A maturação in vitro do oócito é um dos fatores limitantes na produção in vitro de embriões. In vivo, esta maturação é um processo altamente orquestrado no qual a meiose é retomada pela onda de gonadotrofina que antecede a ovulação e que induz à queda dos níveis de AMPc no oócito. No entanto, os oócitos aspirados ao serem retirados dos folículos ovarianos retomam espontaneamente a maturação comprometendo a competência de seu desenvolvimento. O AMPc é sintetizado pela adenilato ciclase (AC) e degradado pelas fosfodiesterases (PDE), existindo algumas relacionadas à degradação do AMPc e outras do GMPc. Sendo assim, a proposição deste trabalho foi averiguar a contribuição de diferentes isoformas de fosfodiesterases na retomada da meiose e nos níveis de GMPc, AMPc e ainda, determinar quando há manutenção de AMPc em níveis elevados observando sua influência na competência oocitária e ativação da MAPK. Para isso, os complexos cumulus-oócito (CCOs) foram maturados in vitro na ausência, presença ou associação de inibidores de PDEs-AMPc e GMPc específicas e FSHr. As amostras foram avaliadas em relação a: 1) taxa de maturação; 2) níveis intracelulares de AMPc e GMPc nos CCOs; 3) taxa de desenvolvimento de blastocistos ; 4) ativação da MAPK em oócitos e células do cumulus. Os resultados obtidos no primeiro experimento indiaram que o inibidor da PDE3 foi o mais eficaz (p<0,05) em atrasar a retomada da meiose, às nove horas de maturação, porém, isolado ou em associação com o inibidor da PDE8, não foi capaz de alterar (p>0,05) os níveis de AMPc. No experimento dois, o inibidor da PDE5 isolado não influenciou a retomada da meiose (p>0,05), porém, quando associado aos inibidores da PDE3 e 8 houve atraso na retomada (p<0,05) e ainda alteraram os níveis de GMPc e AMPc (p<0,05) nas primeiras horas de maturação. O experimento três mostrou a influencia do FSHr durante a MIV, o qual estimulou a retomada da meiose, mas em associação com inibidores da PDE5 e 8 atrasa a retomada (p<0,05). Além disso, o FSHr provoca aumento do nível de AMPc e sua associação com inibidores de PDE5 e PDE8 ocasionou elevação adicional (p<0,05). As condições de cultivo estudadas no experimento quatro mostraram que a maturação induzida (pré-MIV de duas horas com agentes para elevar AMPc seguindo de 22 horas de MIV com FSH associado a inibidores de PDEs) atrasaram a retomada da meiose às nove horas de maturação, mas não afetaram progressão da meiose às 24, 28 e 30 horas. Os tratamentos, porém, não melhoraram a competência oocitária após a fertilização in vitro e ocasionaram pequenas variações na ativação da MAPK em oócitos e células do cumulus. / In vitro maturation of oocytes is a limiting factor in the in vitro production of bovine embryos. In vivo, this maturation is a highly orchestrated process in which meiosis resumption by the gonadotropin surge that precedes ovulation induces the decrease in cAMP levels in the oocyte. However, when oocytes are removed from follicles, they spontaneously resume maturation compromising the competence for its development. cAMP is synthesized by adenylyl cyclase (AC) and degraded by phosphodiesterases (PDE), and there are some PDEs related to degradation of cAMP and/or cGMP. Thus, the purpose of this work was to investigate the contribution of different isoforms of phosphodiesterases in the resumption of meiosis and levels of cAMP and, also, to determine differences in signaling pathways when maintaining high levels of cAMP and its influence on oocyte competence. For this purpose, cumulus-oocyte complexes (COC) were matured in vitro in the presence, absence or combination of inhibitors of cAMP- and cGMP-specific PDEs and FSH. Samples be were evaluated in relation to: 1) maturation rate, 2) intracellular levels of cAMP and cGMP in COCs, 3) rate of blastocyst development and 4) activation of MAPK in oocytes and cumulus cells. The results of the first experiment showed that the PDE3 inhibitor is more effective (p <0.05) in delaying meiosis resumption, at nine hours of maturation, but was not capable of altering cAMP levels (p> 0.05) either alone or in combination with the PDE8 inhibitor. In experiment two, the PDE5 inhibitor alone did not affect the meiosis resumption (p> 0.05), however, when associated with PDE3 and PDE8 inhibitors it delayed their resumption (p <0.05) and also altered cGMP and cAMP levels of (p <0.05) in the early hours of maturation. The third experiments showed the influence of FSHr during IVM, which stimulated the resumption of meiosis, but in combination with PDE5 and PDE8 inhibitors meiosis was delayed (p <0.05). Furthermore, FSHr causes increased levels of cAMP and its association with PDE5 and PDE8 inhibitors caused an additional increase (p <0.05). Culture conditions studied in experiment four showed that induced maturation (pre-IVM for two hours with agents to elevate cAMP followed by 22 hours IVM with FSH associated with PDE inhibitors) delayed the resumption of meiotic maturation at nine hours, but has no effect on meiosis progression at 24, 28 and 30 hours. The treatments, however, did not improve oocyte competence after in vitro fertilization and caused minor variations in the activation of MAPK in oocytes and cumulus cells.

