A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans.

Seborrheic keratoses (SKs) are common, benign epithelial tumors of the skin that do not, or very rarely, progress into malignancy, for reasons that are not understood. We investigated this by gene expression profiling of human SKs and cutaneous squamous cell carcinomas (SCCs) and found that several genes previously connected with keratinocyte tumor development were similarly modulated in SKs and SCCs, whereas the expression of others differed by only a few fold. In contrast, the tyrosine kinase receptor FGF receptor-3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs. We also showed that increased FGFR3 activity was sufficient to induce FOXN1 expression, counteract the inhibitory effect of EGFR signaling on FOXN1 expression and differentiation, and induce differentiation in a FOXN1-dependent manner. Knockdown of FOXN1 expression in primary human keratinocytes cooperated with oncogenic RAS in the induction of SCC-like tumors, whereas increased FOXN1 expression triggered the SCC cells to shift to a benign SK-like tumor phenotype, which included increased FGFR3 expression. Thus,we have uncovered a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype.

Assessment of melanocytic skin lesions with a high-definition laser Doppler imaging system.

BACKGROUND: Early detection is a major goal in the management of malignant melanoma. Besides clinical assessment many noninvasive technologies such as dermoscopy, digital dermoscopy and in vivo laser scanner microscopy are used as additional methods. Herein we tested a system to assess lesional perfusion as a tool for early melanoma detection.¦METHODS: Laser Doppler flow (FluxExplorer) and mole analyser (MA) score (FotoFinder) were applied to histologically verified melanocytic nevi (33) and malignant melanomas (12).¦RESULTS: Mean perfusion and MA scores were significantly increased in melanoma compared to nevi. However, applying an empirically determined threshold of 16% perfusion increase only 42% of the melanomas fulfilled the criterion of malignancy, whereas with the mole analyzer score 82% of the melanomas fulfilled the criterion of malignancy.¦CONCLUSION: Laser Doppler imaging is a highly sensitive technology to assess skin and skin tumor perfusion in vivo. Although mean perfusion is higher in melanomas compared to nevi the high numbers of false negative results hamper the use of this technology for early melanoma detection.

International survey on skin patch test procedures, attitudes and interpretation.

BACKGROUND Skin patch test is the gold standard method in diagnosing contact allergy. Although used for more than 100 years, the patch test procedure is performed with variability around the world. A number of factors can influence the test results, namely the quality of reagents used, the timing of the application, the patch test series (allergens/haptens) that have been used for testing, the appropriate interpretation of the skin reactions or the evaluation of the patient's benefit. METHODS We performed an Internet -based survey with 38 questions covering the educational background of respondents, patch test methods and interpretation. The questionnaire was distributed among all representatives of national member societies of the World Allergy Organization (WAO), and the WAO Junior Members Group. RESULTS One hundred sixty-nine completed surveys were received from 47 countries. The majority of participants had more than 5 years of clinical practice (61 %) and routinely carried out patch tests (70 %). Both allergists and dermatologists were responsible for carrying out the patch tests. We could observe the use of many different guidelines regardless the geographical distribution. The use of home-made preparations was indicated by 47 % of participants and 73 % of the respondents performed 2 or 3 readings. Most of the responders indicated having patients with adverse reactions, including erythroderma (12 %); however, only 30 % of members completed a consent form before conducting the patch test. DISCUSSION The heterogeneity of patch test practices may be influenced by the level of awareness of clinical guidelines, different training backgrounds, accessibility to various types of devices, the patch test series (allergens/haptens) used for testing, type of clinical practice (public or private practice, clinical or research-based institution), infrastructure availability, financial/commercial implications and regulations among others. CONCLUSION There is a lack of a worldwide homogeneity of patch test procedures, and this raises concerns about the need for standardization and harmonization of this important diagnostic procedure.

