Are the light-harvesting I complexes from Rhodospirillum rubrum arranged around the reaction centre in a square geometry?

The basic photosynthetic unit containing the reaction centre and the light-harvesting I complex (RC-LHI) of the purple non-sulphur bacterium Rhodospirillum rubrum was purified and reconstituted into two-dimensional (2D) membrane crystals. Transmission electron microscopy using conventional techniques and cryoelectron microscopy of the purified single particles and of 2D crystals yielded a projection of the RC-LHI complex at a resolution of at least 1.6 nm. In this projection the LHI ring appears to have a square symmetry and packs in a square crystal lattice. The square geometry of the LHI ring was observed also in images of single isolated particles of the RC-LHI complex. However, although the LHI units are packed identically within the crystal lattice, a new rotational analysis developed here showed that the reaction centres take up one of four possible orientations within the ring. This fourfold disorder supports our interpretation of a square ring symmetry and suggests that a hitherto undetected component may be present within the photosynthetic unit.

Policy Environment and Public Service Motivation

This article analyzes whether and to what extent the policy environment of civil servants has an impact on their level of Public Service Motivation (PSM). It hypothesizes that public employees working in different policy domains and stages of the policy cycle are diversely motivated by four PSM orientations (Compassion, Commitment to the public interest, Self-sacrifice and Attraction to politics). The empirical results are based on a survey of 6885 Swiss civil servants. They show that those in charge of Welfare State policies are inclined to have higher levels of 'Compassion', whereas those performing core state functions report lower levels. Furthermore, employees whose main tasks are related to policy formulation display high levels of the 'Attraction to politics' dimension of PSM. This study questions the generalization of previous findings on PSM that are based on heterogeneous survey populations.

VEGF is a mediator of retinal pigment epithelium permeability leading to photoreceptor cell death in light-induced retinal degeneration : gene therapy strategy to prevent AMD-disorders

