25 years of epidermal stem cell research.

This is a chronicle of concepts in the field of epidermal stem cell biology and a historic look at their development over time. The past 25 years have seen the evolution of epidermal stem cell science, from first fundamental studies to a sophisticated science. The study of epithelial stem cell biology was aided by the ability to visualize the distribution of stem cells and their progeny through lineage analysis studies. The excellent progress we have made in understanding epidermal stem cell biology is discussed in this article. The challenges we still face in understanding epidermal stem cells include defining molecular markers for stem and progenitor sub-populations, determining the locations and contributions of the different stem cell niches, and mapping regulatory pathways of epidermal stem cell proliferation and differentiation. However, our rapidly evolving understanding of epidermal stem cells has many potential uses that promise to translate into improved patient therapy

Phenotypic and Functional Characterization of Human Mammary Stem/Progenitor Cells in Long Term Culture

Background: Cancer stem cells exhibit close resemblance to normal stem cells in phenotype as well as function. Hence, studying normal stem cell behavior is important in understanding cancer pathogenesis. It has recently been shown that human breast stem cells can be enriched in suspension cultures as mammospheres. However, little is known about the behavior of these cells in long-term cultures. Since extensive self-renewal potential is the hallmark of stem cells, we undertook a detailed phenotypic and functional characterization of human mammospheres over long-term passages. Methodology: Single cell suspensions derived from human breast `organoids' were seeded in ultra low attachment plates in serum free media. Resulting primary mammospheres after a week (termed T1 mammospheres) were subjected to passaging every 7th day leading to the generation of T2, T3, and T4 mammospheres. Principal Findings: We show that primary mammospheres contain a distinct side-population (SP) that displays a CD24(low)/CD44(low) phenotype, but fails to generate mammospheres. Instead, the mammosphere-initiating potential rests within the CD44(high)/CD24(low) cells, in keeping with the phenotype of breast cancer-initiating cells. In serial sphere formation assays we find that even though primary (T1) mammospheres show telomerase activity and fourth passage T4 spheres contain label-retaining cells, they fail to initiate new mammospheres beyond T5. With increasing passages, mammospheres showed an increase in smaller sized spheres, reduction in proliferation potential and sphere forming efficiency, and increased differentiation towards the myoepithelial lineage. Significantly, staining for senescence-associated beta-galactosidase activity revealed a dramatic increase in the number of senescent cells with passage, which might in part explain the inability to continuously generate mammospheres in culture. Conclusions: Thus, the self-renewal potential of human breast stem cells is exhausted within five in vitro passages of mammospheres, suggesting the need for further improvisation in culture conditions for their long-term maintenance

Developing a framework for assessing respiratory sensitization: A workshop report

Respiratory tract sensitization can have significant acute and chronic health implications. While induction of respiratory sensitization is widely recognized for some chemicals, validated standard methods or frameworks for identifying and characterizing the hazard are not available. A workshop on assessment of respiratory sensitization was held to discuss the current state of science for identification and characterization of respiratory sensitizer hazard, identify information facilitating development of validated standard methods and frameworks, and consider the regulatory and practical risk management needs. Participants agreed on a predominant Th2 immunological mechanism and several steps in respiratory sensitization. Some overlapping cellular events in respiratory and skin sensitization are well understood, but full mechanism(s) remain unavailable. Progress on non-animal approaches to skin sensitization testing, ranging from in vitro systems, –omics, in silico profiling, and structural profiling were acknowledged. Addressing both induction and elicitation phases remains challenging. Participants identified lack of a unifying dose metric as increasing the difficulty of interpreting dosimetry across exposures. A number of research needs were identified, including an agreed list of respiratory sensitizers and other asthmagens, distinguishing between adverse effects from immune-mediated versus non immunological mechanisms. A number of themes emerged from the discussion regarding future testing strategies, particularly the need for a tiered framework respiratory sensitizer assessment. These workshop present a basis for moving towards a weight-of-evidence assessment

Modeling the Future California Electricity Grid and Renewable Energy Integration with Electric Vehicles

This study focuses on determining the impacts and potential value of unmanaged and managed uni-directional and bi-directional charging of plug-in electric vehicles (PEVs) to integrate intermittent renewable resources in California in the year 2030. The research methodology incorporates the utilization of multiple simulation tools including V2G-SIM, SWITCH, and GridSim. SWITCH is used to predict a cost-effective generation portfolio to meet the renewable electricity goals of 60% in California by 2030. PEV charging demand is predicted by incorporating mobility behavior studies and assumptions charging infrastructure and vehicle technology improvements. Finally, the production cost model GridSim is used to quantify the impacts of managed and unmanaged vehicle-charging demand to electricity grid operations. The temporal optimization of charging sessions shows that PEVs can mitigate renewable oversupply and ramping needs substantially. The results show that 3.3 million PEVs can mitigate over-generation by ~4 terawatt hours in California—potentially saving the state up to about USD 20 billion of capital investment costs in stationary storage technologies

La déshumanisation dans un contexte organisationnel : examen de ses antécédents et de son impact sur le burnout professionnel

