Tutkijoiden erillissota : Suomalaisten historiantutkijoiden erillissotakeskustelu 2000-luvulla

Suomessa on oikeastaan heti jatkosodan alusta lähtien keskusteltu siitä, käytiinkö sotaa itsenäisesti vai liitossa natsi-Saksan kanssa. Erillissotateesin mukaan jatkosota ei liittynyt samaan aikaan käynnissä olevaan toiseen maailmansotaan, vaan oli erillinen Suomen ja Neuvostoliiton välinen konflikti, ja Suomen Saksalta saama taloudellinen sekä aseellinen apu ei sitonut sitä Saksan koalitioon. Sodan aikana erillissotateesillä haettiin oikeutusta sodalle sekä kansallisesti että kansainvälisesti. Sodan jälkeen erillissotateesiä käyttivät ensimmäistä kertaa sotasyyllisyysoikeudenkäynnissä syytettyinä olleet henkilöt puolustuksensa strategiana. Siitä lähtien keskustelu erillissotateesin pätevyydestä on siirtynyt enemmän historiantutkijoiden harteille. Tämä tutkielma käsittelee suomalaisten historiantutkijoiden käymää erillissotakeskustelua vuosina 2000–2012. Historiantutkijoiden käymässä erillissotakeskustelussa on löydettävissä useita eri vaiheita. Tutkielman tarkoitus on erottaa 2000-luvun erillissotakeskustelu selkeästi yhdeksi vaiheeksi erillissotakeskustelun historiassa. 2000-luvun erillissotakeskustelulla tarkoitetaan vuosien 2000-2012 aikana käytyä keskustelua. Tutkielman aineisto koostuu historiantutkijoiden tuottamista puheenvuoroista, jotka liittyvät jollain tavalla erillissotateemaan. Tutkimuskohteiksi on hyväksytty sellaiset tutkijat, jotka selkeästi kuuluvat historiantutkijoiden tiedeyhteisöön. Lähdeaineistona työssä käytetään tutkimuskirjallisuutta, tieteellisiä artikkeleita sekä muita puheenvuoroja printti- tai verkkomediassa. Tutkielman kolmannessa ja neljännessä pääluvussa esitellään historiantutkijoiden 2000-luvun erillissotakeskustelu kronologisesti. Jäsentelyn apuna käytetään tapahtumia, joiden ympärillä keskustelua on käyty. Tällaisia tapahtumia ovat esimerkiksi eräiden aiheeseen liittyvien kirjojen julkaisut. Erillissotakeskustelun puheenvuoroja tarkastellaan historiapolitiikkana ja niiden oletetaan pyrkivän vaikuttamaan jatkosodan historiakuvaan. Tutkijoiden käymä keskustelu pyritään esittämään mahdollisimman kattavasti ja tasapuolisesti. Viimeisessä pääluvussa erillissotakeskustelua tarkastellaan kansallisen historian näkökulmasta. Lähdeaineiston pohjalta voidaan päätellä, että 2000-luvun erillissotakeskustelun myötä jatkosodan historiakuva on muuttunut. Vielä 2000-luvun alkuvaiheilla uuspatrioottista kansallista historiakuvaa kyseenalaistavat puheenvuorot saavat aikaan kiivasta vastustusta, mutta aikarajauksen loppupuolella erilaisia tulkintoja siedetään huomattavasti enemmän. Tämä ei tarkoita sitä, että erillissotakeskustelussa olisi löytynyt minkäänlaista konsensusta, vaan pikemminkin sitä, että suomalainen historiakulttuuri on ainakin akateemisella tasolla muuttunut avoimemmaksi. Jatkosodan osalta tilanne on se, että sellaista uutta lähdeaineistoa, joka muuttaisi kokonaiskuvaa ratkaisevasti, tuskin enää löytyy. Niinpä jatkossa kyse on enemmänkin vanhan lähdeaineiston tulkinnasta. Erillissotakeskustelu siis jatkuu, mutta varmasti avoimempana ja sellaisena, ettei yhtenäistä ja kansallista tulkintaa enää välttämättä pyritäkkään luomaan

Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model

BACKGROUND: The TGFβ1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFβ1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new players in epithelial cell differentiation. RESULTS: The expression of 372 genes out of 5188 arrayed sequences was significantly altered, and 47 of them were altered by both mediators. The data were validated and the altered genes are presented in ontology classes. For the genes tested the expressions in protein level were in accordance with the mRNA results. We also found 194 genes with no known function to be potentially important in epithelial cell differentiation. The mRNA expression changes induced by TGFβ1 were bigger than changes induced by soluble factors secreted by IMR-90 mesenchymal cells. The gene expression data was depicted in already known signaling pathway routes. CONCLUSION: Our results reveal potential new signaling pathways and several new genes affected by TGFβ in epithelial cell differentiation. The differentiation induced by TGFβ1 appears to be more potent than the differentiation induced by mesenchymal cells. This study indicates that our cell culture model is a suitable tool in studying regulatory mechanisms during epithelial cell differentiation in intestine. Furthermore the present results indicate that our model is a good tool for finding new players acting in the differentiation of epithelial cells

