Metastatic lung cancer in a new mouse model inheriting p53 and latent K-ras mutations

Lung cancer is a devastating disease with very poor prognosis. The design of better treatments for patients would be greatly aided by mouse models that closely resemble the human disease. The most common type of human lung cancer is adenocarcinoma with frequent metastasis. Unfortunately, current models for this tumor are inadequate due to the absence of metastasis. Based on the molecular findings in human lung cancer and metastatic potential of osteosarcomas in mutant p53 mouse models, I hypothesized that mice with both K-ras and p53 missense mutations might develop metastatic lung adenocarcinomas. Therefore, I incorporated both K-rasLA1 and p53RI72HΔg alleles into mouse lung cells to establish a more faithful model for human lung adenocarcinoma and for translational and mechanistic studies. Mice with both mutations ( K-rasLA1/+ p53R172HΔg/+) developed advanced lung adenocarcinomas with similar histopathology to human tumors. These lung adenocarcinomas were highly aggressive and metastasized to multiple intrathoracic and extrathoracic sites in a pattern similar to that seen in lung cancer patients. This mouse model also showed gender differences in cancer related death and developed pleural mesotheliomas in 23.2% of them. In a preclinical study, the new drug Erlotinib (Tarceva) decreased the number and size of lung lesions in this model. These data demonstrate that this mouse model most closely mimics human metastatic lung adenocarcinoma and provides an invaluable system for translational studies. ^ To screen for important genes for metastasis, gene expression profiles of primary lung adenocarcinomas and metastases were analyzed. Microarray data showed that these two groups were segregated in gene expression and had 79 highly differentially expressed genes (more than 2.5 fold changes and p<0.001). Microarray data of Bub1b, Vimentin and CCAM1 were validated in tumors by quantitative real-time PCR (QPCR). Bub1b , a mitotic checkpoint gene, was overexpressed in metastases and this correlated with more chromosomal abnormalities in metastatic cells. Vimentin, a marker of epithelial-mesenchymal transition (EMT), was also highly expressed in metastases. Interestingly, Twist, a key EMT inducer, was also highly upregulated in metastases by QPCR, and this significantly correlated with the overexpression of Vimentin in the same tumors. These data suggest EMT occurs in lung adenocarcinomas and is a key mechanism for the development of metastasis in K-ras LA1/+ p53R172HΔg/+ mice. Thus, this mouse model provides a unique system to further probe the molecular basis of metastatic lung cancer.^

Net primary productivity, POC export, Th234 and U238 activities and abundance of autotrophs during U.S.C.G.C. Healy cruises HLY0802 and HLY0803

Seasonal patterns in the partitioning of phytoplankton carbon during receding sea ice conditions in the eastern Bering Sea water column are presented using rates of 14C net primary productivity (NPP), phototrophic plankton carbon content, and POC export fluxes from shelf and slope waters in the spring (March 30-May 6) and summer (July 3-30) of 2008. At ice-covered and marginal ice zone (MIZ) stations on the inner and middle shelf in spring, NPP averaged 76 ± 93 mmol C/m**2/d, and in ice-free waters on the outer shelf NPP averaged 102 ± 137 mmol C/m**2/d. In summer, rates of NPP were more uniform across the entire shelf and averaged 43 ± 23 mmol C/m**2/d over the entire shelf. A concomitant shift was observed in the phototrophic pico-, nano-, and microplankton community in the chlorophyll maximum, from a diatom dominated system (80 ± 12% autotrophic C) in ice covered and MIZ waters in spring, to a microflagellate dominated system (71 ± 31% autotrophic C) in summer. Sediment trap POC fluxes near the 1% PAR depth in ice-free slope waters increased by 70% from spring to summer, from 10 ± 7 mmol C/m**2/d to 17 ± 5 mmol C/m**2/d, respectively. Over the shelf, under-ice trap fluxes at 20 m were higher, averaging 43 ± 17 mmol C/m**2/d POC export over the shelf and slope estimated from 234Th deficits averaged 11 ± 5 mmol C/m**2/d in spring and 10 ± 2 mmol C/m**2/d in summer. Average e-ratios calculated on a station-by-station basis decreased by ~ 30% from spring to summer, from 0.46 ± 0.48 in ice-covered and MIZ waters, to 0.33 ± 0.26 in summer, though the high uncertainty prevents a statistical differentiation of these data.

