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Palomaki S.,University of Oulu | Pietila M.,University of Oulu | Laitinen S.,Finnish Red Cross Blood Service | Pesala J.,University of Oulu | And 3 more authors.
Stem Cells | Year: 2013

Human mesenchymal stem cells (hMSCs) are multipotent cells that have aroused great expectations in regenerative medicine. They are assumed to originate from hypoxic stem cell niches, especially in the bone marrow. This suggests that O2 is of importance in their regulation. In order to characterize regulation of the oxygen sensing pathway in these cells, we studied hMSCs isolated from three origins, adult and pediatric bone marrow and umbilical cord blood (UCB). Surprisingly, pediatric bone marrow and UCB MSCs showed normoxic stabilization of hypoxia-inducible factor-1α (HIF-1α) that is normally degraded completely by HIF prolyl 4-hydroxylases in the presence of oxygen. This was due to a high expression level of HIF-1α mRNA rather than inappropriate post-translational degradation of HIF-1α protein. HIF-1α mRNA was also induced in normoxic adult bone marrow MSCs, but 40% less than in the pediatric cells, and this was apparently not enough to stabilize the protein. The high normoxic HIF expression in all the hMSCs studied was accompanied by increased expression of a large number of glycolytic HIF target genes and increased glycolysis. Osteogenic differentiation of bone marrow-derived hMSCs reduced HIF-1α mRNA and protein expression and the expression of glycolytic mRNAs, resulting in decreased glycolysis and induction of oxidative metabolism. Induced mitochondrial biogenesis, changes in mitochondrial morphology and size indicative of increased oxidative phosphorylation, and induction of extracellular matrix synthesis were observed following osteogenic differentiation. Altogether, these data suggest that HIF-1α is a general regulator controlling the metabolic fate and multipotency of the hMSCs. Stem Cells 2013;31:1902-1909 © AlphaMed Press.

Wacklin P.,Finnish Red Cross Blood Service
American Journal of Gastroenterology | Year: 2014

Objectives:A significant fraction of celiac disease patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD) and normalized small bowel mucosa. The commonly suggested reasons, such as inadvertent gluten-intake or presence of other gastrointestinal disease, do not explain the symptoms in all these patients. Recently, alterations in intestinal microbiota have been associated with autoimmune disorders, including celiac disease. This led us to test a hypothesis that abnormal intestinal microbiota may be associated with persisting gastrointestinal symptoms in treated celiac disease patients.Methods:Duodenal microbiota was analyzed in 18 GFD-treated patients suffering from persistent symptoms and 18 treated patients without symptoms by 16S rRNA gene pyrosequencing. The celiac disease patients had been following a strict GFD for several years and had restored small bowel mucosa and negative celiac autoantibodies. Their symptoms on GFD were assessed with Gastrointestinal Symptom Rating Scale.Results:The results of several clustering methods showed that the treated celiac disease patients with persistent symptoms were colonized by different duodenal microbiota in comparison with patients without symptoms. The treated patients with persistent symptoms had a higher relative abundance of Proteobacteria (P=0.04) and a lower abundance of Bacteroidetes (P=0.01) and Firmicutes (P=0.05). Moreover, their microbial richness was reduced. The results indicated intestinal dysbiosis in patients with persistent symptoms even while adhering to a strict GFD.Conclusions:Our findings indicate that dysbiosis of microbiota is associated with persistent gastrointestinal symptoms in treated celiac disease patients and open new possibilities to treat this subgroup of patients.Am J Gastroenterol advance online publication, 18 November 2014; doi:10.1038/ajg.2014.355. © 2014 American College of Gastroenterology