Effect of Temperature on the Development and Survival of the Argentine Ant, Linepithema humile

The influence of temperature on the developmental times and survival of insects can largely determine their distribution. For invasive species, like the Argentine ant, Linepithema humile Mayr (Hymenoptera: Formicidae), these data are essential for predicting their potential range based on mechanistic models. In the case of this species, such data are too scarce and incomplete to make accurate predictions based on its physiological needs. This research provides comprehensive new data about brood survival and developmental times at a wide range of temperatures under laboratory conditions. Temperature affected both the complete brood development from egg to adult worker and each of the immature stages separately. The higher the temperature, the shorter the development times. Brood survival from egg to adult was low, with the maximum survival rate being only 16% at 26° C. Temperature also affected survival of each of the immature stages differently: eggs were negatively affected by high temperatures, while larvae were negatively affected by low temperatures, and the survival of pupae was apparently independent of environmental temperature. At 32° C no eggs survived, while at 18° C less than 2% of the eggs hatched into larva. The data from the present study are essential for developing prediction models about the distribution range of this tramp species based on its physiological needs in relation to temperature

Euromelanoma: a dermatology-led European campaign against nonmelanoma skin cancer and cutaneous melanoma: past, present and future.

Euromelanoma is a dermatologist-led skin cancer prevention programme conducting an annual screening and public education campaign in over 20 European countries. Within its 10-year history, Euromelanoma has screened over 260,000 individuals across Europe, detecting a significant number of cutaneous melanomas and nonmelanoma skin cancers, identifying high-risk individuals for further surveillance and promoting awareness on the suspicious features of melanoma and the hazardous effects of ultraviolet exposure. In this review article, we summarize the history of the Euromelanoma campaign, present its organizational structure and discuss the results of the campaign in individual countries and on a European scale. Euromelanoma has had a significant impact on melanoma prevention and early diagnosis in participating countries and, despite many challenges, has positively influenced public health attitudes towards regular mole examination and the implementation of preventive measures against skin cancer.

