Dissolution of Calcite in the Twilight Zone: Bacterial Control of Dissolution of Sinking Planktonic Carbonates Is Unlikely

We investigated the ability of bacterial communities to colonize and dissolve two biogenic carbonates (Foraminifera and oyster shells). Bacterial carbonate dissolution in the upper water column is postulated to be driven by metabolic activity of bacteria directly colonising carbonate surfaces and the subsequent development of acidic microenvironments. We employed a combination of microsensor measurements, scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and image analysis and molecular documentation of colonising bacteria to monitor microbial processes and document changes in shell surface topography. Bacterial communities rapidly colonised shell surfaces, forming dense biofilms with extracellular polymeric substance (EPS) deposits. Despite this, we found no evidence of bacterially mediated carbonate dissolution. Dissolution was not indicated by Ca2+ microprofiles, nor was changes in shell surface structure related to the presence of colonizing bacteria. Given the short time (days) settling carbonate material is actually in the twilight zone (500–1000 m), it is highly unlikely that microbial metabolic activity on directly colonised shells plays a significant role in dissolving settling carbonates in the shallow ocean

Multi-Parameter Laser Imaging Reveals Complex Microscale Biofilm Matrix in a Thick (4,000 μm) Aerobic Methanol Oxidizing Community

Although methanol has frequently been used as an inexpensive supplementary carbon source to support treatment processes, knowledge of the resultant microbial biofilms, their 3D architecture, microenvironments, exopolymer chemistry and populations remains limited. We supplied methanol as a supplementary carbon source to biofilms developing in rotating annular reactors. Analysis of circulation waters (1.0 l d−1) indicated that dissolved organic carbon was reduced by 25%, NO3-nitrogen by 95%, and total phosphorus by 70%. Analyses of populations using culture based techniques and fluorescence in situ hybridization indicated enrichment of nitrifiers, denitrifiers, and methylotrophic bacteria relative to reference biofilms not receiving methanol. The biofilms that developed were up to 4,000 μm thick. Staining with fluor conjugated lectins in combination with nucleic acid stains, revealed the presence of discrete bacterial cells inside complex globular polymeric structures. These structures were in turn surrounded by an interstitial polymer containing a variety of bacterial cell types. The globular structures bound FITC-conjugated lectins, from Canavalia ensiformis and Ulex europeaus. The FITC-lectin of Phaseolus vulgaris bound the surface of the globular structures and more generally within the matrix. Chemical analyses of the polymer paralleled the results of lectin analyses indicating that the dominant neutral sugars were glucose, galactose, mannose, rhamnose, with fucose and ribose as minor constituents. Amino sugars were not detected. Dual channel imaging with pH sensitive probes indicated that pH gradients from pH 4 to 7 occurred across the globular microcolonies. Critically for the maintenance of aerobic conditions throughout the thick biofilm it was extensively penetrated by a fine fissure network revealed by the location of fluorescent latex microbeads as detected by confocal laser scanning microscopy. Microelectrode studies confirmed the absence of any detectable Eh gradients within the biofilm. However, mobility of various size-fractionated fluorescent probes indicated that the basal region was only penetrated by the lowest molecular weight probes with a hydrated radius of 2.2 nm or less. These observations indicate the selection of a unique, thick (>4,000 μm) microbial community in which a self-organized architecture promotes the maintenance of optimal conditions and metabolism throughout the biofilm community

Incorporating Inductances in Tissue-Scale Models of Cardiac Electrophysiology

In standard models of cardiac electrophysiology, including the bidomain and monodomain models, local perturbations can propagate at infinite speed. We address this unrealistic property by developing a hyperbolic bidomain model that is based on a generalization of Ohm's law with a Cattaneo-type model for the fluxes. Further, we obtain a hyperbolic monodomain model in the case that the intracellular and extracellular conductivity tensors have the same anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is equivalent to a cable model that includes axial inductances, and the relaxation times of the Cattaneo fluxes are strictly related to these inductances. A purely linear analysis shows that the inductances are negligible, but models of cardiac electrophysiology are highly nonlinear, and linear predictions may not capture the fully nonlinear dynamics. In fact, contrary to the linear analysis, we show that for simple nonlinear ionic models, an increase in conduction velocity is obtained for small and moderate values of the relaxation time. A similar behavior is also demonstrated with biophysically detailed ionic models. Using the Fenton-Karma model along with a low-order finite element spatial discretization, we numerically analyze differences between the standard monodomain model and the hyperbolic monodomain model. In a simple benchmark test, we show that the propagation of the action potential is strongly influenced by the alignment of the fibers with respect to the mesh in both the parabolic and hyperbolic models when using relatively coarse spatial discretizations. Accurate predictions of the conduction velocity require computational mesh spacings on the order of a single cardiac cell. We also compare the two formulations in the case of spiral break up and atrial fibrillation in an anatomically detailed model of the left atrium, and [...].Comment: 20 pages, 12 figure

