Food Justice and Practices in the Five Points Community of Knoxville, Tennessee: A Survey of Residents Living in an Urban Food Desert

This thesis identifies the views related to traditional and alternative food systems and practices among residents living in East Knoxville, Tennessee, which has been designated by the United States Department of Agriculture (USDA) as a food desert. These views were obtained from a mail survey sent out to adult residents living in the community who were responsible for obtaining food for their household. Its foundation is based on general place-based theory and findings associated with environmental and food justice literature. It builds upon this work by identifying and describing key variables and how they may be related via a theoretical model and nine hypotheses. The basic model assumes that a direct effect exists between attitudes about food access and security, traditional food systems, alternative food systems and perceived barriers and bridges for adopting alternative food practices, and general support for alternatives. The findings show that residents who have greater food security in their households, have more knowledge about alternative food systems, view alternative food systems more positively, and believe that there are more bridges than barriers for obtaining fresh fruits and vegetables are more likely to have greater support for alternative food systems and practices

A Core Response to the CDX2 Homeoprotein During Development and in Pathologies

Whether a gene involved in distinct tissue or cell functions exerts a core of common molecular activities is a relevant topic in evolutionary, developmental, and pathological perspectives. Here, we addressed this question by focusing on the transcription factor and regulator of chromatin accessibility encoded by the Cdx2 homeobox gene that plays important functions during embryonic development and in adult diseases. By integrating RNAseq data in mouse embryogenesis, we unveiled a core set of common genes whose expression is responsive to the CDX2 homeoprotein during trophectoderm formation, posterior body elongation and intestinal specification. ChIPseq data analysis also identified a set of common chromosomal regions targeted by CDX2 at these three developmental steps. The transcriptional core set of genes was then validated with transgenic mouse models of loss or gain of function of Cdx2. Finally, based on human cancer data, we highlight the relevance of these results by displaying a significant number of human orthologous genes to the core set of mouse CDX2-responsive genes exhibiting an altered expression along with CDX2 in human malignancies

Modulation of mitochondrial capacity and angiogenesis by red wine polyphenols via estrogen receptor, NADPH oxidase and nitric oxide synthase pathways.

Red wine polyphenolic compounds (RWPC) are reported to exert vasculoprotective properties on endothelial cells, involving nitric oxide (NO) release via a redox-sensitive pathway. This NO release involves the activation of the estrogen receptor-alpha (ERα). Paradoxical effects of a RWPC treatment occur in a rat model of post-ischemic neovascularization, where a low-dose is pro-angiogenic while a higher dose is anti-angiogenic. NO and ERα are key regulators of mitochondrial capacity, and angiogenesis is a highly energetic process associated with mitochondrial biogenesis. However, whether RWPC induces changes in mitochondrial capacity has never been addressed. We investigated the effects of RWPC at low (10(-4)g/l, LCP) and high concentration (10(-2)g/l, HCP) in human endothelial cells. Mitochondrial respiration, expression of mitochondrial biogenesis factors and mitochondrial DNA content were assessed using oxygraphy and quantitative PCR respectively. In vitro capillary formation using ECM gel(®) was also performed. Treatment with LCP increased mitochondrial respiration, with a maximal effect achieved at 48h. LCP also increased expression of several mitochondrial biogenesis factors and mitochondrial DNA content. In contrast, HCP did not affect these parameters. Furthermore, LCP modulated both mitochondrial capacity and angiogenesis through mechanisms sensitive to ER, NADPH oxidase and NO-synthase inhibitors. Finally, the inhibition of mitochondrial protein synthesis abolished the pro-angiogenic capacity of LCP. These results suggest a possible association between the modulation of mitochondrial capacity by LCP and its pro-angiogenic activity. These data provide evidence for a role of mitochondria in the regulation of angiogenesis by RWPC

Role of the mitochondria on the paradoxical effect of red wine polyphenols on angiogenesis

Red wine polyphenol (RWPC) extracts has been reported to possess vasoprotective properties that involve nitric oxide (NO) release from endothelial cells via a redox- sensitive pathway. Besides, the molecular target of RWPC to release NO has been recently revealed and it involves the activation of the estrogen receptor alpha (ERα). Paradoxical effects of RWPC have been shown with regard to angiogenesis. Indeed in a rat model of postischemic neovascularization, low- dose is pro-  whereas high dose is anti- angiogenic. NO and ERα  are key regulators of mitochondrial function. Furthermore, angiogenesis is a highly energetic process associated with mitochondrial biogenesis. However, whether RWPC induces changes in mitochondrial function has never been addressed and it is the aim of this study. The effects of RWPC at low concentration (10- 4 g/l, LCP) and high concentration (10- 2 g/l, HCP) after 48 hours time exposure were investigated on human endothelial cells. Mitochondrial respiration, expression of biogenesis factors and DNA content was assessed using oxygraphy and qRT- PCR, respectively. In vitro capillary formation using Matrigel® was performed. The mechanism involved with respect to ER using the ER- antagonist fulvestrant was studied. The involvement of both NADPH oxidase and NO synthase was addressed using apocynin and L- NA respectively. LCP, but not HCP, increased mitochondrial respiration. The effect of LCP was associated with an increase of both expression of several mitochondrial biogenesis factors (NRF- 1, NRF- 2, ERRα, Tfam, PolG) and mitochondrial DNA content whereas HCP had no effect on these parameters. All the effects of LCP on mitochondrial respiration are prevented by fulvestrant, apocynin and L- NA. LCP also promoted in vitro capillary elongation that was prevented by fulvestrant, apocynin and L- NA. Finally, the inhibition of mitochondrial protein synthesis using chloramphenicol suppressed the pro- angiogenic property of LCP. The present study highlights the implication of the axis ER, NADPH oxidase and NOS pathways on both increase mitochondrial function and capillary elongation in response to RWPC at low concentration. They explain the paradoxical effect of RWPC depending on the concentration with respect to angiogenesis, mitochondria being key targets for its pro- angiogenic properties