A comparative study of reactive hyperemia in human forearm skin and muscle

Résumé en français: L'hyperémie réactive dans la microcirculation musculature et cutanée de l'avant-bras permet d'évaluer l'atteinte vasculaire dans les maladie cardiovasculaires. Cette méthode permet d'obtenir un reflet de la progression de l'atteinte vasculaire, de traquer la progression de la maladie ainsi que le risque cardio-vasculaires. Elle est en étude également pour tester l'efficacité d'une intervention thérapeutique. L'hyperémie réactive est dépendante d'une dilatation post ischémique par diminution des résistances artériolaires. Au niveau des membres, l'ischémie peut-être débutée et interrompue très facilement par une manchette à pression gonflée au-dessus de la pression systolique suivie quelques minutes plus tard de son dégonflement. Les mesures de flux sanguin musculaire et cutané au niveau d'un membre sont facile à réaliser chez l'homme, tout particulièrement au niveau de l'avant-bras. Pour l'instant aucune étude utilisant cette approche ne spécifiait quel avant-bras était utilisé. Il est cependant concevable que la réponse varie selon que l'on teste le bras dominant ou non-dominant. Il parait donc important de clarifier ce point. Le premier but de l'étude consiste donc à investiguer une éventuelle différence entre le bras dominant et le bras non-dominant d'un sujet lors de tests de l'hyperémie réactive dans le muscle et la peau. Il est connu que l'hyperémie réactive au niveau musculaire peut-être diminuée par les médicaments antiinflammatoires non stéro~idiens (AINS), indiquant une implication partielle des métabolites de la cyclo-oxygénase. L'influence des AINS sur la réponse cutanée est moins clairement établie. Ainsi, le second but de cette étude est de comparer l'effet de l'inhibition de la cyclo-oxygénase sur l'hyperémie réactive musculaire et cutanée chez des sujets sains. Le collectif de patients consiste en 23 sujets masculins volontaires, en bonne santé, non fumeurs, de 18 à 30 ans. Aucuns antécédents médicaux ne sont connus et aucune médication n'est prise durant la période de l'étude. Tous . les sujets ont donné leur consentement par écrit. Le flux sanguin musculaire de l'avant-bras est mesuré au moyen d'une pléthysmographie par occlusion veineuse, et le flux cutané l'est par imagerie laser Doppler. Les expériences ont lieu entre 16 et 18 h dans une chambre calme à température constante (23-24°C) chez un sujet couché. Les participants n'ont pas consommé d'AINS durant la semaine précédente ni bu de café dans les 12 h précédant l'expérience. Les mesures sont effectuées en triplicat au niveau musculaire puis cutané ou inversement selon un ordre aléatoire. Suite à une occlusion artérielle l'étude du flux se fait sur 3 min et 5 min de récupération sont prises entre 2 mesures. L'expérience 1 consiste à tester un possible effet systématique de la latéralisation du bras dominant ou non sur la réponse à l'hyperémie réactive dans la peau et le muscle de l'avant-bras. 16 sujets sont étudiés à 2 reprises, espacées de 1 à 3 jours. A la première visite, l'hyperémie musculaire est étudiée dans un avant-bras, la réaction cutanée dans l'autre et inversement lors de la deuxième visite. Une précaution est observée afin de mesurer le flux sanguin cutané à la même distance du poignet dans les 2 avant-bras. L'expérience 2 est développée pour évaluer l'impact d'une inhibition des cyclo-oxygénases. Sept sujet sont considérés à 2 occasions espacées de 7 à 10 j. L'étude s'effectue uniquement au niveau de l'avant-bras dominant. Le site cutané au niveau du poignet est marqué lors de la première visite afin d'utiliser le même site de mesure lors de la seconde visite. Le sujet ingère 1,8 g d'Aspegic (équivalant à 1 g d'acide acétylsalilcylique) dissout dans 125 ml de jus d'orange ou le jus d'orange seul lors de l'autre visite selon un ordre randomisé. Les mesures sont débutées 2 h après la prise. Summary Reactive hyperemia (RH) in forearm muscle or skin microcirculation has been considered as a surrogate endpoint in clinical studies of cardiovascular disease. We evaluated two potential confounders that might limit such use of RH, namely laterality of measurement and intake of non-steroidal anti-inflammatory drugs (NSAIDS). Twenty-three young non-smoking healthy adults were enrolled. In Experiment 1 (n=16), the RH elicited by 3 min of ischemia was recorded in the muscle (strain gauge plethysmography, hand excluded) and skin (laser Doppler imaging) of both forearms. In Experiment 2 (n=7), RH was determined in the dominant forearm only, one hour following oral acetylsalicylic acid (1 g) or placebo. In Experiment 1, peak RH was identical in both forearms, and so were the corresponding durations of responses. RH lasted significantly less in muscle than in skin (p=0.003), a hitherto unrecognized fact. In the skin, acetylsalicylate reduced duration (43 vs 57.4 s for placebo, p=0.03), without affecting the peak response. In muscle, duration tended to decrease with acetylsalicylate (21.4 vs 26.0 s with placebo, p=0.06) and the peak increase in blood flow was blunted (27.2 vs 32.4 ml/min/100 ml tissue with placebo, p=0.003). We conclude that, when using RH as a surrogate endpoint in studies of cardiovascular disease, a confounding by laterality of measurement need not be feared, but NSAIDS may have an influence, although perhaps not on the peak response in the skin.

Plasmacytoid dendritic cells in the skin: to sense or not to sense nucleic acids.

Plasmacytoid dendritic cells (pDCs) are specialized sensors of viral nucleic acids that initiate protective immunity through the production of type I interferons (IFNs). Normally, pDCs fail to sense host-derived self-nucleic acids but do so when self-nucleic acids form complexes with endogenous antimicrobial peptides produced in damaged skin. Whereas regulated expression of antimicrobial peptides may lead to pDC activation and protective immune responses to skin injury, overexpression of antimicrobial peptides in psoriasis drives excessive sensing of self-nucleic acids by pDCs resulting in IFN-driven autoimmunity. In skin tumors, pDCs are unable to sense self-nucleic acids; however, therapeutic activation of pDCs by synthetic nucleic acids or analogues can be exploited to generate antitumor immunity.

