Consumer Acceptance of Novel Breads Containing Vitamin D and Soy Given Three Different Nutrition Information Conditions

Functional foods are an innovative area of food science that improve the health of consumers through the use of synergistic ingredients. A Vitamin D bread with soy was developed by scientists at the Ohio State University and is poised to reduce the deficiency of Vitamin D in the United States. A survey was conducted to see which identifying claims on four different breads (whole wheat, whole wheat with soy, whole wheat with 50% Vitamin D, and whole wheat with 100% Vitamin D) would make this product most appealing to consumers. The survey compared three levels of nutrition information: a front of pack (FOP) claim, a FOP claim with the traditional nutrition facts label, and a FOP claim with the proposed new nutrition facts label. It was hosted through Qualtrics, LLC and distributed to consumers in the state of Ohio. Across all three levels of information, a majority of respondents preferred traditional wheat bread, although a statistically significant shift of consumer preference towards whole wheat bread with 100% Vitamin D occurred between the FOP claim and the FOP claim with a nutrition label. Additionally, a majority of consumers, preferred to pay $2.00-2.99 per loaf, while a significant shift in willingness to pay occurred between the FOP claim and the FOP claim with a nutrition label. No change was noted in consumer preference with the new nutrition label. It was concluded that the financial success of the bread in the market place could not be guaranteed through the results of this survey alone, and that further study was necessary to understand consumer perception of claims, nutrition labels, and the impact of Vitamin D in the body.Food Innovation CenterNo embargoAcademic Major: Food Science and Technolog

The Cincinnati Environmental Justice Ordinance: Proposing a New Model for Environmental Justice Regulations by the States

The majority of environmental justice policies today exist as extremely decentralized municipal ordinances or as extremely centralized government agency strategies. Each system of regulation presents distinct advantages. Therefore, an analysis of the City of Cincinnati Environmental Justice Ordinance within the context of the ongoing debate between the benefits of centralized versus decentralized environmental regulations (the centralization-decentralization debate) examines the advantages of each scheme of regulations more extensively. However, each argument in favor of one type of regulation represents a disadvantage of the other, so this Note argues that by implementing environmental justice regulations at the state level, with the Cincinnati Ordinance as a model, the benefits of both local and national policies can be combined while mitigating the relative disadvantages. To illustrate the inadequacies of both federal and local level attempts to achieve environmental justice, this Note canvasses a brief history of the environmental justice movement at the federal, state, and local levels, including a description of the specific provisions of the Ordinance. As the history of the movement will show, neither the federal, state, nor local level governments provide effective or efficient legal remedies for environmental justice. However, state administrative agencies, whose regulatory authority mirrors those at the federal level, have the flexibility to expand their environmental justice policies with the cooperation of state legislatures. Part III of this Note then provides an analysis of the Ordinance regarding the effectiveness of its provisions in achieving the goals of the environmental justice movement. The Ordinance provides an effective model for future environmental justice policies because it enhances government accountability. Additionally, Part III analyzes the Ordinance with respect to the centralization -decentralization debate. Theoretically, environmental justice regulations can be promulgated at any level of government--either by the national government as the supreme law of the land or under the state and local police powers. However, an analysis of the Ordinance within the context of the centralization-decentralization debate is necessary to show that practical considerations weigh in favor of neither local nor national environmental just policies, but for regulations at the state level instead

The Cincinnati Environmental Justice Ordinance: Proposing a New Model for Environmental Justice Regulations by the States

