Stromal control of oncogenic traits expressed in response to the overexpression of GLI2, a pleiotropic oncogene.

Hedgehog signaling is often activated in tumors, yet it remains unclear how GLI2, a transcription factor activated by this pathway, acts as an oncogene. We show that GLI2 is a pleiotropic oncogene. The overexpression induces genomic instability and blocks differentiation, likely mediated in part by enhanced expression of the stem cell gene SOX2. GLI2 also induces transforming growth factor (TGF)B1-dependent transdifferentiation of foreskin and tongue, but not gingival fibroblasts into myofibroblasts, creating an environment permissive for invasion by keratinocytes, which are in various stages of differentiation having downregulated GLI2. Thus, upregulated GLI2 expression is sufficient to induce a number of the acquired characteristics of tumor cells; however, the stroma, in a tissue-specific manner, determines whether certain GLI2 oncogenic traits are expressed

Specific IgE Response to Purified and Recombinant Allergens in Latex Allergy

Background In recent years, allergy to natural rubber latex has emerged as a major allergy among certain occupational groups and patients with underlying diseases. The sensitization and development of latex allergy has been attributed to exposure to products containing residual latex proteins. Although improved manufacturing procedures resulted in a considerable reduction of new cases, the potential risk for some patient groups is still great. In addition the prevalent cross-reactivity of latex proteins with other food allergens poses a major concern. A number of purified allergens and a few commercial kits are currently available, but no concerted effort was undertaken to evaluate them. Methods We studied 11 purified latex allergens, Hev b 1 to Hev b 10, and Hev b 13 along with several crude allergen extracts and two commercial ImmunoCAP assays to evaluate specific IgE antibody in the sera from latex allergic patients and controls. Health care workers and spina bifida patients with clinical symptoms of latex allergy, spina bifida patients without latex allergy, and non-atopic health care workers have been studied. Results The results suggest that Hev b 2, 5, 6, and 13 together identified over 80 percent health care workers with latex allergy, while Hev b 6 along with Hev b 1 or 3 detected specific IgE antibody in all sera studied from patients with spina bifida and latex allergy. The ImmunoCAP results using both Hev b 5 amplified and non-amplified closely agreed with the clinical diagnosis of latex allergy in health care workers and in spina bifida. Conclusion Although the purified allergens and crude extracts reacted diversely with IgE from different patient groups, the results indicated that use of certain combinations of purified recombinant antigens will be useful in commercial kits or in in-house assays for detecting specific IgE antibody in the sera. The results suggest that a combination of Hev b 2, 3, 5, 6, and 13 together detected specific IgE in 80% of the sera from latex allergic patients. Both ImmunoCAPs correctly identified over 95% of latex allergic patients, however, showed reactivity with a few normal control subject

Promotion of protocell self-assembly from mixed amphiphiles at the origin of life

Vesicles formed from single-chain amphiphiles (SCAs) such as fatty acids probably played an important role in the origin of life. A major criticism of the hypothesis that life arose in an early ocean hydrothermal environment is that hot temperatures, large pH gradients, high salinity and abundant divalent cations should preclude vesicle formation. However, these arguments are based on model vesicles using 1–3 SCAs, even though Fischer–Tropsch-type synthesis under hydrothermal conditions produces a wide array of fatty acids and 1-alkanols, including abundant C10–C15 compounds. Here, we show that mixtures of these C10–C15 SCAs form vesicles in aqueous solutions between pH ~6.5 and >12 at modern seawater concentrations of NaCl, Mg2+ and Ca2+. Adding C10 isoprenoids improves vesicle stability even further. Vesicles form most readily at temperatures of ~70 °C and require salinity and strongly alkaline conditions to self-assemble. Thus, alkaline hydrothermal conditions not only permit protocell formation at the origin of life but actively favour it

Spatial and temporal overlaps between leopards (Panthera pardus) and their competitors in the African large predator guild

