Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities

Following in the Wake of Anger: When Not Discriminating Is Discriminating

Does seeing a scowling face change your impression of the next person you see? Does this depend on the race of the two people? Across four studies, White participants evaluated neutrally expressive White males as less threatening when they followed angry (relative to neutral) White faces; Black males were not judged as less threatening following angry Black faces. This lack of threat-anchored contrast for Black male faces is not attributable to a general tendency for White targets to homogenize Black males—neutral Black targets following smiling Black faces were contrasted away from them and seen as less friendly—and emerged only for perceivers low in motivation to respond without prejudice (i.e., for those relatively comfortable responding prejudicially). This research provides novel evidence for the overperception of threat in Black males

Heterogeneous Ice Nucleation by Soufriere Hills Volcanic Ash Immersed in Water Droplets

Fine particles of ash emitted during volcanic eruptions may sporadically influence cloud properties on a regional or global scale as well as influencing the dynamics of volcanic clouds and the subsequent dispersion of volcanic aerosol and gases. It has been shown that volcanic ash can trigger ice nucleation, but ash from relatively few volcanoes has been studied for its ice nucleating ability. In this study we quantify the efficiency with which ash from the Soufriere Hills volcano on Montserrat nucleates ice when immersed in supercooled water droplets. Using an ash sample from the 11th February 2010 eruption, we report ice nucleating efficiencies from 246 to 265 K. This wide range of temperatures was achieved using two separate droplet freezing instruments, one employing nanolitre droplets, the other using microlitre droplets. Soufriere Hills volcanic ash was significantly more efficient than all other ash samples that have been previously examined. At present the reasons for these differences are not understood, but may be related to mineralogy, amorphous content and surface chemistry

I only have eyes for you: Ovulation redirects attention (but not memory) to attractive men

A number of studies have found a disjunction between women’s attention to, and memory for, handsome men. Although women pay initial attention to handsome men, they do not remember those men later. The present study examines how ovulation might differentially affect these attentional and memory processes. We found that women near ovulation increased their visual attention to attractive men. However, this increased visual attention did not translate into better memory. Discussion focuses on possible explanations, in the context of an emerging body of findings on disjunctions between attention to, and memory for, other people.National Institute of Mental Health (U.S.) (R01MH064734

Thermal structure of a gas-permeable lava dome and timescale separation in its response to perturbation

The thermal boundary layer at the surface of a volcanic lava dome is investigated through a continuum model of the thermodynamic advection diffusion processes resulting from magmatic gas flow through the dome matrix. The magmatic gas mass flux, porosity and permeability of the rock are identified as key parameters. New, theoretical, nonlinear steady-state thermal profiles are reported which give a realistic surface temperature of 210 degC for a region of lava dome surface through which a gas flux of 3.5 x 10-3 kg s-1 m-2 passes. This contrasts favourably with earlier purely diffusive thermal models, which cool too quickly. Results are presented for time-dependent perturbations of the steady states as a response to: changes in surface pressure, a sudden rockfall from the lava dome surface, and a change in the magmatic gas mass flux at depth. Together with a generalized analysis using the method of multiple scales, this identifies two characteristic time scales associated with the thermal evolution of a dome carapace: a short time scale of several minutes, over which the magmatic gas mass flux, density, and pressure change to a new quasi-steady-state, and a longer time scale of several days, over which the thermal profile changes to a new equilibrium distribution. Over the longer time scale the dynamic properties of the dome continue to evolve, but only in slavish response to the ongoing temperature evolution. In the light of this time scale separation, the use of surface temperature measurements to infer changes in the magmatic gas flux for use in volcanic hazard prediction is discussed

Increased entropy of signal transduction in the cancer metastasis phenotype

Studies into the statistical properties of biological networks have led to important biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis. Further exploration of such integrated cancer expression and protein interaction networks will therefore be a fruitful endeavour.Comment: 5 figures, 2 Supplementary Figures and Table

Triggering of a volcanic dome collapse by rainwater infiltration

The thermodynamic processes in a one-dimensional model of a porous lava dome are considered in the presence of a rising magmatic gas flux through the void spaces and rainfall interacting with the dome surface. The steady state surface temperature of the dome depends on both magmatic gas mass flux and rainfall rate. A critical rainfall rate is determined, that cools the dome surface to 100°C. Rainfall rates above this critical value allow liquid infiltration into the void spaces of the dome, thus restricting the escape of magmatic gas. A model which restricts the gas flow through the surface predicts internal gas pressures much higher than the overburden pressure in the top few meters, approximately one hour after the onset of rainfall. For a marginally stable dome, this could cause small Vulcanian explosions, which (depending on their location) could trigger a dome collapse, on a timescale consistent with observations

The confounded nature of angry men and happy women.

Findings of 7 studies suggested that decisions about the sex of a face and the emotional expressions of anger or happiness are not independent: Participants were faster and more accurate at detecting angry expressions on male faces and at detecting happy expressions on female faces. These findings were robust across different stimulus sets and judgment tasks and indicated bottom-up perceptual processes rather than just top-down conceptually driven ones. Results from additional studies in which neutrally expressive faces were used suggested that the connections between masculine features and angry expressions and between feminine features and happy expressions might be a property of the sexual dimorphism of the face itself and not merely a result of gender stereotypes biasing the perception

Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency

NOTCH1 pathway activation contributes to the pathogenesis of over 60% of T-cell acute lymphoblastic leukemia (T-ALL). While Notch is thought to exert the majority of its effects through transcriptional activation of Myc, it also likely has independent roles in T-ALL malignancy. Here, we utilized a zebrafish transgenic model of T-ALL, where Notch does not induce Myc transcription, to identify a novel Notch gene expression signature that is also found in human T-ALL and is regulated independently of Myc. Cross-species microarray comparisons between zebrafish and mammalian disease identified a common T-ALL gene signature, suggesting that conserved genetic pathways underlie T-ALL development. Functionally, Notch expression induced a significant expansion of pre-leukemic clones; however, a majority of these clones were not fully transformed and could not induce leukemia when transplanted into recipient animals. Limiting-dilution cell transplantation revealed that Notch signaling does not increase the overall frequency of leukemia-propagating cells (LPCs), either alone or in collaboration with Myc. Taken together, these data indicate that a primary role of Notch signaling in T-ALL is to expand a population of pre-malignant thymocytes, of which a subset acquire the necessary mutations to become fully transformed LPCs