Observations of Buried Lake Drainage on the Antarctic Ice Sheet.

Between 1992 and 2017, the Antarctic Ice Sheet (AIS) lost ice equivalent to 7.6 ± 3.9 mm of sea level rise. AIS mass loss is mitigated by ice shelves that provide a buttress by regulating ice flow from tributary glaciers. However, ice-shelf stability is threatened by meltwater ponding, which may initiate, or reactivate preexisting, fractures, currently poorly understood processes. Here, through ground penetrating radar (GPR) analysis over a buried lake in the grounding zone of an East Antarctic ice shelf, we present the first field observations of a lake drainage event in Antarctica via vertical fractures. Concurrent with the lake drainage event, we observe a decrease in surface elevation and an increase in Sentinel-1 backscatter. Finally, we suggest that fractures that are initiated or reactivated by lake drainage events in a grounding zone will propagate with ice flow onto the ice shelf itself, where they may have implications for its stability

Experimental design for three interrelated marine ice sheet and ocean model intercomparison projects: MISMIP v. 3 (MISMIP +), ISOMIP v. 2 (ISOMIP +) and MISOMIP v. 1 (MISOMIP1)

Coupled ice sheet–ocean models capable of simulating moving grounding lines are just becoming available. Such models have a broad range of potential applications in studying the dynamics of marine ice sheets and tidewater glaciers, from process studies to future projections of ice mass loss and sea level rise. The Marine Ice Sheet–Ocean Model Intercomparison Project (MISOMIP) is a community effort aimed at designing and coordinating a series of model intercomparison projects (MIPs) for model evaluation in idealized setups, model verification based on observations, and future projections for key regions of the West Antarctic Ice Sheet (WAIS). Here we describe computational experiments constituting three interrelated MIPs for marine ice sheet models and regional ocean circulation models incorporating ice shelf cavities. These consist of ice sheet experiments under the Marine Ice Sheet MIP third phase (MISMIP+), ocean experiments under the Ice Shelf-Ocean MIP second phase (ISOMIP+) and coupled ice sheet–ocean experiments under the MISOMIP first phase (MISOMIP1). All three MIPs use a shared domain with idealized bedrock topography and forcing, allowing the coupled simulations (MISOMIP1) to be compared directly to the individual component simulations (MISMIP+ and ISOMIP+). The experiments, which have qualitative similarities to Pine Island Glacier Ice Shelf and the adjacent region of the Amundsen Sea, are designed to explore the effects of changes in ocean conditions, specifically the temperature at depth, on basal melting and ice dynamics. In future work, differences between model results will form the basis for the evaluation of the participating models

Preventing Nerve Function Impairment in Leprosy: Validation and Updating of a Prediction Rule

Leprosy is caused by a bacterium that attacks the peripheral nerves. This may cause nerve function impairment (NFI), resulting in handicaps and disabilities. Therefore, prediction and prevention of NFI is extremely important in the management of leprosy. In 2000, a prediction rule for NFI was published, but circumstances have changed since the study was performed in the 1990s: the leprosy detection delay has shortened and the definition of NFI has changed. The original rule used ‘leprosy classification’ and ‘NFI present at diagnosis’ to predict future NFI. In the current patient population we studied an adjusted rule based on ‘leprosy classification’ and ‘presence of antibodies’. This adjusted rule predicted NFI more often than the original rule. With the adjusted rule it is now also possible to assess NFI risk before the first nerve damage event takes place. This may help doctors and health workers to improve surveillance for people at high risk. Early detection and treatment can then prevent permanent disabilities

A High-End Estimate of Sea Level Rise for Practitioners

Sea level rise (SLR) is a long-lasting consequence of climate change because global anthropogenic warming takes centuries to millennia to equilibrate for the deep ocean and ice sheets. SLR projections based on climate models support policy analysis, risk assessment and adaptation planning today, despite their large uncertainties. The central range of the SLR distribution is estimated by process-based models. However, risk-averse practitioners often require information about plausible future conditions that lie in the tails of the SLR distribution, which are poorly defined by existing models. Here, a community effort combining scientists and practitioners builds on a framework of discussing physical evidence to quantify high-end global SLR for practitioners. The approach is complementary to the IPCC AR6 report and provides further physically plausible high-end scenarios. High-end estimates for the different SLR components are developed for two climate scenarios at two timescales. For global warming of +2°C in 2100 (RCP2.6/SSP1-2.6) relative to pre-industrial values our high-end global SLR estimates are up to 0.9 m in 2100 and 2.5 m in 2300. Similarly, for a (RCP8.5/SSP5-8.5), we estimate up to 1.6 m in 2100 and up to 10.4 m in 2300. The large and growing differences between the scenarios beyond 2100 emphasize the long-term benefits of mitigation. However, even a modest 2°C warming may cause multi-meter SLR on centennial time scales with profound consequences for coastal areas. Earlier high-end assessments focused on instability mechanisms in Antarctica, while here we emphasize the importance of the timing of ice shelf collapse around Antarctica. This is highly uncertain due to low understanding of the driving processes. Hence both process understanding and emission scenario control high-end SLR

CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23

<p>Abstract</p> <p>Background</p> <p>Recurrent loss of part of the long arm of chromosome 11 is a well established hallmark of a subtype of aggressive neuroblastomas. Despite intensive mapping efforts to localize the culprit 11q tumour suppressor gene, this search has been unsuccessful thus far as no sufficiently small critical region could be delineated for selection of candidate genes.</p> <p>Methods</p> <p>To refine the critical region of 11q loss, the chromosome 11 status of 100 primary neuroblastoma tumours and 29 cell lines was analyzed using a BAC array containing a chromosome 11 tiling path. For the genes mapping within our refined region of loss, meta-analysis on published neuroblastoma mRNA gene expression datasets was performed for candidate gene selection. The DNA methylation status of the resulting candidate gene was determined using re-expression experiments by treatment of neuroblastoma cells with the demethylating agent 5-aza-2'-deoxycytidine and bisulphite sequencing.</p> <p>Results</p> <p>Two small critical regions of loss within 11q23 at chromosomal band 11q23.1-q23.2 (1.79 Mb) and 11q23.2-q23.3 (3.72 Mb) were identified. In a first step towards further selection of candidate neuroblastoma tumour suppressor genes, we performed a meta-analysis on published expression profiles of 692 neuroblastoma tumours. Integration of the resulting candidate gene list with expression data of neuroblastoma progenitor cells pinpointed <it>CADM1 </it>as a compelling candidate gene. Meta-analysis indicated that <it>CADM1 </it>expression has prognostic significance and differential expression for the gene was noted in unfavourable neuroblastoma versus normal neuroblasts. Methylation analysis provided no evidence for a two-hit mechanism in 11q deleted cell lines.</p> <p>Conclusion</p> <p>Our study puts <it>CADM1 </it>forward as a strong candidate neuroblastoma suppressor gene. Further functional studies are warranted to elucidate the role of <it>CADM1 </it>in neuroblastoma development and to investigate the possibility of <it>CADM1 </it>haploinsufficiency in neuroblastoma.</p

Analysing 454 amplicon resequencing experiments using the modular and database oriented Variant Identification Pipeline

<p>Abstract</p> <p>Background</p> <p>Next-generation amplicon sequencing enables high-throughput genetic diagnostics, sequencing multiple genes in several patients together in one sequencing run. Currently, no open-source out-of-the-box software solution exists that reliably reports detected genetic variations and that can be used to improve future sequencing effectiveness by analyzing the PCR reactions.</p> <p>Results</p> <p>We developed an integrated database oriented software pipeline for analysis of 454/Roche GS-FLX amplicon resequencing experiments using Perl and a relational database. The pipeline enables variation detection, variation detection validation, and advanced data analysis, which provides information that can be used to optimize PCR efficiency using traditional means. The modular approach enables customization of the pipeline where needed and allows researchers to adopt their analysis pipeline to their experiments. Clear documentation and training data is available to test and validate the pipeline prior to using it on real sequencing data.</p> <p>Conclusions</p> <p>We designed an open-source database oriented pipeline that enables advanced analysis of 454/Roche GS-FLX amplicon resequencing experiments using SQL-statements. This modular database approach allows easy coupling with other pipeline modules such as variant interpretation or a LIMS system. There is also a set of standard reporting scripts available.</p

Brainstem Respiratory Oscillators Develop Independently of Neuronal Migration Defects in the Wnt/PCP Mouse Mutant looptail

The proper development and maturation of neuronal circuits require precise migration of component neurons from their birthplace (germinal zone) to their final positions. Little is known about the effects of aberrant neuronal position on the functioning of organized neuronal groups, especially in mammals. Here, we investigated the formation and properties of brainstem respiratory neurons in looptail (Lp) mutant mice in which facial motor neurons closely apposed to some respiratory neurons fail to migrate due to loss of function of the Wnt/Planar Cell Polarity (PCP) protein Vangl2. Using calcium imaging and immunostaining on embryonic hindbrain preparations, we found that respiratory neurons constituting the embryonic parafacial oscillator (e-pF) settled at the ventral surface of the medulla in Vangl2Lp/+ and Vangl2Lp/Lp embryos despite the failure of tangential migration of its normally adjacent facial motor nucleus. Anatomically, the e-pF neurons were displaced medially in Lp/+ embryos and rostro-medially Lp/Lp embryos. Pharmacological treatments showed that the e-pF oscillator exhibited characteristic network properties in both Lp/+ and Lp/Lp embryos. Furthermore, using hindbrain slices, we found that the other respiratory oscillator, the preBötzinger complex, was also anatomically and functionally established in Lp mutants. Importantly, the displaced e-pF oscillator established functional connections with the preBötC oscillator in Lp/+ mutants. Our data highlight the robustness of the developmental processes that assemble the neuronal networks mediating an essential physiological function