p62 at the Crossroads of Autophagy, Apoptosis, and Cancer

The signaling adaptor p62 is a multidomain protein implicated in the activation of the transcription factor NF-κB. Recent findings link p62 activity to the extrinsic apoptosis pathway, and Mathew et al. (2009) now show that the modulation of p62 by autophagy is a key factor in tumorigenesis. These findings place p62 at critical decision points that control cell death and survival

Fine-tuning the balance between crystallization and gelation and enhancement of CO2 uptake on functionalized calcium based MOFs and metallogels

The synthesis, structure, gas adsorption and catalytic properties of a new 3D porous, crystalline metal–organic framework (Ca-5TIA-MOF) as well as stable viscoelastic metallogels (Ca-5TIA-Gel) are reported. Remarkably, the preparation of both types of materials can be carried out starting from the same organic ligand (i.e. 5-(1,2,4-triazoleyl)isophthalic acid (5TIA)), divalent metal ion (i.e. Ca(II)) and organic solvent (i.e. DMF). In this particular case, the presence of water in the solvent system favors the formation of a crystalline MOF, whereas a pure organic solvent induces gelation. The characterization of the materials was carried out using a series of techniques including XRD, FT-IR, TGA, TEM, SEM, SAXS and dynamic rheology. Experimental PXRD peaks of both Ca-5TIA-xerogel and Ca-5TIA-MOF matched reasonably well with simulated PXRD, suggesting the presence of, at least, some common structural elements in the 3D networks of both xerogel and crystalline phases. Moreover, the nature of the metal counteranion was found to have a critical influence on the gelation phenomenon. To the best of our knowledge, this report describes unprecedented Ca-based LMW-metallogels, as well as the first porous Ca-based MOF, which shows adsorption capacity for CO2 at 1 atm pressure. Interestingly, Ca-5TIA-xerogel presented 20% higher CO2-uptake than the crystalline Ca-5TIA-MOF at 1 atm and 298 K. Both Ca-5TIA-MOF and Ca-5TIA-Gel also displayed a modest catalytic activity towards the hydrosilylation of benzaldehyde, with slightly better performance for the gel phase material

Decontamination of Diesel particles from air by using the Counterfog (R) system

The existence of particles with diameter under 10m in air is strongly correlated with respiratory diseases. These particles are profusely produced by heating systems, traffic, and Diesel engines creating a serious problem to modern cities. Natural mechanisms removing particles from the atmosphere are too slow to deal with the huge amount of particles daily released by human activity. The objective of this work is to measure the effectiveness of a new technology called Counterfog (R) to eliminate airborne particles. The results show that Counterfog (R) is able to wash out PM10, PM5, and PM2.5 Diesel-generated airborne particles quite efficiently.This work has been funded by the FP7-SEC-2012-1 program of the EU Commission under grant number 312804

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome-pathology correlation identified casein kinase 1ε (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients. Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA. Additionally, we were able to show that pTDP-43 itself binds RNA. CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs. Pathological TDP-43 phosphorylation is therefore, reciprocally regulated by CK1E activity and TDP-43 RNA binding. Our framework of transcriptome-pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration

Metalloproteinase-dependent TLR2 ectodomain shedding is involved in soluble toll-like receptor 2 (sTLR2) production

Toll-like receptor (TLR) 2, a type I membrane receptor that plays a key role in innate immunity, recognizes conserved molecules in pathogens, and triggering an inflammatory response. It has been associated with inflammatory and autoimmune diseases. Soluble TLR2 (sTLR2) variants have been identified in human body fluids, and the TLR2 ectodomain can negatively regulate TLR2 activation by behaving as a decoy receptor. sTLR2 generation does not involve alternative splicing mechanisms, indicating that this process might involve a post-translational modification of the full-length receptor; however, the specific mechanism has not been studied. Using CD14+ peripheral human monocytes and the THP-1 monocytic leukemia-derived cell line, we confirm that sTLR2 generation increases upon treatment with pro-inflammatory agents and requires a post-translational mechanism. We also find that the constitutive and ligand-induced release of sTLR2 is sensitive to pharmacological metalloproteinase activator and inhibitors leading us to conclude that metalloproteinase TLR2 shedding contributes to soluble receptor production. By expressing human TLR2 in ADAM10- or ADAM17-deficient MEF cells, we find both enzymes to be implicated in TLR2 ectodomain shedding. Moreover, using a deletion mutant of the TLR2 juxtamembrane region, we demonstrate that this domain is required for sTLR2 generation. Functional analysis suggests that sTLR2 generated by metalloproteinase activation inhibitsTLR2-induced cytokine production by this monocytic leukemia-derived cell line. The identification of the mechanisms involved in regulating the availability of soluble TLR2 ectodomain and cell surface receptors may contribute further research on TLR2-mediated processes in innate immunity and inflammatory disorders

Multiwavelength study of the starburst galaxy NGC7714. I: Ultraviolet-Optical spectroscopy

We have studied the physical conditions in the central 300 pc of the proto-typical starburst galaxy NGC 7714. Our analysis is based on ultraviolet spectroscopy with the HST+GHRS and ground-based optical observations.The data are interpreted using evolutionary models optimized for young starburst regions. The massive stellar population is derived in a self-consistent way using the continuum and stellar absorption lines in the ultraviolet and the nebular emission line optical spectrum. The central starburst has an age of about 4.5 Myr, with little evidence for an age spread. Wolf-Rayet features at the ultraviolet indicates a stellar population of $\sim$ 2000 Wolf-Rayet stars. The overall properties of the newly formed stars are quite similar to those derived, e.g., in 30 Doradus. A standard Salpeter IMF is consistent with all observational constraints. We find evidence for spatial structure within the central 300 pc sampled. Therefore it is unlikely that the nucleus of NGC 7714 hosts a single star cluster exceeding the properties of other known clusters. Contrary to previous suggestions, we find no evidence for a nuclear supernova rate that would significantly exceed the total disk-integrated rate. About one supernova event per century is predicted.Comment: 19 pages, 9 figures in a tar file. Accepted for publication in ApJ, 1999, March, issue 51