•The hAAG-modified comet assay, a new tool for the detection of some alkylated bases.•hAAG detects ethenoadenines and hypoxanthine in an oligonucleotide-cleavage assay.•Fpg-modified comet assay ...detects N7-methylguanines indirectly after lysis at pH 10.
The enzyme-modified comet assay is widely used for the detection of oxidized DNA lesions. Here we describe for the first time the use of the human alkyladenine DNA glycosylase (hAAG) for the detection of alkylated bases. hAAG was titrated using untreated and methyl methanesulfonate (MMS)-treated TK-6 cells. The hAAG-modified comet assay was compared to the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay, widely used to detect oxidized lesions but that also detects ring-opened purines derived from some alkylated lesions, using cells treated with potassium bromate (oxidizing agent) or MMS. Moreover, neutral and alkaline lysis conditions were used to determine the nature of detected lesions. When alkaline lysis was employed (condition normally used), the level of hAAG-sensitive sites was higher than the Fpg-sensitive sites in MMS-treated cells and hAAG, unlike Fpg, did not detect oxidized bases. After neutral lysis, Fpg did not detect MMS-induced lesions; however, results obtained with hAAG remained unchanged. As expected, Fpg detected oxidized purines and imidazole ring-opened purines, derived from N7-methylguanines under alkaline conditions. It seems that hAAG detected N7-methylguanines, the ring-opened purines derived at high pH, and 3-methlyladenines. Specificity of hAAG towards different DNA lesions was evaluated using a multiplex oligonucleotide-cleavage assay, confirming the ability of hAAG to detect ethenoadenines and hypoxanthine. The hAAG-modified comet assay is a new tool for the detection of alkylated bases.
The 7 + 3 regimen is the front-line induction chemotherapy in patients with newly diagnosed acute myeloid leukemia, with a response rate of 60-80%. But it’s not suitable for all patients especially ...old/unfit patients because of a higher treatment related toxicity. Therefore, safer and more effective induction therapies are required. In this retrospective study, 50 patients with newly diagnosed acute myeloid leukemia received decitabine combined with HAAG (homoharringtonine, aclarubicin, low-dose cytarabine and G-CSF) as induction chemotherapy. Complete remission (CR) rate was 96% (48/50) and overall response rate was 100%. Of note, All 7 patients harboring
FLT3-ITD
mutation achieved CR. The median overall survival (OS) was 40.0 months (range 2.0, 58.0). The OS at 1, 3, and 5 years were 75.3%, 54.2%, and 49.3%. The median relapse free survival (RFS) was 38.0 months (range 2.0, 58.0). The RFS at 1, 3, and 5 years were 67.3%, 48.9%, and 45.1%. The OS and RFS of patients who received hematopoietic stem cell transplantation (HSCT) were significantly higher than those who did not undergo HSCT (
p
=0.017; 0.016). The incidence of grade 3-4 neutropenia and thrombocytopenia was 84% and 88%. Meanwhile, the incidence of grade 3-4 infection and bleeding was only 16% and 6%. There was no early death. In conclusion, DAC+HAAG regimen is effective and well-tolerated as induction therapy in patients with newly diagnosed AML.
Gondwana breakup changed the global continental configuration, leading to opening of major oceanic gateways, shifts in the climate system and significant impacts on the biosphere, hydrosphere and ...cryosphere. Although of global importance, the earliest stages of the supercontinental fragmentation are poorly understood. Reconstructing the processes driving Gondwana breakup within the ice-covered Weddell Sea Rift System (WSRS) has proven particularly challenging. Paleomagnetic data and tectonic reconstructions of the WSRS region indicate that major Jurassic translation and rotation of microcontinental blocks were a key precursor to Gondwana breakup by seafloor spreading. However, geophysical interpretations have provided little support for major motion of crustal blocks during Jurassic extension in the WSRS. Here we present new compilations of airborne magnetic and airborne gravity data, together with digital enhancements and 2D models, enabling us to re-evaluate the crustal architecture of the WSRS and its tectonic and kinematic evolution. Two provinces are identified within the WSRS, a northern E/W trending province and a southern N/S trending province. A simple extensional or transtensional model including ~500km of crustal extension and Jurassic magmatism accounts for the observed geophysical patterns. Magmatism is linked with rifting between South Africa and East Antarctica in the north, and associated with back-arc extension in the south. Our tectonic model implies ~30° of Jurassic block rotation and juxtaposes the magnetically similar Haag Block and Shackleton Range, despite differences in both Precambrian and Pan African-age surface geology. Although geophysically favoured our new model cannot easily be reconciled with geological and paleomagnetic interpretations that require ~1500km of motion and 90° anticlockwise rotation of the Haag-Ellsworth Whitmore block from a pre-rift position adjacent to the Maud Belt. However, our model provides a simpler view of the WSRS as a broad Jurassic extensional/transtensional province within a distributed plate boundary between East and West Antarctica.
