TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation

The discovery of hydroxymethyl-,formyl- and carboxylcytosine, generated through oxidation of methylcytosine by TET dioxygenases, raised the question how these modifications contribute to epigenetic regulation. As they are subjected to complex regulation in vivo, we dissected links to gene expression with in vitro modified reporter constructs. We used an Oct4 promoter-driven reporter gene and demonstrated that in vitro methylation causes gene silencing while subsequent oxidation with purified catalytic domain of TET1 leads to gene reactivation. To identify proteins involved in this pathway we screened for TET interacting factors and identified TDG, PARP1, XRCC1 and LIG3 that are involved in base-excision repair. Knockout and rescue experiments demonstrated that gene reactivation depended on the glycosylase TDG, but not MBD4, while NEIL1, 2 and 3 could partially rescue the loss of TDG. These results clearly show that oxidation of methylcytosine by TET dioxygenases and subsequent removal by TDG or NEIL glycosylases and the BER pathway results in reactivation of epigenetically silenced genes

The missing link of Rodinia break up in western South America: A petrographical, geochemical, and zircon Pb-Hf isotope study of the volcanosedimentary Chilla beds (Altiplano, Bolivia)

The assembly of Rodinia involved the collision of eastern Laurentia with southwestern Amazonia at ca. 1 Ga. The tectonostratigraphic record of the central Andes records a gap of ∼300 m.y. between 1000 Ma and 700 Ma, i.e., from the beginning of the Neoproterozoic Era to the youngest part of the Cryogenian Period. This gap encompasses the time of final assembly and breakup of the Rodinia supercontinent in this region. We present new petrographic and whole-rock geochemical data and U-Pb ages combined with Hf isotope data of detrital zircons from the volcanosedimentary Chilla beds exposed on the Altiplano southwest of La Paz, Bolivia. The presence of basalt to andesite lavas and tuffs of continental tholeiitic affinity provides evidence of a rift setting for the volcanics and, by implication, the associated sedimentary rocks. U-Pb ages of detrital zircons (n = 124) from immature, quartz-intermediate sandstones have a limited range between 1737 and 925 Ma. A youngest age cluster (n = 3) defines the maximum depositional age of 925 ± 12 Ma. This is considered to coincide with the age of deposition because Cryogenian and younger ages so typical of Phanerozoic units of this region are absent from the data. The zircon age distribution shows maxima between 1300 and 1200 Ma (37% of all ages), the time of the Rondônia–San Ignacio and early Sunsás (Grenville) orogenies in southwestern Amazonia. A provenance mixing model considering the Chilla beds, Paleozoic Andean units, and data from eastern Laurentia Grenville sources shows that >90% of the clastic input was likely derived from Amazonia. This is also borne out by multidimensional scaling (MDS) analysis of the data. We also applied MDS analysis to combinations of U-Pb age and Hf isotope data, namely εHf(t) and 176Hf/177Hf values, and demonstrate again a very close affinity of the Chilla beds detritus to Amazonian sources. We conclude that the Chilla beds represent the first and hitherto only evidence of Rodinia breakup in Tonian time in Andean South America.publishedVersio

Quartärgliederung und Aufbau von Warmzeit-Kaltzeit-Zyklen in Bereichen mit Dominanz periglazialer Hangsedimente, dargestellt am Quartärprofil Dreihausen/Hessen

Das Quartärprofil Dreihausen/Hessen ist durch Verzahnung von Löß bzw. Lößlehm und periglazialen Hangsedimenten gekennzeichnet. Der über 12 m hohe Aufschluß wurde geomorphologisch, stratigraphisch und mikromorphologisch untersucht. Es können 13 Bodenbildungs-Sedimentations-Zyklen unterschieden werden. Aufgrund der erzielten Ergebnisse wird das Idealbild eines quartären Warmzeit-Kaltzeit-Zyklus entworfen.researc

Thermal regime of the Costa Rican convergent margin: 1. Along-strike variations in heat flow from probe measurements and estimated from bottom-simulating reflectors

