Snow-avalanche boulder fans in Jotunheimen, southern Norway: Schmidt-hammer exposure-age dating, geomorphometrics, dynamics and evolution

Eleven snow-avalanche boulder fans were dated from two high-alpine sites in Jotunheimen using Schmidt-hammer exposure-age dating (SHD) and lichenometry. Average exposure ages of the surface boulders ranged from 2285 ± 725 to 7445 ± 1020 years and demonstrate the potential of SHD for dating active landforms and diachronous surfaces. Application of GIS-based morphometric analyses showed that the volume of rock material within 10 of the fans is accounted for by 16-68 % of the combined volume of their respective bedrock chutes and transport zones. It is inferred that the fans were deposited entirely within the Holocene, mainly within the early- to mid Holocene, by frequent avalanches carrying very small debris loads. Relatively small transport-zone volumes are consistent with avalanches of low erosivity. Excess chute volumes appear to represent subaerial erosion in the Younger Dryas and possibly earlier. Debris supply to the fans was likely enhanced by early-Holocene paraglacial processes following deglaciation, and by later permafrost degradation associated with the mid-Holocene Thermal Maximum. The latter, together with the youngest SHD age from one of the fans, may presage a similar increase in geomorphic activity in response to current warming trends

Age and development of active cryoplanation terraces in the alpine permafrost zone at Svartkampan, Jotunheimen, southern Norway

Schmidt-hammer exposure-age dating (SHD) of boulders on cryoplanation terrace treads and associated bedrock cliff faces revealed Holocene ages ranging from 0 ± 825 to 8890 ± 1185 yr. The cliffs were significantly younger than the inner treads, which tended to be younger than the outer treads. Radiocarbon dates from the regolith of 3854 to 4821 cal yr BP (2σ range) indicated maximum rates of cliff recession of ~0.1 mm/year, which suggests the onset of terrace formation prior to the last glacial maximum. Age, angularity and size of clasts, together with planation across bedrock structures and the seepage of groundwater from the cliff foot, all support a process-based conceptual model of cryoplanation terrace development in which frost weathering leads to parallel cliff recession and hence terrace extension. The availability of groundwater during autumn freeze-back is viewed as critical for frost wedging and/or the growth of segregation ice during prolonged winter frost penetration. Permafrost promotes cryoplanation by providing an impermeable frost table beneath the active layer, focusing groundwater flow, and supplying water for sediment transport by solifluction across the tread. Snowbeds are considered an effect rather than a cause of cryoplanation terraces and cryoplanation is seen as distinct from nivation

An Unbiased Survey of 500 Nearby Stars for Debris Disks: A JCMT Legacy Program

We present the scientific motivation and observing plan for an upcoming detection survey for debris disks using the James Clerk Maxwell Telescope. The SCUBA-2 Unbiased Nearby Stars (SUNS) Survey will observe 500 nearby main sequence and sub-giant stars (100 of each of the A, F, G, K and M spectral classes) to the 850 micron extragalactic confusion limit to search for evidence of submillimeter excess, an indication of circumstellar material. The survey distance boundaries are 8.6, 16.5, 22, 25 and 45 pc for M, K, G, F and A stars, respectively, and all targets lie between the declinations of -40 deg to 80 deg. In this survey, no star will be rejected based on its inherent properties: binarity, presence of planetary companions, spectral type or age. This will be the first unbiased survey for debris disks since IRAS. We expect to detect ~125 debris disks, including ~50 cold disks not detectable in current shorter wavelength surveys. A substantial amount of complementary data will be required to constrain the temperatures and masses of discovered disks. High resolution studies will likely be required to resolve many of the disks. Therefore, these systems will be the focus of future observational studies using a variety of observatories to characterize their physical properties. For non-detected systems, this survey will set constraints (upper limits) on the amount of circumstellar dust, of typically 200 times the Kuiper Belt mass, but as low as 10 times the Kuiper Belt mass for the nearest stars in the sample (approximately 2 pc).Comment: 11 pages, 7 figures (3 color), accepted by the Publications of the Astronomical Society of the Pacifi

Impact of progressive global warming on the global-scale yield of maize and soybean

Global surface temperature is projected to warm over the coming decades, with regional differences expected in temperature change, rainfall and the frequency of extreme events. Temperature is a major determinant of crop growth and development, affecting planting date, growing season length and yield. We investigated the effects of increments of mean global temperature warming from 0.5 °C to 4 °C on soybean and maize development and yield, both globally and for the main producing countries, and simulated adaptation through changing planting date and variety. Increasing temperature resulted in reduced growing season lengths and ultimately reduced yields for both crops. The global yield for maize decreased as temperature increased, although the severity of the decrease was dependent on geographic region. Small temperature increases of 0.5 °C had no effect on soybean yield, although yield decreased as temperature increased. These negative effects, however, were partly compensated for by the implementation of adaptation strategies including planting earlier in the season and changing variety. The degree of compensation was dependent on geographical area and crop, with maize adaptation delaying the negative effects of temperature on yield, compared to soybean adaptation which increased yield in China, India and Korea DPR as well as delaying the effects in the remaining countries. The results of this paper indicate the degree to which farmer-controlled adaptation strategies can alleviate the negative impacts of increasing temperature on two major crop species

A Unique Heterozygous CARD11 Mutation Combines Pathogenic Features of Both Gain- and Loss-of-Function Patients in a Four-Generation Family