The majority of environmental justice policies today exist as extremely decentralized municipal ordinances or as extremely centralized government agency strategies. Each system of regulation presents distinct advantages. Therefore, an analysis of the City of Cincinnati Environmental Justice Ordinance within the context of the ongoing debate between the benefits of centralized versus decentralized environmental regulations (the centralization-decentralization debate) examines the advantages of each scheme of regulations more extensively. However, each argument in favor of one type of regulation represents a disadvantage of the other, so this Note argues that by implementing environmental justice regulations at the state level, with the Cincinnati Ordinance as a model, the benefits of both local and national policies can be combined while mitigating the relative disadvantages. To illustrate the inadequacies of both federal and local level attempts to achieve environmental justice, this Note canvasses a brief history of the environmental justice movement at the federal, state, and local levels, including a description of the specific provisions of the Ordinance. As the history of the movement will show, neither the federal, state, nor local level governments provide effective or efficient legal remedies for environmental justice. However, state administrative agencies, whose regulatory authority mirrors those at the federal level, have the flexibility to expand their environmental justice policies with the cooperation of state legislatures. Part III of this Note then provides an analysis of the Ordinance regarding the effectiveness of its provisions in achieving the goals of the environmental justice movement. The Ordinance provides an effective model for future environmental justice policies because it enhances government accountability. Additionally, Part III analyzes the Ordinance with respect to the centralization -decentralization debate. Theoretically, environmental justice regulations can be promulgated at any level of government--either by the national government as the supreme law of the land or under the state and local police powers. However, an analysis of the Ordinance within the context of the centralization-decentralization debate is necessary to show that practical considerations weigh in favor of neither local nor national environmental just policies, but for regulations at the state level instead

Structure de fonctionnement des charrettes en design urbain

Ce document s’inscrit dans la foulée des préoccupations mondiales sur le devenir des villes au XXIe siècle. Il questionne les façons de faire qui contribuent à un développement de qualité des cadres de vie des citoyens. Les processus d’idéation de type atelier et charrette sont retenus en regard de leurs valeurs mobilisatrices et consensuelles qui répondent aux principes du développement durable. La problématique posée concerne l’adaptation de leur structure de fonctionnement au contexte local dans lequel il s’applique et de leur performance à induire les résultats escomptés. Une analyse comparative de trois études de cas révèle que le processus d’idéation se singularise en fonction des modalités de communication nécessaires pour progresser dans la démarche de planification des projets et conjointement à ceci, confirme que leur performance réside en leur capacité de rassembler l’ensemble des acteurs du projet en un même lieu. À l’issue de notre étude, nous fournissons un procédurier préliminaire pour diriger la mise en œuvre de processus d’idéation localement.This paper rejoins worldwide concerns for the future of cities in the XXlth century. It questions the practices, which contribute to the development of environmental qualities in the living environment. The collective creative efforts deployed in charrettes and workshops are considered to be relevant to the mobilization and reconciliation of values; principles necessary for sustainable development. The specific problematic concerns the adaptation of different operating structures of charrettes from one local context to another in order to insure desired outcomes. A comparative analysis of three case studies reveals that the creative processes of charrettes are adapted to the modes of communication required to advance the project planning process and confirms that their performance relies on their capacity to gather consensus in the actors concerned. Finally we supply a preliminary toolkit to help the future implementation of the charrette’s creative processes locally

Conception de miARN artificiels basée sur la caractérisation de la boucle de régulation miR-20/E2F

