Identification of metabolic pathways influenced by the G-protein coupled receptors GprB and GprD in Aspergillus nidulans

Heterotrimeric G-protein-mediated signaling pathways play a pivotal role in transmembrane signaling in eukaryotes. Our main aim was to identify signaling pathways regulated by A. nidulans GprB and GprD G-protein coupled receptors (GPCRs). When these two null mutant strains were compared to the wild-type strain, the DeltagprB mutant showed an increased protein kinase A (PKA) activity while growing in glucose 1% and during starvation. In contrast, the DeltagprD has a much lower PKA activity upon starvation. Transcriptomics and (1)H NMR-based metabolomics were performed on two single null mutants grown on glucose. We noted modulation in the expression of 11 secondary metabolism gene clusters when the DeltagprB and DeltagprD mutant strains were grown in 1% glucose. Several members of the sterigmatocystin-aflatoxin gene cluster presented down-regulation in both mutant strains. The genes of the NR-PKS monodictyphenone biosynthesis cluster had overall increased mRNA accumulation in DeltagprB, while in the DeltagprD mutant strain the genes had decreased mRNA accumulation. Principal component analysis of the metabolomic data demonstrated that there was a significant metabolite shift in the DeltagprD strain. The (1)H NMR analysis revealed significant expression of essential amino acids with elevated levels in the DeltagprD strain, compared to the wild-type and DeltagprB strains. With the results, we demonstrated the differential expression of a variety of genes related mainly to secondary metabolism, sexual development, stress signaling, and amino acid metabolism. We propose that the absence of GPCRs triggered stress responses at the genetic level. The data suggested an intimate relationship among different G-protein coupled receptors, fine-tune regulation of secondary and amino acid metabolisms, and fungal development

The role of prostaglandin E2 (PGE 2) in toll-like receptor 4 (TLR4)-mediated colitis-associated neoplasia

<p>Abstract</p> <p>Background</p> <p>We have previously found that TLR4-deficient (TLR4-/-) mice demonstrate decreased expression of mucosal PGE ₂and are protected against colitis-associated neoplasia. However, it is still unclear whether PGE ₂is the central factor downstream of TLR4 signaling that promotes intestinal tumorigenesis. To further elucidate critical downstream pathways involving TLR4-mediated intestinal tumorigenesis, we examined the effects of exogenously administered PGE ₂in TLR4-/- mice to see if PGE ₂bypasses the protection from colitis-associated tumorigenesis.</p> <p>Method</p> <p>Mouse colitis-associated neoplasia was induced by azoxymethane (AOM) injection followed by two cycles of dextran sodium sulfate (DSS) treatment. Two different doses of PGE ₂(high dose group, 200 μg, n = 8; and low dose group, 100 μg, n = 6) were administered daily during recovery period of colitis by gavage feeding. Another group was given PGE ₂during DSS treatment (200 μg, n = 5). Inflammation and dysplasia were assessed histologically. Mucosal Cox-2 and amphiregulin (AR) expression, prostanoid synthesis, and EGFR activation were analyzed.</p> <p>Results</p> <p>In control mice treated with PBS, the average number of tumors was greater in WT mice (n = 13) than in TLR4-/- mice (n = 7). High dose but not low dose PGE ₂treatment caused an increase in epithelial proliferation. 28.6% of PBS-treated TLR4-/- mice developed dysplasia (tumors/animal: 0.4 ± 0.2). By contrast, 75.0% (tumors/animal: 1.5 ± 1.2, P < 0.05) of the high dose group and 33.3% (tumors/animal: 0.3 ± 0.5) of the low dose group developed dysplasia in TLR4-/- mice. Tumor size was also increased by high dose PGE ₂treatment. Endogenous prostanoid synthesis was differentially affected by PGE ₂treatment during acute and recovery phases of colitis. Exogenous administration of PGE ₂increased colitis-associated tumorigenesis but this only occurred during the recovery phase. Lastly, PGE ₂treatment increased mucosal expression of AR and Cox-2, thus inducing EGFR activation and forming a positive feedback mechanism to amplify mucosal Cox-2.</p> <p>Conclusions</p> <p>These results highlight the importance of PGE ₂as a central downstream molecule involving TLR4-mediated intestinal tumorigenesis.</p

Characterization of three members of the Arabidopsis carotenoid cleavage dioxygenase family demonstrates the divergent roles of this multifunctional enzyme family

Arabidopsis thaliana has nine genes that constitute a family of putative carotenoid cleavage dioxygenases (CCDs). While five members of the family are believed to be involved in synthesis of the phytohormone abscisic acid, the functions of the other four enzymes are less clear. Recently two of the enzymes, CCD7/MAX3 and CCD8/MAX4, have been implicated in synthesis of a novel apocarotenoid hormone that controls lateral shoot growth. Here, we report on the molecular and genetic interactions between CCD1, CCD7/MAX3 and CCD8/ MAX4. CCD1 distinguishes itself from other reported CCDs as being the only member not targeted to the plastid. Unlike ccd7/max3 and ccd8/max4, both characterized as having highly branched phenotypes, ccd1 loss-of-function mutants are indistinguishable from wild-type plants. Thus, even though CCD1 has similar enzymatic activity to CCD7/MAX3, it does not have a role in synthesis of the lateral shoot growth inhibitor. Rather, it may have a role in synthesis of apocarotenoid flavor and aroma volatiles, especially in maturing seeds where loss of function leads to significantly higher carotenoid levels

White racial attitudes: Does it matter how we ask?