CARD11 is a lymphocyte-specific scaffold molecule required for proper activation of B- and T-cells in response to antigen. Germline gain-of-function (GOF) mutations in the CARD11 gene cause a unique B cell lymphoproliferative disorder known as B cell Expansion with NF-κB and T cell Anergy (BENTA). In contrast, patients carrying loss-of-function (LOF), dominant negative (DN) CARD11 mutations present with severe atopic disease. Interestingly, both GOF and DN CARD11 variants cause primary immunodeficiency, with recurrent bacterial and viral infections, likely resulting from impaired adaptive immune responses. This report describes a unique four-generation family harboring a novel heterozygous germline indel mutation in CARD11 (c.701-713delinsT), leading to one altered amino acid and a deletion of 4 others (p.His234_Lys238delinsLeu). Strikingly, affected members exhibit both moderate B cell lymphocytosis and atopic dermatitis/allergies. Ectopic expression of this CARD11 variant stimulated constitutive NF-κB activity in T cell lines, similar to other BENTA patient mutations. However, unlike other GOF mutants, this variant significantly impeded the ability of wild-type CARD11 to induce NF-κB activation following antigen receptor ligation. Patient lymphocytes display marked intrinsic defects in B cell differentiation and reduced T cell responsiveness in vitro. Collectively, these data imply that a single heterozygous CARD11 mutation can convey both GOF and DN signaling effects, manifesting in a blended BENTA phenotype with atopic features. Our findings further emphasize the importance of balanced CARD11 signaling for normal immune responses

A mouse informatics platform for phenotypic and translational discovery

The International Mouse Phenotyping Consortium (IMPC) is providing the world’s first functional catalogue of a mammalian genome by characterising a knockout mouse strain for every gene. A robust and highly structured informatics platform has been developed to systematically collate, analyse and disseminate the data produced by the IMPC. As the first phase of the project, in which 5000 new knockout strains are being broadly phenotyped, nears completion, the informatics platform is extending and adapting to support the increasing volume and complexity of the data produced as well as addressing a large volume of users and emerging user groups. An intuitive interface helps researchers explore IMPC data by giving overviews and the ability to find and visualise data that support a phenotype assertion. Dedicated disease pages allow researchers to find new mouse models of human diseases, and novel viewers provide high-resolution images of embryonic and adult dysmorphologies. With each monthly release, the informatics platform will continue to evolve to support the increased data volume and to maintain its position as the primary route of access to IMPC data and as an invaluable resource for clinical and non-clinical researchers

Association of the tumor necrosis factor-alpha promoter polymorphism with change in triacylglycerol response to sequential meals

Background: Reported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant’s body weight. Hence, we investigated the association of TNFA polymorphism (−308G → A) with body mass index (BMI) and postprandial lipaemia and also determined the impact of BMI on the association of the polymorphism with postprandial lipaemia. Methods: The study participants (n = 230) underwent a sequential meal postprandial study. Blood samples were taken at regular intervals after a test breakfast (t = 0, 49 g fat) and lunch (t =330 min, 29 g fat) to measure fasting and postprandial lipids, glucose and insulin. The Metabolic Challenge Study (MECHE) comprising 67 Irish participants who underwent a 54 g fat oral lipid tolerance test was used as a replication cohort. The impact of genotype on postprandial responses was determined using general linear model with adjustment for potential confounders. Results: The -308G → A polymorphism showed a significant association with BMI (P = 0.03) and fasting glucose (P = 0.006), where the polymorphism explained 13 % of the variation in the fasting glucose. A 30 % higher incremental area under the curve (IAUC) was observed for the postprandial TAG response in the GG homozygotes than A-allele carriers (P = 0.004) and the genotype explained 19 % of the variation in the IAUC. There was a non-significant trend in the impact of BMI on the association of the genotype with TAG IAUC (P = 0.09). These results were not statistically significant in the MECHE cohort, which could be due to the differences in the sample size, meal composition, baseline lipid profile, allelic diversity and postprandial characterisation of participants across the two cohorts. Conclusions: Our findings suggest that TNFA -308G → A polymorphism may be an important candidate for BMI, fasting glucose and postprandial TAG response. Further studies are required to investigate the mechanistic effects of the polymorphism on glucose and TAG metabolism, and determine whether BMI is an important variable which should be considered in the design of future studies. Trial registration: NCT01172951

RNA-Seq Differentiates Tumour and Host mRNA Expression Changes Induced by Treatment of Human Tumour Xenografts with the VEGFR Tyrosine Kinase Inhibitor Cediranib.

Pre-clinical models of tumour biology often rely on propagating human tumour cells in a mouse. In order to gain insight into the alignment of these models to human disease segments or investigate the effects of different therapeutics, approaches such as PCR or array based expression profiling are often employed despite suffering from biased transcript coverage, and a requirement for specialist experimental protocols to separate tumour and host signals. Here, we describe a computational strategy to profile transcript expression in both the tumour and host compartments of pre-clinical xenograft models from the same RNA sample using RNA-Seq. Key to this strategy is a species-specific mapping approach that removes the need for manipulation of the RNA population, customised sequencing protocols, or prior knowledge of the species component ratio. The method demonstrates comparable performance to species-specific RT-qPCR and a standard microarray platform, and allowed us to quantify gene expression changes in both the tumour and host tissue following treatment with cediranib, a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, including the reduction of multiple murine transcripts associated with endothelium or vessels, and an increase in genes associated with the inflammatory response in response to cediranib. In the human compartment, we observed a robust induction of hypoxia genes and a reduction in cell cycle associated transcripts. In conclusion, the study establishes that RNA-Seq can be applied to pre-clinical models to gain deeper understanding of model characteristics and compound mechanism of action, and to identify both tumour and host biomarkers