Storm-induced water dynamics and thermohaline structure at the tidewater Flade Isblink Glacier outlet to theWandel Sea (NE Greenland)

In April 2015, an ice-tethered conductivity&ndash;temperature&ndash;depth (CTD) profiler and a down-looking acoustic Doppler current profiler (ADCP) were deployed from the landfast ice near the tidewater glacier terminus of the Flade Isblink Glacier in the Wandel Sea, NE Greenland. The 3-week time series showed that water dynamics and the thermohaline structure were modified considerably during a storm event on 22&ndash;24 April, when northerly winds exceeded 15 m s⁻¹. The storm initiated downwelling-like water dynamics characterized by on-shore water transport in the surface (0&ndash;40 m) layer and compensating offshore flow at intermediate depths. After the storm, currents reversed in both layers, and the relaxation phase of downwelling lasted ∼&thinsp;4 days. Although current velocities did not exceed 5 cm s⁻¹, the enhanced circulation during the storm caused cold turbid intrusions at 75&ndash;95 m depth, which are likely attributable to subglacial water from the Flade Isblink Ice Cap. It was also found that the semidiurnal periodicities in the temperature and salinity time series were associated with the lunar semidiurnal tidal flow. The vertical structure of tidal currents corresponded to the first baroclinic mode of the internal tide with a velocity minimum at ∼&thinsp;40 m. The tidal ellipses rotate in opposite directions above and below this depth and cause a divergence of tidal flow, which was observed to induce semidiurnal internal waves of about 3 m height at the front of the glacier terminus. <br><br> Our findings provide evidence that shelf&ndash;basin interaction and tidal forcing can potentially modify coastal Wandel Sea waters even though they are isolated from the atmosphere by landfast sea ice almost year-round. The northerly storms over the continental slope cause an enhanced circulation facilitating a release of cold and turbid subglacial water to the shelf. The tidal flow may contribute to the removal of such water from the glacial terminus

Prolyl 4-hydroxlase activity is essential for development and cuticle formation in the human infective parasitic nematode Brugia malayi

Collagen prolyl 4-hydroxylases (C-P4H) are required for formation of extracellular matrices in higher eukaryotes. These enzymes convert proline residues within the repeat regions of collagen polypeptides to 4-hydroxyproline, a modification essential for the stability of the triple helix. C-P4Hs are most often oligomeric complexes, with enzymatic activity contributed by the α subunits, and the β subunits formed by protein disulfide isomerase (PDI). Here we characterise this enzyme class in the important human parasitic nematode Brugia malayi. All potential C-P4H subunits were identified by detailed bioinformatic analysis of sequence databases, function was investigated both by RNAi in the parasite and heterologous expression in Caenorhabditis elegans, while biochemical activity and complex formation were examined via co-expression in insect cells. Simultaneous RNAi of two B. malayi C-P4H α subunit-like genes resulted in a striking, highly penetrant body morphology phenotype in parasite larvae. This was replicated by single RNAi of a B. malayi C-P4H β subunit-like PDI. Surprisingly however, the B. malayi proteins were not capable of rescuing a C. elegans α subunit mutant, whereas the human enzymes could. In contrast, the B. malayi PDI did functionally complement the lethal phenotype of a C. elegans β subunit mutant. Comparison of recombinant and parasite derived material indicates that enzymatic activity may be dependent on a non-reducible, inter-subunit cross-link, present only in the parasite. We therefore demonstrate that C-P4H activity is essential for development of B. malayi and uncover a novel parasite-specific feature of these collagen biosynthetic enzymes that may be exploited in future parasite control

Bottom mixed layer oxygen dynamics in the Celtic Sea

The seasonally stratified continental shelf seas are highly productive, economically important environments which are under considerable pressure from human activity. Global dissolved oxygen concentrations have shown rapid reductions in response to anthropogenic forcing since at least the middle of the twentieth century. Oxygen consumption is at the same time linked to the cycling of atmospheric carbon, with oxygen being a proxy for carbon remineralisation and the release of CO2. In the seasonally stratified seas the bottom mixed layer (BML) is partially isolated from the atmosphere and is thus controlled by interplay between oxygen consumption processes, vertical and horizontal advection. Oxygen consumption rates can be both spatially and temporally dynamic, but these dynamics are often missed with incubation based techniques. Here we adopt a Bayesian approach to determining total BML oxygen consumption rates from a high resolution oxygen time-series. This incorporates both our knowledge and our uncertainty of the various processes which control the oxygen inventory. Total BML rates integrate both processes in the water column and at the sediment interface. These observations span the stratified period of the Celtic Sea and across both sandy and muddy sediment types. We show how horizontal advection, tidal forcing and vertical mixing together control the bottom mixed layer oxygen concentrations at various times over the stratified period. Our muddy-sand site shows cyclic spring-neap mediated changes in oxygen consumption driven by the frequent resuspension or ventilation of the seabed. We see evidence for prolonged periods of increased vertical mixing which provide the ventilation necessary to support the high rates of consumption observed