Understanding the mechanisms facilitating coexistence within species assemblages is a key consideration for conservation as intact assemblages are necessary for maintaining full ecosystem function. The African large predator guild represents one of the few remaining functionally intact large predator assemblages on Earth, and as such, represents a unique study system to understand competitive interactions. Yet, relatively little is known of the coexistence mechanisms between some of its intermediately sized members, particularly leopards (Panthera pardus). Here, we use overlapping spatio‐temporal activity and GPS data on lions (Panthera leo), leopards, African wild dogs (Lycaon pictus) and cheetahs (Acinonyx jubatus) to examine spatial interactions and temporal partitioning between leopards and other guild members in northern Botswana. We found that at the population level, male leopard space use and activity patterns were largely unaffected by intraguild competitors. Leopards showed minimal movement coherence with competitors (avoidance or attraction) when moving through areas of home ranges shared with intraguild species. Moreover, we found evidence to support the hypothesis that guild species’ activity patterns are primarily driven by light availability rather than predator avoidance. Our results suggest predator avoidance has a limited impact on broad‐scale leopard spatio‐temporal niches, with aspects of the leopards’ ecology and life history likely facilitating its ability to thrive in close proximity to competitors. Considered alongside other studies, our results suggest that landscape‐level approaches to conservation may be suitable for aiding leopard conservation

Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic

BACKGROUND: X chromosome inactivation is a spectacular example of epigenetic silencing. In order to deduce how this complex system evolved, we examined X inactivation in a model marsupial, the tammar wallaby (Macropus eugenii). In marsupials, X inactivation is known to be paternal, incomplete and tissue-specific, and occurs in the absence of an XIST orthologue. RESULTS: We examined expression of X-borne genes using quantitative PCR, revealing a range of dosage compensation for different loci. To assess the frequency of 1X- or 2X-active fibroblasts, we investigated expression of 32 X-borne genes at the cellular level using RNA-FISH. In female fibroblasts, two-color RNA-FISH showed that genes were coordinately expressed from the same X (active X) in nuclei in which both loci were inactivated. However, loci on the other X escape inactivation independently, with each locus showing a characteristic frequency of 1X-active and 2X-active nuclei, equivalent to stochastic escape. We constructed an activity map of the tammar wallaby inactive X chromosome, which identified no relationship between gene location and extent of inactivation, nor any correlation with the presence or absence of a Y-borne paralog. CONCLUSIONS: In the tammar wallaby, one X (presumed to be maternal) is expressed in all cells, but genes on the other (paternal) X escape inactivation independently and at characteristic frequencies. The paternal and incomplete X chromosome inactivation in marsupials, with stochastic escape, appears to be quite distinct from the X chromosome inactivation process in eutherians. We find no evidence for a polar spread of inactivation from an X inactivation center.This project was funded by grants to JAMG and PDW from the Australian Research Council

Combustion in thermonuclear supernova explosions

Type Ia supernovae are associated with thermonuclear explosions of white dwarf stars. Combustion processes convert material in nuclear reactions and release the energy required to explode the stars. At the same time, they produce the radioactive species that power radiation and give rise to the formation of the observables. Therefore, the physical mechanism of the combustion processes, as reviewed here, is the key to understand these astrophysical events. Theory establishes two distinct modes of propagation for combustion fronts: subsonic deflagrations and supersonic detonations. Both are assumed to play an important role in thermonuclear supernovae. The physical nature and theoretical models of deflagrations and detonations are discussed together with numerical implementations. A particular challenge arises due to the wide range of spatial scales involved in these phenomena. Neither the combustion waves nor their interaction with fluid flow and instabilities can be directly resolved in simulations. Substantial modeling effort is required to consistently capture such effects and the corresponding techniques are discussed in detail. They form the basis of modern multidimensional hydrodynamical simulations of thermonuclear supernova explosions. The problem of deflagration-to-detonation transitions in thermonuclear supernova explosions is briefly mentioned.Comment: Author version of chapter for 'Handbook of Supernovae,' edited by A. Alsabti and P. Murdin, Springer. 24 pages, 4 figure

