A Minimal Model of Metabolism Based Chemotaxis

Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis

Identification of pediatric septic shock subclasses based on genome-wide expression profiling

<p>Abstract</p> <p>Background</p> <p>Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling.</p> <p>Methods</p> <p>Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization.</p> <p>Results</p> <p>Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the three putative subclasses (analysis of variance, Bonferonni correction, <it>P </it>< 0.05) identified 6,934 differentially regulated genes. K-means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the three subclasses. Leave one out cross-validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C.</p> <p>Conclusion</p> <p>Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.</p

The dynamics of neural fields on bounded domains: an interface approach for Dirichlet boundary conditions

Continuum neural field equations model the large scale spatio-temporal dynamics of interacting neurons on a cortical surface. They have been extensively studied, both analytically and numerically, on bounded as well as unbounded domains. Neural field models do not require the specification of boundary conditions. Relatively little attention has been paid to the imposition of neural activity on the boundary, or to its role in inducing patterned states. Here we redress this imbalance by studying neural field models of Amari type (posed on one- and two-dimensional bounded domains) with Dirichlet boundary conditions. The Amari model has a Heaviside nonlinearity that allows for a description of localised solutions of the neural field with an interface dynamics. We show how to generalise this reduced but exact description by deriving a normal velocity rule for an interface that encapsulates boundary effects. The linear stability analysis of localised states in the interface dynamics is used to understand how spatially extended patterns may develop in the absence and presence of boundary conditions. Theoretical results for pattern formation are shown to be in excellent agreement with simulations of the full neural field model. Furthermore, a numerical scheme for the interface dynamics is introduced and used to probe the way in which a Dirichlet boundary condition can limit the growth of labyrinthine structures

Young off-axis volcanism along the ultraslow-spreading Southwest Indian Ridge

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 3 (2010): 286-292, doi:10.1038/ngeo824.Mid-ocean ridge crustal accretion occurs continuously at all spreading rates through a combination of magmatic and tectonic processes. Fast to slow spreading ridges are largely built by adding magma to narrowly focused neovolcanic zones. In contrast, ultraslow spreading ridge construction significantly relies on tectonic accretion, which is characterized by thin volcanic crust, emplacement of mantle peridotite directly to the seafloor, and unique seafloor fabrics with variable segmentation patterns. While advances in remote imaging have enhanced our observational understanding of crustal accretion at all spreading rates, temporal information is required in order to quantitatively understand mid-ocean ridge construction. However, temporal information does not exist for ultraslow spreading environments. Here, we utilize U-series eruption ages to investigate crustal accretion at an ultraslow spreading ridge for the first time. Unexpectedly young eruption ages throughout the Southwest Indian ridge rift valley indicate that neovolcanic activity is not confined to the spreading axis, and that magmatic crustal accretion occurs over a wider zone than at faster spreading ridges. These observations not only suggest that crustal accretion at ultraslow spreading ridges is distinct from faster spreading ridges, but also that the magma transport mechanisms may differ as a function of spreading rate.This work was supported by the following NSF grants: NSF-OCE 0137325; NSF-OCE 060383800; and NSF-OCE 062705300

A New Digital Preoperative Planning Method for Total Hip Arthroplasties

Preoperative templating is an important part of a THA. The ability to accurately determine magnification of the hip on the radiograph and apply identical magnification to the radiograph and template will improve accuracy of preoperative templating of THA. We designed a templating method using a new way of determining the hip magnification with a linear relationship between magnification of the hip and the reference object on top of the pubis symphysis; the relationship was determined on 50 radiographs. We then compared our method with two other templating methods: an analog method assuming an average hip magnification of 15% and a digital method determining the hip magnification with a one-to-one relationship between the reference object and the hip. All methods were reproducible. Uniform undersizing occurred when templating with the digital method based on the one-to-one relationship; the analog method best predicted the implanted prosthesis size, closely followed by our new digital templating method; the new method will be particularly applicable for preoperative THA when analog methods are replaced by digital methods

The First New Zealanders? An Alternative Interpretation of Stable Isotope Data from Wairau Bar, New Zealand.