Short-term bone biochemical response to a single bout of high-impact exercise

Bone response to a single bout of exercise can be observed with biochemical markers of bone formation and resorption. The purpose of this study was to examine the response of bone biochemical markers to a single bout of exhaustive high-impact exercise. 15 physically active young subjects volunteered to participate. The subjects performed continuous bilateral jumping with the ankle plantarflexors at 65 % of maximal ground reaction force (GRF) until exhaustion. Loading was characterized by analyzing the GRF recorded for the duration of the exercise. Venous blood samples were taken at baseline, immediately after, 2h and on day 1 and day 2 after the exercise. Procollagen type I amino terminal propeptide (P1NP, marker of bone formation) and carboxyterminal crosslinked telopeptide (CTx, marker of bone resorption) were analyzed from the blood samples. CTx increased significantly (32 %, p = 0.015) two days after the exercise and there was a tendensy towards increase seen in P1NP (p = 0.053) one day after the exercise. A significant positive correlation (r = 0.49 to 0.69, p &le; 0.038) was observed between change in P1NP from baseline to day 1 and exercise variables (maximal slope of acceleration, body weight (BW) adjusted maximal GRF, BW adjusted GRF exercise intensity and osteogenic index). Based on the two biochemical bone turnover markers, it can be concluded that bone turnover is increased in response to a very<br /

TGF-β induces the expression of SAP30L, a novel nuclear protein

BACKGROUND: We have previously set up an in vitro mesenchymal-epithelial cell co-culture model which mimics the intestinal crypt villus axis biology in terms of epithelial cell differentiation. In this model the fibroblast-induced epithelial cell differentiation from secretory crypt cells to absorptive enterocytes is mediated via transforming growth factor-β (TGF-β), the major inhibitory regulator of epithelial cell proliferation known to induce differentiation in intestinal epithelial cells. The aim of this study was to identify novel genes whose products would play a role in this TGF-β-induced differentiation. RESULTS: Differential display analysis resulted in the identification of a novel TGF-β upregulated mRNA species, the Sin3-associated protein 30-like, SAP30L. The mRNA is expressed in several human tissues and codes for a nuclear protein of 183 amino acids 70% identical with Sin3 associated protein 30 (SAP30). The predicted nuclear localization signal of SAP30L is sufficient for nuclear transport of the protein although mutating it does not completely remove SAP30L from the nuclei. In the nuclei SAP30L concentrates in small bodies which were shown by immunohistochemistry to colocalize with PML bodies only partially. CONCLUSIONS: By reason of its nuclear localization and close homology to SAP30 we believe that SAP30L might have a role in recruiting the Sin3-histone deacetylase complex to specific corepressor complexes in response to TGF-β, leading to the silencing of proliferation-driving genes in the differentiating intestinal epithelial cells

Exercise-induced expression of angiogenic growth factors in skeletal muscle and in capillaries of healthy and diabetic mice

Background. Diabetes has negative, and exercise training positive, effects on the skeletal muscle vasculature, but the mechanisms are not yet fully understood. In the present experiment the effects of running exercise on the mRNA expression of pro- and antiangiogenic factors were studied in healthy and diabetic skeletal muscle. The responses in capillaries and muscle fibers, collected from the muscle with laser capture microdissection, were also studied separately. Methods. Healthy and streptozotocin-induced diabetic mice were divided into sedentary and exercise groups. Exercise was a single bout of 1 h running on a treadmill. Gastrocnemius muscles were harvested 3 h and 6 h post exercise, and angiogenesis-related gene expressions were analyzed with real-time PCR. In addition to muscle homogenates, capillaries and muscle fibers were collected from the muscle with laser capture microdissection method and analyzed for vascular endothelial growth factor-A (VEGF-A) and thrombospondin-1 (TSP-1) mRNA expression. Results. Of the proangiogenic factors, VEGF-A and VEGF receptor-2 (VEGFR-2) mRNA expression increased significantly (P &lt; 0.05) in healthy skeletal muscle 6 h post exercise. VEGF-B also showed a similar trend (P = 0.08). No significant change was observed post exercise in diabetic muscles in the expression of VEGF-A, VEGFR-2 or VEGF-B. The expression of angiogenesis inhibitor TSP-1 and angiogenic extracellular matrix protein Cyr61 were significantly increased in diabetic muscles (P &lt; 0.05&#8211;0.01). Capillary mRNA expression resembled that in the muscle homogenates, however, the responses were greater in capillaries compared to muscle homogenates and pure muscle fibers. Conclusion. The present study is the first to report the effects of a single bout of exercise on the expression of pro- and antiangiogenic factors in diabetic skeletal muscle, and it provides novel data about the separate responses in capillaries and muscle fibers to exercise and diabetes. Diabetic mice seem to have lower angiogenic responses to exercise compared to healthy mice, and they show markedly increased expression of angiogenesis inhibitor TSP-1. Furthermore, exercise-induced VEGF-A expression was shown to be greater in capillaries than in muscle fibers.peerReviewe

DAPIT Over-Expression Modulates Glucose Metabolism and Cell Behaviour in HEK293T Cells

