Heterotrophic bacteria exhibit a wide range of rates of extracellular production and decay of hydrogen peroxide

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Bond, R. J., Hansel, C. M., & Voelker, B. M. Heterotrophic bacteria exhibit a wide range of rates of extracellular production and decay of hydrogen peroxide. Frontiers in Marine Science, 7, (2020): 72, doi:10.3389/fmars.2020.00072.Bacteria have been implicated as both a source and sink of hydrogen peroxide (H2O2), a reactive oxygen species which can both impact microbial growth and participate in the geochemical cycling of trace metals and carbon in natural waters. In this study, simultaneous H2O2 production and decay by twelve species of heterotrophic bacteria were evaluated in both batch and flow-through incubations. While wide species-to-species variability of cell-normalized H2O2 decay rate coefficients [2 × 10–8 to 5 × 10–6 hr–1 (cell mL–1)–1] was observed, these rate coefficients were relatively consistent for a given bacterial species. By contrast, observed production rates (below detection limit to 3 × 102 amol cell–1 hr–1) were more variable even for the same species. Variations based on incubation conditions in some bacterial strains suggest that external conditions may impact extracellular H2O2 levels either through increased extracellular production or leakage of intracellular H2O2. Comparison of H2O2 production rates to previously determined superoxide (O2–) production rates suggests that O2– and H2O2 production are not necessarily linked. Rates measured in this study indicate that bacteria could account for a majority of H2O2 decay observed in aqueous systems but likely only make a modest contribution to dark H2O2 production.This research was supported by NSF grant OCE-1131734/1246174 to BV and CH

Emergent Orientation Selectivity from Random Networks in Mouse Visual Cortex

The connectivity principles underlying the emergence of orientation selectivity in primary visual cortex (V1) of mammals lacking an orientation map (such as rodents and lagomorphs) are poorly understood. We present a computational model in which random connectivity gives rise to orientation selectivity that matches experimental observations. The model predicts that mouse V1 neurons should exhibit intricate receptive fields in the two-dimensional frequency domain, causing a shift in orientation preferences with spatial frequency. We find evidence for these features in mouse V1 using calcium imaging and intracellular whole-cell recordings. Pattadkal et al. show that orientation selectivity can emerge from random connectivity, and offer a distinct perspective for how computations occur in the neocortex. They propose that a random convergence of inputs can provide signals for orientation preference in contrast with the dominant model that requires a precise arrangement.Fil: Pattadkal, Jagruti J.. University of Texas at Austin; Estados UnidosFil: Mato, German. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: van Vreeswijk, Carl. Centre National de la Recherche Scientifique; FranciaFil: Priebe, Nicholas J.. University of Texas at Austin; Estados UnidosFil: Hansel, David. Centre National de la Recherche Scientifique; Franci

Efeito alelopático de Araucaria angustifolia.

EVINCI. Resumo

Small Molecule Inhibitor Design for Anaplastic Lymphoma Kinase Inhibition

The Anaplastic Lymphoma Kinase (ALK) gene has been linked to tumorigenesis in a number of human cancers, including anaplastic large cell lymphoma (ALCL) and neuroblastoma. While ALK mutations in ALCL and many other cancers occur as a result of gene fusions with wild type kinase domains, those in neuroblastoma stem from single nucleotide polymorphisms (SNPs) in the kinase domain. These lead to autophosphorylation and constitutive signaling by ALK for cell growth and division, ultimately causing cancer. Crizotinib, an ATP-competitive ALK inhibitor, has proven to be an effective inhibitor of both ALKWT and ALKMutant kinase domains, and is in the middle of clinical trials for neuroblastoma treatment. This review used the PyMOL and AutoDock Vina computational biology programs to predict the binding affinities of Crizotinib, Ceritinib (LDK378), and PF-922 to three different ALK kinase mutations in order to determine the most effective inhibitor. The EGFR inhibitors gefitinib and erlotinib were also analyzed in complex with ALK as negative controls to verify the specificity of the ALK inhibitors. The crystalline complexes were then qualitatively analyzed to uncover the mechanics behind the docking results. Based on the results generated by Vina, PF-922, representative of the second generation of ALK inhibitors, is predicted to be the most effective out of the tested compounds. These results may be used to predict the inhibitor that will require the lowest dosage to achieve the greatest inhibitory effect, hopefully leading to fewer side effects from treatment

