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

Age-related changes in the primary motor cortex of newborn to adult domestic pig sus scrofa domesticus

The pig has been increasingly used as a suitable animal model in translational neuroscience. However, several features of the fast-growing, immediately motor-competent cerebral cortex of this species have been adequately described. This study analyzes the cytoarchitecture of the primary motor cortex (M1) of newborn, young and adult pigs (Sus scrofa domesticus). Moreover, we investigated the distribution of the neural cells expressing the calcium-binding proteins (CaBPs) (calretinin, CR; parvalbumin, PV) throughout M1. The primary motor cortex of newborn piglets was characterized by a dense neuronal arrangement that made the discrimination of the cell layers difficult, except for layer one. The absence of a clearly recognizable layer four, typical of the agranular cortex, was noted in young and adult pigs. The morphometric and immunohistochemical analy-ses revealed age-associated changes characterized by (1) thickness increase and neuronal density (number of cells/mm2 of M1) reduction during the first year of life; (2) morphological changes of CR-immunoreactive neurons in the first months of life; (3) higher density of CR-and PV-immunopositive neurons in newborns when compared to young and adult pigs. Since most of the present findings match with those of the human M1, this study strengthens the growing evidence that the brain of the pig can be used as a potentially valuable translational animal model during growth and development

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia–reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine

Solid-state ion exchange of Fe in small pore SSZ-13 zeolite: Characterization of the exchanged species and their relevance for the NOx SCR reaction

Solid state ion exchange was performed for the successful introduction of Fe cations in the small pore CHA structured SSZ-13 zeolite. The produced catalysts were characterized by IR and UV-Vis spectroscopies and thermally programmed reaction techniques to probe the Fe sites formed during the exchange and the catalytic activity for the NOx SCR reaction. The results indicate that highly dispersed and heterogeneous Fe sites are formed, and the type depends on the Al distribution in the zeolite. Dimeric Fe species are formed preferentially at the start of the exchange on the 6- and 8-member rings that contain at least two Al exchange sites and once these sites are fully saturated the Fe is exchanged as isolated cations

SO2 deactivation mechanism of NO oxidation and regeneration of the LaCoO3 perovskite

The deactivation mechanism and methods to cope with the poisoning by SO2 of LaCoO3 perovskite-based NO oxidation catalysts were investigated. The LaCoO3 perovskite was synthesized by a sol-gel method and the fresh, sulphate-deactivated and regenerated catalysts were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, H2-and soot-temperature programmed reduction, temperature programmed desorption and diffuse reflectance infrared Fourier transform spectroscopy. The SO2 poisoning strongly affected the NO oxidation activity. It was demonstrated that the deactivation mechanism proceeds in two stages: initially the active sites with a basic character are blocked by SO3 and subsequently the lanthanum sulphate salts grow progressively on the surface and cobalt is unaffected. Above 500 °C, the surface bound sulphates become mobile and migrate into the bulk of the catalyst. Several prevention and regeneration methods were proposed and tested. By mixing the catalyst with Ca(OH)2 as an adsorbent nearly 50% of the original activity was retained. Regeneration by diesel soot was presented here for the first time, where the blocking oxygen can spill over to the soot oxidizing it and releasing the bound sulphur as SO2 and CO2. Furthermore, a facile regeneration method was explored by washing the deactivated catalyst to dissolve the small amounts of sulphates on the surface

How large-scale geographic factors affect the different dimensions of functional diversity: evidence from the beech forest herb layer (Apennines, Italy)

Background and aims – The research aim was to investigate the relation between large-scale geographic factors and the functional structure of the herbaceous layer of calcareous beech forests in the Apennines, managed as high forest. Material and methods – We selected 163 plots (20 × 20 m), ranging from Central to South Italy, using a random stratified sampling design. We correlated the effect sizes of traits’ community-weighted means, functional richness, evenness, divergence, dispersion, and Rao’s quadratic entropy, with the main axes of variation in species composition. Key results – The geographical range played a weak role in shaping the species composition of the herbaceous layer. However, we found evidence of functional convergence towards the northern sectors of the study area, where traits linked to resource retention strategies and vegetative spread are filtered. We did not find any evidence of convergence northwards for leaf phenology and pollination types. Conclusion – The increase of the intensity in the environmental stress was associated with a decrease of diversity for traits related to resource conservation strategies and vegetative propagation. On the contrary, the lower cold stress intensity southwards fostered a better niche partitioning, ensuring the coexistence of species with different modalities of resource acquisition and conservation