A joint inversion of receiver function and Rayleigh wave phase velocity dispersion data to estimate crustal structure in West Antarctica

We determine crustal shear-wave velocity structure and crustal thickness at recently deployed seismic stations across West Antarctica, using a joint inversion of receiver functions and fundamental mode Rayleigh wave phase velocity dispersion. The stations are from both the UK Antarctic Network (UKANET) and Polar Earth Observing Network/Antarctic Network (POLENET/ANET). The former include, for the first time, 4 stations along the spine of the Antarctic Peninsula, 3 in the Ellsworth Land and 5 stations in the vicinity of the Pine Island Rift. Within the West Antarctic Rift System (WARS) we model a crustal thickness range of 18-28 km, and show that the thinnest crust (∼18 km) is in the vicinity of the Byrd Subglacial Basin and Bentley Subglacial Trench. In these regions we also find the highest ratio of fast (Vs = 4.0-4.3 km/s) (likely mafic) lower crust to felsic/intermediate upper crust. The thickest mafic lower crust we model is in Ellsworth Land, a critical area for constraining the eastern limits of the WARS. Although we find thinner crust in this region (∼30 km) than in the neighbouring Antarctic Peninsula and Haag-Ellsworth Whitmore block (HEW), the Ellsworth Land crust has not undergone as much extension as the central WARS. This suggests that the WARS does not link with the Weddell Sea Rift System through Ellsworth Land, and instead has progressed during its formation towards the Bellingshausen and Amundsen Sea Embayments. We also find that the thin WARS crust extends towards the Pine Island Rift, suggesting that the boundary between the WARS and the Thurston Island block lies in this region, ∼200 km north of its previously accepted position. The thickest crust (38-40 km) we model in this study is in the Ellsworth Mountain section of the HEW block. We find thinner crust (30-33 km) in the Whitmore Mountains and Haag Nunatak sectors of the HEW, consistent with the composite nature of the block. In the Antarctic Peninsula we find a crustal thickness range of 30-38 km and a likely dominantly felsic/intermediate crustal composition. By forward modelling high frequency receiver functions we also assess if any thick, low velocity subglacial sediment accumulations are present, and find a 0.1-0.8 km thick layer at 10 stations within the WARS, Thurston Island and Ellsworth Land. We suggest that these units of subglacial sediment could provide a source region for the soft basal till layers found beneath numerous outlet glaciers, and may act to accelerate ice flow

Cross modal perception of body size in domestic dogs (Canis familiaris)

While the perception of size-related acoustic variation in animal vocalisations is well documented, little attention has been given to how this information might be integrated with corresponding visual information. Using a cross-modal design, we tested the ability of domestic dogs to match growls resynthesised to be typical of either a large or a small dog to size- matched models. Subjects looked at the size-matched model significantly more often and for a significantly longer duration than at the incorrect model, showing that they have the ability to relate information about body size from the acoustic domain to the appropriate visual category. Our study suggests that the perceptual and cognitive mechanisms at the basis of size assessment in mammals have a multisensory nature, and calls for further investigations of the multimodal processing of size information across animal species

Contemporary medical television and crisis in the NHS

This article maps the terrain of contemporary UK medical television, paying particular attention to Call the Midwife as its centrepiece, and situating it in contextual relation to the current crisis in the NHS. It provides a historical overview of UK and US medical television, illustrating how medical television today has been shaped by noteworthy antecedents. It argues that crisis rhetoric surrounding healthcare leading up to the passing of the Health and Social Care Act 2012 has been accompanied by a renaissance in medical television. And that issues, strands and clusters have emerged in forms, registers and modes with noticeable regularity, especially around the value of affective labour, the cultural politics of nostalgia and the neoliberalisation of healthcare