Legionella pneumophila strain 130b evades macrophage cell death independent of the effector SidF in the absence of flagellin

International audienceThe human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF. In the absence of SidF, L. pneumophila was able to replicate, cause loss of mitochondria membrane potential, kill macrophages, and establish infections in lungs of mice. Consistent with this, deletion of BNIP3 and BCL-RAMBO did not affect intracellular L. pneumophila replication, macrophage death rates, and in vivo bacterial virulence. Abrogating mitochondrial cell death by genetic deletion of the effectors of intrinsic apoptosis, BAX, and BAK, or the regulator of mitochondrial permeability transition pore formation, cyclophilin-D, did not affect bacterial growth or the initial killing of macrophages. Loss of BAX and BAK only marginally limited the ability of L. pneumophila to efficiently kill all macrophages over extended periods. L. pneumophila induced killing of macrophages was delayed in the absence of capsase-11 mediated pyroptosis. Together, our data demonstrate that L. pneumophila evades host cell death responses independently of SidF during replication and can induce pyroptosis to kill macrophages in a timely manner

COX-2 in the neurodegenerative process of Parkinson's disease

Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.Peer reviewedPublisher PD

Online support system for students in higher education: Proof-of-concept study

Background: Providing support to the increasing numbers of students facing mental health difficulties in higher education (HE) can be difficult due to stigma or lack of resources. Alternative and/or complementary sources of support are needed, such as online interventions that are recognised for their therapeutic value and cost-effectiveness. Objectives: We aim to provide evidence supporting the conceptual and practical value of a newly developed online multimedia intervention system for HE students who face mild to moderate symptoms of anxiety and depression and study-skills difficulties. Methods: Students from five universities were invited to participate in a cross-sectional proof-of-concept study. Students were invited through the universities' internal communication channels. Following demonstration of each part of the system, students completed a survey with quantitative and qualitative questions. Results: Response was largely positive. Positive responses on the features of the questionnaire ranged between 65% and 86%; on the features of the workshops ranged between 57% and 91%; on 'My place' ranged between 65% and 79%; on the animated videos ranged between 79% and 92%; and on the overall system ranged between 78% and 89%. Participants indicated areas for improvement and ways in which such improvement could be accomplished; these then guided the development of the system. Conclusions: The results confirm the need for such a system. It can complement student support services (SSS) by dealing with cases with mild to moderate difficulties, hence allowing SSS to prioritise and effectively address more severe cases. Potentially this method can provide a meaningful alternative to SSS; this is worth investigating further

JNK signalling in cancer: In need of new, smarter therapeutic targets

Copyright © 2013 The British Pharmacological Society. This is the accepted version of the following article: Bubici, C. and Papa, S. (2014), JNK signalling in cancer: in need of new, smarter therapeutic targets. British Journal of Pharmacology, 171: 24–37, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/bph.12432/abstract.The JNKs are master protein kinases that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival and death. It is increasingly apparent that persistent activation of JNKs is involved in cancer development and progression. Therefore, JNKs represent attractive targets for therapeutic intervention with small molecule kinase inhibitors. However, evidence supportive of a tumour suppressor role for the JNK proteins has also been documented. Recent studies showed that the two major JNK proteins, JNK1 and JNK2, have distinct or even opposing functions in different types of cancer. As such, close consideration of which JNK proteins are beneficial targets and, more importantly, what effect small molecule inhibitors of JNKs have on physiological processes, are essential. A number of ATP-competitive and ATP-non-competitive JNK inhibitors have been developed, but have several limitations such as a lack of specificity and cellular toxicity. In this review, we summarize the accumulating evidence supporting a role for the JNK proteins in the pathogenesis of different solid and haematological malignancies, and discuss many challenges and scientific opportunities in the targeting of JNKs in cancer.Kay Kendall Leukemia Fund, Italian Association for Cancer Research and Foundation for Liver Research

Cizay-la-Madeleine – Abbaye Notre-Dame-d’Asnières

La réalisation d’un drain au nord de l’église abbatiale d’Asnières, fondée au xiie s. par Bernard de Tiron, a été précédée d’une fouille (2 x 60 m). Quelques sondages archéologiques sont venus la compléter pour mieux cerner l’état de conservation des vestiges archéologiques. L’emplacement du cimetière de la communauté n’a pas été retrouvé avec certitude dans le secteur au nord de l’abbaye. Toutefois, les vestiges de deux états successifs d’une construction sur poteaux de bois avec foyer adoss..

Angers – Abbaye Saint-Aubin, place Michel-Debré

Le projet d’édifier de nouveaux locaux par le Conseil général de Maine-et-Loire a fait l’objet d’un diagnostic anticipé dans la partie orientale du parc de l’ancienne abbaye Saint-Aubin bordant le boulevard du Maréchal-Foch. La promenade arborée, surélevée de plus de 3 m au-dessus de l’environnement, est créée lors de la réalisation du parc de la préfecture qui est terminé en 1840. Les occupations anciennes de ce secteur se développent sur une hauteur totale de 5,6 m. Le rempart de la ville a..

HUBUNGAN DUKUNGAN KELUARGA DENGAN TINGKAT DEPRESI PADA NARAPIDANA NAPZA DI RUTAN KELAS IIB KAJHU ACEH BESAR

Banda Ace

Brissac-Quincé, Saint-Jean-des-Mauvrets – Carrefour Saint-Anne (RD748)

La création d’un échangeur sur la RD748 au niveau du carrefour de Sainte-Anne n’a révélé aucun vestige archéologique sur les 2 ha de l’emprise. Les moulins caviers, attestés pour une partie d’entre-eux dès la fin du xviie s., étaient déjà démolis jusqu’au rocher lors de notre intervention en avril 2010