21 pages, 9 figures, 1 tableThe thermal structure of convergent margins provides information related to the tectonics, geodynamics, metamorphism, and fluid flow of active plate boundaries. We report 176 heat flow measurements made with a violin bow style probe across the Costa Rican margin at the Middle America Trench. The probe measurements are collocated with seismic reflection lines. These seismic reflection lines show widespread distribution of bottom-simulating reflectors (BSRs). To extend the spatial coverage of heat flow measurements we estimate heat flow from the depth of BSRs. Comparisons between probe measurements and BSR-derived estimates of heat flow are generally within 10% and improve with distance landward of the deformation front. Together, these determinations provide new information on the thermal regime of this margin. Consistent with previous studies, the margin associated with the northern Nicoya Peninsula is remarkably cool. We define better the southern boundary of the cool region. The northern extent of the cool region remains poorly determined. A regional trend of decreasing heat flow landward of the deformation front is apparent, consistent with the downward advection of heat by the subducting Cocos Plate. High wave number variability at a scale of 5–10 km is significantly greater than the measurement uncertainty and is greater south of the northern Nicoya Peninsula. These heat flow anomalies vary between approximately 20 and 60 mW m−2 and are most likely due to localized fluid flow through mounds and faults on the margin. Simple one-dimensional models show that these anomalies are consistent with flow rates of 7–15 mm yr−1. Across the margin toe variability is significant and likely due to fluid flow through deformation structures associated with the frontal sedimentary prismThis research was support by an NSF award (OCE‐0637120) to R.N.H. We thank R. von Huene, P. Fulton, and G. Spinelli for helpful comments. Heat flow data acquisition was funded by the German Science Foundation (DFG) through grant Vi 133/7‐1 to H.V. and I.G. and the SFB 574 “Volatiles and fluids in subduction zones” at Christan‐Albrechts University, Kiel. This is a contribution of the Barcelona Center for Subsurface Imaging (Barcelona‐CSI) supported by the Kaleidoscope project of REPSOLPeer Reviewe

BAW-Brief Nr. 2 - Juli 2003

574-L, Wechsel der Leitung der Dienststelle Hamburg573-B, Bautechnik, Schweißen an Altstählen572-B, Bautechnik, Materialprüfzeugnisse für Ausrüstungsteile und Schweißzusatzwerkstoffe571-B, Bautechnik, Bericht einer ad-hoc-Arbeitsgruppe "Behindertengerechte Gestaltung von Schleusensteuerständen"570-G, Geotechnik, Neue Oberflächendichtungen für Wasserstraße

TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation

The discovery of hydroxymethyl-,formyl- and carboxylcytosine, generated through oxidation of methylcytosine by TET dioxygenases, raised the question how these modifications contribute to epigenetic regulation. As they are subjected to complex regulation in vivo, we dissected links to gene expression with in vitro modified reporter constructs. We used an Oct4 promoter-driven reporter gene and demonstrated that in vitro methylation causes gene silencing while subsequent oxidation with purified catalytic domain of TET1 leads to gene reactivation. To identify proteins involved in this pathway we screened for TET interacting factors and identified TDG, PARP1, XRCC1 and LIG3 that are involved in base-excision repair. Knockout and rescue experiments demonstrated that gene reactivation depended on the glycosylase TDG, but not MBD4, while NEIL1, 2 and 3 could partially rescue the loss of TDG. These results clearly show that oxidation of methylcytosine by TET dioxygenases and subsequent removal by TDG or NEIL glycosylases and the BER pathway results in reactivation of epigenetically silenced genes

Alley coppice—a new system with ancient roots

International audience& Context Current production from natural forests will not satisfy future world demand for timber and fuel wood, and new land management options are required. & Aims We explore an innovative production system that combines the production of short rotation coppice in wide alleys with the production of high-value trees on narrow strips of land; it is an alternative form of alley cropping which we propose to call 'alley coppice'. The aim is to describe this alley coppice system and to illustrate its potential for produc-ing two diverse products, namely high-value timber and ener-gy wood on the same land unit. & Methods Based on a comprehensive literature review, we compare the advantages and disadvantages of the alley cop-pice system and contrast the features with well-known existing or past systems of biomass and wood production. & Results We describe and discuss the basic aspects of alley coppice, its design and dynamics, the processes of competi-tion and facilitation, issues of ecology, and areas that are open for future research. & Conclusion Based on existing knowledge, a solid founda-tion for the implementation of alley coppice on suitable land is presented, and the high potential of this system could be shown

Investigations on the Usefulness of CEACAMs as Potential Imaging Targets for Molecular Imaging Purposes

Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs) family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well. In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.Germany. Bundesministerium für Bildung und Forschung (TOMCAT, grant number 01EZ0824