Ursus spelaeus del Pleistoceno Superior y fauna asociada de Loutraki (Pella, Macedonia, Grecia): excavaciones de 1999

[Abstract] The large mammal assemblage from the bear-cave A in Loutraki, Pella, Macedonia, Greece, mostly very well preserved, is described and analysed. Among Ursus spelaeus remains, other large mammalian faunal remains, found up to 1999 (the excavation is still in progress) in association with the cave-bears belong to: Crocuta spelaea , Panthera pardus , Vulpes vulpes , Capra ibex , Dama s p . One pyrite artefact, found also in association with the ursid remains, adds great interest to this site. The preliminary study showed the predominant presence of the cave-bear, while only very few specimens represent other animals. The presence of abundant deciduous bear teeth, in spite of their fragility, is remarkable. On some bones there are carnivore trace, either of other ursids or scavengers. The taphonomical approach would show interesting results

Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity

Trained innate immunity, induced via modulation of mature myeloid cells or their bone marrow progenitors, mediates sustained increased responsiveness to secondary challenges. Here, we investigated whether anti-tumor immunity can be enhanced through induction of trained immunity. Pre-treatment of mice with beta-glucan, a fungal-derived prototypical agonist of trained immunity, resulted in diminished tumor growth. The anti-tumor effect of beta-glucan-induced trained immunity was associated with transcriptomic and epigenetic rewiring of granulopoiesis and neutrophil reprogramming toward an anti-tumor phenotype; this process required type I interferon signaling irrespective of adaptive immunity in the host. Adoptive transfer of neutrophils from beta-glucan-trained mice to naive recipients suppressed tumor growth in the latter in a ROS-dependent manner. Moreover, the anti-tumor effect of beta-glucan-induced trained granulopoiesis was transmissible by bone marrow transplantation to recipient naive mice. Our findings identify a novel and therapeutically relevant anti-tumor facet of trained immunity involving appropriate rewiring of granulopoiesis

IL-1β Promotes TGF-β1 and IL-2 Dependent Foxp3 Expression in Regulatory T Cells

Earlier, we have shown that GM-CSF-exposed CD8α− DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1β can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1β on Foxp3 expression in T cells when activated in the presence and absence of DCs. Exogenous IL-12 abolished, but IL-1β enhanced, the ability of GM-CSF-exposed tolerogenic DCs to promote Foxp3 expression. Pre-exposure of DCs to IL-1β and IL-12 had only a modest effect on Foxp3− expressing T cells; however, T cells activated in the absence of DCs but in the presence of IL-1β or IL-12 showed highly significant increase and decrease in Foxp3+ T cell frequencies respectively suggesting direct effects of these cytokines on T cells and a role for IL-1β in promoting Foxp3 expression. Importantly, purified CD4+CD25+ cells showed a significantly higher ability to maintain Foxp3 expression when activated in the presence of IL-1β. Further analyses showed that the ability of IL-1β to maintain Foxp3 expression in CD25+ T cells was dependent on TGF-β1 and IL-2 expression in Foxp3+Tregs and CD25− effectors T cells respectively. Exposure of CD4+CD25+ T cells to IL-1β enhanced their ability to suppress effector T cell response in vitro and ongoing experimental autoimmune thyroidits in vivo. These results show that IL-1β can help enhance/maintain Tregs, which may play an important role in maintaining peripheral tolerance during inflammation to prevent and/or suppress autoimmunity

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

An investigation of the significance of subjectivity in the context of discounted cash flow hotel valuations

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Beiträge zur Morphologie und Entwicklung des Semipoljes Amvrakia (Limni Amvrakia), Westgriechenland. Contributions to the Morphology and Development of the Semipolje Lake Amvrakia (Limni Amvrakia), Western Greece

Lake Amvrakia is judged by the authors to be a semipolje. Chalky formations 1—5 m above present water level indicate that formerly the level was higher. Copyright © 1978 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinhei

Stakeholders' perceptions of the DCF method in hotel valuations

The main stakeholder of any valuation is the commissioning party and the outcome of the valuation process will determine for the commissioning party the value of the asset. The second key stakeholder is the valuer. Often, however, there is third stakeholder group, the lending institution. Lending institutions often provide financing to the buyer and the financing decision is often based on the hotel's valuation. Based on a questionnaire survey of hotel valuation stakeholders this study reports the findings as to the perceived suitability of the discounted cash flow (DCF) valuations in respect of hotel property. The findings reported here suggest that the majority of respondents supported the view that the DCF method was the most suitable method in relation to hotel valuations. However, there are indications that the recommended practice of the need for using supporting valuation approaches might not be widely observed or understood. In addition, there was a view among a significant minority of respondents that the DCF method was only applicable for those properties operating at the higher market levels