The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System.

In vitro differentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimicking in vitro these two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4(+)CD25(+)Foxp3(+) T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4(+)CD161(+)CD196(+) Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-β production. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

Sustained-release steroids for the treatment of diabetic macular edema.

Glucocorticoids have been used for decades in the treatment of ocular disorders via topical, periocular, and more recently intravitreal routes. However, their exact mechanisms of action on ocular tissues remain imperfectly understood. Fortunately, two recently approved intravitreal sustained-release drug delivery systems have opened new perspectives for these very potent drugs. To date, among other retinal conditions, their label includes diabetic macular edema, for which a long-lasting therapeutic effect has been demonstrated both morphologically and functionally in several randomized clinical trials. The rate of ocular complications of intravitreal sustained-release steroids, mainly cataract formation and intraocular pressure elevation, is higher than with anti-vascular endothelial growth factor agents. Yet, a better understanding of the mechanisms underlying these adverse effects and the search for the minimal efficient dose should help optimize their therapeutic window.

Gas-phase photocatalytic oxidation of volatile organic compounds

Substances emitted into the atmosphere by human activities in urban and industrial areas cause environmental problems such as air quality degradation, respiratory diseases, climate change, global warming, and stratospheric ozone depletion. Volatile organic compounds (VOCs) are major air pollutants, emitted largely by industry, transportation and households. Many VOCs are toxic, and some are considered to be carcinogenic, mutagenic, or teratogenic. A wide spectrum of VOCs is readily oxidized photocatalytically. Photocatalytic oxidation (PCO) over titanium dioxide may present a potential alternative to air treatment strategies currently in use, such as adsorption and thermal treatment, due to its advantageous activity under ambient conditions, although higher but still mild temperatures may also be applied. The objective of the present research was to disclose routes of chemical reactions, estimate the kinetics and the sensitivity of gas-phase PCO to reaction conditions in respect of air pollutants containing heteroatoms in their molecules. Deactivation of the photocatalyst and restoration of its activity was also taken under consideration to assess the practical possibility of the application of PCO to the treatment of air polluted with VOCs. UV-irradiated titanium dioxide was selected as a photocatalyst for its chemical inertness, non-toxic character and low cost. In the present work Degussa P25 TiO2 photocatalyst was mostly used. In transient studies platinized TiO2 was also studied. The experimental research into PCO of following VOCs was undertaken: - methyl tert-butyl ether (MTBE) as the basic oxygenated motor fuel additive and, thus, a major non-biodegradable pollutant of groundwater; - tert-butyl alcohol (TBA) as the primary product of MTBE hydrolysis and PCO; - ethyl mercaptan (ethanethiol) as one of the reduced sulphur pungent air pollutants in the pulp-and-paper industry; - methylamine (MA) and dimethylamine (DMA) as the amino compounds often emitted by various industries. The PCO of VOCs was studied using a continuous-flow mode. The PCO of MTBE and TBA was also studied by transient mode, in which carbon dioxide, water, and acetone were identified as the main gas-phase products. The volatile products of thermal catalytic oxidation (TCO) of MTBE included 2-methyl-1-propene (2-MP), carbon monoxide, carbon dioxide and water; TBA decomposed to 2-MP and water. Continuous PCO of 4 TBA proceeded faster in humid air than dry air. MTBE oxidation, however, was less sensitive to humidity. The TiO2 catalyst was stable during continuous PCO of MTBE and TBA above 373 K, but gradually lost activity below 373 K; the catalyst could be regenerated by UV irradiation in the absence of gas-phase VOCs. Sulphur dioxide, carbon monoxide, carbon dioxide and water were identified as ultimate products of PCO of ethanethiol. Acetic acid was identified as a photocatalytic oxidation by-product. The limits of ethanethiol concentration and temperature, at which the reactor performance was stable for indefinite time, were established. The apparent reaction kinetics appeared to be independent of the reaction temperature within the studied limits, 373 to 453 K. The catalyst was completely and irreversibly deactivated with ethanethiol TCO. Volatile PCO products of MA included ammonia, nitrogen dioxide, nitrous oxide, carbon dioxide and water. Formamide was observed among DMA PCO products together with others similar to the ones of MA. TCO for both substances resulted in the formation of ammonia, hydrogen cyanide, carbon monoxide, carbon dioxide and water. No deactivation of the photocatalyst during the multiple long-run experiments was observed at the concentrations and temperatures used in the study. PCO of MA was also studied in the aqueous phase. Maximum efficiency was achieved in an alkaline media, where MA exhibited high fugitivity. Two mechanisms of aqueous PCO – decomposition to formate and ammonia, and oxidation of organic nitrogen directly to nitrite - lead ultimately to carbon dioxide, water, ammonia and nitrate: formate and nitrite were observed as intermediates. A part of the ammonia formed in the reaction was oxidized to nitrite and nitrate. This finding helped in better understanding of the gasphase PCO pathways. The PCO kinetic data for VOCs fitted well to the monomolecular Langmuir- Hinshelwood (L-H) model, whereas TCO kinetic behaviour matched the first order process for volatile amines and the L-H model for others. It should be noted that both LH and the first order equations were only the data fit, not the real description of the reaction kinetics. The dependence of the kinetic constants on temperature was established in the form of an Arrhenius equation.

