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NK cells have been established as an important effector of innate immunity in a variety of viral infections. In HIV-1 infection in humans, alterations of NK cell function, frequency, and expression of various NK receptors have been reported to be associated with differential dynamics of disease progression. Expression of certain alleles of KIR3DL and KIR3DS receptors on NK cells was shown to correlate with levels of virus replication. In the SIV-infected rhesus macaque (RM) model of AIDS, several families of killer inhibitory Ig-related receptors (KIR receptors) corresponding to their human counterparts have been characterized, but only at the level of individual sequence variants. Here we define 14 different alleles of KIR3DL expressed among 38 SIV-infected RM, characterized by either high or low levels of SIV replication, by analyzing multiple sequences from individual animals and show an unequal distribution of certain alleles in these cohorts. High levels of SIV replication were associated with significant increases in KIR3DL mRNA levels in addition to decreases in both the frequency and function of NK cells in these animals. The higher frequency of inheritance of two KIR3DL alleles characterized by a single nucleotide polymorphism 159 H/Q was associated with RM that exhibited high plasma viral load. This data for the first time defines multiple alleles of KIR3DL in RM and shows an association between virus control, NK cell function and genetic polymorphisms of KIR receptors.

The last phase of leaf development, generally referred to as leaf senescence, is an integral part of plant development that involves massive programmed cell death. Due to a sharp decline of photosynthetic capacity in a leaf, senescence limits crop yield and forest plant biomass production. However, the biochemical components and regulatory mechanisms underlying leaf senescence are poorly characterized. Although several approaches such as differential cDNA screening, differential display, and cDNA subtraction have been employed to isolate senescence-associated genes (SAGs), only a limited number of SAGs have been identified, and information regarding the regulation of these genes is fragmentary. Here we report on the utilization of enhancer trap approach toward the identification and analysis of SAGs. We have developed a sensitive large-scale screening method and have screened 1,300 Arabidopsis enhancer trap lines and have identified 147 lines in which the reporter gene GUS (beta-glucuronidase) is expressed in senescing leaves but not in non-senescing ones. We have systematically analyzed the regulation of beta-glucuronidase expression in 125 lines (genetically, each contains single T-DNA insertion) by six senescence-promoting factors, namely abscisic acid, ethylene, jasmonic acid, brassinosteroid, darkness, and dehydration. This analysis not only reveals the complexity of the regulatory circuitry but also allows us to postulate the existence of a network of senescence-promoting pathways. We have also cloned three SAGs from randomly selected enhancer trap lines, demonstrating that reporter expression pattern reflects the expression pattern of the endogenous gene.

Background: Prostate cancer (PCA) has the second incidence and mortality rates among cancers affecting U.S. men. Furthermore, men of African descent (MAD) are at increased risk to develop PCA, be diagnosed with more aggressive cases, and less likely to survive 5-years following diagnosis when compared to men of European descent (EA). Unfortunately, mechanisms contributing to PCA etiology and disparities are poorly characterized. Identification of genetic and environmental factors contributing to PCA development and disease aggressiveness are essential to reducing its incidence, disparity and mortality. Research Goal & Objective: With the ultimate goal of improving clinical management, we systematically evaluated the relationship between oxidative stress-related (OSR) susceptibility factors and PCA outcomes among a case control population of 3,200 men. Hypothesis: We hypothesized individuals inheriting variant OSR loci linked with reduced antioxidation, oxidative DNA damage repair, and apoptotic potential have an increased risk of developing PCA and aggressive disease. Materials and Methods: In order to evaluate the effects of OSR sequence variants on PCA we used SNP profile data collected from 2277 EA participants of the Cancer Genetic Markers of Susceptibility project (1176 cases, 1101 controls) and 923 MAD (224 cases, 699 controls). We evaluated the independent effects of 205 variant OSR genes in relation to PCA risk and aggressive disease using logistic regression and multi-factor dimensionality reduction (MDR) modeling. Results: Among EA, inheritance of at least one minor OSR loci involved in antioxidation [NOS2A_rs2274894, TXNDC5 rs2743993, TXNRD2_rs5746847), DNA repair (OGG1_rs12570, XRCC1_rs1799778), and apoptosis [BNIP3L_rs7813520, CASP3_rs4647693, CDK9_rs3217751, MAPK1_rs743409, MSRA (rs6997224, rs17151728), RASSF5_rs11589, TGFB2_rs1891467, TNFAIP8_rs1112247] associated with PCA risk and aggressive disease (p Conclusions: Our findings suggest that variations in genes involved OSR may play a role in prostate carcinogenesis among EA and MAD. Population attributable risk calculations may allow us to discern whether OSR markers may help to explain prostate cancer incidence disparities among MAD. Further analysis of gene-gene and gene-environment interactions in OSR susceptibility markers will allow us to better characterize a panel capable of predicting PCA risk and disease progression in high-risk subgroups. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 926.