Application of low temperature thermochronology to understanding cooling and exhumation in the Central Swiss Alps

THESIS ABSTRACT : Low-temperature thermochronology relies on application of radioisotopic systems whose closure temperatures are below temperatures at which the dated phases are formed. In that sense, the results are interpreted as "cooling ages" in contrast to "formation ages". Owing to the low closure-temperatures, it is possible to reconstruct exhumation and cooling paths of rocks during their residence at shallow levels of the crust, i.e. within first ~10 km of depth. Processes occurring at these shallow depths such as final exhumation, faulting and relief formation are fundamental for evolution of the mountain belts. This thesis aims at reconstructing the tectono-thermal history of the Aar massif in the Central Swiss Alps by means of zircon (U-Th)/He, apatite (U-Th)/He and apatite fission track thermochronology. The strategy involved acquisition of a large number of samples from a wide range of elevations in the deeply incised Lötschen valley and a nearby NEAT tunnel. This unique location allowed to precisely constrain timing, amount and mechanisms of exhumation of the main orographic feature of the Central Alps, evaluate the role of topography on the thermochronological record and test the impact of hydrothermal activity. Samples were collected from altitudes ranging between 650 and 3930 m and were grouped into five vertical profiles on the surface and one horizontal in the tunnel. Where possible, all three radiometric systems were applied to each sample. Zircon (U-Th)/He ages range from 5.1 to 9.4 Ma and are generally positively correlated with altitude. Age-elevation plots reveal a distinct break in slope, which translates into exhumation rate increasing from ~0.4 to ~3 km/Ma at 6 Ma. This acceleration is independently confirmed by increased cooling rates on the order of 100°C/Ma constrained on the basis of age differences between the zircon (U-Th)/He and the remaining systems. Apatite fission track data also plot on a steep age-elevation curve indicating rapid exhumation until the end of the Miocene. The 6 Ma event is interpreted as reflecting tectonically driven uplift of the Aar massif. The late Miocene timing implies that the increase of precipitation in the Pliocene did not trigger rapid exhumation in the Aar massif. The Messinian salinity crisis in the Mediterranean could not directly intensify erosion of the Aar but associated erosional output from the entire Alps may have tapered the orogenic wedge and caused reactivation of thrusting in the Aar massif. The high exhumation rates in the Messinian were followed by a decrease to ~1.3 km/Ma as evidenced by ~8 km of exhumation during last 6 Ma. The slowing of exhumation is also apparent from apatite (U-Th)1He age-elevation data in the northern part of the Lötschen valley where they plot on a ~0.5km/Ma line and range from 2.4 to 6.4 Ma However, from the apatite (U-Th)/He and fission track data from the NEAT tunnel, there is an indication of a perturbation of the record. The apatite ages are youngest under the axis of the valley, in contrast to an expected pattern where they would be youngest in the deepest sections of the tunnel due to heat advection into ridges. The valley however, developed in relatively soft schists while the ridges are built of solid granitoids. In line with hydrological observations from the tunnel, we suggest that the relatively permeable rocks under the valley floor, served as conduits of geothermal fluids that caused reheating leading to partial Helium loss and fission track annealing in apatites. In consequence, apatite ages from the lowermost samples are too young and the calculated exhumation rates may underestimate true values. This study demonstrated that high-density sampling is indispensable to provide meaningful thermochronological data in the Alpine setting. The multi-system approach allows verifying plausibility of the data and highlighting sources of perturbation. RÉSUMÉ DE THÈSE : La thermochronologie de basse température dépend de l'utilisation de systèmes radiométriques dont la température de fermeture est nettement inférieure à la température de cristallisation du minéral. Les résultats obtenus sont par conséquent interprétés comme des âges de refroidissement qui diffèrent des âges de formation obtenus par le biais d'autres systèmes de datation. Grâce aux