Expression of B-RAF V600E in Type II Pneumocytes Causes Abnormalities in Alveolar Formation, Airspace Enlargement and Tumor Formation in Mice

Growth factor induced signaling cascades are key regulatory elements in tissue development, maintenance and regeneration. Perturbations of these cascades have severe consequences, leading to developmental disorders and neoplastic diseases. As a major function in signal transduction, activating mutations in RAF family kinases are the cause of human tumorigenesis, where B-RAF V600E has been identified as the prevalent mutant. In order to address the oncogenic function of B-RAF V600E, we have generated transgenic mice expressing the activated oncogene specifically in lung alveolar epithelial type II cells. Constitutive expression of B-RAF V600E caused abnormalities in alveolar epithelium formation that led to airspace enlargements. These lung lesions showed signs of tissue remodeling and were often associated with chronic inflammation and low incidence of lung tumors. The inflammatory cell infiltration did not precede the formation of the lung lesions but was rather accompanied with late tumor development. These data support a model where the continuous regenerative process initiated by oncogenic B-RAF-driven alveolar disruption provides a tumor-promoting environment associated with chronic inflammation

Neoproterozoic to Paleozoic long-lived accretionary orogeny in the northern Tarim Craton

The Tarim Craton, located in the center of Asia, was involved in the assembly and breakup of the Rodinia supercontinent during the Neoproterozoic and the subduction-accretion of the Central Asian Orogenic Belt (CAOB) during the Paleozoic. However, its tectonic evolution during these events is controversial, and a link between the Neoproterozoic and Paleozoic tectonic processes is missing. Here we present zircon U-Pb ages, Hf isotopes, and whole-rock geochemical data for the extensive granitoids in the western Kuruktag area, northeastern Tarim Craton. Three distinct periods of granitoid magmatism are evident: circa 830–820 Ma, 660–630 Ma, and 420–400 Ma. The magma sources, melting conditions (pressure, temperature, and water availability), and tectonic settings of various granitoids from each period are determined. Based on our results and the geological, geochronological, geochemical, and isotopic data from adjacent areas, a long-lived accretionary orogenic model is proposed. This model involves an early phase (circa 950–780 Ma) of southward advancing accretion from the Tianshan to northern Tarim and a late phase (circa 780–600 Ma) of northward retreating accretion, followed by back-arc opening and subsequent bidirectional subduction (circa 460–400 Ma) of a composite back-arc basin (i.e., the South Tianshan Ocean). Our model highlights a long-lived accretionary history of the southwestern CAOB, which may have initiated as part of the circum-Rodinia subduction zone and was comparable with events occurring at the southern margin of the Siberian Craton, thus challenging the traditional southward migrating accretionary models for the CAOB

Biological effectiveness of didecyl dimethyl ammonium tetrafluoroborate (DBF) against basidiomycetes following preconditioning in soil bed tests

Evaluation of wood preservatives in soil-contact tests is becoming an important issue since detoxification of wood-protecting compounds by fungi and bacteria found in soil may decrease the resistance of treated wood. In this study, the decay resistance of wood treated with didecyl dimethyl ammonium tetrafluoroborate (DBF), a recently developed quaternary ammonia compound, was evaluated in both soil bed and laboratory decay resistance tests. Small specimens (5x10x100 mm(3)) of DBF-treated and un-treated sugi sapwood were Subjected to decay in laboratory soil bed tests (DIN ENV 807 (2001)) followed by Basidiomycetes tests (DIN EN 113 (1996)). Exposure in field soil and compost soil substrates was used to observe the effects of wood degrading and other soil-inhabiting micro-organisms on the decay resistance of the specimens. Soil bed tests showed that DBF-treated wood specimens at 7.7 kg/m(3) retention level (1% DBF solution concentration) showed better performance compared to 0.01 and 0.1% DBF treatments. The 7.7 kg/m(3) retention level was also effective to protect the wood specimens against Coniophora puteana and Coriolus versicolor in Basidiomycetes tests. It is concluded that detoxification of wood preservatives in soil contact is an Important factor to determine protective properties of treated wood in ground contact applications. Further experiments with larger specimens are needed to observe the performance of DBF-treated wood at higher retention levels in field above ground and ground contact tests