IGF-1 modulates gene expression of proteins involved in inflammation,cytoskeleton, and liver architecture

Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1’s effects on liver by comparing wild-type controls, heterozygous igf1^+/?, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.     

Extensive physiological integration in intact clonal systems of Carex arenaria

1 Carex arenaria forms large clonal fragments (up to 12 m long) in environments in which soil-bound resources limit growth.
2 We hypothesized that extensive integration of C. arenaria would facilitate the exploitation of scarce and patchily distributed soil resources and that the continued functioning of old roots would enable exploitation of resources that are temporally variable.
3 We used labelling with ¹⁴C and acid fuchsin to study the degree and extent of physiological integration and root function of intact clonal systems of C. arenaria in a sand dune area in south Sweden.
4 The uptake and translocation of dye suggests that old roots remain capable of taking up water and nutrients, in contrast with negative reports from previous studies. Water was translocated both acropetally and basipetally.
5 Thirty per cent of the assimilated carbon was found to be translocated towards the growing apex. Smaller, but significant, amounts of carbon were translocated basipetally throughout the fragments (17–74 ramet generations).
6 The results are discussed in terms of the source–sink relations of large clonal systems in the field. The translocation patterns are considered in relation to soil moisture and nutrient availability.     

Seed production and seed quality in a calcareous grassland in elevated CO2

In diverse plant communities the relative contribution of species to community biomass may change considerably in response to elevated CO₂. Along with species‐specific biomass responses, reproduction is likely to change as well with increasing CO₂ and might further accelerate shifts in species composition. Here, we ask if, after 5 years of CO₂ exposure, seed production and seed quality in natural nutrient‐poor calcareous grassland are affected by elevated CO₂ (650 μ L L^?1 vs 360 μ L L^?1) and how this might affect long‐term community dynamics. The effect of elevated CO₂ on the number of flowering shoots (+ 24%, P < 0.01) and seeds (+ 29%, P = 0.06) at the community level was similar to above ground biomass responses in this year, suggesting that the overall allocation to sexual reproduction remained unchanged. Compared among functional groups of species we found a 42% increase in seed number (P < 0.01) of graminoids, a 33% increase (P = 0.07) in forbs, and no significant change in legumes (? 38%, n.s.) under elevated CO₂. Large responses particularly of two graminoid species and smaller responses of many forb species summed up to the significant or marginally significant increase in seed number of graminoids and forbs, respectively. In several species the increase in seed number resulted both from an increase in flowering shoots and an increase in inflorescence size. In most species, seeds tended to be heavier (+ 12%, P < 0.01), and N‐concentration of seeds was significantly reduced in eight out of 13 species. The fraction of germinating seeds did not differ between seeds produced in ambient and elevated CO₂, but time to germination was significantly shortened in two species and prolonged in one species when seeds had been produced in elevated CO₂. Results suggest that species specific increases in seed number and changes in seed quality will exert substantial cumulative effects on community composition in the long run.     

Temperature effects on forest herbs assessed by warming and transplant experiments along a latitudinal gradient

Slow‐colonizing forest understorey plants are probably not able to rapidly adjust their distribution range following large‐scale climate change. Therefore, the acclimation potential to climate change within their actual occupied habitats will likely be key for their short‐ and long‐term persistence. We combined transplant experiments along a latitudinal gradient with open‐top chambers to assess the effects of temperature on phenology, growth and reproductive performance of multiple populations of slow‐colonizing understorey plants, using the spring flowering geophytic forb Anemone nemorosa and the early summer flowering grass Milium effusum as study species. In both species, emergence time and start of flowering clearly advanced with increasing temperatures. Vegetative growth (plant height, aboveground biomass) and reproductive success (seed mass, seed germination and germinable seed output) of A. nemorosa benefited from higher temperatures. Climate warming may thus increase future competitive ability and colonization rates of this species. Apart from the effects on phenology, growth and reproductive performance of M. effusum generally decreased when transplanted southwards (e.g., plant size and number of individuals decreased towards the south) and was probably more limited by light availability in the south. Specific leaf area of both species increased when transplanted southwards, but decreased with open‐top chamber installation in A. nemorosa. In general, individuals of both species transplanted at the home site performed best, suggesting local adaptation. We conclude that contrasting understorey plants may display divergent plasticity in response to changing temperatures which may alter future understorey community dynamics.     