Isolation, structural assignment and total synthesis of Barmumycin

Barmumycin was isolated from an extract of the marine actinomycete Streptomyces sp. BOSC-022A and found to be cytotoxic against various human tumor cell lines. Based on preliminary one- and two-dimensional 1H- and 13C-NMR spectra, the natural compound was initially assigned the structure of macrolactone-type compound 1, which was later prepared by two different routes. However, major spectroscopic differences between isolated barmumycin and 1 led to revision of the proposed structure as E-16. Based on synthesis of this new compound, and subsequent spectroscopic comparison of it to an authentic sample of barmumycin, the structure of the natural compound was indeed confirmed as that of E-16.

Mercury analysis in hair: comparability and quality assessment within the transnational COPHES/DEMOCOPHES project

Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical procedures has often limited the comparison of data at national and international level. The European-funded projects COPHES and DEMOCOPHES developed and tested a harmonized European approach to Human Biomonitoring in response to the European Environment and Health Action Plan. Herein we describe the quality assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother-child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0.20-0.71 and 0.80-1.63) per exercise. The results revealed relative standard deviations of 7.87-13.55% and 4.04-11.31% for the low and high mercury concentration ranges, respectively. A total of 16 out of 18 participating laboratories the QAP requirements and were allowed to analyze samples from the DEMOCOPHES pilot study. Web conferences after each ICI/EQUAS revealed this to be a new and effective tool for improving analytical performance and increasing capacity building. The procedure developed and tested in COPHES/DEMOCOPHES would be optimal for application on a global scale as regards implementation of the Minamata Convention on Mercury.

Dietary resveratrol prevents alzheimer's markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.

Dietary resveratrol prevents alzheimer's markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.

Nutritional behaviour and beliefs of ski-mountaineers: a semi-quantitative and qualitative study.

BACKGROUND: Endurance athletes are advised to optimize nutrition prior to races. Little is known about actual athletes' beliefs, knowledge and nutritional behaviour. We monitored nutritional behaviour of amateur ski-mountaineering athletes during 4 days prior to a major competition to compare it with official recommendations and with the athletes' beliefs. METHODS: Participants to the two routes of the 'Patrouille des Glaciers' were recruited (A, 26 km, ascent 1881 m, descent 2341 m, max altitude 3160 m; Z, 53 km, ascent 3994 m, descent 4090 m, max altitude 3650 m). Dietary intake diaries of 40 athletes (21 A, 19 Z) were analysed for energy, carbohydrate, fat, protein and liquid; ten were interviewed about their pre-race nutritional beliefs and behaviour. RESULTS: Despite belief that pre-race carbohydrate, energy and fluid intake should be increased, energy consumption was 2416 ± 696 (mean ± SD) kcal · day(-1), 83 ± 17 % of recommended intake, carbohydrate intake was only 46 ± 13 % of minimal recommended (10 g · kg(-1) · day(-1)) and fluid intake only 2.7 ± 1.0 l · day(-1). CONCLUSIONS: Our sample of endurance athletes did not comply with pre-race nutritional recommendations despite elementary knowledge and belief to be compliant. In these athletes a clear and reflective nutritional strategy was lacking. This suggests a potential for improving knowledge and compliance with recommendations. Alternatively, some recommendations may be unrealistic.

