A case of primary renal angiosarcoma

A 78-year old man was diagnosed with a left bleeding renal cyst from CT scan results. Serial CT scans revealed the left kidney mass to be increasing in size and a new lesion in the liver. Renal cell carcinoma with liver metastasis was diagnosed and a radical nephrectomy performed. The initial pathological diagnosis was a benign chronic hematoma. However, the liver mass increased in size and multiplied, while another mass emerged in the twelfth thoracic vertebra with spinal paralysis and was immediately removed. Pathological findings for that specimen showed malignancy of stromal cell origin but low atypia. The renal specimen was re-evaluated using whole cross-section analysis and immunohistochemistry, and diagnosed as a primary renal angiosarcoma. Recombinant interleukin-2 therapy was started immediately; however, the patient died of metastatic disease 13 months after the initial operation. Although contrast imaging depicted the primary lesion as a non-specific hematoma with little focal pooling, and low-grade cytological atypia was shown pathologically, the angiosarcoma was extremely aggressive

Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Individually ventilated caging (IVC) systems for rodents are increasingly common in laboratory animal facilities. However, the impact of such substantial change in housing conditions on animal physiology and behavior is still debated. Most importantly, there arise the questions regarding reproducibility and comparison of previous or new phenotypes between the IVC and open cages. The present study was set up for detailed and systematic comparison of behavioral phenotypes in male and female mice of three widely used inbred strains (C57BL/6JRccHsd, DBA/2JRccHsd, 129S2/SvHSd) after being kept in two housing environments (IVC and open cages) for 6?weeks (since 4?weeks of age) before behavioral testing. The tests addressed exploratory, anxiety-like and stress-related behavior (light-dark box, open field, forced swim test, stress-induced hyperthermia), social approach and species-specific behavior (nest building, marble burying). In all tests, large and expected strain differences were found. Somewhat surprisingly, the most striking effect of environment was found for basal body temperature and weight loss after one night of single housing in respective cages. In addition, the performance in light-dark box and open field was affected by environment. Several parameters in different tests showed significant interaction between housing and genetic background. In summary, the IVC housing did not invalidate the well-known differences between the mouse strains which have been established by previous studies. However, within the strains the results can be influenced by sex and housing system depending on the behavioral tasks applied. The bottom-line is that the environmental conditions should be described explicitly in all publications.Peer reviewe

Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project

<p>Abstract</p> <p>Background</p> <p>There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.</p> <p>Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined.</p> <p>Results</p> <p>There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.</p> <p>41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders.</p> <p>Conclusions</p> <p>This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and implementation of studies and for determining the relevance of a disease associated polymorphism for a given population.</p

The Polycomb Repressive Complex 2 Is a Potential Target of SUMO Modifications

The Polycomb Repressive Complex 2 (PRC2) functions as a transcriptional repressor through a mechanism that involves methylation of Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular proliferation, development, and cell fate decisions. PRC2 target genes include important regulators of development and proliferation as well as tumor suppressor genes. Consistent with this, the activity of several Polycomb group (PcG) proteins is deregulated in human cancer suggesting an important role for PcGs in tumor development. Whereas the downstream functions of PcGs are well characterized, the mechanisms of their recruitment to target genes and the regulation of their activity are not fully understood.Here we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo. Among several putative sumoylation sites we have mapped the major site of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2-conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12 sumoylation site does not abolish this binding. Finally, we provide evidence that the E3-ligase PIASXbeta interacts and enhances the sumoylation of SUZ12 in vivo suggesting that PIASXbeta could function as an E3-ligase for SUZ12.Taken together, our data identify sumoylation as a novel post-translational modification of components of the PRC2 complex, which could suggest a potential new mechanism to modulate PRC2 repressive activity. Further work aimed to identify the physiological conditions for these modifications will be required to understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic regulation of transcription

Positive Interactions between Desert Granivores: Localized Facilitation of Harvester Ants by Kangaroo Rats

Facilitation, when one species enhances the environment or performance of another species, can be highly localized in space. While facilitation in plant communities has been intensely studied, the role of facilitation in shaping animal communities is less well understood. In the Chihuahuan Desert, both kangaroo rats and harvester ants depend on the abundant seeds of annual plants. Kangaroo rats, however, are hypothesized to facilitate harvester ants through soil disturbance and selective seed predation rather than competing with them. I used a spatially explicit approach to examine whether a positive or negative interaction exists between banner-tailed kangaroo rat (Dipodomys spectabilis) mounds and rough harvester ant (Pogonomyrmex rugosus) colonies. The presence of a scale-dependent interaction between mounds and colonies was tested by comparing fitted spatial point process models with and without interspecific effects. Also, the effect of proximity to a mound on colony mortality and spatial patterns of surviving colonies was examined. The spatial pattern of kangaroo rat mounds and harvester ant colonies was consistent with a positive interspecific interaction at small scales (<10 m). Mortality risk of vulnerable, recently founded harvester ant colonies was lower when located close to a kangaroo rat mound and proximity to a mound partly predicted the spatial pattern of surviving colonies. My findings support localized facilitation of harvester ants by kangaroo rats, likely mediated through ecosystem engineering and foraging effects on plant cover and composition. The scale-dependent effect of kangaroo rats on abiotic and biotic factors appears to result in greater founding and survivorship of young colonies near mounds. These results suggest that soil disturbance and foraging by rodents can have subtle impacts on the distribution and demography of other species

Perspectives on Disconnects Between Scientific Information and Management Decisions on Post-fire Recovery in Western US

Environmental regulations frequently mandate the use of "best available" science, but ensuring that it is used in decisions around the use and protection of natural resources is often challenging. In the Western US, this relationship between science and management is at the forefront of post-fire land management decisions. Recent fires, post-fire threats (e.g. flooding, erosion), and the role of fire in ecosystem health combine to make post-fire management highly visible and often controversial. This paper uses post-fire management to present a framework for understanding why disconnects between science and management decisions may occur. We argue that attributes of agencies, such as their political or financial incentives, can limit how effectively science is incorporated into decision-making. At the other end of the spectrum, the lack of synthesis or limited data in science can result in disconnects between science-based analysis of post-fire effects and agency policy and decisions. Disconnects also occur because of the interaction between the attributes of agencies and the attributes of science, such as their different spatial and temporal scales of interest. After offering examples of these disconnects in post-fire treatment, the paper concludes with recommendations to reduce disconnects by improving monitoring, increasing synthesis of scientific findings, and directing social-science research toward identifying and deepening understanding of these disconnects