ABSTRACTIn normal tissues, a balance between pro- and anti-angiogenic factors tightly controls angiogenesis. Alterations of this balance may have pathological consequences. For instance, concerning the retina, the vascular endothelial growth factor (VEGF) is a potent pro-angiogenic factor, and has been identified has a key player during ocular neovascularization implicated in a variety of retinal diseases. In the exudative form (wet-form) of age-related macular degeneration (AMD), neovascularizations occurring from the choroidal vessels are responsible for a quick and dramatic loss of visual acuity. In diabetic retinopathy and retinopathy of prematurity, sprouting from the retinal vessels leads to vision loss. Furthermore, the aging of the population, the increased- prevalence of diabetes and the better survival rate of premature infants will lead to an increasing rate of these conditions. In this way, anti-VEGF strategy represents an important therapeutic target to treat ocular neovascular disorders.In addition, the administration of Pigmented Epithelial growth factor, a neurotrophic and an anti- angiogenic factor, prevents photoreceptor cell death in a model of retinal degeneration induced by light. Previous results analyzing end point morphology reveal that the light damage (LD) model is used to mimic retinal degenerations arising from environmental insult, as well as aging and genetic disease such as advanced atrophic AMD. Moreover, light has been identified as a co-factor in a number of retinal diseases, speeding up the degeneration process. This protecting effect of PEDF in the LD retina raises the possibility of involvement of the balance between pro- and anti-angiogenic factors not only for angiogenesis, but also in cell survival and maintenance.The aim of the work presented here was to evaluate the importance of this balance in neurodegenerative processes. To this aim, a model of light-induced retinal degeneration was used and characterized, mainly focusing on factors simultaneously controlling neuron survival and angiogenesis, such as PEDF and VEGF.In most species, prolonged intense light exposure can lead to photoreceptor cell damage that can progress to cell death and vision loss. A protocol previously described to induce retinal degeneration in Balb/c mice was used. Retinas were characterized at different time points after light injury through several methods at the functional and molecular levels. Data obtained confirmed that toxic level of light induce PR cell death. Variations were observed in VEGF pathway players in both the neural retina and the eye-cup containing the retinal pigment epithelium (RPE), suggesting a flux of VEGF from the RPE towards the neuroretina. Concomitantly, the integrity of the outer blood-retinal-barrier (BRB) was altered, leading to extravascular albumin leakage from the choroid throughout the photoreceptor layer.To evaluate the importance of VEGF during light-induced retinal degeneration process, a lentiviral vector encoding the cDNA of a single chain antibody directed against all VEGF-A isoforms was developed (LV-V65). The bioactivity of this vector to block VEGF was validated in a mouse model of laser-induced choroidal neovascularization mediated by VEGF upregulation. The vector was then used in the LD model. The administration of the LV-V65 contributed to the maintenance of functional photoreceptors, which was assessed by ERG recording, visual acuity measurement and histological analyses. At the RPE level, the BRB integrity was preserved as shown by the absence of albumin leakage and the maintenance of RPE cell cohesion.These results taken together indicate that the VEGF is a mediator of light induced PR degeneration process and confirm the crucial role of the balance between pro- and anti-angiogenic factors in the PR cell survival. This work also highlights the prime importance of BRB integrity and functional coupling between RPE and PR cells to maintain the PR survival. VEGF dysregulation was already shown to be involved in wet AMD forms and our study suggests that VEGF dysregulation may also occur at early stages of AMD and could thus be a potential therapeutic target for several RPE related diseases.RESUMEDans les différents tissues de l'organisme, l'angiogenèse est strictement contrôlée par une balance entre les facteurs pro- et anti-angiogéniques. Des modifications survenant dans cette balance peuvent engendrer des conséquences pathologiques. Par exemple, concernant la rétine, le facteur de croissance de l'endothélium vasculaire (VEGF) est un facteur pro-angiogénique important. Ce facteur a été identifié comme un acteur majeur dans les néovascularisations oculaires et les processus pathologiques angiogéniques survenant dans l'oeil et responsables d'une grande variété de maladies rétiniennes. Dans la forme humide de la dégénérescence maculaire liée à l'âge (DMLA), la néovascularisation choroïdienne est responsable de la perte rapide et brutale de l'acuité visuelle chez les patients affectés. Dans la rétinopathie