Role of PPARβ in keratinocyte adhesion and migration during skin wound healing

RESUME L'homéostasie du tissu cutané est assurée par des interactions étroites entre les cellules le composant et par l'équilibre entre la différenciation et la prolifération des kératinocytes devant permettre un renouvellement constant du tissu. Après une blessure, les kératinocytes environnant la zone blessée sont activés par des cytokines. Ils acquièrent alors un phénotype migratoire qui s'accompagne d'une modulation de l'activité protéolytique de la matrice extra cellulaire, d'une modulation de la dynamique du cytosquelette d'active, de la polarisation de la cellule, de l'affaiblissement des contacts entre cellules et de changements dans leurs contacts avec la matrice extra cellulaire. PPARβ est un facteur de transcription activé par les acides gras et leurs dérivés. Il appartient à la famille des récepteurs nucléaires aux hormones et son expression est avérée dans les kératinocytes des follicules pileux et dans les kératinocytes inter-folliculaires activés par la blessure cutanée. Le rôle de PPARβ dans la peau est principalement lié à son effet protecteur contre l'apoptose ainsi qu'à son implication dans l'équilibre dynamique entre la prolifération et la différentiation des kératinocytes. L'objet de ce travail fut de déterminer le rôle de PPARβ dans les processus d'adhésion et de migration des kératinocytes activés durant la régénération de l'épithélium blessé. Nous avons montré que les souris dépourvues du gène codant pour PPARβ ont de sévères imperfections affectant la morphologie de l'épithélium. Ce phénotype est corrélé à la modulation imparfaite du réseau d'active chez les souris dépourvues de PPARβ, à un défaut de localisation de l'intégrine α3 impliquée dans les complexes induisant la migration cellulaire, ainsi qu'à la modulation de l'expression d'acteurs majeurs affectant l'activité protéolytique de la matrice extra cellulaire. En conclusion, nos résultats montrent que PPARβ est impliqué dans le contrôle de la dynamique du cytosquelette d'active et la polarisation des kératinocytes activés. PPARβ étant impliqué dans l'acquisition d'un phénotype migratoire, il est légitime de se demander s'il intervient de même dans d'autres types cellulaires, par exemple dans la transition épithéliale-mésenchymateuse durant le développement, ou encore la progression de cellules tumorales. SUMMARY Highly coordinated intercellular interactions and single cell metabolism ensure cell and tissue maintenance of the skin. Healing of a skin wound involves keratinocyte activation by cytokines and growth factors. Activated keratinocytes acquire a motile phenotype that requires extracellular matrix remodeling and subsequent ligand activation through proteolytic activity, as well as cytoskeletal reorganisation induced by the release of cell-cell junctions and by the signalling relayed via integrin receptors and their cytoplasmic adaptors. PPARβ is a transcription factor activated by polyunsaturated fatty acids and fatty acid derivatives which belong to the nuclear hormone receptor superfamily. It is expressed in activated keratinocytes where it plays an essential role in protecting them from apoptosis. In addition, it plays an important function in hair follicle morphogenesis at the time of elongation, via the regulation of the balance between keratinocyte differentiation and proliferation. The aim of the present work was to determine if PPARβ is also involved in the regulation of migration and adhesion properties of keratinocytes during skin wound healing. We have shown that wounded PPARβ null mice display severe abnormalities of the keratinocyte migratory layer as shown at the histological level and using three-dimensional reconstruction. This altered migratory phenotype is correlated to altered dynamic of the actin cytoskeleton network, impaired α3 integrin localisation in migrating keratinocytes and changes in the expression of a key actor involved in extracellular matrix proteolytic activity. These results show that PPARβ is implicated in the fine tuning of the actin network organisation and the polarisation of activated keratinocytes following an epithelial wound. Whether these mechanisms are also controlled by PPARβ in other cell types during epithelial mesenchymal transition or tumour cell progression is an interesting question to rise.

