Antarctic Peninsula glaciation patterns set by landscape evolution and dynamic topography

The dimensions of past ice sheets provide a record of palaeoclimate but depend on underlying topography, which evolves over geological timescales by tectonic uplift and erosional downcutting. Erosion during the Pleistocene epoch (2,580 to 11.650 thousand years ago) reduced glacier extent in some locations even as climate cooled, but whether other non-climatic influences impacted the glacial–geological record is poorly known. The Antarctic Peninsula provides an opportunity to examine this issue because of its long glacial history and preservation of remnants of a low-relief pre-glacial land surface. Here we reconstructed both palaeo-surface topography and long-wavelength variations of surface uplift for the Antarctic Peninsula by using inverse analysis that assimilates local topographic remnants with the branching structures of entire modern drainage networks. We found that the Antarctic Peninsula rose tectonically by up to 1.5 km due to dynamical support from the mantle. Glaciological models using the current climate and our palaeotopography show greatly reduced ice extent in the northern Antarctic Peninsula compared with modern, indicating that the onset of glaciation identified at offshore sites reflects tectonic uplift of the topography rather than climatic cooling. In the southern Antarctic Peninsula, however, we suggest the low-relief pre-glacial landscape supported a considerably greater ice volume than the modern mountainous topography, illustrating the influence of erosional sculpting on glaciation patterns

Who Controls the Looking Glass? Towards a Conversational Understanding of Organizational Theatre

This paper presents a longitudinal study of interactive organizational theatre. Managers of a large home care organization used 30 instances of organizational theatre over a one year period to effect organizational change. We found that neither management, who had hoped that employees would accept and internalize the messages accompanying the play, nor employees, who used the liminal spaces to express their own take on the organization’s issues, achieved their aims directly. Yet a year later, organizational performance and satisfaction were significantly improved—much of this was attributed to the play. To explain this, we develop a conversational theory of change, one where ‘conversation pieces’ are central. We also speculate on the properties that conversation pieces and conversational systems like organizational theatre must have if they are to effect change.N/

Measuring Slepton Masses and Mixings at the LHC

Flavor physics may help us understand theories beyond the standard model. In the context of supersymmetry, if we can measure the masses and mixings of sleptons and squarks, we may learn something about supersymmetry and supersymmetry breaking. Here we consider a hybrid gauge-gravity supersymmetric model in which the observed masses and mixings of the standard model leptons are explained by a U(1) x U(1) flavor symmetry. In the supersymmetric sector, the charged sleptons have reasonably large flavor mixings, and the lightest is metastable. As a result, supersymmetric events are characterized not by missing energy, but by heavy metastable charged particles. Many supersymmetric events are therefore fully reconstructible, and we can reconstruct most of the charged sleptons by working up the long supersymmetric decay chains. We obtain promising results for both masses and mixings, and conclude that, given a favorable model, precise measurements at the LHC may help shed light not only on new physics, but also on the standard model flavor parameters.Comment: 24 pages; v2: fixed a typo in our computer program that led to some miscalculated branching ratios, various clarifications and minor improvements, conclusions unchanged, published versio

Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B

Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites

Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

BSE Case Associated with Prion Protein Gene Mutation

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle and was first detected in 1986 in the United Kingdom. It is the most likely cause of variant Creutzfeldt-Jakob disease (CJD) in humans. The origin of BSE remains an enigma. Here we report an H-type BSE case associated with the novel mutation E211K within the prion protein gene (Prnp). Sequence analysis revealed that the animal with H-type BSE was heterozygous at Prnp nucleotides 631 through 633. An identical pathogenic mutation at the homologous codon position (E200K) in the human Prnp has been described as the most common cause of genetic CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. A recent epidemiological study revealed that the K211 allele was not detected in 6062 cattle from commercial beef processing plants and 42 cattle breeds, indicating an extremely low prevalence of the E211K variant (less than 1 in 2000) in cattle