La biologie moléculaire et, plus spécifiquement, la régulation de l’expression génique ont été révolutionnées par la découverte des microARN (miARN). Ces petits ARN d’une vingtaine de nucléotides sont impliqués dans la majorité des processus cellulaires et leur expression est dérégulée dans plusieurs maladies, comme le cancer. Un miARN reconnaît ses cibles principalement par son noyau, ce qui lui permet de réguler simultanément la traduction de centaines d’ARN messagers. Nos travaux ont montré l’existence d’une boucle de rétro-activation négative, entre deux miARN du polycistron miR-17-92 et trois facteurs de transcription de la famille E2F. E2F1, 2 et 3 induisent la transcription de miR-20 et miR-17 qui par la suite inhibent leur traduction. Nos résultats suggèrent l’implication de cette boucle dans la résistance à l’apoptose induite par E2F1 dans les cellules du cancer de la prostate, ce qui expliquerait en partie le potentiel oncogénique du polycistron miR-17-92. L’étude de ce motif de régulation nous a donc permis de réaliser le potentiel incroyable qu’ont les miARN à inhiber la traduction de plusieurs gènes. Basé sur les règles de reconnaissance des miARN, nous avons développé et validé MultiTar. Cet outil bioinformatique permet de trouver la séquence d’un miARN artificiel ayant le potentiel d’inhiber la traduction de gènes d’intérêts choisis par l’utilisateur. Afin de valider MultiTar, nous avons généré des multitargets pouvant inhiber l’expression des trois E2F, ce qui nous a permis de comparer leur efficacité à celle de miR-20. Nos miARN artificiels ont la capacité d’inhiber la traduction des E2F et de neutraliser leur fonction redondante de la progression du cycle cellulaire de façon similaire ou supérieur à miR-20. La fonctionnalité de notre programme, ouvre la voie à une stratégie flexible pouvant cibler le caractère multigénique de différents processus cellulaires ou maladies complexes, tel que le cancer. L’utilisation de miARN artificiels pourrait donc représenter une alternative intéressante aux stratégies déjà existantes, qui sont limitées à inhiber des cibles uniques. En plus d’élucider un réseau de régulation complexe impliquant les miARN, nous avons pu tirer profit de leur potentiel d’inhibition par la conception de miARN artificiels.miRNAs are powerful regulators of gene expression in mammals. These small RNAs of around 20 nucleotides are involved in several cellular processes and diseases. MiRNAs recognize their targets mainly by a region comprising nucleotides 2-8, known as the seed. This characteristic gives them the potential to inhibit hundreds of messenger RNAs. Our first goal was to better characterize the complex network involving miRNAs in the regulation of gene expression. To achieve this, we studied the relation between a family of transcription factors, the E2Fs, and a family of miRNAs, the miR-17-92 cluster. Our results suggest a negative feedback loop involving miR-17, miR-20a, E2F1, E2F2 and E2F3. In this loop E2F1, 2 and 3 activate the transcription of the two miRNAs that inhibit their translation in return. The inhibition of the antiapoptotic function of E2F1 by miR-17 and miR-20 in a prostate cancer context, could explain the oncogenic potential of the miR-17-92 cluster that was previously reported. Studying the miR-20/E2F feedback loop made us realize how powerful was the ability of miRNAs to inhibit several targets. To overcome the lack of efficient tools able to inhibit simultaneously the expression of multiple genes, our second goal was to develop MultiTar, an algorithm able to design artificial miRNAs that target a set of predetermined genes. MultiTar was validated in silico, using known targets of endogenous miRNAs and in vivo, taking advantage of our experience with the E2F context. We designed artificial miRNAs against E2F1-3 and expressed them both in normal human fibroblasts and prostate cancer cells where they inhibited cell proliferation and induced cellular senescence. The observed phenotypes were precisely those known for inhibiting E2F activities. Hence, MultiTar can efficiently design artificial micro RNAs able to target multiple genes and is thus a flexible tool that can address the issue of multigenic diseases and complex cellular processes. The use of multitargets could be an alternative to overcome the limits of drugs or siRNAs that are designed generally to regulate only one target

Neuron-Derived Semaphorin 3A Is an Early Inducer of Vascular Permeability in Diabetic Retinopathy via Neuropilin-1

SummaryThe deterioration of the inner blood-retinal barrier and consequent macular edema is a cardinal manifestation of diabetic retinopathy (DR) and the clinical feature most closely associated with loss of sight. We provide evidence from both human and animal studies for the critical role of the classical neuronal guidance cue, semaphorin 3A, in instigating pathological vascular permeability in diabetic retinas via its cognate receptor neuropilin-1. We reveal that semaphorin 3A is induced in early hyperglycemic phases of diabetes within the neuronal retina and precipitates initial breakdown of endothelial barrier function. We demonstrate, by a series of orthogonal approaches, that neutralization of semaphorin 3A efficiently prevents diabetes-induced retinal vascular leakage in a stage of the disease when vascular endothelial growth factor neutralization is inefficient. These observations were corroborated in TgCre-Esr1/Nrp1flox/flox conditional knockout mice. Our findings identify a therapeutic target for macular edema and provide further evidence for neurovascular crosstalk in the pathogenesis of DR