températures de refroidissement basses, il est aisé de reconstruire les chemins de refroidissement et d'exhumation des roches lors de leur résidence dans la croute superficielle (jusqu'à 10 km). Les processus qui entrent en jeu à ces faibles profondeurs tels que l'exhumation finale, la fracturation et le faillage ainsi que la formation du relief sont fondamentaux dans l'évolution des chaînes de montagne. Ces dernières années, il est devenu clair que l'enregistrement thermochronologique dans les orogènes peut être influencé par le relief et réinitialisé par l'advection de la chaleur liée à la circulation de fluides géothermaux après le refroidissement initial. L'objectif de cette thèse est de reconstruire l'histoire tectono-thermique du massif de l'Aar dans les Alpes suisses Centrales à l'aide de trois thermochronomètres; (U-Th)/He sur zircon, (U-Th)/He sur apatite et les traces de fission sur apatite. Afin d'atteindre cet objectif, nous avons récolté un grand nombre d'échantillons provenant de différentes altitudes dans la vallée fortement incisée de Lötschental ainsi que du tunnel de NEAT. Cette stratégie d'échantillonnage nous a permis de contraindre de manière précise la chronologie, les quantités et les mécanismes d'exhumation de cette zone des Alpes Centrales, d'évaluer le rôle de la topographie sur l'enregistrement thermochronologique et de tester l'impact de l'hydrothermalisme sur les géochronomètres. Les échantillons ont été prélevés à des altitudes comprises entre 650 et 3930m selon 5 profils verticaux en surface et un dans le tunnel. Quand cela à été possible, les trois systèmes radiométriques ont été appliqués aux échantillons. Les âges (U-Th)\He obtenus sur zircons sont compris entre 5.l et 9.4 Ma et sont corrélés de manière positive avec l'altitude. Les graphiques représentant l'âge et l'élévation montrent une nette rupture de la pente qui traduisent un accroissement de la vitesse d'exhumation de 0.4 à 3 km\Ma il y a 6 Ma. Cette accélération de l'exhumation est confirmée par les vitesses de refroidissement de l'ordre de 100°C\Ma obtenus à partir des différents âges sur zircons et à partir des autres systèmes géochronologiques. Les données obtenues par traces de fission sur apatite nous indiquent également une exhumation rapide jusqu'à la fin du Miocène. Nous interprétons cet évènement à 6 Ma comme étant lié à l'uplift tectonique du massif de l'Aar. Le fait que cet évènement soit tardi-miocène implique qu'une augmentation des précipitations au Pliocène n'a pas engendré cette exhumation rapide du massif de l'Aar. La crise Messinienne de la mer méditerranée n'a pas pu avoir une incidence directe sur l'érosion du massif de l'Aar mais l'érosion associée à ce phénomène à pu réduire le coin orogénique alpin et causer la réactivation des chevauchements du massif de l'Aar. L'exhumation rapide Miocène a été suivie pas une diminution des taux d'exhumation lors des derniers 6 Ma (jusqu'à 1.3 km\Ma). Cependant, les âges (U-Th)\He sur apatite ainsi que les traces de fission sur apatite des échantillons du tunnel enregistrent une perturbation de l'enregistrement décrit ci-dessus. Les âges obtenus sur les apatites sont sensiblement plus jeunes sous l'axe de la vallée en comparaison du profil d'âges attendus. En effet, on attendrait des âges plus jeunes sous les parties les plus profondes du tunnel à cause de l'advection de la chaleur dans les flancs de la vallée. La vallée est creusée dans des schistes alors que les flancs de celle-ci sont constitués de granitoïdes plus durs. En accord avec les observations hydrologiques du tunnel, nous suggérons que la perméabilité élevée des roches sous l'axe de la vallée à permi l'infiltration de fluides géothermaux qui a généré un réchauffement des roches. Ce réchauffement aurait donc induit une perte d'Hélium et un recuit des traces de fission dans les apatites. Ceci résulterait en un rajeunissement des âges apatite et en une sous-estimation des vitesses d'exhumation sous l'axe de la vallée. Cette étude à servi à démontrer la nécessité d'un échantillonnage fin et précis afin d'apporter des données thermochronologiques de qualité dans le contexte alpin. Cette approche multi-système nous a permi de contrôler la pertinence des données acquises ainsi que d'identifier les sources possibles d'erreurs lors d'études thermochronologiques. RÉSUMÉ LARGE PUBLIC Lors d'une orogenèse, les roches subissent un cycle comprenant une subduction, de