diabétique et celle lié à la prématurité, l'émergence de néovaisseaux rétiniens est la cause de la perte de la vision. Les néovascularisations oculaires représentent la principale cause de cécité dans les pays développés. De plus, l'âge croissant de la population, la progression de la prévalence du diabète et la meilleure survie des enfants prématurés mèneront sans doute à l'augmentation de ces pathologies dans les années futures. Dans ces conditions, les thérapies anti- angiogéniques visant à inhiber le VEGF représentent une importante cible thérapeutique pour le traitement de ces pathologies.Plusieurs facteurs anti-angiogéniques ont été identifiés. Parmi eux, le facteur de l'épithélium pigmentaire (PEDF) est à la fois un facteur neuro-trophique et anti-angiogénique, et l'administration de ce facteur au niveau de la rétine dans un modèle de dégénérescence rétinienne induite par la lumière protège les photorécepteurs de la mort cellulaire. Des études antérieures basées sur l'analyse morphologique ont révélé que les modifications survenant lors de la dégénération induite suite à l'exposition à des doses toxiques de lumière représente un remarquable modèle pour l'étude des dégénérations rétiniennes suite à des lésions environnementales, à l'âge ou encore aux maladies génétiques telle que la forme atrophique avancée de la DMLA. De plus, la lumière a été identifiée comme un co-facteur impliqué dans un grand nombre de maladies rétiniennes, accélérant le processus de dégénération. L'effet protecteur du PEDF dans les rétines lésées suite à l'exposition de des doses toxiques de lumière suscite la possibilité que la balance entre les facteurs pro- et anti-angiogéniques soit impliquée non seulement dans les processus angiogéniques, mais également dans le maintient et la survie des cellules.Le but de ce projet consiste donc à évaluer l'implication de cette balance lors des processus neurodégénératifs. Pour cela, un modèle de dégénération induite par la lumière à été utilisé et caractérisé, avec un intérêt particulier pour les facteurs comme le PEDF et le VEGF contrôlant simultanément la survie des neurones et l'angiogenèse.Dans la plupart des espèces, l'exposition prolongée à une lumière intense peut provoquer des dommages au niveau des cellules photoréceptrices de l'oeil, qui peut mener à leur mort, et par conséquent à la perte de la vision. Un protocole préalablement décrit a été utilisé pour induire la dégénération rétinienne dans les souris albinos Balb/c. Les rétines ont été analysées à différents moments après la lésion par différentes techniques, aussi bien au niveau moléculaire que fonctionnel. Les résultats obtenus ont confirmé que des doses toxiques de lumière induisent la mort des photorécepteurs, mais altèrent également la voie de signalisation du VEGF, aussi bien dans la neuro-rétine que dans le reste de l'oeil, contenant l'épithélium pigmentaire (EP), et suggérant un flux de VEGF provenant de ΙΈΡ en direction de la neuro-rétine. Simultanément, il se produit une altération de l'intégrité de la barrière hémato-rétinienne externe, menant à la fuite de protéine telle que l'albumine, provenant de la choroïde et retrouvée dans les compartiments extravasculaires de la rétine, telle que dans la couche des photorécepteurs.Pour déterminer l'importance et le rôle du VEGF, un vecteur lentiviral codant pour un anticorps neutralisant dirigée contre tous les isoformes du VEGF a été développé (LV-V65). La bio-activité de ce vecteur a été testé et validée dans un modèle de laser, connu pour induire des néovascularisations choroïdiennes chez la souris suite à l'augmentation du VEGF. Ce vecteur a ensuite été utilisé dans le modèle de dégénération induite par la lumière. Les résultats des électrorétinogrammes, les mesures de l'acuité visuelle et les analyses histologiques ont montré que l'injection du LV-V65 contribue à la maintenance de photorécepteurs fonctionnels. Au niveau de l'EP, l'absence d'albumine et la maintenance des jonctions cellulaires des cellules de l'EP ont démontré que l'intégrité de la barrière hémato-rétinienne externe est préservée suite au traitement.Par conséquent, tous les résultats obtenus indiquent que le VEGF est un médiateur important impliquée dans le processus de dégénération induit par la lumière et confirme le rôle cruciale de la balance entre les facteurs pro- et anti-angiogéniques dans la survie des photorécepteurs. Cette étude révèle également l'importance de l'intégrité de la barrière hémato-rétinienne et l'importance du lien fonctionnel et structurel entre l'EP et les photorécepteurs, essentiel pour la survie de ces derniers. Par ailleurs, Cette étude suggère que des dérèglements au niveau de l'équilibre du VEGF ne sont pas seulement impliqués dans la forme humide de la DMLA, comme déjà démontré dans des études antérieures, mais pourraient également contribuer et survenir dans des formes précoces de la DMLA, et par conséquent le VEGF représente une cible thérapeutique potentielle pour les maladies associées à des anomalies au niveau de l'EP.

