Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export

Export of mRNA from the nucleus is linked to proper processing and packaging into ribonucleoprotein complexes. Although several observations indicate a coupling between mRNA 3' end formation and export, it is not known how these two processes are mechanistically connected. Here, we show that a subunit of the mammalian pre-mRNA 3' end processing complex, CF I(m)68, stimulates mRNA export. CF I(m)68 shuttles between the nucleus and the cytoplasm in a transcription-dependent manner and interacts with the mRNA export receptor NXF1/TAP. Consistent with the idea that CF I(m)68 may act as a novel adaptor for NXF1/TAP, we show that CF I(m)68 promotes the export of a reporter mRNA as well as of endogenous mRNAs, whereas silencing by RNAi results in the accumulation of mRNAs in the nucleus. Moreover, CF I(m)68 associates with 80S ribosomes but not polysomes, suggesting that it is part of the mRNP that is remodeled in the cytoplasm during the initial stages of translation. These results reveal a novel function for the pre-mRNA 3' end processing factor CF I(m)68 in mRNA export.

Differential uptake of (68)Ga-DOTATOC and (68)Ga-DOTATATE in PET/CT of gastroenteropancreatic neuroendocrine tumors

PURPOSE Abundant expression of somatostatin receptors (sst) is a characteristic of neuroendocrine tumors (NET). Thus, radiolabeled somatostatin analogs have emerged as important tools for both in vivo diagnosis and therapy of NET. The two compounds most often used in functional imaging with positron emission tomography (PET) are (68)Ga-DOTATATE and (68)Ga-DOTATOC. Both analogs share a quite similar sst binding profile. However, the in vitro affinity of (68)Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately tenfold higher than that of (68)Ga-DOTATOC. This difference may affect their efficiency in detection of NET lesions, as sst2 is the predominant receptor subtype on gastroenteropancreatic NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs ((68)Ga-DOTATATE and (68)Ga-DOTATOC) in the same patients with gastroenteropancreatic NET. PATIENTS AND METHODS Twenty-seven patients with metastatic gastroenteropancreatic NET underwent (68)Ga-DOTATOC and (68)Ga-DOTATATE PET/CT as part of the workup before prospective peptide receptor radionuclide therapy (PRRT). The performance of both imaging methods was analyzed and compared for detection of individual lesions per patient and for eight defined body regions. A region was regarded as positive if at least one lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUV(max)) was compared for concordant lesions and renal parenchyma. RESULTS Fifty-one regions were found positive with both (68)Ga-DOTATATE and (68)Ga-DOTATOC. Overall, however, significantly fewer lesions were detected with (68)Ga-DOTATATE in comparison with (68)Ga-DOTATOC (174 versus 179, p < 0.05). Mean (68)Ga-DOTATATE SUV(max) across all lesions was significantly lower compared with (68)Ga-DOTATOC (16.9 ± 6.8 versus 22.1 ± 12.0, p < 0.01). Mean SUV(max) for renal parenchyma was not significantly different between (68)Ga-DOTATATE and (68)Ga-DOTATOC (12.6 ± 2.6 versus 12.6 ± 2.7). CONCLUSIONS (68)Ga-DOTATOC and (68)Ga-DOTATATE possess similar diagnostic accuracy for detection of gastroenteropancreatic NET lesions (with a potential advantage of (68)Ga-DOTATOC) despite their evident difference in affinity for sst2. Quite unexpectedly, maximal uptake of (68)Ga-DOTATOC tended to be higher than its (68)Ga-DOTATATE counterpart. However, tumor uptake shows high inter- and intraindividual variance with unpredictable preference of one radiopeptide. Thus, our data encourage the application of different sst ligands to enable personalized imaging and therapy of gastroenteropancreatic NET with optimal targeting of tumor receptors.