(Table 1) K and Ar content, and age determination of ODP Holes 126-792E and 126-793B

Results of conventional K-Ar dating on five samples from two sites from the Izu-Bonin forearc are presented. Two samples recovered from a volcanic edifice and overlying sediments drilled on the western side of the forearc basin (Site 792) indicate a basement age of 34 Ma. This is consistent with early Oligocene biostratigraphic ages from the overlying sediments. Three samples from the basement of Hole 793B at the center of the basin are not analytically distinguishable, with a best age of 27.1 +/- 0.6 Ma. This is slightly younger than the 30-33 Ma biostratigraphic and magnetostratigraphic estimates from the overlying sediments, suggesting that alteration processes have lowered the apparent K-Ar ages. These ages suggest that syn-rift volcanism occurred in a forearc location during the middle Oligocene.

Chesterton en Borges

A partir de los aportes críticos de Enrique Anderson Imbert y de Umberto Eco acerca de las posibles relaciones existentes entre los escritos de Borges y Chesterton es que, en el presente trabajo, me propongo estudiar el motivo del cuarto cerrado y su relación con el detective en Seis problemas para don Isidro Parodi de Honorio Bustos Domecq (seudónimo de Adolfo Bioy Casares y Jorge Luis Borges). En tal sentido, intento fundamentar la relación paródica que a nivel de procedimientos se establece con la saga del padre Brown de Gilbert R. Chesterton. Con tal finalidad, reseño el itinerario diacrónico que los tres elementos fundamentales de este tipo de relatos -el cuarto cerrado, el detective y la víctima-, han tenido a lo largo de la historia de la literatura de índole policial con el objetivo preciso de señalar la peculiar textualización de los mismos en la obra analizada. La originalidad del tratamiento de estos motivos típicos, tanto por parte de Biorges como por parte de Chesterton, ha evitado su posible petrificación en el tiempo como tópico literario.

Respuestas fisiológicas a la suplementación con calcio de plántulas de vinal (Prosopis ruscifolia G.) estresadas con NaCl

Vinal (Prosopis ruscifolia G.) es una especie de importancia forestal, nativa de la Región Fitogeográfica del Chaco Occidental, altamente tolerante al estrés salino. El objetivo de este trabajo fue poner a prueba la hipótesis de que la suplementación con CaSO4 disminuye la concentración de iones tóxicos en plántulas de vinal, e incrementa la concentración de prolina, permitiendo un ajuste osmótico. Las plántulas se cultivaron en solución nutritiva de Hoagland al 25%, con o sin la adición de 0,4 mol L-1 de NaCl, y con o sin suplementación de 5 ó 10 mmol L-1 de CaSO4. Se determinó la materia seca, composición mineral, contenido relativo de agua y concentraciones de prolina y azúcares solubles. Se utilizó un diseño experimental completamente aleatorizado con cinco repeticiones, y los resultados se analizaron con ANOVA y test de Tukey. Los resultados obtenidos en este trabajo confirman el rol protector del Ca+2, a través de la manutención de las concentraciones de Ca+2, K+ y Mg+2 en los tejidos, la inhibición de la absorción de Na+ y el ajuste osmótico mediante la síntesis de solutos osmocompatibles.

(Table 1) Geochemistry of ODP Hole 130-807C carbonates across the K/T boundary

Paleontological, stable isotopic, trace elemental abundance, and magnetostratigraphic studies have been performed on limestones spanning the Cretaceous/Tertiary boundary transition at Ocean Drilling Program (ODP) Hole 807C. Paleontological evidence exists for considerable resedimentation, which we attribute to the fact that Hole 807C is located in a basement graben. Age estimates based on planktonic foraminiferal biostratigraphy, as well as magnetostratigraphy, indicate that sedimentation rates could have been on the order of 12-14 m/m.y. This is significantly higher than those documented in other important Deep Sea Drilling Project (DSDP) and ODP Cretaceous/Tertiary boundary sections using the same age control points (e.g., DSDP Hole 577 and ODP Hole 690B), although not as high as those documented from DSDP Hole 524. The expanded nature of this succession has resulted in the Cretaceous/Tertiary boundary d13C decrease occurring over approximately a 9-m interval. Ir analysis of these sediments do not show a single large anomaly, as has been found in other Cretaceous/Tertiary boundary sections, but trivial background levels instead. Ce data support the hypothesis that this section has been expanded by secondary sedimentological processes.