Efficacy of repeated intrathecal triamcinolone acetonide application in progressive multiple sclerosis patients with spinal symptoms

BACKGROUND: There are controversial results on the efficacy of the abandoned, intrathecal predominant methylprednisolone application in multiple sclerosis (MS) in contrast to the proven effectiveness in intractable postherpetic neuralgia. METHODS: We performed an analysis of the efficacy of the application of 40 mg of the sustained release steroid triamcinolone acetonide (TCA). We intrathecally injected in sterile saline dissolved TCA six times within three weeks on a regular basis every third day in 161 hospitalized primary and predominant secondary progressive MS patients with spinal symptoms. The MS patients did not experience an acute onset of exacerbation or recent distinct increased progression of symptoms. We simultaneously scored the MS patients with the EDSS and the Barthel index, estimated the walking distance and measured somatosensory evoked potentials. Additionally the MS patients received a standardized rehabilitation treatment. RESULTS: EDSS score and Barthel index improved, walking distance increased, latencies of somatosensory evoked potentials of the median and tibial nerves shortened in all MS patients with serial evaluation (p < 0.0001 for all variables). Side effects were rare, five patients stopped TCA application due to onset of a post lumbar puncture syndrome. CONCLUSIONS: Repeated intrathecal TCA application improves spinal symptoms, walking distance and SSEP latencies in progressive MS patients in this uncontrolled study. Future trials should evaluate the long-term benefit of this invasive treatment

The importance of biofilm formation for cultivation of a Micrarchaeon and its interactions with its Thermoplasmatales host

Micrarchaeota is a distinctive lineage assigned to the DPANN archaea, which includes poorly characterised microorganisms with reduced genomes that likely depend on interactions with hosts for growth and survival. Here, we report the enrichment of a stable co-culture of a member of the Micrarchaeota (Ca. Micrarchaeum harzensis) together with its Thermoplasmatales host (Ca. Scheffleriplasma hospitalis), as well as the isolation of the latter. We show that symbiont-host interactions depend on biofilm formation as evidenced by growth experiments, comparative transcriptomic analyses and electron microscopy. In addition, genomic, metabolomic, extracellular polymeric substances and lipid content analyses indicate that the Micrarchaeon symbiont relies on the acquisition of metabolites from its host. Our study of the cell biology and physiology of a Micrarchaeon and its host adds to our limited knowledge of archaeal symbioses

Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur: Biofilm Dynamics and EPS Analysis

Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD). Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear. This work focused on how a crenarchaeal isolate Acidianus sp. DSM 29099 interacts with elemental sulfur. Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm. The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates. Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components. Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides. EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells). This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. © 2013 Neal et al

Search for Neutral Higgs Bosons in Events with Multiple Bottom Quarks at the Tevatron

The combination of searches performed by the CDF and D0 collaborations at the Fermilab Tevatron Collider for neutral Higgs bosons produced in association with b quarks is reported. The data, corresponding to 2.6 fb-1 of integrated luminosity at CDF and 5.2 fb-1 at D0, have been collected in final states containing three or more b jets. Upper limits are set on the cross section multiplied by the branching ratio varying between 44 pb and 0.7 pb in the Higgs boson mass range 90 to 300 GeV, assuming production of a narrow scalar boson. Significant enhancements to the production of Higgs bosons can be found in theories beyond the standard model, for example in supersymmetry. The results are interpreted as upper limits in the parameter space of the minimal supersymmetric standard model in a benchmark scenario favoring this decay mode.Comment: 10 pages, 2 figure

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Non-Invasive Exploration of Neonatal Gastric Epithelium by Using Exfoliated Epithelial Cells

Background &amp; Aims: In preterm infants, exfoliated gastric epithelial cells can be retrieved from aspirates sampled through the naso-gastric feeding tube. Our aims were to determine (1) whether the recovery of exfoliated cells is feasible at any time from birth through the removal of the nasogastric tube, (2) whether they can be grown in culture in vitro, and (3) whether the physiological state of exfoliated cells expressing H+/K+-ATPases reflects that of their counterparts remaining in situ at the surface of the gastric epithelium in neonatal rat pups. Methods: In infants, gastric fluid aspirates were collected weekly after birth or every 3 hours over 24-h periods, and related to clinical parameters (Biocollection PROG/09/18). In rat pups submitted to a single fasting/refeeding cycle, we explored circadian exfoliation with the cellular counter-parts in the gland. All samples were analyzed by confocal imaging and Enzyme-Linked Immunosorbent Assay. Results: Epithelial cells were identified by microscopy using membrane-bound anti-H+/K+ ATPases antibody, assessed for nucleus integrity, and the expression of selected proteins (autophagy, circadian clock). On 34 infants, the H+/K+-ATPasepositive cells were consistently found quiescent, regardless of gestational age and feeding schedule from day-5 of life to the day of removal of the naso-gastric tube. By logistic regression analysis, we did find a positive correlation between the intensity of exfoliation (cellular loss per sample) and the postnatal age (p,0.001). The H+/K+ ATPase-positive cell