Ms. hebr. oct. 68 - [Sammelband in 2 Teilen: Handschriftenkonvolut]

Vorbesitzer: Abraham Merzbacher

Ms. Barth. 68 - Abbreviatio Decreti

Vorbesitzer: Kloster Mariengarden in Groß-Burlo; Guilelmus Hacchusius; Bartholomaeusstift Frankfurt am Main

Application of Ga(68) -DOTA-exendin-4 PET/CT to localise an occult insulinoma

A 49 year old female presented to our Neuroendocrine Tumour (NET) centre with recurrent severe and disabling hypoglycaemia. She had previously been extensively investigated with a clinical and biochemical diagnosis of endogenous hyperinsulinemic hypoglycaemia although the source of hormonal hypersecretion could not be localised with MRI, EUS and (111) In-Octreotide scans. After extensive discussion the patient opted for blind surgical resection undergoing a pylorus-preserving pancreaticoduodenectomy in December 2010. Histological examination of the resected operative specimen demonstrated a normal pancreas with no evidence of neuroendocrine tumour. Consistent with this, post-surgery her hypoglycaemic symptoms persisted with fasting capillary blood glucose of 2.1-6.0 mmol/l with increasing hypoglycaemia unawareness. Consequently she sought alternative clinical opinions from two European Neuroendocrine Tumour Society (ENETS) Centres of Excellence who investigated her collaboratively. This article is protected by copyright. All rights reserved.

Influence of catchment quality and altitude on the water and sediment composition of 68 small lakes in Central Europe

68 lakes (63 Swiss, 2 French and 3 Italian) located in an altitudinal range between 334 and 2339m spanning a wide range of land-use have been investigated. The aim of the study was to discuss influences of geographic location, vegetation and land-use in the catchment area on the water and sediment chemistry of small lakes. Detailed quantitative description of land-use, vegetation, and climate in the watershed of all lakes was established. Surface and bottom water samples collected from each lake were analyzed for major ions and nutrients. Correlations were interpreted using linear regression analysis. Chemical parameters of water and sediment reflect the characteristics of the catchment areas. All lakes were alkaline since they were situated on calcareous bedrock. Concentrations of nitrogen and phosphorus strongly increase with increasing agricultural land-use. Na and K, however, are positively correlated with the amount of urbanization within the catchment area. These elements as well as dissolved organic carbon (DOC), Mg, Ca, and alkalinity, increase when the catchment is urbanized or used for agriculture. Total nitrogen and organic carbon in the sediments decrease distinctly if large parts of the catchment consist of bare land. No correlations between sediment composition and maximum water depth or altitude of the lakes were found.¶Striking differences in the water compositions of lakes above and below approximately 700 m of altitude were observed. Concentrations of total nitrogen and nitrate, total phosphorus, DOC, Na, K, Mg, Ca, and alkalinity are distinctly higher in most lakes below 700 m than above, and the pH of the bottom waters of these lakes is generally lower. Estimates of total nitrogen concentrations, even in remote areas, indicate that precipitation is responsible for increased background concentrations. At lower altitudes nitrogen concentrations in lakes is explained by the nitrogen loaded rain from urban areas deposited on the catchment, and with high percentages of agricultural land-use in the watershed.

Ms. Barth. 180 (Ausst. 68) - Lectionarium

Vorbesitzer: Bartholomaeusstift Frankfurt am Main

Na 1 Nachlass Max Horkheimer, 68 - Korrespondenzen u.a. mit Gretl Dupont (p. II 5, 220-439)

6 Briefe zwischen Max Horkheimer und F. Pollock mit Einbezug von Arthur G. Coons vom Occidental College Los Angeles, 1947; 4 Briefe zwischen Kathleen Costello und Max Horkheimer, 1945-1946; 8 Briefe und Beilage zwischen Edward M. David und Max Horkheimer, 24.11.1941-1942; 11 Briefe zwischen dem United States of America, Department of States und Max Horkheimer, 1942-1949; 3 Briefe zwischen Monroe E. Deutsch und Max Horkheimer, 1946; 12 Briefe und Beilage zwischen dem Dictionary of the Arts und Max Horkheimer, 1941-1944 sowie 1 Manuskrip: Sociology of Arts von Max Horkheimer; 2 Briefe zwischen Robert Disraeli und Max Horkheimer, 1945; 21 Briefe und Beilage zwischen Ria Drevermann und Max Horkheimer, 1948-1950; 6 Briefe zwischen Wolf Drewermann und Max Horkheimer, 1948-1949; 2 Briefe von Stephen Duggan vom Institute of International Education an Max Horkheimer, 1942-1947; 6 Briefe zwischen Joseph Dunner und Max Horkheimer, 1945-1947; 24 Briefe und Beilage zwischen Gretl Dupont und Max Horkheimer, 1942-1948; 3 Briefe zwischen Clarence A. Dykstra und Max Horkheimer, 1946-1947, 1947;