The matri-cellular proteins 'cysteine-rich, angiogenic-inducer, 61' and 'connective tissue growth factor' are regulated in experimentally-induced sepsis with multiple organ dysfunction

Organ failure is a severe complication in sepsis for which the pathophysiology remains incompletely understood. Recently, the matri-cellular cysteine-rich, angiogenic induced, 61 (Cyr61/CCN1); connective tissue growth factor (Ctgf/CCN2); and nephroblastoma overexpressed gene (Nov/CCN3) (CCN)-protein family have been attributed organ-protective properties. Their expression is sensitive to mediators of sepsis pathophysiology but a potential role in sepsis remains elusive. To provide an initial assessment, 50 rats were subjected to 18?h of cecal-ligation and puncture or sham operation. Hepatic and pulmonary CCN1 mRNA displayed an average 7.4- and 3.3-fold induction, while its cardiac expression was unchanged. The changes coincided with excessive hepatic and pulmonary inflammatory gene activation and a restricted cardiac inflammation. Furthermore, hepatocytes displayed a dosage-dependent CCN1 mRNA response in?vitro, supporting a cytokine-mediated CCN1 regulation in sepsis. CCN2 mRNA was 2.2-fold induced in the liver, while 2.0-fold and 1.4-fold repressed in the heart and lung. Meanwhile, it did not respond to TNF-α exposure in?vitro, which indicates different means of regulation than for CCN1. Taken together, this study provides the first evidence for multi-organ regulation of CCN1 and CCN2 in early stages of sepsis, and implies the eruption of inflammatory mediators as a potential mechanism behind the observed CCN1 regulation.     

Effect of leaf age on CAM activity in Littorella uniflora

In this study the effect of ontogenetic drift on crassulacean acid metabolism (CAM) was investigated in the aquatic CAM-isoetid Littorella uniflora. The results of this study strengthen the general hypothesis of CAM being a carbon-conserving mechanism in aquatic plants, because high-CAM capacity (45–183 μequiv. g⁻¹ FW) was present in all leaves of L. uniflora irrespective of age. Since possession of CAM in aquatic plants allows CO₂ uptake throughout the light/dark cycle, presence of CAM in all leaves influences the carbon balance of L. uniflora positively. On average for all lakes, different leaf classes accounted for 11–36% of the total dark CO₂ uptake by the individual plant.

The capacity for both CAM and photosynthesis declined with increasing leaf age, and was in the oldest leaves only 25–53% of the capacity in the youngest. The photosynthetic capacity was estimated to be sufficiently high to ensure refixation of the CO₂ released from malate during decarboxylation in the daytime. In line with this, a linear coupling between CAM capacity and photosynthetic capacity was found. Parallel to the change in photosynthetic capacity, an age-related change in total ribulose-bisphosphate carboxylase/oxygenase (rubisco) activity from 732 μmol C g⁻¹ DW h⁻¹ in the youngest leaves to 346 μmol C g⁻¹ DW h⁻¹ in the oldest was observed. In contrast, no significant change in phosphoenolpyruvate carboxylase (PEPcase) activity with leaf age was observed (means ranged between 46 and 156 μmol C g⁻¹ DW h⁻¹).     

Macroecology in the age of Big Data – Where to go from here?

Recent years have seen an exponential increase in the amount of data available in all sciences and application domains. Macroecology is part of this “Big Data” trend, with a strong rise in the volume of data that we are using for our research. Here, we summarize the most recent developments in macroecology in the age of Big Data that were presented at the 2018 annual meeting of the Specialist Group Macroecology of the Ecological Society of Germany, Austria and Switzerland (GfÖ). Supported by computational advances, macroecology has been a rapidly developing field over recent years. Our meeting highlighted important avenues for further progress in terms of standardized data collection, data integration, method development and process integration. In particular, we focus on (a) important data gaps and new initiatives to close them, for example through space- and airborne sensors, (b) how various data sources and types can be integrated, (c) how uncertainty can be assessed in data-driven analyses and (d) how Big Data and machine learning approaches have opened new ways of investigating processes rather than simply describing patterns. We discuss how Big Data opens up new opportunities, but also poses new challenges to macroecological research. In the future, it will be essential to carefully assess data quality, the reproducibility of data compilation and analytical methods, and the communication of uncertainties. Major progress in the field will depend on the definition of data standards and workflows for macroecology, such that scientific quality and integrity are guaranteed, and collaboration in research projects is made easier.     

18F-FET MicroPET and MicroMRI for Anti-VEGF and Anti-PlGF Response Assessment in an Orthotopic Murine Model of Human Glioblastoma

BackgroundConflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of ¹⁸F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of ¹⁸F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts.MethodsMice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), ¹⁸F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours.ResultsAnti-VEGF monotherapy increased survival and decreased ¹⁸F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. ¹⁸F-FET SUV_max tumour-to-brain (T/B) ratio was significantly lower after one week (114±6%, n = 11 vs. 143±8%, n = 13; p = 0.02) and two weeks of treatment (116±12%, n = 8 vs. 190±24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours.Conclusion¹⁸F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of ¹⁸F-FET PET for response evaluation in future studies.     

Native ecosystem engineer facilitates recruitment of invasive crab and native invertebrates

Native ecosystem engineers that add physical structure to ecosystems can facilitate invasive species. In this study we determined the effects of the native tube-forming serpulid worm, Galeolaria caespitose on the recruitment of the invasive New Zealand porcelain crab, Petrolisthes elongatus, and whether invasive crab recruitment was related to the recruitment of native species. P. elongatus is abundant beneath intertidal rocks around Tasmania, southern Australia, and the underside of these rocks is usually covered with a calcareous matrix formed by the serpulid. We used an experimental approach to investigate whether rocks, serpulids on the underside of rocks and adult P. elongatus influenced the recruitment P. elongatus and native communities. P. elongatus and native invertebrates only recruited in the presence of rocks indicating the importance of rock as primary recruitment habitat. Moreover, the presence of serpulids on the underside of rocks significantly increased the recruitment of P. elongatus and native invertebrates compared to rocks without serpulids. Rocks with higher densities of adult P. elongatus at the end of the experiment also had higher densities of P. elongatus recruits. The density of P. elongatus recruits did not influence native species richness and abundance although there was some evidence that high P. elongatus recruitment was correlated with shifts in native community structure. We have shown that a native ecosystem engineer facilitates recruitment of an invasive crab but this does not appear to influence the recruitment of native species.