Test of Guttmann and Enting's conjecture in the eight-vertex model

We investigate the analyticity property of the partially resummed series expansion(PRSE) of the partition function for the eight-vertex model. Developing a graphical technique, we have obtained a first few terms of the PRSE and found that these terms have a pole only at one point in the complex plane of the coupling constant. This result supports the conjecture proposed by Guttmann and Enting concerning the ``solvability'' in statistical mechanical lattice models.Comment: 15 pages, 3 figures, RevTe

Slow Switching in Globally Coupled Oscillators: Robustness and Occurrence through Delayed Coupling

The phenomenon of slow switching in populations of globally coupled oscillators is discussed. This characteristic collective dynamics, which was first discovered in a particular class of the phase oscillator model, is a result of the formation of a heteroclinic loop connecting a pair of clustered states of the population. We argue that the same behavior can arise in a wider class of oscillator models with the amplitude degree of freedom. We also argue how such heteroclinic loops arise inevitably and persist robustly in a homogeneous population of globally coupled oscillators. Although the heteroclinic loop might seem to arise only exceptionally, we find that it appears rather easily by introducing the time-delay in the population which would otherwise exhibit perfect phase synchrony. We argue that the appearance of the heteroclinic loop induced by the delayed coupling is then characterized by transcritical and saddle-node bifurcations. Slow switching arises when the system with a heteroclinic loop is weakly perturbed. This will be demonstrated with a vector model by applying weak noises. Other types of weak symmetry-breaking perturbations can also cause slow switching.Comment: 10 pages, 14 figures, RevTex, twocolumn, to appear in Phys. Rev.

Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness

<div><p>Background</p><p><b>P</b>ractical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS) is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF).</p><p>Methods</p><p>We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 <i>per protocol</i>). Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl) or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM), a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1) was quantified from nasal epithelial curettage samples taken before and after challenge.</p><p>Results</p><p>Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8) and CCL3 (MIP-1α) (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS). At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05). Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS).</p><p>Conclusions</p><p>Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.</p><p>Key Messages</p><p>Ultrapure LPS was used as innate immune stimulus in a human nasal challenge model, with serial sampling of nasal mucosal lining fluid (MLF) by nasosorption using a synthetic absorptive matrix (SAM), and nasal curettage of mucosal cells. A dose response could be demonstrated in terms of levels of IL-1β, IL-6, CXCL8 and CCL3 in MLF, as well as ICAM-1 mRNA in nasal curettage specimens, and levels of neutrophils in nasal lavage. Depending on higher baseline levels of inflammation, there were occasional magnified innate inflammatory responses to LPS.</p><p>Trial Registration</p><p>Clinical Trials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02284074?term=nasal+lipopolysaccharide&rank=1" target="_blank">NCT02284074</a></p></div

Enriched iron(III)-reducing bacterial communities are shaped by carbon substrate and iron oxide mineralogy

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Microbiology 3 (2012): 404, doi:10.3389/fmicb.2012.00404.Iron (Fe) oxides exist in a spectrum of structures in the environment, with ferrihydrite widely considered the most bioavailable phase. Yet, ferrihydrite is unstable and rapidly transforms to more crystalline Fe(III) oxides (e.g., goethite, hematite), which are poorly reduced by model dissimilatory Fe(III)-reducing microorganisms. This begs the question, what processes and microbial groups are responsible for reduction of crystalline Fe(III) oxides within sedimentary environments? Further, how do changes in Fe mineralogy shape oxide-hosted microbial populations? To address these questions, we conducted a large-scale cultivation effort using various Fe(III) oxides (ferrihydrite, goethite, hematite) and carbon substrates (glucose, lactate, acetate) along a dilution gradient to enrich for microbial populations capable of reducing Fe oxides spanning a wide range of crystallinities and reduction potentials. While carbon source was the most important variable shaping community composition within Fe(III)-reducing enrichments, both Fe oxide type and sediment dilution also had a substantial influence. For instance, with acetate as the carbon source, only ferrihydrite enrichments displayed a significant amount of Fe(III) reduction and the well-known dissimilatory metal reducer Geobacter sp. was the dominant organism enriched. In contrast, when glucose and lactate were provided, all three Fe oxides were reduced and reduction coincided with the presence of fermentative (e.g., Enterobacter spp.) and sulfate-reducing bacteria (e.g., Desulfovibrio spp.). Thus, changes in Fe oxide structure and resource availability may shift Fe(III)-reducing communities between dominantly metal-respiring to fermenting and/or sulfate-reducing organisms which are capable of reducing more recalcitrant Fe phases. These findings highlight the need for further targeted investigations into the composition and activity of speciation-directed metal-reducing populations within natural environments.This work was supported by a National Science Foundation Graduate Research Fellowship under grant no. DGE-0946799 and DGE-1144152 awarded to Christopher J. Lentini