Introduction Diabetes Associated Protein in Insulin-sensitive Tissues (DAPIT) is a subunit of mitochondrial ATP synthase and has also been found to associate with the vacuolar H+-ATPase. Its expression is particularly high in cells with elevated aerobic metabolism and in epithelial cells that actively transport nutrients and ions. Deletion of DAPIT is known to induce loss of mitochondrial ATP synthase but the effects of its over-expression are obscure. Results In order to study the consequences of high expression of DAPIT, we constructed a transgenic cell line that constitutively expressed DAPIT in human embryonal kidney cells, HEK293T. Enhanced DAPIT expression decreased mtDNA content and mitochondrial mass, and saturated respiratory chain by decreasing H+-ATP synthase activity. DAPIT over-expression also increased mitochondrial membrane potential and superoxide level, and translocated the transcription factors hypoxia inducible factor 1α (Hif1α) and β-catenin to the nucleus. Accordingly, cells over-expressing DAPIT used more glucose and generated a larger amount of lactate compared to control cells. Interestingly, these changes were associated with an epithelial to mesenchymal (EMT)-like transition by changing E-cadherin to N-cadherin and up-regulating several key junction/adhesion proteins. At physiological level, DAPIT over-expression slowed down cell growth by G1 arrest and migration, and enhanced cell detachment. Several cancers also showed an increase in genomic copy number of Usmg5 (gene encoding DAPIT), thereby providing strong correlative evidence for DAPIT possibly having oncogenic function in cancers. Conclusions DAPIT over-expression thus appears to modulate mitochondrial functions and alter cellular regulations, promote anaerobic metabolism and induce EMT-like transition. We propose that DAPIT over-expression couples the changes in mitochondrial metabolism to physiological and pathophysiological regulations, and suggest it could play a critical role in H+-ATP synthase dysfunctions.Public Library of Science open acces

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy

Background: Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. Methods: Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks. Results: Treatment of mdx mice with ActRIIB-Fc resulted in significantly increased body and muscle weights in both sedentary and exercising mice. Femoral mu CT analysis showed increased bone volume and trabecular number (BV/TV +80%, Tb.N +70%, P <0.05) in both ActRIIB-Fc treated groups. Running also resulted in increased bone volume and trabecular number in PBS-treatedmice. However, there was no significant difference in trabecular bone structure or volumetric bone mineral density between the ActRIIB-Fc and ActRIIB-Fc-R indicating that running did not further improve bone structure in ActRIIB-Fc-treated mice. ActRIIB-Fc increased bone mass also in vertebrae (BV/TV +20%, Tb.N +30%, P <0.05) but the effects were more modest. The number of osteoclasts was decreased in histological analysis and the expression of several osteoblast marker genes was increased in ActRIIB-Fc treated mice suggesting decreased bone resorption and increased bone formation in these mice. Increased bone mass in femurs translated into enhanced bone strength in biomechanical testing as the maximum force and stiffness were significantly elevated in ActRIIB-Fc-treated mice. Conclusions: Our results indicate that treatment of mdx mice with the soluble ActRIIB-Fc results in a robust increase in bone mass, without any additive effect by voluntary running. Thus ActRIIB-Fc could be an attractive option in the treatment of musculoskeletal disorders.Peer reviewe

Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer

Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to investigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Importantly, A. muciniphila improved enterocyte monolayer integrity, as shown by a significant increase in the transepithelial electrical resistance (TER) of cocultures of Caco-2 cells with the bacterium. Further, A. muciniphila induced interleukin 8 (IL-8) production by enterocytes at cell concentrations 100-fold higher than those for Escherichia coli, suggesting a very low level of proinflammatory activity in the epithelium. In conclusion, our results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier. These results support earlier associative in vivo studies and provide insights into the interaction of A. muciniphila with the host.Peer reviewe

Effects of diet-induced obesity and voluntary wheel running on the microstructure of the murine distal femur

Background. Obesity and osteoporosis, two possibly related conditions, are rapidly expanding health concerns in modern society. Both of them are associated with sedentary life style and nutrition. To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (μCT) together with peripheral quantitative computed tomography (pQCT) to examine the microstructure of the distal femoral metaphysis in mice. Methods. Forty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C), control + running (CR), high-fat diet (HF), and high-fat diet + running (HFR). After a 21-week intervention, all the mice were sacrificed and the left femur dissected for pQCT and μCT measurements. Results. The mice fed the high-fat diet showed a significant weight gain (over 70% for HF and 60% for HFR), with increased epididymal fat pad mass and impaired insulin sensitivity. These obese mice had significantly higher trabecular connectivity density, volume, number, thickness, area and mass, and smaller trabecular separation. At the whole bone level, they had larger bone circumference and cross-sectional area and higher density-weighted maximal, minimal, and polar moments of inertia. Voluntary wheel running decreased all the cortical bone parameters, but increased the trabecular mineral density, and decreased the pattern factor and structure model index towards a more plate-like structure. Conclusions. The results suggest that in mice the femur adapts to obesity by improving bone strength both at the whole bone and micro-structural level. Adaptation to running exercise manifests itself in increased trabecular density and improved 3D structure, but in a limited overall bone growthpeerReviewe