Why The Dreyfus Affair Matters

Novelist and lawyer Louis Begley, author of Wartime Lies, About Schmidt, and Matters of Honor, presents his book Why the Dreyfus Affair Matters (Yale University Press, 2009). Begley investigates the abuses of judicial and military power that led to the persecution of Dreyfus for treason in 1894 and caused bitter divisions in French society for years afterward. His study sheds new light on the Affair and makes clear its continuing significance for contemporary American legal and political debates. To download a podcast of the lecture, choose one of the additional files below. To view the event poster, select the Download button at upper right

Bile acids destabilise HIF-1a and promote anti-tumour phenotypes in cancer cell models.

BACKGROUND: The role of the microbiome has become synonymous with human health and disease. Bile acids, as essential components of the microbiome, have gained sustained credibility as potential modulators of cancer progression in several disease models. At physiological concentrations, bile acids appear to influence cancer phenotypes, although conflicting data surrounds their precise physiological mechanism of action. Previously, we demonstrated bile acids destabilised the HIF-1a subunit of the Hypoxic-Inducible Factor-1 (HIF-1) transcription factor. HIF-1 overexpression is an early biomarker of tumour metastasis and is associated with tumour resistance to conventional therapies, and poor prognosis in a range of different cancers. METHODS: Here we investigated the effects of bile acids on the cancer growth and migratory potential of cell lines where HIF-1a is known to be active under hypoxic conditions. HIF-1a status was investigated in A-549 lung, DU-145 prostate and MCF-7 breast cancer cell lines exposed to bile acids (CDCA and DCA). Cell adhesion, invasion, migration was assessed in DU-145 cells while clonogenic growth was assessed in all cell lines. RESULTS: Intracellular HIF-1a was destabilised in the presence of bile acids in all cell lines tested. Bile acids were not cytotoxic but exhibited greatly reduced clonogenic potential in two out of three cell lines. In the migratory prostate cancer cell line DU-145, bile acids impaired cell adhesion, migration and invasion. CDCA and DCA destabilised HIF-1a in all cells and significantly suppressed key cancer progression associated phenotypes; clonogenic growth, invasion and migration in DU-145 cells. CONCLUSIONS: These findings suggest previously unobserved roles for bile acids as physiologically relevant molecules targeting hypoxic tumour progression

Gut microbiota functions: metabolism of nutrients and other food components

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays

Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof

Risk to human health related to the presence of perfluoroalkyl substances in food

Acknowledgements: The Panel wishes to thank the following for their support provided to this scientific output as Hearing experts: Klaus Abraham, Esben Budtz-Jørgensen, Tony Fletcher, Philippe Grandjean, Hans Mielke and Hans Rumke and EFSA staff members: Davide Arcella, Marco Binaglia, Petra Gergelova, Elena Rovesti and Marijke Schutte. The Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output. The Panel would also like to thank the following authors and co-authors for providing additional information in relation to their respective studies: Berit Granum, Margie M Peden-Adams, Thomas Webster.Peer reviewedPublisher PD

About Schmidt/ Begley

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Heidelberger Poetikdozentur 2006 - Louis Begley: Between Facts and Fiction

Als erster Roman Louis Begleys erschien 1990 der vielfach ausgezeichnete Bestseller "War Time Lies", der die Geschichte eines dem Holocaust entkommenen jüdischen Jungen erzählt. Es folgten anschließend die Romane "The Man", "Who Was Late", "As Max Saw It" und "About Schmidt". Der letztgenannte Titel war die Romanvorlage für den gleichnamigen Hollywood-Film mit Jack Nicholson in der Hauptrolle. Von 1993 bis 1995 war Louis Begley Präsident des Amerikanischen P.E.N.-Zentrums. Der Schriftsteller hat sich durch seinen so sorgfältig-prägnanten wie geistreichen Stil eine herausragende Position in der amerikanischen Erzählliteratur erschrieben. Die Themen, die Metaphorik und die erzählerische Eleganz seiner Romane erinnern an Henry James, Marcel Proust und Thomas Mann. Im Frühjahr 2007 wird der aktuelle Roman "Matters of Honor" in deutscher Übersetzung im Suhrkamp Verlag erscheinen. Louis Begley, der 1933 in Polen geboren wurde, konnte dem Holocaust entkommen und zog nach dem Zweiten Weltkrieg mit seiner Familie in die Vereinigten Staaten; 1953 wurde er amerikanischer Staatsbürger. Mit der Unterstützung eines Stipendiums studierte er zunächst Englische Literatur an der Harvard Universität. Nach seiner Göttinger Militärzeit kehrte er nach Harvard zurück und machte seinen Abschluss als Anwalt. Bis in die neunziger Jahre arbeitete Begley in der New Yorker Großkanzlei Debevoise & Plimpton zunächst als Mitarbeiter, dann als Teilhaber. Teil 1: Eröffnung der Poetik-Dozentur, Donnerstag, 16. November 2006 in der Alten Aula der Universität, Einführung durch Prof. Dr. Helmuth Kiesel Teil 2: Between Facts and Fiction (1) Autobiography or Novel: Fact or Fiction?, Donnerstag, 16. November 2006 Teil 3: Between Facts and Fiction (2) A Story is Born: Epithalamion 2004: A Fable, Donnerstag, 23. November 2006 Teil 4: Between Facts and Fiction (3) Leaving Well Enough Alone, Donnerstag, 30. November 2006 Digital Video & Bildkonzeption: Klaus Kirchner, Medienzentrum des URZ Heidelberger Poetik-Dozentur: PD Dr. Michaela Kopp-Marx Sylvia Piotrowski Germanistisches Semina

Lipid-containing lubricants for dry eye: A systematic review

10.1097/OPX.0b013e31826f32e0Optometry and Vision Science89111654-1661OVSC