This thesis examines the practice of the camp meeting as a significant factor in the growth of the Methodist Episcopal Church in nineteenth-century New England. Such a comprehensive investigation into camp meetings in New England has never been done before. Also, with the exception of one book and one other recent dissertation, the general history of Methodism in New England is a topic that was overlooked for nearly a century. This research helps to fill those gaps. Many scholars give credit to camp meetings for fostering conversion, though the focus has generally been on camps held in the American South and the western frontier. After briefly recounting the rise of Methodism and camp meetings in the United States, the thesis turns to a more specific focus on the rise of Methodism and camp meetings in New England prior to 1823. Zion's Herald newspaper provides a steady and previously untapped source of primary information about camp meetings in New England from its first appearance in 1823 to well into the twentieth century. After discussion of some key developments of New England Methodism relevant to camp meetings between 1823 and 1871, a thick description of one camp meeting in 1823 is presented to show how the many parts worked together. This is followed by an account of aspects of the camp meetings that might be classified broadly as ritual, how these changed over time, and the impact they had on the process of identity formation at the camps. The spotlight is then directed toward the liturgical aspects of camp meetings as practiced in New England. These include components of worship practices common to Methodist congregations of the period as they gathered for prayer meetings, Sunday worship and quarterly conferences, such as preaching, praying, singing, and love feasts, and also those acts of worship developed specifically for camp meetings such as dedicating the grounds, and the closing ritual procession and "parting hand." As with the ritual practices, attention is again given both to how these worship practices influenced worshippers, and how they changed over time. Finally the interpretive framework of "poetic discourse" offered by Stephen Cooley is used to analyze the most potent ritual elements involved in the process of conversion and church growth in conversation with contemporary scholars in the fields of sociology and ritual studies. In the end this study shows not only the factors that fostered conversions and church growth, but also how the camp meetings gradually lost their potency as they changed over time. / 2017-01-01T00:00:00Z

L’objectif de mon travail de thèse était d’une part, de mieux comprendre le rôle des différentes familles de phosphodiestérases (PDEs) dans la régulation de la signalisation dépendante de l’AMPc (PDE-AMPc) dans les cellules musculaires lisses vasculaires (CMLVs), et d’autre part, d’évaluer leur implication fonctionnelle dans la réactivité vasculaire et leur altération potentielle dans un modèle physiopathologique, l’insuffisance cardiaque (IC). Mon travail s’est articulé autour de deux modèles de muscle lisse vasculaire : (1) des CMLVs isolées en culture ayant acquis un phénotype synthétique sur lesquelles une approche d’imagerie en temps réel (FRET : Transfert d’Energie de Fluorescence par Résonance) a été appliquée afin de visualiser in situ la dynamique spatiotemporelle des signaux dépendants de l’AMPc. Nos résultats indiquent que, dans ces cellules, l’augmentation des niveaux d’AMPc provoquée par la stimulation β-adrénergique (β-AR) implique différents récepteurs suivant le compartiment intracellulaire considéré (β1- et β2-ARs dans le cytosol et seulement β2-ARs dans le compartiment sous-membranaire). Nous avons par ailleurs observé que l’expression des ARNm des différentes isoformes de PDE-AMPc et la contribution fonctionnelle de ces enzymes dans la régulation des signaux AMPc intracellulaires étaient dépendantes de la densité des CMLVs en culture.