (ß5i) and LMP2 (ß1i) sites of the immunoproteasome, and LU-102, inhibitor of proteasome ß2 sites, exhibited synergistic cytotoxicity. Treatment with ONX-0914 significantly delayed the growth of orthotopic ALL xenograft tumors in mice. T-cell ALL lines were also sensitive to pharmacologically relevant concentrations of ONX-0914. This study provides a strong rationale for testing clinical stage immunoproteasome inhibitors KZ-616 and M3258 in ALL

Baryogenesis and the New Cosmology

In this talk I begin with a brief review of the status of approaches to understanding the origin of the baryon asymmetry of the universe (BAU). I then describe a recent model unifying three seemingly-distict problems facing particle cosmology: the origin of inflation, the generation of the BAU and the nature of dark energy.Comment: 16 pages, RevTeX, Plenary talk presented at PASCOS-03, Mumbai, India; COSMO-02, Chicago, and at the Aspen Winter 2003 Conference on Particle Physics: At the Frontiers of Particle Physics, Aspen Center for Physics. To appear in the proceedings of PASCOS-0

Enterotoxin-producing Escherichia coli O169:H41, United States

From 1996 to 2003, 16 outbreaks of enterotoxigenic Escherichia coli (ETEC) infections in the United States and on cruise ships were confirmed. E. coli serotype O169:H41 was identified in 10 outbreaks and was the only serotype in 6. This serotype was identified in 1 of 21 confirmed ETEC outbreaks before 1996

Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158Val/Val Genotype

The tendency to choose lesser immediate benefits over greater long-term benefits characterizes alcoholism and other addictive disorders. However, despite its medical and socioeconomic importance, little is known about its neurobiological mechanisms. Brain regions that are activated when deciding between immediate or delayed rewards have been identified