Environmental variables and multivariate seabed classification maps via k means clustering of Potter Cove, Antarctica, link to input and result files in GeoTIFF format

This study subdivides the Potter Cove, King George Island, Antarctica, into seafloor regions using multivariate statistical methods. These regions are categories used for comparing, contrasting and quantifying biogeochemical processes and biodiversity between ocean regions geographically but also regions under development within the scope of global change. The division obtained is characterized by the dominating components and interpreted in terms of ruling environmental conditions. The analysis includes in total 42 different environmental variables, interpolated based on samples taken during Australian summer seasons 2010/2011 and 2011/2012. The statistical errors of several interpolation methods (e.g. IDW, Indicator, Ordinary and Co-Kriging) with changing settings have been compared and the most reasonable method has been applied. The multivariate mathematical procedures used are regionalized classification via k means cluster analysis, canonical-correlation analysis and multidimensional scaling. Canonical-correlation analysis identifies the influencing factors in the different parts of the cove. Several methods for the identification of the optimum number of clusters have been tested and 4, 7, 10 as well as 12 were identified as reasonable numbers for clustering the Potter Cove. Especially the results of 10 and 12 clusters identify marine-influenced regions which can be clearly separated from those determined by the geological catchment area and the ones dominated by river discharge.

K-Ar age determination of Paleozoic rock samples from northern Victoria Land, Antarctica

K-Ar ages of 82 slate and schist (white-mica-rich whole rock) samples are reported for Late Precambrian-Early Ordovician metamorphic rocks of the Wilson, Bowers and Robertson Bay terranes of northern Victoria Land. These are amalgamated in two vertical sections along composite NE-SW horizontal profiles across (1) Oates Coast in the north, and (2) Terra Nova Bay area in the south. The ages are in the range 328-517 Ma. Both profiles show some age variation with altitude, but more importantly, they define an inverted wedge shaped pattern, reflecting a "pop-up" strucure. This is oriented NW-SE at the eastern margin of the Wilson terrane, and the edges coincide with the Exiles and Wilson Thrusts which cross the region. Ages inside the "pop-up" structure are younger, ca. 460-480 Ma, than those along its eastern and western flanks, ca. 490-520 Ma. The K-Ar age patterns thus demonstrate a late Ross Orogenic age (ca. 460 Ma) for this structure, which may be associated with assembly of the Wilson and Bowers terranes.

Total number of benthic foraminifera in sediments below the K/T boundary in the Atlantic and Pacific Ocean

Most species of Late Cretaceous deep-sea benthic foraminifera are believed to be cosmopolitan and therefore to exhibit only minor biogeographical differences. In this preliminary report, six Deep Sea Drilling Project (DSDP) sites from different oceans, paleolatitudes, and paleodepths were analyzed for terminal Cretaceous abyssal-bathyal benthic foraminifera in order to investigate their assumed cosmopolitan distribution and the question of whether different faunal compositions are related to time, different paleolatitudes, and/or different paleodepths. The material studied was obtained from the low-latitude Site 465 (Pacific Ocean), and the intermediate-latitude Sites 384 (North Atlantic) and 356, 516, 525, and 527 (South Atlantic). The material analyzed represents a time slice encompassing the last 20-50 k.y. of the Cretaceous. The faunas contain numerous "Velasco-type" species, such as Gavelinella beccariiformis (White), Cibicidoides velascoensis (Cushman), Nuttallides truempyi (Nuttall), Gaudryina pyramidata Cushman, and various gyroidinoids and buliminids. The results contradict the general assumption of the cosmopolitan nature of Late Cretaceous deep-sea benthic foraminifera advocated in the literature. Only about 9% of the taxa identified were found to be truly "cosmopolitan" through their occurrence at all the sites analyzed. On the basis of correspondence analysis and relative abundance data, three assemblages and three subassemblages were recognized: (1) a bathyal-abyssal assemblage [Nuttallinella sp. A, Cibicidoides hyphalus (Fisher), Valvalabamina sp. evolute form, and Gyroidinoides spp.] at the South Atlantic Sites 356, 516, 525, and 527, divided into three subassemblages, namely (a) a middle bathyal subassemblage [Eouvigerina subsculptura McNeil and Caldwell, Truaxia aspera (Cushman), and G. pyramidata] at Sites 516 and 525, (b) a lower bathyal subassemblage [Osangularia? sp., Pyramidina rudita (Cushman and Parker), and Quadrimorphina camerata (Brotzen)] at Site 356, and (c) an abyssal subassemblage [Gyroidinoides sp. C, Hyperammina-Bathysiphon, Gyroidinoides beisseli (White), and Globorotalites sp. B] at Site 527; (2) an abyssal assemblage [Buliminella cf. plana (Cushman and Parker) and Bulimina incisa Cushman] at the North Atlantic Site 384; and (3) a middle bathyal assemblage [Vulvulina sp. A, Osangularia navarroana (Cushman), Alabamina? sp., Bulimina velascoensis (Cushman), Spiroplectammina spp. calcareous forms, and Bulimina trinitatensis Cushman and Jarvis] at the Pacific Site 465.