(2) des anneaux d’artères intactes issues de deux lits vasculaires différents (aorte et artère mésentérique) isolées à partir de rats sains et IC, permettant d’étudier leur fonction contractile et donc la régulation de celle-ci par la voie de l’AMPc. Nous avons montré que les familles de PDE-AMPc contribuent de façon différente au contrôle du tonus vasculaire dans l’aorte thoracique (PDE3 = PDE4 sans participation de la PDE2) et dans l’artère mésentérique (PDE4 > PDE2 sans participation de la PDE3), l’endothélium exerçant un rôle essentiel dans la régulation de l’activité de ces PDEs musculaires lisses, notamment par le biais de la production de NO. Nous avons également mis en évidence des altérations de la réactivité vasculaire, et notamment de son contrôle par la voie de l’AMPc/PDE, dans notre modèle de rat IC. Dans l’aorte, la dysfonction endothéliale liée à l’altération de la voie du NO est à l’origine d’une augmentation de l’activité PDE3 masquant l’activité PDE4 et la relaxation β-adrénergique. Dans l’artère mésentérique des rats IC, dont la fonction endothéliale apparaît préservée, les PDE2, 3 et 4 restent fonctionnelles.L’ensemble de nos travaux souligne le rôle essentiel des PDEs dans la régulation de la signalisation AMPc vasculaire, et montre que l’activité et la fonction des différentes familles de PDE-AMPc sont finement modulées par de nombreux paramètres (phénotype et densité cellulaire des CMLVs) ou situations physio-pathologiques (nature du lit vasculaire, présence de l’endothélium, situation d’IC). / The aim of my thesis was to investigate the role of cyclic nucleotide phosphodiesterases (cAMP-PDEs) in the regulation of cAMP-dependent signaling in vascular smooth muscle cells (VSMCs), and to assess their functional involvement in vascular reactivity and their potential alteration in a pathophysiological model of heart failure (HF). My work was based on two models of vascular smooth muscle:(1) Isolated VSMCs in culture having acquired a synthetic phenotype, in which an approach of real-time imaging (FRET: Fluorescence Resonance Energy Transfer) was applied in situ to visualize the spatiotemporal dynamics of cAMP-dependent signals. Our results indicate that, in these cells, increased levels of cAMP induced by β-adrenergic stimulation (β-AR) involve different β-ARs subtypes according to the intracellular compartment considered (β1-and β2-ARs in the cytosol and only β2-ARs in the submembrane compartment). We also observed that the mRNA expression of cAMP-PDEs isoforms and the functional contribution of these enzymes in the regulation of intracellular cAMP signals were dependent on the VSMCs seeding density in culture.(2) Arterial blood vessels from two different vascular beds (aorta and mesenteric artery) isolated from healthy and HF rats, to study their contractile function and thus the regulation by the cAMP pathway. We showed that cAMP-PDE families contribute differently to the control of vascular tone in the thoracic aorta (PDE3 = PDE4, no PDE2) and mesenteric artery (PDE4 > PDE2, no PDE3), endothelium exerting a crucial role in the regulation of their functional activities, especially through the production of nitric oxide (NO). We also demonstrated alterations in vascular reactivity during HF, including its control through the cAMP-PDEs. In the aorta, endothelial dysfunction associated with the alteration of the NO pathway leads to an increase in PDE3 activity which masks PDE4 activity and β-AR relaxation. In mesenteric artery from HF rats, endothelial function is preserved and PDE2, 3 and 4 are functional.This study underlines the importance of PDEs in regulating vascular cAMP signaling, and shows that the activity and function of different cAMP-PDE families are tightly modulated by many parameters (VSMCs phenotype and seeding density) and/or physiopathological situations (vascular bed, endothelium and HF).

