Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.     

Common variation at 10p12.31 near MLLT10 influences meningioma risk

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.     

Comparative ecology of Sarcobatus baileyi and Sarcobatus vermiculatus in estern California

Greasewood ( Sarcobatus ) is a succulent-leaved, halophytic shrub of North American origin. The genus comprises 2 species: Sarcobatus baileyi and Sarcobatus vermiculatus. Sarcobatus vermiculatus is common throughout much of western North America, but S. baileyi is much more limited in distribution and was previously thought to be endemic to Nevada. Here we document and describe a S. baileyi population in eastern California, comparing its morphology and ecology to an adjacent S. vermiculatus population. Morphologically, S. baileyi is smaller in stature but produces larger seeds; however, fewer S. baileyi seeds germinated and survived a 20-day laboratory incubation compared to seeds of S. vermiculatus. Sarcobatus baileyi has higher leaf Na concentrations and operates at much lower plant water potentials than S. vermiculatus under field conditions; however, no significant differences were observed between the 2 species in long-term water-use efficiency as measured by leaf δ13C. Leaf Na concentrations were very low in both species. Overall, these species differ greatly in a number of traits that are consistent with the upland, nonphreatophytic character of S. baileyi, which is in stark contrast to the phreatophytic character of S. vermiculatus. Both species, however, are very salt tolerant and have low leaf N concentrations, indicating the low nutrient availability and the potentially high salinity of their extreme habitats. Further investigation of comparable desert ridge environments should be conducted to determine the extent of S. baileyi in eastern California, and common garden comparisons of the 2 species should be conducted to compare their ecophysiological traits. El ";greasewood” ( Sarcobatus ) es un arbusto halofítico de origen norteamericano con hojas suculentas. El género consta de dos especies: Sarcobatus baileyi y Sarcobatus vermiculatus. Aunque S. vermiculatus es común en gran parte del oeste de Norteamerica, S. baileyi tiene una distribución mucho más limitada. Se pensaba anteriormente que S. baileyi era endémico a Nevada, pero aquí documentamos y describimos una población en el este de California, comparando su morfología y ecología con las de una población adyacente de S. vermiculatus. Morfológicamente, S. baileyi es más pequeña de altura, pero produce semillas más grandes. Sin embargo, menos semillas de S. baileyi germinaron y sobrevivieron a una incubación en laboratorio de 20 días, comparado con S. vermiculatus. Sarcobatus baileyi opera con potenciales de agua mucho más bajos que los de S. vermiculatus en condiciones de campo y tiene mayores concentraciones de Na en sus hojas. No obstante, no se observaron diferencias significativas en la eficiencia del uso de agua a largo plazo, medida en términos de δ13C entre las 2 especies. Las concentraciones de N en las hojas fueron muy bajas en ambas especies. En general, estas especies difieren mucho en varios rasgos que son consistentes con el carácter no freatofítico de S. baileyi de tierras altas, el cual contrasta claramente con el carácter freatofítico de S. vermiculatus. Ambas especies, sin embargo, son bastante tolerantes a la sal y tienen concentraciones bajas de N en hojas, lo cual indica la baja disponibilidad de nutrientes y la potencial alta salinidad en sus hábitats extremos. Investigaciones adicionales en ambientes comparables de bordes desérticos deberán llevarse a cabo para determinar la extensión S. baileyi en el este de California, además de comparaciones de las dos especies en jardín para comparar sus rasgos ecofisiológicos.     

Composition of forest stands used by White-headed Woodpeckers for nesting in Washington