MicroRNA signatures in vitreous humour and plasma of patients with exudative AMD

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide affecting individuals over the age of 50. The neovascular form (NV AMD) is characterized by choroidal neovascularization (CNV) and responsible for the majority of central vision impairment. Using non-biased microRNA arrays and individual TaqMan qPCRs, we profiled miRNAs in the vitreous humour and plasma of patients with NV AMD. We identified a disease-associated increase in miR-146a and a decrease in miR-106b and miR-152 in the vitreous humour which was reproducible in plasma. Moreover, miR-146a/miR-106b ratios discriminated patients with NV AMD with an area under the Receiver Operating Characteristic curve (ROC AUC) of 0,977 in vitreous humour and 0,915 in plasma suggesting potential for a blood-based diagnostic. Furthermore, using the AMD Gene Consortium (AGC) we mapped a NV AMD-associated SNP (rs1063320) in a binding site for miR-152-3p in the HLA-G gene. The relationship between our detected miRNAs and NV AMD related genes was also investigated using gene sets derived from the Ingenuity Pathway Analysis (IPA). To our knowledge, our study is the first to correlate vitreal and plasma miRNA signatures with NV AMD, highlighting potential future worth as biomarkers and providing insight on NV AMD pathogenesis

A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation

Microglia, the mononuclear phagocytes of the central nervous system (CNS), are important for the maintenance of CNS homeostasis, but also critically contribute to CNS pathology. Here we demonstrate that the nuclear factor kappa B (NF-kappa B) regulatory protein A20 is crucial in regulating microglia activation during CNS homeostasis and pathology. In mice, deletion of A20 in microglia increases microglial cell number and affects microglial regulation of neuronal synaptic function. Administration of a sublethal dose of lipopolysaccharide induces massive microglia activation, neuroinflammation, and lethality in mice with microgliaconfined A20 deficiency. Microglia A20 deficiency also exacerbates multiple sclerosis (MS) like disease, due to hyperactivation of the NIrp3 inflammasome leading to enhanced interleukin-113 secretion and CNS inflammation. Finally, we confirm a NIrp3 inflammasome signature and IL-1 beta expression in brain and cerebrospinal fluid from MS patients. Collectively, these data reveal a critical role for A20 in the control of microglia activation and neuroinflammation

Designing small multiple-target artificial RNAs

MicroRNAs (miRNAs) are naturally occurring small RNAs that regulate the expression of several genes. MiRNAs’ targeting rules are based on sequence complementarity between their mature products and targeted genes’ mRNAs. Based on our present understanding of those rules, we developed an algorithm to design artificial miRNAs to target simultaneously a set of predetermined genes. To validate in silico our algorithm, we tested different sets of genes known to be targeted by a single miRNA. The algorithm finds the seed of the corresponding miRNA among the solutions, which also include the seeds of new artificial miRNA sequences potentially capable of targeting these genes as well. We also validated the functionality of some artificial miRNAs designed to target simultaneously members of the E2F family. These artificial miRNAs reproduced the effects of E2Fs inhibition in both normal human fibroblasts and prostate cancer cells where they inhibited cell proliferation and induced cellular senescence. We conclude that the current miRNA targeting rules based on the seed sequence work to design multiple-target artificial miRNAs. This approach may find applications in both research and therapeutics

TDP-43 induces p53-mediated cell death of cortical progenitors and immature neurons

TAR DNA-binding protein 43 (TDP-43) is a key player in neurodegenerative diseases including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Accumulation of TDP-43 is associated with neuronal death in the brain. How increased and disease-causing mutant forms of TDP-43 induce cell death remains unclear. Here we addressed the role of TDP-43 during neural development and show that reduced TDP-43 causes defects in neural stem/progenitor cell proliferation but not cell death. However, overexpression of wild type and TDP-43A315T proteins induce p53-dependent apoptosis of neural stem/progenitors and human induced pluripotent cell (iPS)-derived immature cortical neurons. We show that TDP-43 induces expression of the proapoptotic BH3-only genes Bbc3 and Bax, and that p53 inhibition rescues TDP-43 induced cell death of embryonic mouse, and human cortical neurons, including those derived from TDP-43G298S ALS patient iPS cells. Hence, an increase in wild type and mutant TDP-43 induces p53-dependent cell death in neural progenitors developing neurons and this can be rescued. These findings may have important implications for accumulated or mutant TDP-43 induced neurodegenerative diseases