la déformation, du métamorphisme et, finalement, un retour à la surface (ou exhumation). L'exhumation résulte de la déformation au sein de la zone de collision, menant à un raccourcissement et un apaissessement de l'édifice rocheux, qui se traduit par une remontée des roches, création d'une topographie et érosion. Puisque l'érosion agit comme un racloir sur la partie supérieure de l'édifice, des tentatives de corrélation entre les épisodes d'exhumation rapide et les périodes d'érosion intensive, dues aux changements climatiques, ont été effectuées. La connaissance de la chronologie et du lieu précis est d'une importance capitale pour une quelconque reconstruction de l'évolution d'une chaîne de montagne. Ces critères sont donnés par un retraçage des changements de la température de la roche en fonction du temps, nous donnant le taux de refroidissement. L'instant auquel les roches ont refroidit, passant une certaine température, est contraint par l'application de techniques de datation par radiométrie. Ces méthodes reposent sur la désintégration des isotopes radiogéniques, tels que l'uranium et le potassium, tous deux abondants dans les roches de la croûte terrestre. Les produits de cette désintégration ne sont pas retenus dans les minéraux hôtes jusqu'au moment du refroidissement de la roche sous une température appelée 'de fermeture' , spécifique à chaque système de datation. Par exemple, la désintégration radioactive des atomes d'uranium et de thorium produit des atomes d'hélium qui s'échappent d'un cristal de zircon à des températures supérieures à 200°C. En mesurant la teneur en uranium-parent, l'hélium accumulé et en connaissant le taux de désintégration, il est possible de calculer à quel moment la roche échantillonnée est passée sous la température de 200°C. Si le gradient géothermal est connu, les températures de fermeture peuvent être converties en profondeurs actuelles (p. ex. 200°C ≈ 7km), et le taux de refroidissement en taux d'exhumation. De plus, en datant par système radiométrique des échantillons espacés verticalement, il est possible de contraindre directement le taux d'exhumation de la section échantillonnée en observant les différences d'âges entre des échantillons voisins. Dans les Alpes suisses, le massif de l'Aar forme une structure orographique majeure. Avec des altitudes supérieures à 4000m et un relief spectaculaire de plus de 2000m, le massif domine la partie centrale de la chaîne de montagne. Les roches aujourd'hui exposées à la surface ont été enfouies à plus de 10 km de profond il y a 20 Ma, mais la topographie actuelle du massif de l'Aar semble surtout s'être développée par un soulèvement actif depuis quelques millions d'années, c'est-à-dire depuis le Néogène supérieur. Cette période comprend un changement climatique soudain ayant touché l'Europe il y a environ 5 Ma et qui a occasionné de fortes précipitations, entraînant certainement une augmentation de l'érosion et accélérant l'exhumation des Alpes. Dans cette étude, nous avons employé le système de datation (U-TH)/He sur zircon, dont la température de fermeture de 200°C est suffisamment basse pour caractériser l'exhumation du Néogène sup. /Pliocène. Les échantillons proviennent du Lötschental et du tunnel ferroviaire le plus profond du monde (NEAT) situé dans la partie ouest du massif de l'Aar. Considérés dans l'ensemble, ces échantillons se répartissent sur un dénivelé de 3000m et des âges de 5.1 à 9.4 Ma. Les échantillons d'altitude supérieure (et donc plus vieux) documentent un taux d'exhumation de 0.4 km/Ma jusqu'à il y a 6 Ma, alors que les échantillons situés les plus bas ont des âges similaires allant de 6 à 5.4 Ma, donnant un taux jusqu'à 3km /Ma. Ces données montrent une accélération dramatique de l'exhumation du massif de l'Aar il y a 6 Ma. L'exhumation miocène sup. du massif prédate donc le changement climatique Pliocène. Cependant, lors de la crise de salinité d'il y a 6-5.3 Ma (Messinien), le niveau de la mer Méditerranée est descendu de 3km. Un tel abaissement de la surface d'érosion peut avoir accéléré l'exhumation des Alpes, mais le bassin sud alpin était trop loin du massif de l'Aar pour influencer son érosion. Nous arrivons à la conclusion que la datation (U-Th)/He permet de contraindre précisément la chronologie et l'exhumation du massif de l'Aar. Concernant la dualité tectonique-érosion, nous suggérons que, dans le cas du massif de l'Aar, la tectonique prédomine.

