33 research outputs found
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis
No full textMacrophages, which are abundant in the tumour microenvironment, enhance malignancy. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer
Erfolgreiches strategisches Bankenmanagement in turbulenten Zeiten – Shareholder Value Generierung im Spannungsfeld zwischen Werttreibern und regulatorischen Restriktionen
No full textVirucidal activity of three standard chemical disinfectants against Ebola virus suspended in tripartite soil and whole blood
No full textProper disinfection and inactivation of highly pathogenic viruses is an essential component of public health and prevention. Depending on environment, surfaces, and type of contaminant, various methods of disinfection must be both efficient and available. To test both established and novel chemical disinfectants against risk group 4 viruses in our maximum containment facility, we developed a standardized protocol and assessed the chemical inactivation of the two Ebola virus variants Mayinga and Makona suspended in two different biological soil loads. Standard chemical disinfectants ethanol and sodium hypochlorite completely inactivate both Ebola variants after 30 s in suspension at 70% and 0.5% v/v, respectively, concentrations recommended for disinfection by the World Health Organization. Additionally, peracetic acid is also inactivating at 0.2% v/v under the same conditions. Continued vigilance and optimization of current disinfection protocols is extremely important due to the continuous presence of Ebola virus on the African continent and increased zoonotic spillover of novel viral pathogens. Furthermore, to facilitate general pandemic preparedness, the establishment and sharing of standardized protocols is very important as it allows for rapid testing and evaluation of novel pathogens and chemical disinfectants
The vocalisations and anti-predatory behaviour of wild white-handed gibbons (Hylobates lar) in Khao Yai National Park, Thailand
No full textThe loud songs of gibbons (Hylobatidae) usually consist of a duet by the mated pair delivered each morning. These songs can transmit over a kilometre through dense forest habitat and therefore presumably play a role in long-distance communication. There is some evidence to suggest that gibbons use song in contexts other than their daily duets, such as predation, but these songs have not been well studied. Close- range communication is also relevant for gibbons, but these quieter calls have completely escaped any detailed observation.
The responses of wild white-handed gibbons (Hylobates lar) to simulated visual and acoustic predators (tiger, clouded leopard, reticulated python and crested serpent eagle) were studied in Khao Yai National Park, Thailand to address the lack of empirical data about these important events. Little is known about gibbons’ anti- predatory behaviour in general, and simulated predator encounters provided an opportunity to investigate these responses as well.
Results showed that gibbons used song as part of their anti-predator strategy and that subtle combinatorial changes were meaningful to conspecifics. They also showed marked behavioural changes in the short-term, and some evidence of longer-term changes as well. Quiet calls were also part of the gibbons’ response repertoire with the hoo call being particularly relevant. Hoos were used as a prelude to singing both normal duets and predator songs, but there were consistent differences between each context. Hoos were also delivered independently in a number of other contexts outside predation. When analysed, these hoos showed consistent contextual differences in a number of spectral parameters.
Within the duet context, important contextual subtleties were evident also revealing a remarkable vocal plasticity. In addition, gibbons voluntarily attended to specific vocal elements of other gibbon duets, indicating that certain sequences are more pertinent than others.
Results suggest both gibbon song and gibbon hoos are powerful communication tools that reliably reference external objects and events; this ability is also a critical feature of human language
Der doppelte Po und die Musik
No full textPublishedM. Gredig: Prolog – D. Andry: Chasper Pos Humor – R. Caduff: Chasper Pos rhythmische Versgestaltung: eine „hinkende Mähre“? – R. Valär: Rätoromanische Nachdichtungen chinesischer Lyrik bei Gian Fadri Caderas und Peider Lansel. Eine Spurensuche – M. Gredig: China in rätoromanischen Zeitungen, Zeitschriften und literarischen Texten – M. Eggert: Schwalbenflug in Gedichten von Li Bai und Chasper Po – T. Geissmann: Die Rolle der Gibbons beim chinesischen Dichter Li Bai – M. Winter: „Chinas Dichterfürst“. Die Rezeption Li Bais als literarischer Superstar im Westen – E. Schestag: „A most difficult man“. Ezra Pound als Übersetzer von Li Bai, mit einem Seitenblick auf Shigeyoshi Obata – O. Schröder: Chinesische Li-Bai-Vertonungen in Jahren der Unruhe – M. Gredig: Quantitative Überlegungen zum Phänomen der Li-Bai-Vertonungen im Westen. Mit Beobachtungen zu drei Vertonungen des Gedichtes Chun ye Luo cheng wen di (In einer Frühlingsnacht in Luoyang eine Flöte hören) – G. Schröder: „Die Hüften schwingen sich nun nicht mehr“. Li-Bai-Vertonungen von Komponistinnen – H. Aerni: Li-Bai-Vertonungen in der Schweiz – M. Schmidt: Übersetzung ohne Original? Gustav Mahler, Anton Webern und Li Bai – C. Haffter: Szenen der Selbstenttäuschung. Hanns Eislers Die rote und die weiße Rose nach Li Bai und die Antinomien der Kriegslyrik – T. Meyer: „Wunderlich im Spiegelbilde“. Zu einigen Vertonungen des Pavillon-Gedichts – M. Gredig: Gedanken über Li Bais Jing Ye Si (Gedanken in einer stillen Nacht) und dessen Vertonungen im Westen – M. Skamletz: „I’ve turned into a great reviser.“ Lee Hoibys Vertonung von Li Bais The River-Merchant’s Wife: A Letter und ihr möglicher Bezug zu Harry Partch – M. Skamletz: „Of course I am a weak shadow of Lee Hoiby as a Kitharist.“ Five letters by Harry Partch, 1948-1958 – M. Kilchenmann: Ben Johnstons Verhältnis zu Harry Partch und seine Three Chinese Lyrics – E. Ralli: Parallelen und Modifikationen der Notation in verschiedenen Quellen von Harry Partchs Seventeen Lyrics by Li Po. Schwierigkeiten und Transkriptionsvorschläge – C. Corey: Gesture and Intention in the Art Songs of Harry Partch – C. J. Walter: Sprechmelodie als Quelle von Melodik und Harmonik. The Intruder aus Harry Partchs Li-Bai-Vertonungen – R. Brotbeck: Der Sprechgesang bei Arnold Schönberg und Harry Partch. Eine Annäherun
