The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice

Objective and designCystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury.Materials and methodsCFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response.ResultsPharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution.ConclusionsLack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury

Environmental metabarcoding reveals contrasting belowground and aboveground fungal communities from poplar at a Hg phytomanagement site

Characterization of microbial communities in stressful conditions at a field level is rather scarce, especially when considering fungal communities from aboveground habitats. We aimed at characterizing fungal communities from different poplar habitats at a Hg-contaminated phytomanagement site by using Illumina-based sequencing, network analysis approach, and direct isolation of Hg-resistant fungal strains. The highest diversity estimated by the Shannon index was found for soil communities, which was negatively affected by soil Hg concentration. Among the significant correlations between soil operational taxonomic units (OTUs) in the co-occurrence network, 80% were negatively correlated revealing dominance of a pattern of mutual exclusion. The fungal communities associated with Populus roots mostly consisted of OTUs from the symbiotic guild, such as members of the Thelephoraceae, thus explaining the lowest diversity found for root communities. Additionally, root communities showed the highest network connectivity index, while rarely detected OTUs from the Glomeromycetes may have a central role in the root network. Unexpectedly high richness and diversity were found for aboveground habitats, compared to the root habitat. The aboveground habitats were dominated by yeasts from the Lalaria, Davidiella, and Bensingtonia genera, not detected in belowground habitats. Leaf and stem habitats were characterized by few dominant OTUs such as those from the Dothideomycete class producing mutual exclusion with other OTUs. Aureobasidium pullulans, one of the dominating OTUs, was further isolated from the leaf habitat, in addition to Nakazawaea populi species, which were found to be Hg resistant. Altogether, these findings will provide an improved point of reference for microbial research on inoculation-based programs of tailings dumps

Integrative genetic map of repetitive DNA in the sole Solea senegalensis genome shows a Rex transposon located in a proto-sex chromosome

Repetitive sequences play an essential role in the structural and functional evolution of the genome, particularly in the sexual chromosomes. The Senegalese sole (Solea senegalensis) is a valuable flatfish in aquaculture albeit few studies have addressed the mapping and characterization of repetitive DNA families. Here we analyzed the Simple Sequence Repeats (SSRs) and Transposable elements (TEs) content from fifty-seven BAC clones (spanning 7.9 Mb) of this species, located in chromosomes by multiple fluorescence in situ hybridization (m-BAC-FISH) technique. The SSR analysis revealed an average density of 675.1 loci per Mb and a high abundance (59.69%) of dinucleotide coverage was observed, being 'AC' the most abundant. An SSR-FISH analysis using eleven probes was also carried out and seven of the 11 probes yielded positive signals. 'AC' probes were present as large clusters in almost all chromosomes, supporting the bioinformatic analysis. Regarding TEs, DNA transposons (Class II) were the most abundant. In Class I, LINE elements were the most abundant and the hAT family was the most represented in Class II. Rex/Babar subfamily, observed in two BAC clones mapping to chromosome pair 1, showed the longest match. This chromosome pair has been recently reported as a putative sexual proto-chromosome in this species, highlighting the possible role of the Rex element in the evolution of this chromosome. In the Rex1 phylogenetic tree, the Senegalese sole Rex1 retrotransposon could be associated with one of the four major ancient lineages in fish genomes, in which it is included O. latipes

TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells

Lipopolysaccharides (LPS), the major components of the wall of gram-negative bacteria, trigger powerful defensive responses in the airways via mechanisms thought to rely solely on the Toll-like receptor 4 (TLR4) immune pathway. Here we show that airway epithelial cells display an increase in intracellular Ca2+ concentration within seconds of LPS application. This response occurs in a TLR4-independent manner, via activation of the transient receptor potential vanilloid 4 cation channel (TRPV4). We found that TRPV4 mediates immediate LPS-induced increases in ciliary beat frequency and the production of bactericidal nitric oxide. Upon LPS challenge TRPV4-deficient mice display exacerbated ventilatory changes and recruitment of polymorphonuclear leukocytes into the airways. We conclude that LPS-induced activation of TRPV4 triggers signaling mechanisms that operate faster and independently from the canonical TLR4 immune pathway, leading to immediate protective responses such as direct antimicrobial action, increase in airway clearance, and the regulation of the inflammatory innate immune reaction.B.B. was funded by a Ph.D. grant of the Agency for Innovation by Science and Technology (IWT). Research was supported by grants from the Belgian Federal Government (IUAP P7/13), the FWO (G.0702.12, 1.5.068.16 N) and the Research Council of the KU Leuven (Grants GOA/14/011 and PF-TRPLe), the Spanish Ministry of Economy and Competitiveness (SAF2015-69762-R and María de Maeztu Programme for Units of Excellence in R&D MDM-2014-0370), Fondo de Investigación Sanitaria (RD12/0042/0014), and the FEDER Fund

Eocambrian—Cambrian palaeomagnetism of the Armorican Massif, France

In an attempt to clarify pre-Hercynian continental configurations, palaeomagnetic data were collected from the spilites de Paimpol (640 ± 12 Myr), the diorite de St Quay (583 ± 40 Myr), the gabbro de Keralain (undated), the granite de Port-Scarff (557 ± 16 Myr), the rhyolitic ignimbrites of LÉzardrieux (546 ± 8 Myr) and the rhyolites de St Germain-le-Gaillard (Undated) from the unmetamorphosed to slightly metamorphosed Eocambrian–Cambrian terranes of the Domnonean Domain of northern Brittany and north-western Normandy. Upon stepwise thermal and/or alternating field demagnetization and using vector subtraction, the spilites de Paimpol yield a characteristic direction with declination ( D ) = 226.4°, inclination ( I ) =– 15.7°. Local remagnetization by microgranite dykes (approximately 560 Myr old) produced a dircction of D = 235.1°, I =+ 63.4°. The diorite de St Quay exhibits multivectorial behaviour revealing a characteristic component of D = 31.2°, I =– 2.3°, and a secondary component of D = 299.9°, I =+ 38.2°. The gabbro de Keralain shows a characteristic component ( D = 290.9°, I = 41.4°) similar to the diorite's secondary component, and gives a secondary component of D = 221.0°, I =+ 55.8°. This secondary component of the gabbro appears again as the characteristic (although somewhat scattered) directions of the granite de Porz-Scarff. Thus, the gabbro may be relatively dated as having been magnetized before the intrusion and cooling of the granite (557 ± 16 Myr) and after that of the diorite (583 ± 40 Myr). The data from the rhyolites are the least certain because of ambiguities in the radiometric dating and uncertain bedding corrections, but they contain directions near to those of the granite and the microgranite dykes, all believed to be of the same episode of acidic volcanism. The trend in palaeomagnetic poles from the Armorican Massif for the Eocambrian–Cambrian corresponds well with coeval data from the southern United Kingdom and Czechoslovakia (Bohemian Massif), suggesting that a single continental mass, Armorica, contained all three areas. A comparison with poles from Gondwanaland also shows a remarkable agreement and suggests a period of coherent movement during the Latest Precambrian and the Cambrian for Armorica and Gondwana, followed by later separation. This leaves the Armorica plate as a separate continental unit at the outset of the Caledonian orogeny later in the Palaeozoic.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75303/1/j.1365-246X.1980.tb04830.x.pd