Human Resource Information System; individual Users with Work Reporting Guide, April 2003

Guide manual for using the Human Resource Information System for the state of Iowa.

Improving Transition Outcomes: Prototype Work Plan Template

Work Plan template developed for the Improving Transition Outcomes community demonstration prototypes.

Teaching cardiac auscultation to trainees in internal medicine and family practice: does it work?

BACKGROUND: The general proficiency in physical diagnostic skills seems to be declining in relation to the development of new technologies. The few studies that have examined this question have invariably used recordings of cardiac events obtained from patients. However, this type of evaluation may not correlate particularly well with bedside skills. Our objectives were 1) To compare the cardiac auscultatory skills of physicians in training with those of experienced cardiologists by using real patients to test bedside diagnostic skills. 2) To evaluate the impact of a five-month bedside cardiac auscultation training program. METHODS: 1) In an academic primary care center, 20 physicians (trainees in internal medicine and family practice) and two skilled academic cardiologists listened to 33 cardiac events in 13 patients directly at bedside and identified the cardiac events by completing an open questionnaire. Heart sounds, murmurs and diagnosis were determined beforehand by an independent skilled cardiologist and were validated by echocardiography. Thirteen primary cardiologic diagnoses were possible.2) Ten of the physicians agreed to participate in a course of 45-minute sessions once a week for 5 months. After the course they listened again to the same patients (pre/post-interventional study). RESULTS: 1) The experts were the most skillful, achieving 69% recognition of heart sounds and murmurs and correct diagnoses in 62% of cases. They also heard all of the diastolic murmurs. The residents heard only 40% of the extra heart sounds and made a correct diagnosis in 24% of cases. 2) After the weekly training sessions, their mean percentage for correct diagnosis was 35% [an increase of 66% (p < 0.05)]. CONCLUSIONS: The level of bedside diagnostic skills in this relatively small group of physicians in training is indeed low, but can be improved by a course focusing on realistic bedside teaching.

Consumer Advisory Bulletin, Warning: "Work-at-Home" Schemes, October 2004

The Attorney General’s Consumer Protection Division receives hundreds of calls and consumer complaints every year. Follow these tips to avoid unexpected expense and disappointments. This record is about: Warning: "Work-at-Home" Schemes

Disability, capacity for work and the business cycle: An international perspective

An important policy issue in recent years concerns the number of people claimingdisability benefits for reasons of incapacity for work. We distinguish between workdisability , which may have its roots in economic and social circumstances, and healthdisability which arises from clear diagnosed medical conditions. Although there is a linkbetween work and health disability, economic conditions, and in particular the businesscycle and variations in the risk of unemployment over time and across localities, mayplay an important part in explaining both the stock of disability benefit claimants andinflows to and outflow from that stock. We employ a variety of cross?country andcountry?specific household panel data sets, as well as administrative data, to testwhether disability benefit claims rise when unemployment is higher, and also toinvestigate the impact of unemployment rates on flows on and off the benefit rolls. Wefind strong evidence that local variations in unemployment have an importantexplanatory role for disability benefit receipt, with higher total enrolments, loweroutflows from rolls and, often, higher inflows into disability rolls in regions and periodsof above?average unemployment. Although general subjective measures of selfreporteddisability and longstanding illness are also positively associated withunemployment rates, inclusion of self?reported health measures does not eliminate thestatistical relationship between unemployment rates and disability benefit receipt;indeed including general measures of health often strengthens that underlyingrelationship. Intriguingly, we also find some evidence from the United Kingdom and theUnited States that the prevalence of self?reported objective specific indicators ofdisability are often pro?cyclical that is, the incidence of specific forms of disability arepro?cyclical whereas claims for disability benefits given specific health conditions arecounter?cyclical. Overall, the analysis suggests that, for a range of countries and datasets, levels of claims for disability benefits are not simply related to changes in theincidence of health disability in the population and are strongly influenced by prevailingeconomic conditions. We discuss the policy implications of these various findings.