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•Two distinct aeromagnetic provinces identified within the Weddell Sea Rift System•Approximately 500km continental extension suggested by 2D potential field models•Alternative simple model for tectonic evolution of Weddell Sea Rift System proposed
Haag and Dessau's 1984 mechanism of protolytic alkane cracking is a landmark because it links petroleum refining chemistry to Olah's hydrocarbon chemistry in superacids. According to this now widely ...accepted mechanism, at about 800
K an acidic catalyst such as a zeolite protonates an alkane to give carbonium ion transition states that collapse to give alkanes (or dihydrogen) and carbenium ions, which give back protons to the catalyst to form alkenes. The cracking products include dihydrogen, methane, and ethane (as observed in large-scale petroleum cracking), in contrast to those of classical catalytic cracking. The Haag–Dessau mechanism is favored by medium-pore zeolite catalysts that allow the monomolecular reaction while restricting the bimolecular (hydride transfer) reaction of classical cracking because of the steric limitations in the pores; protolytic cracking is kinetically significant only when alkene concentrations are low, because alkenes are much better proton acceptors than alkanes, and their protonation leads to classical cracking. The Haag–Dessau mechanism is the key to unraveling the competing mechanisms of catalytic cracking (including classical cracking and oligomerization cracking) and to successful quantitative representation of these simultaneous reactions — one of the most successful examples of microkinetics analysis. Understanding of protolytic cracking has helped in the diagnosis of shape selectivity and mass transfer effects in zeolite-catalyzed cracking. Furthermore, protolytic cracking is one of the surface-catalyzed reactions most susceptible to theoretical modeling with density functional methods; the theory shows that the assumption of a carbonium ion transition state is simplified and that bonding of the transition state to the catalyst surface is significant.
•New U-Pb zircon data has identified four distinct magmatic events from the Mesoproterozoic Haag Nunataks crustal block; at 1238 ± 4, ~1170, 1064 ± 4 and 1056 ± 8 Ma.•Juvenile arc magmatism of the ...Namaqua-Natal-Maud metamorphic belt have a magmatic history with key events at ~1240 and ~1170 Ma and suggest a close correlation between the early magmatic history at Haag Nunataks and the Natal Embayment.•The ~1240 and ~1170 Ma episodes of magmatism at Haag Nunataks do not correlate with the magmatic/tectonic events of Laurentia (Llano Uplift region). The younger phases of magmatism at Haag Nunataks (~1060 Ma) are however, suggested to have a closer relationship to the Ottawan phase deformation following the collision of the Kalahari and Laurentian continents.•A Mesoproterozoic correlation and continuation with the Natal Embayment is favoured for the Haag Nunataks crustal block. Juvenile arc terranes (Namaqua-Natal belt) developed from ~1240 to 1160 Ma on the margins of the proto-Kalahari craton and are not associated with any significant deformation events.
Understanding the accretionary stages of Rodinia evolution and the arrangement of cratons and arc terranes is dependent upon high-precision geochronology from key piercing points of Mesoproterozoic rocks. U-Pb zircon dating is presented here from the Mesoproterozoic Haag Nunataks gneiss complex of West Antarctica where the dominant granodiorite protolith was emplaced at 1238 ± 4 Ma, aplite/pegmatite sheets were intruded at 1064 ± 4 Ma and the final intrusive phase of microgranite sheets were emplaced at 1056 ± 8 Ma. A separate magmatic event at ~1170 Ma is recorded as inherited zircons in the later stage intrusions. Based on field relationships, the main phase of deformation at Haag Nunataks is thought to have developed prior to the emplacement of the microgranite sheet at ~1056 Ma but after the ~1064 Ma aplite/pegmatite intrusive phase. Potentially correlative units from the Shackleton Range and Coats Land of East Antarctica are also dated to test supposed correlations with arc terranes and crustal blocks at the margins of Laurentia and the proto-Kalahari craton. An ice-transported granite pegmatite sample recovered from the Brunt Ice Shelf is used as a partial proxy for unexposed rocks of the ice-covered Coats Land block and has been dated at ~1100 Ma. A diorite gneiss from the Shackleton Range was also analysed as it forms part of a magnetic domain shared with the Haag Nunataks crustal block. Core zircon ages of ~2470 Ma were determined, and the age of migmatisation is interpreted at ~1740 Ma and rules out any potential correlation with the Haag Nunataks gneiss complex. The magmatic precursors of the Haag Nunataks orthogneisses were emplaced in a juvenile arc setting. We argue that this arc was located in the Natal Embayment region, contiguous with the Namaqua-Natal-Maud belt of arc terranes typified by enhanced magmatism at ~1240 Ma and ~1170 Ma not associated with any significant deformation events. The later magmatic events at Haag Nunataks at ~1060 Ma are more closely associated with collision of Laurentia with the proto-Kalahari craton and the associated deformation is correlated with the Ottawan phase of the Grenville orogeny.
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