PLOS ONE Volume 8 includes an article “The First New Zealanders: Patterns of Diet and Mobility Revealed through Isotope Analysis”. The paper proposes that burial groups within the settlement phase site of Wairau Bar differ in terms of dietary stable isotopes and 87Sr/86Sr. The authors argue this difference is probably due to one group being a founding population while the other burials are later. Here we review the work of Kinaston et al. and present an alternative analysis and interpretation of the isotopic data. Treating the isotope data independently from cultural and biological factors we find that sex best explains dietary variation. Our reassessment of 87Sr/86Sr confirms the authors original finding of high mobility of early New Zealanders but suggests a larger range of individuals should be considered ‘non-local’ on current evidence

Isolation of microplastics in biota-rich seawater samples and marine organisms.

notes: PMCID: PMC3970126types: Journal Article; Research Support, Non-U.S. Gov'tThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Microplastic litter is a pervasive pollutant present in aquatic systems across the globe. A range of marine organisms have the capacity to ingest microplastics, resulting in adverse health effects. Developing methods to accurately quantify microplastics in productive marine waters, and those internalized by marine organisms, is of growing importance. Here we investigate the efficacy of using acid, alkaline and enzymatic digestion techniques in mineralizing biological material from marine surface trawls to reveal any microplastics present. Our optimized enzymatic protocol can digest >97% (by weight) of the material present in plankton-rich seawater samples without destroying any microplastic debris present. In applying the method to replicate marine samples from the western English Channel, we identified 0.27 microplastics m(-3). The protocol was further used to extract microplastics ingested by marine zooplankton under laboratory conditions. Our findings illustrate that enzymatic digestion can aid the detection of microplastic debris within seawater samples and marine biota.Natural Environment Research Council (NERC

Two NAD-linked redox shuttles maintain the peroxisomal redox balance in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, peroxisomes are the sole site of fatty acid β-oxidation. During this process, NAD(+) is reduced to NADH. When cells are grown on oleate medium, peroxisomal NADH is reoxidised to NAD(+) by malate dehydrogenase (Mdh3p) and reduction equivalents are transferred to the cytosol by the malate/oxaloacetate shuttle. The ultimate step in lysine biosynthesis, the NAD(+)-dependent dehydrogenation of saccharopine to lysine, is another NAD(+)-dependent reaction performed inside peroxisomes. We have found that in glucose grown cells, both the malate/oxaloacetate shuttle and a glycerol-3-phosphate dehydrogenase 1(Gpd1p)-dependent shuttle are able to maintain the intraperoxisomal redox balance. Single mutants in MDH3 or GPD1 grow on lysine-deficient medium, but an mdh3/gpd1Δ double mutant accumulates saccharopine and displays lysine bradytrophy. Lysine biosynthesis is restored when saccharopine dehydrogenase is mislocalised to the cytosol in mdh3/gpd1Δ cells. We conclude that the availability of intraperoxisomal NAD(+) required for saccharopine dehydrogenase activity can be sustained by both shuttles. The extent to which each of these shuttles contributes to the intraperoxisomal redox balance may depend on the growth medium. We propose that the presence of multiple peroxisomal redox shuttles allows eukaryotic cells to maintain the peroxisomal redox status under different metabolic conditions

Early Elevation of Matrix Metalloproteinase-8 and -9 in Pediatric ARDS Is Associated with an Increased Risk of Prolonged Mechanical Ventilation

BACKGROUND: Matrix metalloproteinases (MMP) -8 and -9 may play key roles in the modulation of neutrophilic lung inflammation seen in pediatric Acute Respiratory Distress Syndrome (ARDS). We aimed to perform a comprehensive analysis of MMP-8 and MMP-9 activity in tracheal aspirates of pediatric ARDS patients compared with non-ARDS controls, testing whether increased MMP-8 and -9 activities were associated with clinical outcomes. METHODS: Tracheal aspirates were collected from 33 pediatric ARDS patients and 21 non-ARDS controls at 48 hours of intubation, and serially for those who remained intubated greater than five days. MMPs, tissue inhibitor of metalloproteinases (TIMPs), human neutrophil elastase (HNE) and myeloperoxidase (MPO) activity were measured by ELISA, and correlated with clinical indicators of disease severity such as PRISM (Pediatric Risk of Mortality) scores, oxygen index (OI), multi-organ system failure (MOSF) and clinical outcome measures including length of intubation, ventilator-free days (VFDs) and mortality in the Pediatric Intensive Care Unit (PICU). RESULTS: Active MMP-9 was elevated early in pediatric ARDS subjects compared to non-ARDS controls. Higher MMP-8 and active MMP-9 levels at 48 hours correlated with a longer course of mechanical ventilation (r = 0.41, p = 0.018 and r = 0.75, p<0.001; respectively) and fewer number of VFDs (r = -0.43, p = 0.013 and r = -0.76, p<0.001; respectively), independent of age, gender and severity of illness. Patients with the highest number of ventilator days had the highest levels of active MMP-9. MMP-9 and to a lesser extent MMP-8 activities in tracheal aspirates from ARDS subjects were sensitive to blockade by small molecule inhibitors. CONCLUSIONS: Higher MMP-8 and active MMP-9 levels at 48 hours of disease onset are associated with a longer duration of mechanical ventilation and fewer ventilator-free days among pediatric patients with ARDS. Together, these results identify early biomarkers predictive of disease course and potential therapeutic targets for this life threatening disease