Apremilast,a novel PDE4 inhibitor,inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis

Introduction  

Type 4 phosphodiesterases (PDE4) play an important role in immune cells through the hydrolysis of the second messenger, cAMP. Inhibition of PDE4 has previously been shown to suppress immune and inflammatory responses, demonstrating PDE4 to be a valid therapeutic target for immune-mediated pathologies. We assessed the anti-inflammatory effects of a novel PDE4 inhibitor, apremilast, in human synovial cells from rheumatoid arthritis (RA) patients, as well as two murine models of arthritis.     

First Aegean International Conference on Molecular Recognition

This meeting report describes some of the highlights of the First Biennial Aegean International Conference on Molecular Recognition that took place in Hersonissos, Crete, Greece, between 6 and 11 June 2010. The conference comprised four sessions devoted to: dynamic and combinatorial molecular recognition; B-cell epitope prediction, synthesis and vaccines; nanotechnology approaches to molecular recognition; and host-pathogen interactions. A total of 35 oral communications and 15 posters were presented. The second Aegean International Conference on Molecular Recognition is scheduled to take place in the spring of 2012.     

Primary cilia bend LKB1 and mTOR to their will

Primary cilia are cell surface organelles that act as sensory antennae for various input signals. In a recent issue of Nature Cell Biology, Boehlke et?al. (2010) demonstrate that bending of cilia regulates cell size through a signaling pathway involving the LKB1 and mTOR kinases.     

IL-1β activation as a response to metabolic disturbances

IL-1β is a major regulator of islet inflammation in type 2 diabetes. Several factors contribute to the induction of islet-derived IL-1β, including glucose, free fatty acids, and leptin. A recent report in Nature Immunology (Masters et?al., 2010) identifies amyloid polypeptide as an additional enhancer of IL-1β production.     

Stressed-out mitochondria get MAD

Mechanisms maintaining mitochondrial integrity range from specific repair pathways to wholesale degradation of damaged organelles. A recent study in Molecular Cell (Heo et?al., 2010) adds another mechanism to this mitochondrial homeostasis toolkit: mitochondria-associated protein degradation (MAD) that ultimately directs endoplasmic reticulum-associated protein degradation (ERAD) pathway components to oxidatively stressed mitochondria.     

Structural basis for apoptosis inhibition by Epstein-Barr virus BHRF1

Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid cells, BHRF1 also binds a selective sub-set of pro-apoptotic proteins (Bid, Puma, Bak) expressed by host cells. A consequence of BHRF1 expression is marked resistance to a range of cytotoxic agents and in particular, we show that its expression renders a mouse model of Burkitt lymphoma untreatable. As current small organic antagonists of Bcl-2 do not target BHRF1, the structures of it in complex with Bim or Bak shown here will be useful to guide efforts to target BHRF1 in EBV-associated malignancies, which are usually associated with poor clinical outcomes.     

The effects of tidal advection and mixing on the statistical dispersion of zooplankton

Series of six repeated vertical Zooplankton hauls 5 min apart were made on a hourly basis during 7 h at an anchor station in the upper St. Lawrence Estuary, Québec. A hierarchical analysis of variance showed that hour-to-hour variations in numbers of most Zooplankton components were of greater magnitude than those found within 30 min or caused by counting errors.The increase of variance for increasing lengths of the sampling period was investigated using a 175 h time series of Zooplankton samples taken 30 min apart at the same location. The results show that the confidence interval of a single observation at the anchor station increases as the scale of the experiment approaches that of the main advective processes (semidiurnal tidal currents) after which it remains relatively stable. For a given sampling scale, the statistical dispersion of Zooplankton is not permanent but varies in time and space under the effects of tidal advection and mixing. These results show that, in tidal estuaries, advection phenomena are more easily recognizable than turbulence effects.     

Nitrate reductase and cytochrome bnitrate reductase structural genes as parts of the nitrate reductase operon

Summary The existence of a nitrate-reductase operon in the tryptophane region was deduced from the effects of prophage insertion in each of chl I and chl C genes and from transposition of the Mu-mediated host DNA fragments on F-prime. This operon appears to be polarized from chlC to chlI and the gene order in the region is trp-chlI-chlC-purB.