Microfabrics in carbonate mylonites along a large-scale shear zone (Helvetic Alps)

Carbonate mylonites with varying proportions of second-phase minerals were collected at positions of increasing metamorphic grade along the basal thrust of the Morcles nappe (Helvetic nappes, Switzerland). Variations of temperature, stress, and strain rate, changes in chemistry of solid and fluid phases, and differing degrees of strain localization and annealing were tracked by measuring the shapes, mean sizes, and size distributions of both matrix and second-phase grains, as well as crystal preferred orientation (CPO) of the matrix. Field structures suggest that strain rate was constant along the fault. The mean and distribution of the calcite grain sizes were affected most profoundly by temperature: Increased temperature, presumably accompanied by decreased stress, correlated with larger mean sizes and wider size distributions. At a given location, the matrix grains in mylonites with more second-phase particles are, on average, smaller, have narrower size distributions, and have more elongate shapes. For example, mylonites with 50 vol.% of second phases have matrix grain sizes half that of pure mylonites. Changes in calcite chemistry and the presence of synkinematic fluids seemed to influence microfabric only weakly. Temporal variations in conditions, such as exhumation-induced cooling, apparently provoke changes in temperature, stress, and strain rate along the nappe. These changes result in further strain localization during retrograde conditions and cause the grain size to be reduced by an additional 50%. The matrix CPO strengthens with increasing temperature or strain, but weakens and rotates with increasing second-phase content, These fabric changes suggest differing rates of grain growth, grain size reduction, and development of CPO owing to variations in the deformation conditions and, perhaps, mechanisms. To interpret natural mylonite structures or to extrapolate mechanical data to natural situations requires careful characterization of the microfabric, and, in particular, second-phase minerals. (c) 2007 Elsevier B.V, All rights reserved.

Cedar Rapids-Iowa City Goose Hunting Zone, 2005

Regulations for hunting in Iowa.

Take-the-best and other simple strategies: Why and when they work 'well' in binary choice

The effectiveness of decision rules depends on characteristics of bothrules and environments. A theoretical analysis of environments specifiesthe relative predictive accuracies of the lexicographic rule 'take-the-best'(TTB) and other simple strategies for binary choice. We identify threefactors: how the environment weights variables; characteristics of choicesets; and error. For cases involving from three to five binary cues, TTBis effective across many environments. However, hybrids of equal weights(EW) and TTB models are more effective as environments become morecompensatory. In the presence of error, TTB and similar models do not predictmuch better than a naïve model that exploits dominance. We emphasizepsychological implications and the need for more complete theories of theenvironment that include the role of error.

Protestants and Catholics: Similar work ethic, different social ethic

This article develops two hypotheses about economically-relevant values of Christianbelievers, according to which Protestants should work more and more effectively, as in the work ethic argument of Max Weber, or display a stronger social ethic that would lead themto monitor each other s conduct, support political and legal institutions and hold morehomogeneous values. Tests using current survey data confirm substantial partial correlations andpossible different effects in mutual social control, institutional performance and homogeneityof values but no difference in work ethics. Protestantism therefore seems conducive to capitalisteconomic development, not by the direct psychological route of the Weberian work ethic butrather by promoting an alternative social ethic that facilitates impersonal trade.

How binding are legal limits? Transitions from temporary to permanent work in Spain

This paper studies the duration pattern of xed-term contracts and the determinantsof their conversion into permanent ones in Spain, where the share of xed-termemployment is the highest in Europe. We estimate a duration model for temporaryemployment, with competing risks of terminating into permanent employment versusalternative states, and exible duration dependence. We nd that conversion rates aregenerally below 10%. Our estimated conversion rates roughly increase with tenure,with a pronounced spike at the legal limit, when there is no legal way to retain theworker on a temporary contract. We argue that estimated di¤erences in conversionrates across categories of workers can stem from di¤erences in worker outside optionsand thus the power to credibly threat to quit temporary jobs.