Rautonen J.,Finnish Red Cross Blood Service
Biologicals | Year: 2010

The relationship between free trade, self-sufficiency and safety of blood and blood components has been a perennial discussion topic in the blood service community. Traditionally, national self-sufficiency has been perceived as the ultimate goal that would also maximize safety. However, very few countries are, or can be, truly self-sufficient when self-sufficiency is understood correctly to encompass the whole value chain from the blood donor to the finished product. This is most striking when plasma derived medicines are considered. Free trade of blood products, or competition, as such can have a negative or positive effect on blood safety. Further, free trade of equipment and reagents and several plasma medicines is actually necessary to meet the domestic demand for blood and blood derivatives in most countries. Opposing free trade due to dogmatic reasons is not in the best interest of any country and will be especially harmful for the developing world. Competition between blood services in the USA has been present for decades. The more than threefold differences in blood product prices between European blood services indicate that competition is long overdue in Europe, too. This competition should be welcomed but carefully and proactively regulated to avoid putting safe and secure blood supply at risk. © 2009 The International Association for Biologicals.

Wasmund N.,Leibniz Institute for Baltic Sea Research | Tuimala J.,Finnish Red Cross Blood Service | Suikkanen S.,Finnish Environment Institute | Vandepitte L.,Flanders Marine Institute VLIZ | Kraberg A.,Alfred Wegener Institute for Polar and Marine Research
Journal of Marine Systems | Year: 2011

The phytoplankton biomass data of the period 1979-2005 of the Belt Sea area and the Baltic Proper, separated into spring, summer and autumn data, were checked for trends, together with the relevant abiotic factors (temperature, salinity, and nutrient concentrations). The Mann-Kendall test was used for detecting monotonic trends over the whole investigation period or, if trend breaks occurred, over the period before and after the trend breaks. The relationships between phytoplankton community composition and the environmental variables were assessed by a redundancy analysis (RDA), which could support some results of the trend analyses. Water temperature increased but salinity and inorganic nitrogen concentrations decreased in the southern Baltic Proper. Spring phytoplankton biomass and chlorophyll a concentrations increased in the Baltic Proper and decreased in Mecklenburg Bight. The biomass of Diatomophyceae decreased in spring at some stations but increased in autumn. If the Diatomophyceae spring blooms decreased, the total Dinophyceae biomass increased. Strong spring blooms of Diatomophyceae occurred in the 1980s and since 2000, but those of Dinophyceae in the 1990s. These two groups showed alternating oscillations. Trends in most phytoplankton components were different in the Baltic Proper and the Belt Sea area, confirming that Darss Sill is a biological border. © 2011 Elsevier B.V.

Croke M.,Washington University in St. Louis | Ross F.P.,Washington University in St. Louis | Korhonen M.,Finnish Red Cross Blood Service | Williams D.A.,Childrens Hospital Boston | And 2 more authors.
Journal of Cell Science | Year: 2011

Summary Cdc42 mediates bone resorption principally by stimulating osteoclastogenesis. Whether its sister GTPase, Rac, meaningfully impacts upon the osteoclast and, if so, by what means, is unclear. We find that whereas deletion of Rac1 or Rac2 alone has no effect, variable reduction of Rac1 in osteoclastic cells of Rac2 2/2 mice causes severe osteopetrosis. Osteoclasts lacking Rac1 and Rac2 in combination (Rac double-knockout, RacDKO), fail to effectively resorb bone. By contrast, osteoclasts are abundant in RacDKO osteopetrotic mice and, unlike those deficient in Cdc42, express the maturation markers of the cells normally. Hence, the osteopetrotic lesion of RacDKO mice largely reflects impaired function, and not arrested differentiation, of the resorptive polykaryon. The dysfunction of RacDKO osteoclasts represents failed cytoskeleton organization as evidenced by reduced motility of the cells and their inability to spread or generate the key resorptive organelles (i.e. actin rings and ruffled borders), which is accompanied by abnormal Arp3 distribution. The cytoskeleton-organizing capacity of Rac1 is mediated through its 20-amino-acid effector domain. Thus, Rac1 and Rac2 are mutually compensatory. Unlike Cdc42 deficiency, their combined absence does not impact upon differentiation but promotes severe osteopetrosis by dysregulating the osteoclast cytoskeleton. © 2011. Published by The Company of Biologists Ltd.

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