Temperature-dependent elasticity of microtubules

Central to the biological function of microtubules is their ability to modify their length which occurs by addition and removal of subunits at the ends of the polymer, both in vivo and in vitro. This dynamic behavior is strongly influenced by temperature. Here, we show that the lateral interaction between tubulin subunits forming microtubule is strongly temperature dependent. Microtubules deposited on prefabricated substrates were deformed in an atomic force microscope during imaging, in two different experimental geometries. Microtubules were modeled as anisotropic, with the Young's modulus corresponding to the resistance of protofilaments to stretching and the shear modulus describing the weak interaction between the protofilaments. Measurements involving radial compression of microtubules deposited on flat mica confirm that microtubule elasticity depends on the temperature. Bending measurements performed on microtubules deposited on lithographically fabricated substrates show that this temperature dependence is due to changing shear modulus, implying that the lateral interaction between the protofilaments is strongly determined by the temperature. These measurements are in good agreement with previously reported measurements of the disassembly rate of microtubules, demonstrating that the mechanical and dynamic properties of microtubules are closely related.

Comparative winter thermoregulation and body temperature in three sympatric Apodemus species (A-alpicola, A-flavicollis, and A-sylvaticus)

When living in sympatry with Apodemus sylvaticus and A. flavicollis, A. alpicola dominates numerically at higher altitudes. A more efficient winter thermal isolation or a higher winter thermogenic capacity procuring a physiological advantage could explain at least part of this domination. We therefore measured body temperature (Tb), oxygen consumption (VO2), wet minimal thermal conductance (C) and non shivering thermogenesis (NST) at different ambient temperatures (Ta) on winter acclimated mice of the three species, and this for the first time in A. alpicola. NST was high and C low in the three species. No significant difference could be noticed either in Tb between 5 and -10 degrees C, in VO2 measurements at a Ta of -10 degrees C or in C. The NST measurements represent, respectively, 135.2% for A. sylvaticus, 142.8% for A. flavicollis and 140.5% for A. alpicola of the expected values, the values for A. sylvaticus being significantly lower than for the other two species. The basal metabolic rates (BMR) represent 169.4% for A. sylvaticus, 161.6% for A. flavicollis and 138.3% for A. alpicola of the expected values. Having removed the effect of body weight, the BMR value was significantly lower in A. alpicola than in A. flavicollis, but no difference could be noticed between A. sylvaticus and the other two species. In conclusion, the three species of mice have very similar acclimated thermoregulatory characteristics, well adapted to cold ambient conditions. One discriminating and advantageous factor could be the lower basal metabolic rate measured in A. alpicola compared to the other two species.

Linking temperature estimates and microstructures in deformed polymineralic mantle rocks

To constrain deformation temperatures of mantle shear zones, we studied a strike-slip shear zone (Hilti massif, Semail ophiolite, Oman) and focused on the interaction between microstructural mechanisms and chemical equilibration processes. Quantitative microfabric analysis on harzburgites with different deformation intensity (porphyroclastic tectonite, mylonite, and ultramylonite) was combined with orthopyroxene geothermometry. The average grain size of all phases decreases with decreasing shear zone thickness. Dynamic recrystallization of porphyroclasts in combination with dissolution-precipitation and nucleation result in small-sized, chemically equilibrated pyroxenes. The composition of orthopyroxene was used to calculate deformation temperatures. In the case of the porphyroclastic tectonites, the chemical composition of orthopyroxene has been reset by diffusion yielding temperature estimates of 880-900 degrees C. The mylonites were deformed by dislocation creep of olivine and show a broad range of calculated temperatures, which result from a combination of grain size reduction and inheritance of equilibrium compositions from earlier high-temperature events and diffusion. In mylonites, diffusion profiles combined with geothermometry and grain size analysis indicate a mylonitic deformation temperature of 800-900 degrees C possibly followed by diffusion. In ultramylonites, the smallest grains (<30 mu m) reveal equilibration at temperatures of similar to 700 degrees C during the last stages of ductile deformation, which was dominated by diffusion creep of olivine. Our results provide a crucial link between temperature and evolution of microstructures from dislocation creep to diffusion creep in mantle shear zones.