Dans notre société actuelle contrôlée par le capitalisme et la recherche de productivité, l’organisation considère parfois l’individu comme une propriété ou une ressource qu’elle peut utiliser à ses fins, plutôt que comme une personne qui pense, ressent et possède des désirs et buts individuels. Toutefois, certains supérieurs et certaines organisations sont particulièrement sensibles au bien-être de leurs employés. Le présent mémoire a ainsi pour objectif d’étudier la déshumanisation dans un contexte organisationnel, en examinant ses antécédents (à savoir le traitement par les membres de l’organisation et le soutien organisationnel perçu) et ses conséquences en termes de bien-être au travail (à savoir l’épuisement professionnel et le cynisme). Par ailleurs, l’étude vise également à analyser l’effet modérateur de la représentation de l’organisation par le supérieur, sur la relation entre le traitement par les membres de l’organisation et le soutien organisationnel perçu. La première partie du mémoire présente les théories et études empiriques existantes dans la littérature et permettant d’expliquer la formulation de nos six hypothèses de recherche. La seconde partie du mémoire, quant à elle, présente notre recherche menée sur le terrain et les résultats par rapport aux hypothèses émises. Ceux-ci ont été obtenus par le moyen de questionnaires électroniques, diffusés via notre réseau et dans deux entreprises du secteur privé. Les résultats de la recherche indiquent que le support perçu du supérieur entretient une relation négative avec la déshumanisation organisationnelle par le biais du soutien organisationnel perçu. En outre, la représentation de l’organisation par le supérieur a un effet modérateur sur la relation entre le support perçu du supérieur et le soutien organisationnel perçu, l’effet entre ces variables étant d’autant plus fort que le supérieur représente plus fortement son organisation. Toutefois, le leadership éthique semble avoir un impact sur la déshumanisation organisationnelle seulement de manière indirecte, et son effet avec la représentation de l’organisation par le supérieur sur le soutien organisationnel perçu, n’a pas pu être confirmé. Enfin, la déshumanisation organisationnelle permet d’expliquer la relation entre le soutien organisationnel perçu et le bien-être des travailleurs (en termes d’épuisement professionnel et de cynisme). Le mémoire s’achève ensuite par une interprétation des résultats obtenus, une discussion autour des limites de notre étude, des suggestions de pistes pour de futures recherches, des conseils d’implications pratiques et par une conclusion générale.Master [120] en sciences psychologiques, Université catholique de Louvain, 201

Allergic inflammation in the upper respiratory tract of the rat upon repeated inhalation exposure to the contact allergen dinitrochlorobenzene (DNCB).

Previously, the contact allergen dinitrochlorobenzene (DNCB) was identified as a sensitizer by inhalation in BALB/c mice; in addition, DNCB induced a lymphocytic infiltrate in the larynx of dermally sensitized Th1-prone Wistar rats upon a single inhalation challenge. In the present study, repeated inhalation exposures to DNCB were investigated using the same protocol as the single-challenge study: female Wistar rats were dermally sensitized with DNCB and subsequently challenged by inhalation exposure to 7 or 15 mg/m(3) DNCB twice a week for 4 weeks. Allergy-related apnoeic breathing was not observed. DNCB-specific IgG antibodies were found in the serum and--predominantly lymphocytic--inflammations were found in the nasal tissues and larynx. Similar effects were observed in animals repeatedly exposed by inhalation without previous dermal contact, indicating sensitization by inhalation. The inflammation may be the upper respiratory tract analogue of hypersensitivity pneumonitis/allergic alveolitis. Possible progression of the airway inflammation upon long-term exposure should be investigated to support or dismiss discrimination between contact and respiratory allergens in relation to respiratory allergy. (c) 2010 Elsevier Ireland Ltd. All rights reserved

Inventarisatie van toepassingen van chroom-6 op de werkplek

Afgelopen jaren was er veel aandacht voor mogelijke blootstelling aan chroom-6 en de schadelijke effecten daarvan op de gezondheid van werknemers. Chroom-6 verbindingen zijn in verschillende materialen en producten terug te vinden. De stof beschermt namelijk tegen roestvorming en andere vormen van verwering van de ondergrond waarop hij is aangebracht. In Nederland kunnen mensen op de werkplek nog steeds aan chroom-6 worden blootgesteld. Het RIVM heeft daarom de toepassingen van en blootstelling aan chroom-6 voor werknemers in Nederland geïnventariseerd. Dat is in opdracht van het ministerie van Sociale Zaken en Werkgelegenheid (SZW) gedaan. Chroom-6 wordt veel gebruikt om de oppervlakten van metalen en plastics te behandelen, zoals hardverchromen en decoratief verchromen. Op beperkte schaal komt chroom-6 ook voor in primers en coatings, bijvoorbeeld voor specifieke toepassingen in de luchtvaart industrie. Voor bepaalde producten, zoals cement en leer, geldt een wettelijk maximum voor de hoeveelheid chroom-6 dat ze mogen bevatten. Toch is het niet uitgesloten dat werknemers tijdens het productieproces of het gebruik van deze producten, aan chroom-6 blootgesteld kunnen worden. Verder kan het gebruik van chroom-6 vanuit het verleden op dit moment nog blootstelling aan chroom-6 veroorzaken. Bijvoorbeeld bij het schuren of stralen van oude verflagen of het verzagen van met chroom-6 verduurzaamd hout. Dat kan ook bij hoogenergetische bewerkingen van chroomhoudende materialen, zoals lassen. Uit de inventarisatie blijkt ook dat er de laatste jaren meer aandacht is voor de gezondheidseffecten en de risico's die blootstelling aan deze stof met zich meebrengt. Hierdoor zijn onder andere werkgevers zich bewuster van risico's en bevorderen zij maatregelen om veilig met chroom-6 te werken