La voie β-adrénergique (β-AR)/AMPc est cruciale pour l’adaptation de la fonction cardiaque. Dans l’insuffisance cardiaque (IC), cette signalisation est perturbée et une part importante des patients meurt de troubles du rythme. Classiquement, les effets inotrope et lusitrope positifs de l’AMPc sont attribués à la phosphorylation par la protéine kinase AMPc dépendante (PKA) des protéines clés du couplage excitation–contraction (CEC). L’AMPc active aussi le facteur d’échange Epac, impliqué dans l’hypertrophie cardiaque et le contrôle de l’homéostasie calcique. Une cible d’Epac est la CaMKII, une kinase modulée par le Ca2+ et la calmoduline qui phosphoryle aussi les protéines clés du CEC, et dont l’activation est pro-arythmique.Les phosphodiestérases (PDEs) de type 3 et 4 sont majeures pour dégrader l’AMPc et contrôler l’homéostasie calcique et le CEC. Les inhibiteurs de PDE3 sont de puissants cardiotoniques mais leur utilisation est limitée par leurs effets pro-arythmiques. De plus, l’invalidation de gènes codant pour PDE4 conduit à des arythmies ventriculaires. Mon travail a permis d’identifier les perturbations de l’homéostasie calcique responsables de la survenue d’arythmies lorsque l’activité des PDE3 et des PDE4 est diminuée. Mes résultats montrent que les inhibiteurs de PDEs exercent des effets inotropes via PKA, mais suscitent des vagues de Ca2+ pro-arythmiques impliquant la PKA et la CaMKII activée en partie via Epac. Ceci suggère l'utilisation potentielle d'inhibiteurs de CaMKII comme compléments aux inhibiteurs de PDEs pour limiter leurs effets délétères, une hypothèse que j’ai pu vérifier dans un modèle porcin plus proche du patient. / The β-adrenergic pathway (β-AR)/cAMP is crucial for the adaptation of the cardiac function upon stress. In heart failure (HF), this signaling pathway is disrupted and a significant proportion of patients dies of cardiac arrhythmias. Classically, the inotropic and lusitropic effects of cAMP are attributed to the phosphorylation by the cAMP-dependent protein kinase (PKA) of the key proteins of the excitation-contraction coupling (ECC). cAMP also activates the exchange factor Epac, which is involved in cardiac hypertrophy and controls intracellular Ca2+ homeostasis. Epac activates CaMKII, another kinase modulated by Ca2+ and calmodulin which phosphorylates the same key proteins of the ECC, and is involved in arrhythmogenesis.Phosphodiesterases (PDEs) type 3 and 4 are crucial enzyme to degrade cAMP and to control Ca2+ homeostasis, thus ECC. PDE3 inhibitors are potent cardiotonic drugs but their use is limited by their pro-arrhythmic effects. Furthermore, the invalidation of genes encoding PDE4 results in ventricular arrhythmias. My work allowed characterizing the perturbations of Ca2+ homeostasis which lead to arrhythmias when PDE3 and PDE4 activities are decreased. My results show that PDE inhibitors exert inotropic effects via PKA, but evoke pro-arrhythmic Ca2+ waves via both PKA and CaMKII, the latter being activated in part via Epac. Altogether, these results suggest the potential use of CaMKII inhibitors as adjuncts to PDEs inhibitors to limit their deleterious effects, a hypothesis I also tested in a porcine model closer to the patient.

Jordan is a developing country and there are ten Palestine refugee camps throughout Jordansince the Arab-Israel conflict in 1948 and the Arab-Israel war in 1967. The camps are run byUnited Nation Relief and Works Agency for Palestine Refugees in the Near East (UNRWA)which is the main provider of health care in the camp. Today, the fourth generation ofrefugees lives in the camps which are extremely overpopulated. The social and economicconditions in the camps are poor. The nurses&apos; workload in the Health care centre in the campis getting harder and UNRWA&apos;s resources are getting strained due to funding shortfalls. Weasked ourselves the question: How do the nurses experience providing care for the patientswith limited resources? The aim of this study is to elucidate the nurses&apos; experiences ofworking and caring in a Palestine refugee camp in Jordan and also to describe challengeswhile conducting a qualitative study within this field. Qualitative data were collected byperforming interviews with an open ended question with nurses who are working in one of theHealth care centres in the largest Palestine refugee camp in Jordan. Methodologicalreflections were made out of our experiences while conducting the study. The nurses talkedabout providing good care for the patients and their satisfaction when caring. They alsoreflected over the resources in the Health care centre. Since the Palestine refugee camp is thenurses&apos; home and workplace, a place where they have their professional and private life, itseems that there is a very strong connection between the nurse and the patient. / <p>Program: Sjuksköterskeutbildning</p><p>Uppsatsnivå: C</p>

This dissertation examines the emergence of the 1978 Camp David Accords and the consequences for Israel, the Palestinians, and the wider Middle East. Utilizing archival sources and oral history interviews from across Israel, Palestine, Lebanon, the United States, and the United Kingdom, Camp David’s Shadow recasts the early history of the peace process. It explains how a comprehensive settlement to the Arab-Israeli conflict with provisions for a resolution of the Palestinian question gave way to the facilitation of bilateral peace between Egypt and Israel. As recently declassified sources reveal, the completion of the Camp David Accords—via intensive American efforts— actually enabled Israeli expansion across the Green Line, undermining the possibility of Palestinian sovereignty in the occupied territories. By examining how both the concept and diplomatic practice of autonomy were utilized to address the Palestinian question, and the implications of the subsequent Israeli and U.S. military intervention in Lebanon, the dissertation explains how and why the Camp David process and its aftermath adversely shaped the prospects of a negotiated settlement between Israelis and Palestinians in the 1990s. In linking the developments of the late 1970s and 1980s with the Madrid Conference and Oslo Accords in the decade that followed, the dissertation charts the role played by American, Middle Eastern, international, and domestic actors in curtailing the possibility of Palestinian self-determination.