Osakeyhtiön varsinaisen toiminnan loppuminen ja edullisin tapa saada kiinteistöomaisuudesta tuotto

Tutkimus on tehty tilaustyönä pienelle osakeyhtiölle, jonka varsinainen toiminta loppui vuoden 2007 lopussa. Yhtiö oli lopettaessaan toiminnan velaton ja omaisuus käsitti liiketilan, kaksi asuinhuoneistoa ja käteistä. Lisäksi yhtiöllä oli elinkeinoverolain alaisia tappioita, joita ei voitu käyttää ilman toimialan muuttamista. Tutkielman päätavoitteena oli selvittää edullisin tapa saada kiinteistöomaisuudesta tuotto, kun tutkittavan osakeyhtiön varsinainen toiminta on loppunut. Edullisinta tapaa mitataan yhtiön ja osakkaan maksamien verojen jälkeen jäävänä puhtaana tuottona osakkaalle. Tutkimuksen alussa on selvitetty eri toimintavaihtoehdot yhtiön varsinaisen toiminnan loppuessa. Päävaihtoehtoina on ollut toiminnan jatkaminen ennallaan osakeyhtiön muodossa, toimialan muuttaminen sijoitusyhtiöksi, yhtiön purkaminen ja osakekannan tai omaisuuden myyminen. Jokaisesta näistä vaihtoehdosta on tutkittu niiden veroseuraamukset yhtiön ja osakkaan kannalta sekä laskettu omistajan saama puhdas tuotto. Case-yhtiön omistajalle on kannattavinta vaihtaa yhtiön toimiala kiinteistösijoittamiseksi ja jatkaa toimintaa osakeyhtiönä, jolloin yhtiö saa käyttöönsä vanhat elinkeinoverolain alaiset tappionsa. Toimialan vaihtamisessa piilee verotuksellinen riski, jonka suuruuteen voidaan vaikuttaa. Yhtiön kannattaa jakaa joka vuosi yhtiön nettovarallisuudesta yhdeksän prosenttia osinkona, joka on osingonsaajalle verovapaata. Osinkona kannattaa pääsääntöisesti jakaa ensimmäisenä käteiset varat, seuraavana in natura –osinkona asuinhuoneistot ja viimeisenä liiketila. In natura –osinko kannattaa arvostaa alihintaan, jolloin yhtiö sekä omistaja säästävät veroissa.

Urban transport governance reform in Barcelona

The unusual mixed public-private structure of the urban bus market in the metropolitan area of Barcelona provides an interesting context in which to analyze the management challenges and opportunities of the partial privatization of public services. Initiatives used by the public regulator to promote competition for contracts, such as short term concessions to private contractors and the removal of entry barriers, have considerable potential for improving efficiency and quality. The growth in the share of routes managed by private firms in recent years shows that privatization is a credible threat that may well stimulate improved performance among public managers. The type of reform implemented in Barcelona is of interest to all metropolitan areas large enough to operate under constant returns to scale regimes, and suitable for potential concessions of routes in segregated areas inside the metropolitan area, so as not to miss out on the benefits of economies of density.

Price rivalry in airline markets: A study of a successful strategy of a network carrier against a low-cost carrier

Competition in airline markets may be tough. In this context, network carriers have two alternative strategies to compete with low-cost carriers. First, they may establish a low-cost subsidiary. Second, they may try to reduce costs using the main brand. This paper examines a successful strategy of the first type implemented by Iberia in the Spanish domestic market. Our analysis of data and the estimation of a pricing equation show that Iberia has been able to charge lower prices than rivals with its low-cost subsidiary. The pricing policy of the Spanish network carrier has been particularly aggressive in less dense routes and shorter routes.

