Some Glosses on Recent Mongol Studies

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Das Epenmotiv vom Kampf Gesers mit dem schwarzgefleckten Tiger

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The present state of the Mongolian epic and some topics for future research

In the March 1993 issue of the bulletin Folklore Fellows Network Lauri Honko raised the question: "What is an epic?" As a small contribution of my own I shall confine myself here to the question of what we know about the recent state of the Mongolian epic (Bawden 1980). Had it not been for the intensive and praiseworthy collection of the first Mongolian epic by Russian and Finnish scholars during the last decades of the nineteenth century and the beginning of the present century, we might not have reached the present stage in this branch of literary research. Through their recording projects, these scholars demonstrated the existence and dominance of the Mongolian epic.1Issue title; "Epics Along the Silk Roads.

DNA as Tunable Adaptor for siRNA Polyplex Stabilization and Functionalization

siRNA and microRNA are promising therapeutic agents, which are engaged in a natural mechanism called RNA interference that modulates gene expression posttranscriptionally. For intracellular delivery of such nucleic acid triggers, we use sequence-defined cationic polymers manufactured through solid phase chemistry. They consist of an oligoethanamino amide core for siRNA complexation and optional domains for nanoparticle shielding and cell targeting. Due to the small size of siRNA, electrostatic complexes with polycations are less stable, and consequently intracellular delivery is less efficient. Here we use DNA oligomers as adaptors to increase size and charge of cargo siRNA, resulting in increased polyplex stability, which in turn boosts transfection efficiency. Extending a single siRNA with a 181-nucleotide DNA adaptor is sufficient to provide maximum gene silencing aided by cationic polymers. Interestingly, this simple strategy was far more effective than merging defined numbers (4-10) of siRNA units into one DNA scaffolded construct. For DNA attachment, the 3' end of the siRNA passenger strand was beneficial over the 5' end. The impact of the attachment site however was resolved by introducing bioreducible disulfides at the connection point. We also show that DNA adaptors provide the opportunity to readily link additional functional domains to siRNA. Exemplified by the covalent conjugation of the endosomolytic influenza peptide INF-7 to siRNA via a DNA backbone strand and complexing this construct with a targeting polymer, we could form a highly functional polyethylene glycol-shielded polyplex to downregulate a luciferase gene in folate receptor-positive cells

Functional analysis of human and chimpanzee promoters

BACKGROUND: It has long been argued that changes in gene expression may provide an additional and crucial perspective on the evolutionary differences between humans and chimpanzees. To investigate how often expression differences seen in tissues are caused by sequence differences in the proximal promoters, we tested the expression activity in cultured cells of human and chimpanzee promoters from genes that differ in mRNA expression between human and chimpanzee tissues. RESULTS: Twelve promoters for which the corresponding gene had been shown to be differentially expressed between humans and chimpanzees in liver or brain were tested. Seven showed a significant difference in activity between the human promoter and the orthologous chimpanzee promoter in at least one of the two cell lines used. However, only three of them showed a difference in the same direction as in the tissues. CONCLUSION: Differences in proximal promoter activity are likely to be common between humans and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This suggests that several genetic differences between humans and chimpanzees might be responsible for a single expression difference and thus that relevant expression differences between humans and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences

Integrated stratigraphy and 40Ar/39Ar chronology of the Early to Middle Miocene Upper Freshwater Molasse in eastern Bavaria (Germany)