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

Validation of three-dimensional hydrodynamic models of the Gulf of Finland

A model-intercomparison study was conducted, the first of its kind for the Baltic Sea, whose aim was to systematically simulate the basic three-dimensional hydrographic properties of a realistic, complex basin. Simulations of the hydrographic features of the Gulf of Finland for the summer–autumn of 1996 by six three-dimensional hydrodynamic models were compared. Validation was undertaken using more than 300 vertical hydrographic profiles of salinity and temperature. The analysis of model performance, including averaging of the ensemble results, was undertaken with a view to assessing the potential suitability of the models in reproducing the physics of the Baltic Sea accurately enough to serve as a basis for accurate simulations of biogeochemistry once ecosystem models are incorporated. The performance of the models was generally satisfactory. Nevertheless, all the models had some difficulties in correctly simulating vertical profiles of temperature and salinity, and hence mixed layer dynamics, particularly in the eastern Gulf of Finland. Results emphasized the need for high resolution in both vertical and horizontal directions in order to resolve the complex dynamics and bathymetry of the Baltic Sea. Future work needs to consider the choice of mixing and advection schemes, moving to higher resolution, high-frequency forcing, and the accurate representation of river discharges and boundary conditions

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

High export of dissolved silica from the Greenland Ice Sheet

Silica is an essential element for marine life and plays a key role in the biogeochemistry of the ocean. Glacial activity stimulates rock weathering, generating dissolved silica that is exported to coastal areas along with meltwater. The magnitude of the dissolved silica export from large glacial areas such as the Greenland Ice Sheet is presently poorly quantified and not accounted for in global budgets. Here we present data from two fjord systems adjacent to the Greenland Ice Sheet which reveal a large export of dissolved silica by glacial meltwater relative to other macronutrients. Upscaled to the entire Greenland Ice Sheet, the export of dissolved silica equals 22 ± 10 Gmol Si yr−1. When the silicate-rich meltwater mixes with upwelled deep water, either inside or outside Greenland's fjords, primary production takes place at increased silicate to nitrate ratios. This likely stimulates the growth of diatoms relative to other phytoplankton groups

Choosing sensitivity analyses for randomised trials: principles

Background Sensitivity analyses are an important tool for understanding the extent to which the results of randomised trials depend upon the assumptions of the analysis. There is currently no guidance governing the choice of sensitivity analyses. Discussion We provide a principled approach to choosing sensitivity analyses through the consideration of the following questions: 1) Does the proposed sensitivity analysis address the same question as the primary analysis? 2) Is it possible for the proposed sensitivity analysis to return a different result to the primary analysis? 3) If the results do differ, is there any uncertainty as to which will be believed? Answering all of these questions in the affirmative will help researchers to identify relevant sensitivity analyses. Treating analyses as sensitivity analyses when one or more of the answers are negative can be misleading and confuse the interpretation of studies. The value of these questions is illustrated with several examples. Summary By removing unreasonable analyses that might have been performed, these questions will lead to relevant sensitivity analyses, which help to assess the robustness of trial results

Non-classical protein secretion in bacteria

BACKGROUND: We present an overview of bacterial non-classical secretion and a prediction method for identification of proteins following signal peptide independent secretion pathways. We have compiled a list of proteins found extracellularly despite the absence of a signal peptide. Some of these proteins also have known roles in the cytoplasm, which means they could be so-called "moon-lightning" proteins having more than one function. RESULTS: A thorough literature search was conducted to compile a list of currently known bacterial non-classically secreted proteins. Pattern finding methods were applied to the sequences in order to identify putative signal sequences or motifs responsible for their secretion. We have found no signal or motif characteristic to any majority of the proteins in the compiled list of non-classically secreted proteins, and conclude that these proteins, indeed, seem to be secreted in a novel fashion. However, we also show that the apparently non-classically secreted proteins are still distinguished from cellular proteins by properties such as amino acid composition, secondary structure and disordered regions. Specifically, prediction of disorder reveals that bacterial secretory proteins are more structurally disordered than their cytoplasmic counterparts. Finally, artificial neural networks were used to construct protein feature based methods for identification of non-classically secreted proteins in both Gram-positive and Gram-negative bacteria. CONCLUSION: We present a publicly available prediction method capable of discriminating between this group of proteins and other proteins, thus allowing for the identification of novel non-classically secreted proteins. We suggest candidates for non-classically secreted proteins in Escherichia coli and Bacillus subtilis. The prediction method is available online

Stochastic Model for Modulus of Elasticity of Lumber

A model was developed for generating the lengthwise variability in modulus of elasticity (MOE) of lumber. A limited grade selection of southern pine visual and machine stress-rated (MSR) grades formed the basic data base, A second-order Markov model was used to generate serially correlated MOE's along 30-inch segments for a piece of lumber. Modulus of elasticity indexes were obtained by dividing each correlated MOE by the average MOE of the piece of lumber. The MOE of each segment was obtained by multiplying the MOE indexes by a single random observation from a distribution of MOE. The distribution characteristics of the generated MOE values are preserved, and the first- and second-order lengthwise serial correlations are preserved