Cancers cutanés envahissant la base du crâne [Skin cancers infiltrating the skull base].

Squamous cell and basocellular carcinoma of the face have an excellent prognosis. Nevertherless, a small proportion therefore of these cancers differs by a much more aggressive behavior, caracterised by a tendency to infiltrate the deep facial soft tissues and facial bones. The invasion of the craniofacial skeleton and the intracranial structures follows the embryonic fusion lines or the facial sensitive or motor nerves, sometimes years after the initial treatment. The development of craniofacial surgery, reconstruction techniques and conformational radiotherapy allows us now to offer curative guided treatments, for these advanced staged tumors with a remaining limited prognosis. A therapeutic benefit implies a rigorous selection of these patients.

Evaluating thermal treeline indicators based on air and soil temperature using an air-to-soil temperature transfer model

In recent research, both soil (root-zone) and air temperature have been used as predictors for the treeline position worldwide. In this study, we intended to (a) test the proposed temperature limitation at the treeline, and (b) investigate effects of season length for both heat sum and mean temperature variables in the Swiss Alps. As soil temperature data are available for a limited number of sites only, we developed an air-to-soil transfer model (ASTRAMO). The air-to-soil transfer model predicts daily mean root-zone temperatures (10cm below the surface) at the treeline exclusively from daily mean air temperatures. The model using calibrated air and root-zone temperature measurements at nine treeline sites in the Swiss Alps incorporates time lags to account for the damping effect between air and soil temperatures as well as the temporal autocorrelations typical for such chronological data sets. Based on the measured and modeled root-zone temperatures we analyzed. the suitability of the thermal treeline indicators seasonal mean and degree-days to describe the Alpine treeline position. The root-zone indicators were then compared to the respective indicators based on measured air temperatures, with all indicators calculated for two different indicator period lengths. For both temperature types (root-zone and air) and both indicator periods, seasonal mean temperature was the indicator with the lowest variation across all treeline sites. The resulting indicator values were 7.0 degrees C +/- 0.4 SD (short indicator period), respectively 7.1 degrees C +/- 0.5 SD (long indicator period) for root-zone temperature, and 8.0 degrees C +/- 0.6 SD (short indicator period), respectively 8.8 degrees C +/- 0.8 SD (long indicator period) for air temperature. Generally, a higher variation was found for all air based treeline indicators when compared to the root-zone temperature indicators. Despite this, we showed that treeline indicators calculated from both air and root-zone temperatures can be used to describe the Alpine treeline position.

Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons.

Plasmacytoid dendritic cells (pDCs) are specialized type I interferon (IFN-α/β)-producing cells that express intracellular toll-like receptor (TLR) 7 and TLR9 and recognize viral nucleic acids in the context of infections. We show that pDCs also have the ability to sense host-derived nucleic acids released in common skin wounds. pDCs were found to rapidly infiltrate both murine and human skin wounds and to transiently produce type I IFNs via TLR7- and TLR9-dependent recognition of nucleic acids. This process was critical for the induction of early inflammatory responses and reepithelization of injured skin. Cathelicidin peptides, which facilitate immune recognition of released nucleic acids by promoting their access to intracellular TLR compartments, were rapidly induced in skin wounds and were sufficient but not necessary to stimulate pDC activation and type I IFN production. These data uncover a new role of pDCs in sensing tissue damage and promoting wound repair at skin surfaces.