Aliments et boissons allégés: qu'en penser [Light food and beverages: what to think about?].

Light food and beverages are increasing on the market for many years, first for economic reasons and, more and more for aesthetisme, however without aimed a defined population. The interest of these products is not evident, reason why it is difficult to get a clear and objective opinion without being influenced by marketing messages. Under what circumstances can they be a solution? Can we advise them? Do they have an influence in the loss or weight control? This article offers some thoughts and suggestions on the use of these specific products.

Life-course socioeconomic environment and health risk behaviours: a multilevel small-area analysis of young-old persons in an urban neighbourhood in Lausanne, Switzerland

With a life expectancy at the age of 65 of around 20 years, damaging health risk behaviours of young-old adults have become a target for preventive actions. Such risk factors necessitate an accurate understanding of the present and past socioeconomic conditions associated with health risk behaviours. The aim of our study is to assess the impact of certain life events as well as economic and environmental factors on health risk behaviours. We included 1309 participants of the Lausanne Cohort Lc65+ aged 65-70 years and employed logistic regression analyses, with individuals nested within areas. The results illustrate the influences of socioeconomic factors from childhood to young-old age. Life experiences in adulthood and economic resources in young-old age are both associated with unfavourable health behaviours. Neighbourhood is a modest determinant as well, particularly regarding alcohol consumption. Therefore, prevention against health risk behaviours should focus on population subgroups defined on the basis of their socioeconomic and living contexts.

Emplacement of ultramafic rocks into the continental crust monitored by light and other trace elements: An example from the Geisspfad body (Swiss-Italian Alps)

In order to evaluate the influence of continental crustal rocks on trace element budgets of serpentinized peridotites incorporated into the continental crust, we have analyzed the chemical composition of whole rock samples and minerals of the Geisspfad ultramafic complex (Swiss-Italian Alps). This complex represents a relict oceanic succession composed of serpentinites, ophicarbonates and metabasic rocks, emplaced into crustal gneisses during Alpine collision. Following peak metamorphic amphibolite facies conditions, fluid flow modified some of the trace element contents of ophicarbonates and deformed serpentinites close to the contact with country rocks. The fluid originated from the surrounding continental crustal rocks as documented by the increase of Pb in the serpentinites, and by the strongly negative all) values (-112 parts per thousand) of some ultramafic rocks close to the contact with surrounding gneisses. Little or no modification of the fluid mobile elements Li, B or U was observed in the serpentinite. In-situ analysis of light elements of serpentinite minerals indicate redistribution of light elements coupled to changes of mineral modes towards the outer 100-150 m of the massif. In the centre of the massif, Li is preferentially concentrated in olivine, while Be and B are hosted by tremolite. In contrast, at the outer rim of the massif, Li and Be are preferentially incorporated into diopside, and B into antigorite. This redistribution of light elements among the different minerals is visible in the serpentinite, at a maximum distance of -100-150 m from the ophicarbonate-metabasite contact. Our results show that interaction of ultramafic rocks and crust-derived fluids can be easily detected by studies of Pb and partial derivative D in whole rocks. We argue that small ultramafic bodies potentially record an emplacement-related trace element signature, and that crustal light element values in ultramafic rocks are not necessarily derived from a subducting slab. (C) 2008 Elsevier B.V. All rights reserved.

Dissolution-reprecipitation of zircon at low-temperature, high-pressure conditions (Lanzo Massif, Italy)

An eclogite facies meta-plagiogranite from the Lanzo massif (western Alps, Italy) contains crystals of zircon intimately associated with allanite. Zircon displays different microtextures ranging from pristine, euhedral, and magmatic to fractured, porous varieties with mosaic zoning, and pervasive recrystallization into euhedral microcrystals. Fractures and voids in the recrystallized zircon microcrystals are mainly filled by high-pressure Na-rich pyroxene. Electron backscattered diffraction analysis revealed a similar crystallographic orientation for primary magmatic zircon crystals and microcrystals, with less than 2 degrees misorientation among neighboring microdomains. The textural change is coupled with chemical and isotopic modifications: recrystallized zircon domains contain significantly less Th and light- to mid-REE, but are richer in Sr than magmatic zircon crystals. Magmatic zircon preserves the protolith U-Pb age of 163.5 +/- 1.7 Ma, whereas zircon microcrystals have a mean age of 55 +/- 1 Ma. The coexisting allanite also contains inclusions of Na-rich pyroxene and has chemical features (elevated Sr and Ni contents and lack of Eu anomaly) indicating formation at high pressure. Despite being associated texturally with zircon, allanite yields a younger Th-Pb age of 46.5 +/- 3.0 Ma, suggesting that the Lanzo unit remained at relatively high pressure conditions for similar to 8 m.y. Zircon recrystallization proceeded with volume reduction and loss of material to an alkaline metamorphic fluid that acted as the agent for a coupled dissolution-reprecipitation process. Recrystallization occurred with minimum transport, in a low-strain environment, and was not significantly enhanced by metamictization. The source of the fluid for zircon recrystallization is most probably related to prograde devolatilization reactions in the surrounding serpentinite.