Tracking Invasion Histories in the Sea: Facing Complex Scenarios Using Multilocus Data

In recent years, new analytical tools have allowed researchers to extract historical information contained in molecular data, which has fundamentally transformed our understanding of processes ruling biological invasions. However, the use of these new analytical tools has been largely restricted to studies of terrestrial organisms despite the growing recognition that the sea contains ecosystems that are amongst the most heavily affected by biological invasions, and that marine invasion histories are often remarkably complex. Here, we studied the routes of invasion and colonisation histories of an invasive marine invertebrate Microcosmus squamiger (Ascidiacea) using microsatellite loci, mitochondrial DNA sequence data and 11 worldwide populations. Discriminant analysis of principal components, clustering methods and approximate Bayesian computation (ABC) methods showed that the most likely source of the introduced populations was a single admixture event that involved populations from two genetically differentiated ancestral regions - the western and eastern coasts of Australia. The ABC analyses revealed that colonisation of the introduced range of M. squamiger consisted of a series of non-independent introductions along the coastlines of Africa, North America and Europe. Furthermore, we inferred that the sequence of colonisation across continents was in line with historical taxonomic records - first the Mediterranean Sea and South Africa from an unsampled ancestral population, followed by sequential introductions in California and, more recently, the NE Atlantic Ocean. We revealed the most likely invasion history for world populations of M. squamiger, which is broadly characterized by the presence of multiple ancestral sources and non-independent introductions within the introduced range. The results presented here illustrate the complexity of marine invasion routes and identify a cause-effect relationship between human-mediated transport and the success of widespread marine non-indigenous species, which benefit from stepping-stone invasions and admixture processes involving different sources for the spread and expansion of their range.

Communication skills in diagnostic pathology.

Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

Ocean surface winds drive dynamics of transoceanic aerial movements

Global wind patterns influence dispersal and migration processes of aerial organisms, propagules and particles, which ultimately could determine the dynamics of colonizations, invasions or spread of pathogens. However, studying how wind-mediated movements actually happen has been hampered so far by the lack of high resolution global wind data as well as the impossibility to track aerial movements. Using concurrent data on winds and actual pathways of a tracked seabird, here we show that oceanic winds define spatiotemporal pathways and barriers for large-scale aerial movements. We obtained wind data from NASA SeaWinds scatterometer to calculate wind cost (impedance) models reflecting the resistance to the aerial movement near the ocean surface. We also tracked the movements of a model organism, the Cory's shearwater (Calonectris diomedea), a pelagic bird known to perform long distance migrations. Cost models revealed that distant areas can be connected through"wind highways" that do not match the shortest great circle routes. Bird routes closely followed the low-cost"wind-highways" linking breeding and wintering areas. In addition, we found that a potential barrier, the near surface westerlies in the Atlantic sector of the Intertropical Convergence Zone (ITCZ), temporally hindered meridional trans-equatorial movements. Once the westerlies vanished, birds crossed the ITCZ to their winter quarters. This study provides a novel approach to investigate wind-mediated movements in oceanic environments and shows that large-scale migration and dispersal processes over the oceans can be largely driven by spatiotemporal wind patterns.

Delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory IgA targeting local dendritic cells confers protective immunity.

BACKGROUND: Transmission of mucosal pathogens relies on their ability to bind to the surfaces of epithelial cells, to cross this thin barrier, and to gain access to target cells and tissues, leading to systemic infection. This implies that pathogen-specific immunity at mucosal sites is critical for the control of infectious agents using these routes to enter the body. Although mucosal delivery would ensure the best onset of protective immunity, most of the candidate vaccines are administered through the parenteral route. OBJECTIVE: The present study evaluates the feasibility of delivering the chemically bound p24gag (referred to as p24 in the text) HIV antigen through secretory IgA (SIgA) in nasal mucosae in mice. RESULTS: We show that SIgA interacts specifically with mucosal microfold cells present in the nasal-associated lymphoid tissue. p24-SIgA complexes are quickly taken up in the nasal cavity and selectively engulfed by mucosal dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-positive dendritic cells. Nasal immunization with p24-SIgA elicits both a strong humoral and cellular immune response against p24 at the systemic and mucosal levels. This ensures effective protection against intranasal challenge with recombinant vaccinia virus encoding p24. CONCLUSION: This study represents the first example that underscores the remarkable potential of SIgA to serve as a carrier for a protein antigen in a mucosal vaccine approach targeting the nasal environment.