Much of our systematic knowledge of the nature and correlates of white racial attitudes is based on sample surveys administered by interviewers. Questions are often raised about the validity of such data due to social desirability pressures to appear racially liberal. Using a quasi-experimental design, this study investigates the nature and extent of this bias and its relevance to understanding white racial attitudes. Specifically, responses are compared in three conditions of administration: a standard condition where interviewers asked all the questions; a modified face-to-face condition where respondents answered a subset of questions in a self-administered form; and a completely non-interviewer condition where questionnaires were mailed to respondents. The primary hypothesis of this study was that white respondents will express less liberal racial attitudes as conditions increase in confidentiality, and that this should be especially true of those with more education. The underlying assumption is that liberal racial attitudes have become increasingly expected in the United States, and that the presence of an interviewer increases pressures on respondents to say what is "socially desirable." More educated respondents would be more aware of such norms and feel pressure with greater force. These hypotheses were believed to operate differently for different types of racial questions, so questions that varied in their likely sensitivity to social desirability were used. The original sample consisted of essentially a cross-section of the white population of the metropolitan Detroit area, divided randomly into the three conditions. The three samples were comparable in response rates and on most demographic variables, with the key exception being a higher educational level for the mail survey, which was then controlled through weighting and multivariate analysis. Although there was initial support for the main hypotheses, some puzzling findings led to a second hypothesis: less educated respondents are subject to another form of social pressure--a tendency to agree with cliched statements. This tendency, known in survey methods literature as "acquiescence," might be expected to be heightened in a survey condition where an interviewer reads a plausible sounding statement. When the racial questions were reanalyzed in terms of both social desirability and acquiescence, the results provided support for both theoretical assumptions. This quantitative analysis was supplemented by depth interviews with a small sub-sample of mail survey respondents. These additional qualitative data were used to enrich the interpretation of the survey results, especially to show the complexity of the racial attitudes of white Americans. This complexity might otherwise be missed when we speak too simply of "social desirability.".Ph.D.SociologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/104809/1/9610170.pdfDescription of 9610170.pdf : Restricted to UM users only

Foreclosing on Community: Residential segregation and the long-term effects of the housing crisis in Cook County

On March 19, 2013, IGPA teamed with the Illinois Service Federal Savings and Loan Association and the Coalition of African-American Leaders to host a conference about the effects of the foreclosure crisis on Cook County and surrounding Illinois communities. The conference, “Foreclosing on Community: The Crisis and the Search for Solutions,” was organized by IGPA Senior Fellow Clarence Wood and IGPA sociologist Maria Krysan. This summary, compiled by IGPA Communications Coordinator Kelsey McCoy, incorporates information shared at the conference (updated to reflect recent data and events) and a new analysis by Krysan of the racial dynamics of the crisis in the Chicago area. At IGPA’s event in 2013, a panel of individuals working on housing issues in the communities hardest hit by the foreclosure crisis shared possible solutions. All members of the panel work closely with local governments, community organizations, and public officials. The panel included: Rob Rose, Vice President of Lending at the Chicago Community Loan Fund, which strategically utilizes investor funds to address housing issues and community development. Adam Gross, Director of the Affordable Housing Program at Business and Professional People for the Public Interest (BPI), which works with community organizations to develop programs that preserve and create affordable housing opportunities. 3 Rugh, Jacob S. and Douglas S. Massey. </div

Racial residential segregation and the housing search process

A new study on the housing search process adds to a growing body of research questioning the myth that racial minorities self-segregate. A 2004-2005 survey of residents of the Chicago area touched on a variety of topics related to neighborhoods, preferences, and housing searches. The results revealed that whites, blacks and Latinos all prefer to live in diverse neighborhoods in which their group is the largest, but not the majority. Yet no group ends up doing so. Although whites who had searched in the last 10 years report wanting to live in a diverse neighborhood, they search in places that are on average 68 percent white. Their current neighborhoods reflect their search patterns: the average white searcher lives in a neighborhood that is 74 percent white. In contrast, black and Latino residents search in areas that match their desired, diverse neighborhood. However, they end up living in neighborhoods with more residents of their own group than they say they prefer. Blacks in the study searched in neighborhoods that are 40 percent black, but end up in neighborhoods that are 66 percent black. Latinos search in neighborhoods that are 32 percent Latino, but end up in neighborhoods that are 51 percent Latino. The researchers ask: what happens between the search and the move that results in blacks and Latinos living in less diverse neighborhoods than they desire and in which they search? Possible explanations are that there is a lack of information or inadequate finances, but neither can fully account for the mismatch. Respondents—whites in particular—may also have been answering the survey in ways they perceived to be socially desirable. This does not explain the mismatch for blacks and Latinos because their search locations match their preferred neighborhood. The researchers suggest that it might be that blacks and Latinos search in diverse communities, and learn something about the neighborhood that makes it undesirable. Or, they may experience hostility or discrimination when searching, which creates barriers that impede them from translating their attitudes into actions. </div

A Portrait of African American and White Racial Attitudes

How do people feel about race? For those who believe that we live in a post-racial society, this question may seem simple. Although survey data collected since the 1940s do show that racial attitudes held by whites and African Americans have changed, that change is much more complicated than generally assumed. As state and federal policies have been adopted to battle racial inequality—from the desegregation of schools to preventing housing discrimination to affirmative action—there have been changes in some aspects of the nation’s racial climate. But has there been change in the hearts and minds of Americans? The answer to this question is complex. This report provides a portrait of the trends in racial attitudes held by white and African American citizens as told through the record of survey research. </div