Effects of common origin and common rearing environment on variance in ectoparasite load and phenotype of nestling Alpine swifts

Knowledge of the quantitative genetics of resistance to parasitism is key to appraise host evolutionary responses to parasite selection. Here, we studied effects of common origin (i.e. genetic and pre-hatching parental effects) and common rearing environment (i.e. post-hatching parental effects and other environment effects) on variance in ectoparasite load in nestling Alpine swifts (Apus melba). This colonial bird is intensely parasitized by blood sucking louse-flies that impair nestling development and survival. By cross-fostering half of the hatchlings between pairs of nests, we show strong significant effect of common rearing environment on variance (90.7% in 2002 and 90.9% in 2003) in the number of louse-flies per nestling and no significant effect of common origin on variance in the number of louse-flies per nestling. In contrast, significant effects of common origin were found for all the nestling morphological traits (i.e. body mass, wing length, tail length, fork length and sternum length) under investigation. Hence, our study suggests that genetic and pre-hatching parental effects play little role in the distribution of parasites among nestling Alpine swifts, and thus that nestlings have only limited scope for evolutionary responses against parasites. Our results highlight the need to take into consideration environmental factors, including the evolution of post-hatching parental effects such as nest sanitation, in our understanding of host-parasite relationships.

Looking for orders of magnitude : five essays in trade and the environment and economic geography