Classical monocytes from patients with pancreatic ductal adenocarcinoma exhibit a significantly altered transcriptome profile compared with healthy volunteers
No full textThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the authorPancreatic Ductal Adenocarcinoma (PDAC) affects approximately 8000
people every year in the UK and is the fifth leading cause of cancer related
death. At a molecular level PDAC is characterized by a significant immune
infiltrate. Tumour-associated macrophages (TAMs) infiltrate the tumour and
contribute to a worse prognosis by promoting growth, metastasis and
resistance to chemotherapy. TAMs are derived from circulating ‘classical’
CD14++ CD16- monocytes in the peripheral blood. Current work in murine
models suggests targeting monocyte recruitment in PDAC can reduce TAM
infiltration and disease burden therefore improving survival. This project aims
to identify markers specific to monocytes from PDAC patients and to
investigate their biological relevance and potential for therapeutic
intervention.
Gene expression and metabolomics analysis was carried out on classical
CD14++ CD16- monocytes from locally advanced PDAC patients and age
matched healthy donors. Transcriptomic profiling revealed a significantly
altered gene expression profile in classical monocytes from patients and
genes with the highest fold change difference were chosen for validation
using qPCR. Validated gene targets were investigated further in vitro and
large-scale gene expression analysis from pancreatic tumours assessed.
The results from my work demonstrate that the gene expression profile of
classical monocytes from PDAC patients is significantly different compared
to healthy volunteers. Identification and validation of up-regulated genes and
their biological relevance may represent a relevant novel novel biomarker or
therapeutic strategyies to target monocytes and myeloid recruitment in
cancer.This work is funded by MedImmune (Grant number CIF1RA3R
Aftertreatment of malleolar fractures following ORIF—functional compared to protected functional in a vacuum-stabilized orthesis: a randomized controlled trial
No full text
Collaborative Delivery with Energy-Constrained Mobile Robots
No full textInternational audienceWe consider the problem of collectively delivering some message from a specified source to a designated target location in a graph, using multiple mobile agents. Each agent has a limited energy which constrains the distance it can move. Hence multiple agents need to collaborate to move the message, each agent handing over the message to the next agent to carry it forward. Given the positions of the agents in the graph and their respective budgets, the problem of finding a feasible movement schedule for the agents can be challenging. We consider two variants of the problem: in non-returning delivery, the agents can stop anywhere; whereas in returning delivery, each agent needs to return to its starting location, a variant which has not been studied before. We first provide a polynomial-time algorithm for returning delivery on trees, which is in contrast to the known (weak) NP-hardness of the non-returning version. In addition, we give resource-augmented algorithms for returning delivery in general graphs. Finally, we give tight lower bounds on the required resource augmentation for both variants of the problem. In this sense, our results close the gap left by previous research. 1998 ACM Subject Classification F.2.2 Nonnumerical Algorithms and Problem
IL-4 and retinoic acid synergistically induce regulatory dendritic cells expressing Aldh1a2
No full textAlthough activated inflammatory monocytes (IMCs) and inflammatory dendritic cells (IDCs) are potent T cell suppressors, nonactivated IMCs and IDCs promote T cell activation and Th1-Th17 cell differentiation. In this study, we investigated how to reduce the proinflammatory properties of IMCs and IDCs and further convert them into immune regulatory dendritic cells (DCs). We found that IL-4 and retinoic acid (RA) cotreatment of GM-CSF-differentiated IDCs synergistically induced the expression of aldehyde dehydrogenase family 1, subfamily A2, a rate-limiting enzyme for RA synthesis in DCs. IL-4 plus RA-treated IDCs upregulated CD103 expression and markedly reduced the production of proinflammatory cytokines upon activation. IL-4 plus RA-treated IDCs strongly induced CD4+Foxp3+ regulatory T cell differentiation and suppressed Th1 and Th17 differentiation. Mechanistically, the transcription factors Stat6 and RA receptor b play important roles in aldehyde dehydrogenase family 1, subfamily A2, induction. In addition, IL-4 and RA signaling pathways interact closely to enhance the regulatory function of treated DCs. Adoptive transfer of IL-4 plus RA-treated DCs significantly increased regulatory T cell frequency in vivo. Direct treatment with IL-4 and RA also markedly suppressed actively induced experimental autoimmune encephalomyelitis. Our data demonstrate the synergistic effect of IL-4 and RA in inducing a regulatory phenotype in IDCs, providing a potential treatment strategy for autoimmune diseases. 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