IL-6 and leukemia-inhibitory factor are involved in the generation of tumor-associated macrophage: regulation by IFN-γ

Tumor-associated macrophages (TAMs), the most abundant immunosuppressive myeloid cells in the tumor microenvironment, exhibit an IL-10highIL-12low profile called M2, opposite to the immunostimulatory M1. We reported that ovarian cancer ascites switched monocyte differentiation into TAM-like cells that exhibit most phenotypic and functional characteristics of TAMs, suggesting that soluble mediators are involved in the differentiation of monocytes into TAM-like cells. We observed that leukemia-inhibitory factor and IL-6, present at high concentrations in ovarian cancer ascites, skew monocyte differentiation into TAM-like cells by increasing macrophage colony-stimulating factor consumption. Moreover, we observed that IFN-γ switches established TAMs into immunostimulatory M1 cells and skews monocyte differentiation from TAM-like cells to M1s. In addition to revealing a new tumor-escape mechanism associated with TAM generation via leukemia-inhibitory factor and IL-6, these findings offer novel therapeutic perspectives to subvert TAM-induced immunosuppression and to improve antitumor immunotherapy efficacy

Functional interaction between the homeoprotein CDX1 and the transcriptional machinery containing the TATA-binding protein

We have previously reported that the CDX1 homeoprotein interacts with the TATA-box binding protein (TBP) on the promoter of the glucose-6-phosphatase (G6Pase) gene. We show here that CDX1 interacts with TBP via the homeodomain and that the transcriptional activity additionally requires the N-terminal domain upstream of the homeodomain. CDX1 interacting with TBP is connected to members of the TFIID and Mediator complexes, two major elements of the general transcriptional machinery. Transcription luciferase assays performed using an altered-specificity mutant of TBP provide evidence for the functionality of the interaction between CDX1 and TBP. Unlike CDX1, CDX2 does not interact with TBP nor does it transactivate the G6Pase promoter. Swapping experiments between the domains of CDX1 and CDX2 indicate that, despite opposite functional effects of the homeoproteins on the G6Pase promoter, the N-terminal domains and homeodomains of both CDX1 and CDX2 have the intrinsic ability to activate transcription and to interact with TBP. However, the carboxy domains define the specificity of CDX1 and CDX2. Thus, intra-molecular interactions control the activity and partner recruitment of CDX1 and CDX2, leading to different molecular functions

Severe head dysgenesis resulting from imbalance between anterior and posterior ontogenetic programs

Head dysgenesis is a major cause of fetal demise and craniofacial malformation. Although mutations in genes of the head ontogenetic program have been reported, many cases remain unexplained. Head dysgenesis has also been related to trisomy or amplification of the chromosomal region overlapping the CDX2 homeobox gene, a master element of the trunk ontogenetic program. Hence, we investigated the repercussion on head morphogenesis of the imbalance between the head and trunk ontogenetic programs, by means of ectopic rostral expression of CDX2 at gastrulation. This caused severe malformations affecting the forebrain and optic structures, and also the frontonasal process associated with defects in neural crest cells colonization. These malformations are the result of the downregulation of genes of the head program together with the abnormal induction of trunk program genes. Together, these data indicate that the imbalance between the anterior and posterior ontogenetic programs in embryos is a new possible cause of head dysgenesis during human development, linked to defects in setting up anterior neuroectodermal structures

Estrogen Receptor α Participates to the Beneficial Effect of Red Wine Polyphenols in a Mouse Model of Obesity-Related Disorders

Red wine polyphenol extracts (polyphenols) ameliorate cardiovascular and metabolic disorders associated with obesity. Previously, we demonstrated that the alpha isoform of estrogen receptor (ERα) triggers the vascular protection of polyphenols. Here, we investigated the contribution of ERα on the effects of polyphenols on cardiovascular and metabolic alterations associated with obesity. We used ovariectomized wild type or ERα-deficient mice receiving standard (SD) or western (WD) diets, or SD and WD containing polyphenols (SD+polyphenols and WD+polyphenols, respectively) over a 12-week period. Body weight was measured during treatment. Echocardiography examination was performed before sacrifice. Blood and tissues were sampled for biochemical and functional analysis with respect to nitric oxide (NO(•)) and oxidative stress. Vascular reactivity and liver mitochondrial complexes were analyzed. In WD-fed mice, polyphenols reduced adiposity, plasma triglycerides and oxidative stress in aorta, heart, adipose and liver tissues and enhanced NO(•) production in aorta and liver. ERα deletion prevented or reduced the beneficial effects of polyphenols, especially visceral adiposity, aortic and liver oxidative stresses and NO(•) bioavailability. ERα deletion, however, had no effect on polyphenol\u27s ability to decrease the fat accumulation and oxidative stress of subcutaneous adipose tissue. Also, ERα deletion did not modify the decrease of ROS levels induced by polyphenols treatment in the visceral adipose tissue and heart from WD-fed mice. Dietary supplementation of polyphenols remarkably attenuates features of metabolic syndrome; these effects are partially mediated by ERα-dependent mechanisms. This study demonstrates the therapeutic potential of this extract in metabolic and cardiovascular alterations linked to excessive energy intake