General Summary Although the chapters of this thesis address a variety of issues, the principal aim is common: test economic ideas in an international economic context. The intention has been to supply empirical findings using the largest suitable data sets and making use of the most appropriate empirical techniques. This thesis can roughly be divided into two parts: the first one, corresponding to the first two chapters, investigates the link between trade and the environment, the second one, the last three chapters, is related to economic geography issues. Environmental problems are omnipresent in the daily press nowadays and one of the arguments put forward is that globalisation causes severe environmental problems through the reallocation of investments and production to countries with less stringent environmental regulations. A measure of the amplitude of this undesirable effect is provided in the first part. The third and the fourth chapters explore the productivity effects of agglomeration. The computed spillover effects between different sectors indicate how cluster-formation might be productivity enhancing. The last chapter is not about how to better understand the world but how to measure it and it was just a great pleasure to work on it. "The Economist" writes every week about the impressive population and economic growth observed in China and India, and everybody agrees that the world's center of gravity has shifted. But by how much and how fast did it shift? An answer is given in the last part, which proposes a global measure for the location of world production and allows to visualize our results in Google Earth. A short summary of each of the five chapters is provided below. The first chapter, entitled "Unraveling the World-Wide Pollution-Haven Effect" investigates the relative strength of the pollution haven effect (PH, comparative advantage in dirty products due to differences in environmental regulation) and the factor endowment effect (FE, comparative advantage in dirty, capital intensive products due to differences in endowments). We compute the pollution content of imports using the IPPS coefficients (for three pollutants, namely biological oxygen demand, sulphur dioxide and toxic pollution intensity for all manufacturing sectors) provided by the World Bank and use a gravity-type framework to isolate the two above mentioned effects. Our study covers 48 countries that can be classified into 29 Southern and 19 Northern countries and uses the lead content of gasoline as proxy for environmental stringency. For North-South trade we find significant PH and FE effects going in the expected, opposite directions and being of similar magnitude. However, when looking at world trade, the effects become very small because of the high North-North trade share, where we have no a priori expectations about the signs of these effects. Therefore popular fears about the trade effects of differences in environmental regulations might by exaggerated. The second chapter is entitled "Is trade bad for the Environment? Decomposing worldwide SO2 emissions, 1990-2000". First we construct a novel and large database containing reasonable estimates of SO2 emission intensities per unit labor that vary across countries, periods and manufacturing sectors. Then we use these original data (covering 31 developed and 31 developing countries) to decompose the worldwide SO2 emissions into the three well known dynamic effects (scale, technique and composition effect). We find that the positive scale (+9,5%) and the negative technique (-12.5%) effect are the main driving forces of emission changes. Composition effects between countries and sectors are smaller, both negative and of similar magnitude (-3.5% each). Given that trade matters via the composition effects this means that trade reduces total emissions. We next construct, in a first experiment, a hypothetical world where no trade happens, i.e. each country produces its imports at home and does no longer produce its exports. The difference between the actual and this no-trade world allows us (under the omission of price effects) to compute a static first-order trade effect. The latter now increases total world emissions because it allows, on average, dirty countries to specialize in dirty products. However, this effect is smaller (3.5%) in 2000 than in 1990 (10%), in line with the negative dynamic composition effect identified in the previous exercise. We then propose a second experiment, comparing effective emissions with the maximum or minimum possible level of SO2 emissions. These hypothetical levels of emissions are obtained by reallocating labour accordingly across sectors within each country (under the country-employment and the world industry-production constraints). Using linear programming techniques, we show that emissions are reduced by 90% with respect to the worst case, but that they could still be reduced further by another 80% if emissions were to be minimized. The findings from this chapter go together with those from chapter one in the sense that trade-induced composition effect do not seem to be the main source of pollution, at least in the recent past. Going now to the economic geography part of this thesis, the third chapter, entitled "A Dynamic Model with Sectoral Agglomeration Effects" consists of a short note that derives the theoretical model estimated in the fourth chapter. The derivation is directly based on the multi-regional framework by Ciccone (2002) but extends it in order to include sectoral disaggregation and a temporal dimension. This allows us formally to write present productivity as a function of past productivity and other contemporaneous and past control variables. The fourth chapter entitled "Sectoral Agglomeration Effects in a Panel of European Regions" takes the final equation derived in chapter three to the data. We investigate the empirical link between density and labour productivity based on regional data (245 NUTS-2 regions over the period 1980-2003). Using dynamic panel techniques allows us to control for the possible endogeneity of density and for region specific effects. We find a positive long run elasticity of density with respect to labour productivity of about 13%. When using data at the sectoral level it seems that positive cross-sector and negative own-sector externalities are present in manufacturing while financial services display strong positive own-sector effects. The fifth and last chapter entitled "Is the World's Economic Center of Gravity Already in Asia?" computes the world economic, demographic and geographic center of gravity for 1975-2004 and compares them. Based on data for the largest cities in the world and using the physical concept of center of mass, we find that the world's economic center of gravity is still located in Europe, even though there is a clear shift towards Asia. To sum up, this thesis makes three main contributions. First, it provides new estimates of orders of magnitudes for the role of trade in the globalisation and environment debate. Second, it computes reliable and disaggregated elasticities for the effect of density on labour productivity in European regions. Third, it allows us, in a geometrically rigorous way, to track the path of the world's economic center of gravity.

New approach for weight reduction by a combination of diet, light resistance exercise and the timing of ingesting a protein supplement.