The kinase activity of PKR represses inflammasome activity

The protein kinase R (PKR) functions in the antiviral response by controlling protein translation and inflammatory cell signaling pathways. We generated a transgenic, knock-in mouse in which the endogenous PKR is expressed with a point mutation that ablates its kinase activity. This novel animal allows us to probe the kinase-dependent and -independent functions of PKR. We used this animal together with a previously generated transgenic mouse that is ablated for PKR expression to determine the role of PKR in regulating the activity of the cryopyrin inflammasome. Our data demonstrate that, in contradiction to earlier reports, PKR represses cryopyrin inflammasome activity. We demonstrate that this control is mediated through the established function of PKR to inhibit protein translation of constituents of the inflammasome to prevent initial priming during innate immune signaling. These findings identify an important role for PKR to dampen inflammation during the innate immune response and caution against the previously proposed therapeutic strategy to inhibit PKR to treat inflammation.     

Regulation of CFTR chloride channel macroscopic conductance by extracellular bicarbonate

The CFTR contributes to Cl? and HCO?? transport across epithelial cell apical membranes. The extracellular face of CFTR is exposed to varying concentrations of Cl? and HCO?? in epithelial tissues, and there is evidence that CFTR is sensitive to changes in extracellular anion concentrations. Here we present functional evidence that extracellular Cl? and HCO?? regulate anion conduction in open CFTR channels. Using cell-attached and inside-out patch-clamp recordings from constitutively active mutant E1371Q-CFTR channels, we show that voltage-dependent inhibition of CFTR currents in intact cells is significantly stronger when the extracellular solution contains HCO?? than when it contains Cl?. This difference appears to reflect differences in the ability of extracellular HCO?? and Cl? to interact with and repel intracellular blocking anions from the pore. Strong block by endogenous cytosolic anions leading to reduced CFTR channel currents in intact cells occurs at physiologically relevant HCO?? concentrations and membrane potentials and can result in up to ～50% inhibition of current amplitude. We propose that channel block by cytosolic anions is a previously unrecognized, physiologically relevant mechanism of channel regulation that confers on CFTR channels sensitivity to different anions in the extracellular fluid. We further suggest that this anion sensitivity represents a feedback mechanism by which CFTR-dependent anion secretion could be regulated by the composition of the secretions themselves. Implications for the mechanism and regulation of CFTR-dependent secretion in epithelial tissues are discussed.     

The Lerhamn drill core and its bearing for the graptolite biostratigraphy of the Ordovician Tøyen Shale in Scania,southern Sweden

Maletz, J. & Ahlberg, P. 2011: The Lerhamn drill core and its bearing for the graptolite biostratigraphy of the Ordovician Tøyen Shale in Scania, southern Sweden. Lethaia, Vol. 44, pp. 350–368. A drill core through the Lower Ordovician Tøyen Shale Formation at Lerhamn, NW Scania, southern Sweden, provides important new information for the precise biostratigraphic resolution of the Floian to lower Darriwilian time interval in southern Scandinavia. The Hunnegraptus copiosus, Tetragraptus phyllograptoides, Cymatograptus protobalticus (new), Baltograptus vacillans (new), Baltograptus sp. cf. Baltograptus deflexus (new), Baltograptus minutus (new), Isograptus victoriae, Undulograptus austrodentatus (Arienigraptus zhejiangensis and Undulograptus sinicus Subzones) and the (?)Corymbograptus retroflexus (new) biozones are differentiated in the core and their correlation in Scania is discussed. The Lerhamn drill core provides the most detailed graptolite record of the Floian Stage in Scandinavia. The interval is dominated by a number of species of the genus Baltograptus, endemic to the Atlantic Faunal realm and highly useful for regional biostratigraphic correlation. The biostratigraphic framework is based on endemic and pandemic faunal elements. The mixture of both elements in the drill core allows a more precise inter‐continental correlation of Lower to Middle Ordovician graptolite faunas and may – in the future – provide information as to the climatic history of regions dominated by Baltograptus faunas in the Floian. The (?)C. retroflexus Biozone is based on species originally described from Bohemia, but the record of the zone in the Lerhamn drill core indicates a wider distribution of its fauna. □Biostratigraphy, graptolites, Ordovician, Scania, Sweden.