iPLA2β: front and center in human monocyte chemotaxis to MCP-1

Monocyte chemoattractant protein-1 (MCP-1) directs migration of blood monocytes to inflamed tissues. Despite the central role of chemotaxis in immune responses, the regulation of chemotaxis by signal transduction pathways and their in vivo significance remain to be thoroughly deciphered. In this study, we examined the intracellular location and functions of two recently identified regulators of chemotaxis, Ca2+-independent phospholipase (iPLA2β) and cytosolic phospholipase (cPLA2α), and substantiate their in vivo importance. These enzymes are cytoplasmic in unstimulated monocytes. Upon MCP-1 stimulation, iPLA2β is recruited to the membrane-enriched pseudopod. In contrast, cPLA2α is recruited to the endoplasmic reticulum. Although iPLA2β or cPLA2α antisense oligodeoxyribonucleotide (ODN)–treated monocytes display reduced speed, iPLA2β also regulates directionality and actin polymerization. iPLA2β or cPLA2α antisense ODN–treated adoptively transferred mouse monocytes display a profound defect in migration to the peritoneum in vivo. These converging observations reveal that iPLA2β and cPLA2α regulate monocyte migration from different intracellular locations, with iPLA2β acting as a critical regulator of the cellular compass, and identify them as potential targets for antiinflammatory strategies

Establishment of the Coast Range ophiolite microbial observatory (CROMO): Drilling objectives and preliminary outcomes

Abstract. This project aimed to establish a subsurface microbial observatory in ultramafic rocks, by drilling into an actively serpentinizing peridotite body, characterizing cored rocks, and outfitting the boreholes for a program of long-term observation and experimentation to resolve the serpentinite-hosted subsurface biosphere. We completed drilling in August 2011, drilling two boreholes with core recovery and possibility for down-hole experimentation, and six smaller-diameter monitoring wells arrayed around the two primary holes, in the Coast Range ophiolite (CRO) locality in the UC-Davis McLaughlin Natural Reserve, Lower Lake, CA. Every effort was made during drilling to keep the cores and wells as free of drilling-induced contamination as possible: clean, purified water was used as drilling fluid, fluorescent microbead tracers were suspended in that water for quantification of drilling fluid penetration into the cores, and high resolution next generation sequencing approaches were used to characterize the microbial populations in the drill fluids and core materials. In December 2011, we completed installation of well pumps (slow flow bladder pumps) in the monitoring wells, and have deployed a set of in situ incubation experiments in the two uncased boreholes. Preliminary findings illustrate natural variability in actively serpentinizing strata, and confirm distinct groundwater flow regimes and microbial ecosystems in (a) shallow, surface-impacted soil water horizons and (b) deeper, ultramafic bedrock-sourced formation fluids

Structural insights on TRPV5 gating by endogenous modulators.

TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery

The Sarmatian/Pannonian boundary at the western margin of the Vienna Basin (City of Vienna, Austria)

Abstract Sarmatian and Pannonian cores, drilled at the western margin of the Vienna Basin in the City of Vienna, reveal a complex succession of marine and lacustrine depositional environments during the middle to late Miocene transition. Two Sarmatian and two Pannonian transgressive-regressive sequences were studied in detail. Identical successions of benthic faunal assemblages and similar patterns in magnetic susceptibility logs characterise these sequences. This allows a correlation of the boreholes over a distance of ~3.5 km across one of the major marginal faults of the Vienna Basin. Biostratigraphic data, combined with rough estimates of sedimentation rates, reveal large gaps between these sequences, suggesting that only major transgressions reached this marginal area. In particular, during the Sarmatian-Pannonian transition, the basin margin completely emerged and turned into a terrestrial setting for at least 600 ka

Nontrivial Polydispersity Exponents in Aggregation Models

We consider the scaling solutions of Smoluchowski's equation of irreversible aggregation, for a non gelling collision kernel. The scaling mass distribution f(s) diverges as s^{-tau} when s->0. tau is non trivial and could, until now, only be computed by numerical simulations. We develop here new general methods to obtain exact bounds and good approximations of $\tau$. For the specific kernel KdD(x,y)=(x^{1/D}+y^{1/D})^d, describing a mean-field model of particles moving in d dimensions and aggregating with conservation of ``mass'' s=R^D (R is the particle radius), perturbative and nonperturbative expansions are derived. For a general kernel, we find exact inequalities for tau and develop a variational approximation which is used to carry out the first systematic study of tau(d,D) for KdD. The agreement is excellent both with the expansions we derived and with existing numerical values. Finally, we discuss a possible application to 2d decaying turbulence.Comment: 16 pages (multicol.sty), 6 eps figures (uses epsfig), Minor corrections. Notations improved, as published in Phys. Rev. E 55, 546

Scaling laws and vortex profiles in 2D decaying turbulence

We use high resolution numerical simulations over several hundred of turnover times to study the influence of small scale dissipation onto vortex statistics in 2D decaying turbulence. A self-similar scaling regime is detected when the scaling laws are expressed in units of mean vorticity and integral scale, as predicted by Carnevale et al., and it is observed that viscous effects spoil this scaling regime. This scaling regime shows some trends toward that of the Kirchhoff model, for which a recent theory predicts a decay exponent $\xi=1$. In terms of scaled variables, the vortices have a similar profile close to a Fermi-Dirac distribution.Comment: 4 Latex pages and 4 figures. Submitted to Phys. Rev. Let