We have reported that ingesting a meal immediately after exercise increased skeletal muscle accretion and less adipose tissue accumulation in rats employed in a 10 week resistance exercise program. We hypothesized that a possible increase in the resting metabolic rate (RMR) as a result of the larger skeletal muscle mass might be responsible for the less adipose deposition. Therefore, the effect of the timing of a protein supplement after resistance exercise on body composition and the RMR was investigated in 17 slightly overweight men. The subjects participated in a 12-week weight reduction program consisting of mild energy restriction (17% energy intake reduction) and a light resistance exercise using a pair of dumbbells (3-5 kg). The subjects were assigned to two groups. Group S ingested a protein supplement (10 g protein, 7 g carbohydrate, 3.3 g fat and one-third of recommended daily allowance (RDA) of vitamins and minerals) immediately after exercise. Group C did not ingest the supplement. Daily intake of both energy and protein was equal between the two groups and the protein intake met the RDA. After 12 weeks, the bodyweight, skinfold thickness, girth of waist and hip and percentage bodyfat significantly decreased in the both groups, however, no significant differences were observed between the groups. The fat-free mass significantly decreased in C, whereas its decrease in S was not significant. The RMR and post-meal total energy output significantly increased in S, while these variables did not change in C. In addition, the urinary nitrogen excretion tended to increase in C but not in S. These results suggest that the RMR increase observed in S might be associated with an increase in body protein synthesis.

Tumor cell budding and laminin-5 expression in colorectal carcinoma can be modulated by the tissue micro-environment.

Expression of laminin-5 alpha3, beta3 and gamma2 protein subunits was investigated in colorectal adenocarcinomas using immunostaining and confocal microscopy. The laminin-5 heterotrimer was found in basement membranes and as extracellular deposits in tumor stroma. In contrast to the alpha3 subunit, which was under-expressed, the gamma2 and beta3 subunits were detected in the cytoplasm of carcinoma cells dissociating (budding) from neoplastic tubules, suggestive of focal alterations in laminin-5 assembly and secretion. Laminin-5 gamma2 or beta3 subunit-reactive budding carcinoma cells expressed cytokeratins but not vimentin; they did not proliferate and were not apoptotic. Furthermore, expression of laminin-5 gamma2 and beta3 subunits in budding cells was associated with focal under-expression of the E-cadherin-beta-catenin complex. Results from xenograft experiments showed that budding activity in colorectal adenocarcinomas could be suppressed when these tumors grew at ectopic s.c. sites in nude mice. In vitro, cultured colon carcinoma cells, but not adenoma-derived tumor cells, shared the laminin-5 phenotype expressed by carcinoma cells in vivo. Using colon carcinoma cell lines implanted orthotopically and invading the cecum of nude mice, the laminin-5-associated budding was restored, indicating that this phenotype is not only determined by tumor cell properties but also dependent on the tissue micro-environment. Our results indicate that both laminin-5 alpha3 subunit expression and cell-cell cohesiveness are altered in budding carcinoma cells, which we consider to be actively invading. We propose that the local tissue micro-environment contributes to these events.

Exposure to stallion accelerates the onset of mares' cyclicity.

Horses (Equus caballus) belong to the group of seasonally polyestrous mammals. Estrous cycles typically start with increasing daylight length after winter, but mares can differ greatly in the timing of onset of regular estrus cycles. Here, we test whether spatial proximity to a stallion also plays a role. Twenty-two anestrous mares were either exposed to one of two stallions (without direct physical contact) or not exposed (controls) under experimental conditions during two consecutive springs (February to April). Ovarian activity was monitored via transrectal ultrasound and stallion's direct contact time with each mare was determined three times per week for one hour each. We found that mares exposed to a stallion ovulated earlier and more often during the observational period than mares that were not exposed to stallions. Neither stallion identity nor direct contact time, mare age, body condition, size of her largest follicle at the onset of the experiment, or parasite burden significantly affected the onset of cyclicity. In conclusion, the timing of estrous cycles and cycle frequency, i.e., crucial aspects of female reproductive strategy, strongly depend on how the mares perceive their social environment. Exposing mares to the proximity of a stallion can therefore be an alternative to, for example, light programs or elaborated hormonal therapies to start the breeding season earlier and increase the number of estrous cycles in horses.