Adenylyl cyclases are key points for the concurrent integration of diverse signaling pathways. Controlling production of the second messenger cAMP, adenylyl cyclases provide an important mechanism for the regulation of physiological functions by amplifying signaling events to stimulate downstream effectors. While different isoforms of adenylyl cyclase exhibit distinct patterns of expression and regulation, of particular interest are two groups of Ca2+ regulated isoforms that are highly expressed in the central nervous system. Adenylyl cyclase type 5 (AC5) is a Ca2+ inhibited isoform that is highly expressed in the striatum, and whose activity is involved in the regulation of movement, pain, and metabolism. Adenylyl cyclase type 8 (AC8) is stimulated by Ca2+ in a calmodulin dependent manner, and appears to be involved with long-term memory, anxiety, and reward pathways. Studying the signaling characteristics of these adenylyl cyclase isoforms is necessary for improving our scientific understanding of biological pathways, as well identifying therapeutic targets that can be exploited for treatment of disease. In this work, we investigated changes in the protein interaction network of AC5 following prolonged Gi/o-mediated inhibition that results in heterologous sensitization. The diversity of signaling pathways and multitude of protein interactions that have been implicated in the development of the heterologous sensitization response prompted the development of a novel screening strategy to capture and identify AC5-protein interactions which occur following prolonged Gi/o-mediated inhibition. We utilized bimolecular fluorescence complementation (BiFC) in conjunction with fluorescence activated cell sorting (FACS) and Next Generation sequencing to capture, identify, and characterize novel AC5 interacting partners. We further studied the effects of increased AC5 activity by functionally characterizing a series of gain-of-function mutations that have been identified in patients diagnosed with Familial Dyskinesia and Facial Myokymia (FDFM). Our results demonstrate that the AC5 mutants exhibit enhanced activity to Gs-mediated stimulation and reduced inhibition by Gi/o-coupled receptors. We further suggest that this dysregulation of AC5 in striatal medium spiny neurons likely results in an imbalance in the direct and indirect striatal signaling pathways that coordinate the initiation and maintenance of movement. Genetic models of AC8 regulation have implicated its activity in signaling pathways that may regulate comorbid long-term anxiety and ethanol consumption. Therefore, we developed and conducted a high-throughput screen and validation paradigm of small molecules for the discovery of AC8 selective inhibitors. The screening effort identified two lead compounds that demonstrate enhanced efficacy and selectivity over AC1 compared to currently available adenylyl cyclase inhibitors.