A detailed integrated stratigraphic study was carried out on middle Miocene fluvial successions of the Upper Freshwater Molasse (OSM) from the North Alpine Foreland Basin, in eastern Bavaria, Germany. The biostratigraphic investigations yielded six new localities thereby refining the OSM biostratigraphy for units C to E (sensu; Heissig, Actes du Congres BiochroM'1997) and further improving biostratigraphic correlations between the different sections throughout eastern Bavaria. Radioisotopic ages of 14.55 ± 0.19 and 14.88 ± 0.11 Ma have been obtained for glass shards from the main bentonite horizon and the Ries impactite: two important stratigraphic marker beds used for confirming our magnetostratigraphic calibration to the Astronomical Tuned Neogene Time Scale (ATNTS04; Lourens et al. in Geologic Time Scale 2004, Cambridge University Press, 2004). Paleomagnetic analysis was performed using alternating field (AF) and thermal (TH) demagnetization methods. The AF method revealed both normal and reverse polarities but proofs to yield unreliable ChRM directions for the Puttenhausen section. Using the biostratigraphic information and radioisotopic ages, the magnetostratigraphic records of the different sections are tentatively correlated to the Astronomical Tuned Neogene Time Scale (ATNTS04; Lourens et al. in Geologic Time Scale 2004, Cambridge University Press, 2004). This correlation implies that the main bentonite horizon coincides to chron C5ADn, which is corroborated by its radioisotopic age of 14.55 Ma, whereas the new fossil locality Furth 460, belonging to OSM unit E, probably correlates to chron C5Bn.1r. The latter correlation agrees well with the Swiss Molasse locality Frohberg. Correlations of the older sections are not straightforward. The Brock horizon, which comprises limestone ejecta from the Ries impact, possibly correlates to C5ADr (14.581 ± 14.784 Ma), implying that, although within error, the radioisotopic age of 14.88 ± 0.11 Ma is somewhat too old. The fossil localities in Puttenhausen, belonging to the older part of OSM unit C, probably coincide with chron C5Cn.2n or older, which is older than the correlations established for the Swiss Molasse. © Springer-Verlag 2007

Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells

Embryonic stem cells (ESCs) could potentially compensate for the lack of blood platelets available for use in transfusions. Here, we describe a new method for generating mouse ESC-derived platelets (ESPs) that can contribute to hemostasis in vivo. Flow cytometric sorting of cells from embryoid bodies on day 6 demonstrated that c-Kit+ integrin αIIb (αIIb)+ cells, but not CD31+ cells or vascular endothelial cadherin+ cells, are capable of megakaryopoiesis and the release of platelet-like structures by day 12. αIIbβ3-expressing ESPs exhibited ectodomain shedding of glycoprotein (GP)Ibα, GPV, and GPVI, but not αIIbβ3 or GPIbβ. ESPs showed impaired αIIbβ3 activation and integrin-mediated actin reorganization, critical events for normal platelet function. However, the administration of metalloproteinase inhibitors GM6001 or TAPI-1 during differentiation increased the expression of GPIbα, improving both thrombogenesis in vitro and posttransfusion recovery in vivo. Thus, the regulation of metalloproteinases in culture could be useful for obtaining high-quality, efficacious ESPs as an alternative platelet source for transfusions

Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9–mediated progenitor cell mobilization

Mast cells accumulate in tissues undergoing angiogenesis during tumor growth, wound healing, and tissue repair. Mast cells can secrete angiogenic factors such as vascular endothelial growth factor (VEGF). Ionizing irradiation has also been shown to have angiogenic potential in malignant and nonmalignant diseases. We observed that low-dose irradiation fosters mast cell–dependent vascular regeneration in a limb ischemia model. Irradiation promoted VEGF production by mast cells in a matrix metalloproteinase-9 (MMP-9)–dependent manner. Irradiation, through MMP-9 up-regulated by VEGF in stromal and endothelial cells, induced the release of Kit-ligand (KitL). Irradiation-induced VEGF promoted migration of mast cells from the bone marrow to the ischemic site. Irradiation-mediated release of KitL and VEGF was impaired in MMP-9–deficient mice, resulting in a reduced number of tissue mast cells and delayed vessel formation in the ischemic limb. Irradiation-induced vasculogenesis was abrogated in mice deficient in mast cells (steel mutant, Sl/Sld mice) and in mice in which the VEGF pathway was blocked. Irradiation did not induce progenitor mobilization in Sl/Sld mice. We conclude that increased recruitment and activation of mast cells following irradiation alters the ischemic microenvironment and promotes vascular regeneration in an ischemia model. These data show a novel mechanism of neovascularization and suggest that low-dose irradiation may be used for therapeutic angiogenesis to augment vasculogenesis in ischemic tissues