Comparing conservation value maps and mapping methods in a rural landscape in southern Finland

Peer reviewe

Activin Receptor Ligand Blocking and Cancer Have Distinct Effects on Protein and Redox Homeostasis in Skeletal Muscle and Liver

Muscle wasting in cancer cachexia can be alleviated by blocking activin receptor type 2 (ACVR2) ligands through changes in protein synthesis/degradation. These changes in cellular and protein metabolism may alter protein homeostasis. First, we elucidated the acute (1-2 days) and 2-week effects of blocking ACVR2 ligands by soluble activin receptor 2B (sACVR2B-Fc) on unfolded protein response (UPR), heat shock proteins (HSPs) and redox balance in a healthy mouse skeletal muscle. Second, we examined UPR, autophagy and redox balance with or without sACVR2B-Fc administration in muscle and liver of C26 tumor-bearing mice. The indicators of UPR and HSPs were not altered 1-2 days after a single sACVR2B-Fc administration in healthy muscles, but protein carbonyls increased (p <0.05). Two weeks of sACVR2B-Fc administration increased muscle size, which was accompanied by increased UPR markers: GRP78 <0.05), phosphorylated elF2 alpha <0.01) and HSP47 (p <0.01). Additionally, protein carbonyls and reduced form of glutathione increased (GSH) (p <0.05). On the other hand, C26 cancer cachexia manifested decreased UPR markers (p-elF2 alpha, HSP47, p-JNK; p <0.05) and antioxidant GSH (p <0.001) in muscle, whereas the ratio of oxidized to reduced glutathione increased (GSSG/GSH; p <0.001). Administration of sACVR2B-Fc prevented the decline in GSH and increased some of the UPR indicators in tumor-bearing mice. Additionally, autophagy markers LC3II/I (p <0.05), Beclin-1 (p <0.01), and P62 (p <0.05) increased in the skeletal muscle of tumor-bearing mice. Finally, indicators of UPR, PERK, p-elF2 alpha and GRP78, increased (p <0.05), whereas ATF4 was strongly decreased (p <0.01) in the liver of tumor-bearing mice while sACVR2B-Fc had no effect. Muscle GSH and many of the altered UPR indicators correlated with tumor mass, fat mass and body mass loss. In conclusion, experimental cancer cachexia is accompanied by distinct and tissue-specific changes in proteostasis. Muscle hypertrophy induced by blocking ACVR2B ligands may be accompanied by the induction of UPR and increased protein carbonyls but blocking ACVR2B ligands may upregulate antioxidant protection.Peer reviewe

Blocking Activin Receptor Ligands Is Not Sufficient to Rescue Cancer-Associated Gut Microbiota—A Role for Gut Microbial Flagellin in Colorectal Cancer and Cachexia?

Colorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. Further, we examined the possible relationship between the microbial surface molecule flagellin and CRC. CRC cells (C26) were inoculated into mice. Activin receptor (ACVR) ligands were blocked, either before tumor formation or before and after, to increase muscle mass and prevent muscle loss. The effects of flagellin on C26-cells were studied in vitro. The occurrence of similar phenomena were studied in murine and human tumors. Cancer modulated the gut microbiota without consistent effects of blocking the ACVR ligands. However, continued treatment for muscle loss modified the association between microbiota and weight loss. Several abundant microbial taxa in cancer were flagellated. Exposure of C26-cells to flagellin increased IL6 and CCL2/MCP-1 mRNA and IL6 excretion. Murine C26 tumors expressed more IL6 and CCL2/MCP-1 mRNA than C26-cells, and human CRC tumors expressed more CCL2/MCP-1 than healthy colon sites. Additionally, flagellin decreased caspase-1 activity and the production of reactive oxygen species, and increased cytotoxicity in C26-cells. Conditioned media from flagellin-treated C26-cells deteriorated C2C12-myotubes and decreased their number. In conclusion, cancer increased flagellated microbes that may promote CRC survival and cachexia by inducing inflammatory proteins such as MCP-1. Cancer-associated gut microbiota could not be rescued by blocking ACVR ligands

Blocking Activin Receptor Ligands Is Not Sufficient to Rescue Cancer-Associated Gut Microbiota—A Role for Gut Microbial Flagellin in Colorectal Cancer and Cachexia?

Colorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. Further, we examined the possible relationship between the microbial surface molecule flagellin and CRC. CRC cells (C26) were inoculated into mice. Activin receptor (ACVR) ligands were blocked, either before tumor formation or before and after, to increase muscle mass and prevent muscle loss. The effects of flagellin on C26-cells were studied in vitro. The occurrence of similar phenomena were studied in murine and human tumors. Cancer modulated the gut microbiota without consistent effects of blocking the ACVR ligands. However, continued treatment for muscle loss modified the association between microbiota and weight loss. Several abundant microbial taxa in cancer were flagellated. Exposure of C26-cells to flagellin increased IL6 and CCL2/MCP-1 mRNA and IL6 excretion. Murine C26 tumors expressed more IL6 and CCL2/MCP-1 mRNA than C26-cells, and human CRC tumors expressed more CCL2/MCP-1 than healthy colon sites. Additionally, flagellin decreased caspase-1 activity and the production of reactive oxygen species, and increased cytotoxicity in C26-cells. Conditioned media from flagellin-treated C26-cells deteriorated C2C12-myotubes and decreased their number. In conclusion, cancer increased flagellated microbes that may promote CRC survival and cachexia by inducing inflammatory proteins such as MCP-1. Cancer-associated gut microbiota could not be rescued by blocking ACVR ligands

Beneficial effects of running and milk protein supplements on Sirtuins and risk factors of metabolic disorders in rats with low aerobic capacity

Background Physical activity and dietary intake of dairy products are associated with improved metabolic health. Dairy products are rich with branched chain amino acids that are essential for energy production. To gain insight into the mechanisms underlying the benefit of the sub-chronic effects of running and intake of milk protein supplements, we studied Low Capacity Runner rats (LCR), a rodent exercise model with risk for metabolic disorders. We especially focused on the role of Sirtuins, energy level dependent proteins that affect many cellular metabolic processes. Methods Forty-seven adult LCR female rats sedentary or running voluntarily in wheels were fed normal chow and given supplements of either whey or milk protein drink (PD)-supplemented water, or water only for 21 weeks. Physiological responses were measured in vivo. Blood lipids were determined from serum. Mitochondrial markers and Sirtuins (Sirt1-7) including downstream targets were measured in plantaris muscle by western blotting. Results For the first 10 weeks whey-drinking rats ran about 50% less compared to other groups; still, in all runners glucose tolerance improved and triglycerides decreased. Generally, running induced a ∼six-fold increase in running capacity and a ∼8% decrease in % body fat. Together with running, protein supplements increased the relative lean mass of the total body weight by ∼11%. In comparison with sedentary controls, running and whey increased HDL (21%) and whey, with or without running, lowered LDL (−34%). Running increased mitochondrial biogenesis and Sirtuins 3 and 4. When combined with exercise, both whey and milk protein drink induced about a 4-fold increase in Sirt3, compared to runners drinking water only, and about a 2-fold increase compared to the respective sedentary group. Protein supplements, with or without running, enhanced the phosphorylation level of the acetyl-coA-carboxylase, suggesting increased fat oxidation. Both supplemented diets increased Sirt5 and Sirt7 without an additional effect from exercise. Running diminished and PD supplement increased Sirt6. Conclusion We demonstrate in rats new sub-chronic effects of milk proteins on metabolism that involve Sirtuins and their downstream targets in skeletal muscle. The results show that running and milk proteins act on reducing the risk factors of metabolic disorders and suggest that the underlying mechanisms may involve Sirtuins. Notably, we found that milk protein supplements have some favorable effects on metabolism even without running.Peer reviewe

Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease

Peer reviewe

Blocking activin receptor ligands is not sufficient to rescue cancer-associated gut microbiota - a role for gut microbial flagellin in colorectal cancer and cachexia?

Colorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. Further, we examined the possible relationship between the microbial surface molecule flagellin and CRC. CRC cells (C26) were inoculated into mice. Activin receptor (ACVR) ligands were blocked, either before tumor formation or before and after, to increase muscle mass and prevent muscle loss. The effects of flagellin on C26-cells were studied in vitro. The occurrence of similar phenomena were studied in murine and human tumors. Cancer modulated the gut microbiota without consistent effects of blocking the ACVR ligands. However, continued treatment for muscle loss modified the association between microbiota and weight loss. Several abundant microbial taxa in cancer were flagellated. Exposure of C26-cells to flagellin increased IL6 and CCL2/MCP-1 mRNA and IL6 excretion. Murine C26 tumors expressed more IL6 and CCL2/MCP-1 mRNA than C26-cells, and human CRC tumors expressed more CCL2/MCP-1 than healthy colon sites. Additionally, flagellin decreased caspase-1 activity and the production of reactive oxygen species, and increased cytotoxicity in C26-cells. Conditioned media from flagellin-treated C26-cells deteriorated C2C12-myotubes and decreased their number. In conclusion, cancer increased flagellated microbes that may promote CRC survival and cachexia by inducing inflammatory proteins such as MCP-1. Cancer-associated gut microbiota could not be rescued by blocking ACVR ligands.</p

Satellite observations for detecting and forecasting sea-ice conditions: A summary of advances made in the SPICES Project by the EU's Horizon 2020 Programme

The detection, monitoring, and forecasting of sea-ice conditions, including their extremes, is very important for ship navigation and offshore activities, and for monitoring of sea-ice processes and trends. We summarize here recent advances in the monitoring of sea-ice conditions and their extremes from satellite data as well as the development of sea-ice seasonal forecasting capabilities. Our results are the outcome of the three-year (2015-2018) SPICES (Space-borne Observations for Detecting and Forecasting Sea-Ice Cover Extremes) project funded by the EU's Horizon 2020 programme. New SPICES sea-ice products include pancake ice thickness and degree of ice ridging based on synthetic aperture radar imagery, Arctic sea-ice volume and export derived from multisensor satellite data, and melt pond fraction and sea-ice concentration using Soil Moisture and Ocean Salinity (SMOS) radiometer data. Forecasts of July sea-ice conditions from initial conditions in May showed substantial improvement in some Arctic regions after adding sea-ice thickness (SIT) data to the model initialization. The SIT initialization also improved seasonal forecasts for years with extremely low summer sea-ice extent. New SPICES sea-ice products have a demonstrable level of maturity, and with a reasonable amount of further work they can be integrated into various operational sea-ice services

Effects of Vegetation, Corridor Width and Regional Land Use on Early Successional Birds on Powerline Corridors

Powerline rights-of-way (ROWs) often provide habitat for early successional bird species that have suffered long-term population declines in eastern North America. To determine how the abundance of shrubland birds varies with habitat within ROW corridors and with land use patterns surrounding corridors, we ran Poisson regression models on data from 93 plots on ROWs and compared regression coefficients. We also determined nest success rates on a 1-km stretch of ROW. Seven species of shrubland birds were common in powerline corridors. However, the nest success rates for prairie warbler (Dendroica discolor) and field sparrow (Spizella pusilla) were <21%, which is too low to compensate for estimated annual mortality. Some shrubland bird species were more abundant on narrower ROWs or at sites with lower vegetation or particular types of vegetation, indicating that vegetation management could be refined to favor species of high conservation priority. Also, several species were more abundant in ROWs traversing unfragmented forest than those near residential areas or farmland, indicating that corridors in heavily forested regions may provide better habitat for these species. In the area where we monitored nests, brood parasitism by brown-headed cowbirds (Molothrus ater) occurred more frequently close to a residential area. Although ROWs support dense populations of shrubland birds, those in more heavily developed landscapes may constitute sink habitat. ROWs in extensive forests may contribute more to sustaining populations of early successional birds, and thus may be the best targets for habitat management