Les réseaux de capteurs sans fil sont conçus dans le but de remplir différentes tâches de surveillance dans des conditions environnementales variées. Ces petits appareils électroniques sont capables de détecter, traiter et transmettre des données environnementales avec des communications multi-sauts et peuvent par conséquent aussi se coordonner. En même temps, ces dispositifs ont des ressources limitées (mémoire, capacités de calcul) et doivent fonctionner le plus souvent sur des batteries. C’est pour ces raisons que les recherches menées dans le domaine des réseaux de capteurs possèdent naturellement une forte partie qui concerne la réduction de la consommation d’énergie et une auto-organisation du réseau.Nos recherches considèrent les applications critiques de surveillance. Ces applications peuvent avoir des exigences très différentes des réseaux de capteurs traditionnels. De plus, nous utilisons des capteurs images, dont l’activité est définie en fonction de la criticité de l’application. Un ordonnancement basé sur la criticité permet de définir des nœuds sentinelles qui possèderont une vitesse de capture plus grande, cela afin d’avoir une probabilité plus élevée de détecter des intrusions et d’alerter leurs nœuds voisins. Au niveau de la couche de contrôle d’accès au medium (couche MAC), les approches alternant activité-sommeil (consistant à allumer et éteindre la radio de manière cyclique) sont utilisées pour préserver l’énergie et prolonger la durée de vie du réseau. Cependant, tout en conservant l’énergie, les applications critiques de surveillance ne doivent pas compromettre la qualité de la surveillance et le réseau doit être toujours en mesure de propager rapidement les messages d’alerte. Notre but est de définir un protocole MAC qui pourrait réduire la latence de propagation d’alerte ainsi que de prolonger la durée de vie du réseau. Nous proposons tout d’abord une approche originale pour déterminer dynamiquement la durée de la période d’activité radio des nœuds pour augmenter la probabilité de propager rapidement les alertes. Les résultats des simulations ont confirmé que notre approche réussit à améliorer la réactivité du système par rapport à une approche statique. En même temps, notre proposition permet de réduire considérablement la consommation d’énergie du réseau. Ensuite, nous avons implémenter notre approche sur des capteurs réels et les résultats obtenus sont très proches des résultats de simulation. / Wireless Sensor Networks (WSNs) are designed for the purpose of completing different monitoring tasks under various environmental conditions. The small electronic devices called sensors are capable of sensing, processing and communicating the environmental data through multi-hop communication and coordination. These devices have limited resources (memory, computing capabilities) and usually run on batteries. This is the reason the research on wireless sensor networks have been focused on energy efficiency and self-organization of the network. We consider mission-critical surveillance applications in our research work. These applications can have different requirements than traditional WSNs. In addition, we use image sensor nodes, whose activity is defined based on criticality of the application. The criticality-based scheduling scheme defines sentry nodes with faster capture rates, to have higher probability to detect intrusions and to alert neighbor nodes. At Medium Access Control (MAC) Layer level, duty cycled approaches are used to preserve energy and prolong the network lifetime. However, while conserving energy, mission-critical surveillance applications cannot compromise on quality of surveillance and the network should still be able to quickly propagate the alert messages. In this thesis, we propose a low latency, energy efficient adaptive MAC protocol. We first propose an original approach to dynamically determine the duty-cycle length of sensor nodes to increase the probability of quick propagation of alerts. Simulation results confirmed that our approach succeeds in improving the system responsiveness when compared to a static duty-cycling approach. At the same time, our proposition considerably reduces the energy consumption of the network. Then, we implemented our approach on sensor node hardware and results were found to be very close to our simulation results.

Einleitung: / Introduction:

Pseudomonas aeruginosa is a gram-negative pathogen that causes opportunistic infections in immunocompromised individuals. Whereas clinical isolates from acute infections are characterized by host cell cytotoxicity and motility, isolates from chronic infections are characterized by biofilm formation and persistence. The type III secretion system (T3SS) causes cytotoxicity by injecting effectors into host cells. T3SS gene expression is activated by ExsA, an AraC family transcriptional regulator. Transcription of exsA is controlled by two promoters, PexsC and PexsA, which are regulated by ExsA and the cAMP-Vfr system, respectively. Additional global regulatory systems also influence T3SS including the second messenger signaling molecule c-di-GMP and the RsmAYZ regulatory system. c-di-GMP signaling increases biofilm production and decreases acute virulence factor expression. A previous study found that c-di-GMP alters cAMP levels and affect cAMP-Vfr signaling. Other studies found that c-di-GMP signaling alters expression of the small non-coding regulatory RNAs, rsmY and rsmZ. The RsmAYZ post-transcriptional regulatory system regulates ExsA translation. We hypothesize that c-di-GMP regulates T3SS expression by altering exsA transcription through the cAMP-Vfr dependent PexsA promoter. Overexpression of YfiN, a c-di-GMP synthase, decreases T3SS reporter activity in PA103 and requires a functional GGDEF active site for full inhibition. Inhibition by YfiN does not require rsmYZ. YfiN expression decreases cAMP-Vfr signaling and coordinately inhibits PexsA-lacZ reporter activity. Consistent with the proposed model, YfiN expression in a vfr mutant does not further decrease T3SS reporter activity. These data indicate that the YfiN alters T3SS expression through transcriptional control of the cAMP-Vfr dependent PexsA promoter.