In this study, I examined the composition of managed ponderosa pine ( Pinus ponderosa ) forests used by nesting White-headed Woodpeckers ( Picoides albolarvatus ) along the eastern slope of the Cascade Range in Washington. I sampled trees and snags using the point-centered quarter method to assess species composition, tree and snag density, and stand basal area in 16 forest stands containing White-headed Woodpecker nests. All stands had a history of timber management and 2 had been burned and salvage-logged. Mean live-tree density (≥10.16 cm dbh) was 182.3 trees · ha –1 (SE = 13.52), mean snag density (≥10.16 cm dbh) was 11.5 snags · ha –1 (SE = 1.92), and mean stand basal area was 17.2 m 2 · ha –1 (SE = 1.58). Ponderosa pine had the highest importance value (mean = 220.9, SE = 17.25) of any tree species in all but 2 stands. Mean dbh of ponderosa pines was 33.0 cm (SE = 0.26) and ranged from 26.1 to 50.2 cm within stands. Mean density of ponderosa pine was greatest in the 20.3–30.5 cm dbh size class and lowest in the 50.8–61.0 cm and >61.0 cm dbh size classes. Tree density was up to 5.3 times greater than densities believed to be typical of ponderosa pine forests prior to fire suppression. Snag densities were within the range estimated for historical dry forests of the eastern Cascades, yet only 50% of all snags sampled had a dbh >25.4 cm. Although White-headed Woodpeckers are considered strongly associated with old-growth ponderosa pine, my results suggest that they may be more adaptable to using forests dominated by smaller diameter trees. En este estudio, examiné la composición de los bosques manejados de pino ponderosa ( Pinus ponderosa ), utilizados para anidamiento por el pájaro carpintero cabeciblanco ( Picoides albolarvatus ), a lo largo de la vertiente oriental de la cordillera Cascade del Estado de Washington. Muestreé árboles vivos y muertos usando el método de cuadrantes al punto central en 16 rodales con nidos del pájaro carpintero cabeciblanco para evaluar la composición de especies, la densidad de árboles vivos y muertos y el área basal del rodal. Todas las áreas tenían una historia de manejo maderable y 2 habían sido quemadas y taladas para recuperar madera. La densidad promedio de árboles vivos (≥10.16 cm DAP) fue 182.3 árboles · ha –1 (DE = 13.52), la densidad promedio de árboles muertos (≥10.16 cm DAP) fue 11.5 árboles muertos · ha –1 (DE = 1.92) y el área basal promedio de los rodales fue 17.2 m 2 · ha –1 (DE = 1.58). El pino ponderosa tuvo el valor de importancia más alto (promedio = 220.9, DE = 17.25) de las especies de árboles en todos, menos 2 rodales. El DAP promedio de los pinos ponderosa fue 33.0 cm (DE = 0.26) y variaba de 26.1 a 50.2 cm dentro de rodales. La densidad promedio del pino ponderosa fue la mayor en la clase de 20.3–30.5 cm DAP y menor de las clases de 50.8–61.0 cm y >61.0 cm DAP. La densidad de árboles fue hasta 5.3 veces mayor que las consideradas típicas para bosques de pino ponderosa antes de la intervención para prevenir incendios. Las densidades de árboles muertos estuvo dentro del rango estimado para los bosques secos históricos del oriente de la cordillera Cascade, no obstante sólo 50% de los árboles muertos muestreados tuvieron un DAP >25.4 cm. Aunque se considera que los pájaros carpinteros cabeciblancos están estrechamente asociados con bosques primarios de pino ponderosa, mis resultados sugieren que podrían ser más adaptados a usar bosques donde predominan árboles de diámetro menor.     

Changes in kit fox–coyote–prey relationships in the Great Basin Desert, Utah

Variation in kit fox ( Vulpes macrotis ) population parameters can be influenced by vegetative cover and the distribution and abundance of other predator and prey species. Dramatic changes to Great Basin Desert habitats, which can potentially impact mammalian species, have occurred in some areas in Utah. We examined kit fox demographics and prey populations from 1999 to 2001 on Dugway Proving Ground (DPG), a U.S. Army facility in Utah, and compared some parameters to historical levels (1956–1958, 1966–1969). Adult survival rates were fairly consistent between 1999 and 2000 and between 1999 and 2001; however, survival was greater in 2001 than in 2000. Reproductive rates ranged from 1.0 to 3.8 pups per female in 1999–2000 and were similar to historical numbers (1.0–4.2 pups per female). We found a decrease in pre-whelping kit fox density from the 1960s (0.12 foxes ? km –2 ) to 1999–2001 (0.04 foxes ? km –2 ); however, densities were similar between the current study and the 1950s (0.08 foxes ? km –2 ). Using 9 years of data, we found density dependence between reproductive rates of the current year and annual fox density from the previous year. Using 7 years of data, we found a slight correlation between kit fox annual density and a 1-year lag in leporid abundance, even though leporid abundance was lower during the present study than it was historically. Compared to historical levels, current small mammal abundance and species composition has changed in several habitats. Kit fox breeding density and annual density were inversely correlated with coyote ( Canis latrans ) density. Changes to the landscape at DPG, especially due to invasion of cheatgrass ( Bromus tectorum ) and addition of artificial water sources, have caused a change in available kit fox habitat and prey species, and have increased the abundance of coyotes, the kit fox's major competitor.