Iron Sequestration by Galloyl-Silane Nano Coatings Inhibits Biofilm Formation of Sulfitobacter sp.

Microbially-induced corrosion is the acceleration of corrosion induced by bacterial biofilms. The bacteria in the biofilms oxidize metals on the surface, especially evident with iron, to drive metabolic activity and reduce inorganic species such as nitrates and sulfates. Coatings that prevent the formation of these corrosion-inducing biofilms significantly increase the service life of submerged materials and significantly decrease maintenance costs. One species in particular, a member of the Roseobacter clade, Sulfitobacter sp., has demonstrated iron-dependent biofilm formation in marine environments. We have found that compounds that contain the galloyl moiety can prevent Sulfitobacter sp. biofilm formation by sequestering iron, thus making a surface unappealing for bacteria. Herein, we have fabricated surfaces with exposed galloyl groups to test the effectiveness of nutrient reduction in iron-rich media as a non-toxic method to reduce biofilm formation.

Novel niobium-doped titanium oxide towards electrochemical destruction of forever chemicals.

Electrochemical advanced oxidative processes (EAOP) are a promising route to destroy recalcitrant organic contaminants such as per- and polyfluoroalkyl substances (PFAS) in drinking water. Central to EAOP are catalysis-induced reactive free radicals for breaking the carbon fluorine bonds in PFAS. Generating these reactive species electrochemically at electrodes provides an advantage over other oxidation processes that rely on chemicals or other harsh conditions. Herein, we report on the performance of niobium (Nb) doped rutile titanium oxide (TiO2) as a novel EAOP catalytic material, combining theoretical modeling with experimental synthesis and characterization. Calculations based on density functional theory are used to predict the overpotential for oxygen evolution at these candidate electrodes, which must be high in order to oxidize PFAS. The results indicate a non-monotonic trend in which Nb doping below 6.25 at.% is expected to reduce performance relative to TiO2, while higher concentrations up to 12.5 at.% lead to increased performance, approaching that of state-of-the-art Magnéli Ti4O7. TiO2 samples were synthesized with Nb doping concentration at 10 at.%, heat treated at temperatures from 800 to 1100 °C, and found to exhibit high oxidative stability and high generation of reactive oxygen free radical species. The capability of Nb-doped TiO2 to destroy two common species of PFAS in challenge water was tested, and moderate reduction by ~ 30% was observed, comparable to that of Ti4O7 using a simple three-electrode configuration. We conclude that Nb-doped TiO2 is a promising alternative EAOP catalytic material with increased activity towards generating reactive oxygen species and warrants further development for electrochemically destroying PFAS contaminants.

Precision multidimensional neural population code recovered from single intracellular recordings.

Neurons in sensory cortices are more naturally and deeply integrated than any current neural population recording tools (e.g. electrode arrays, fluorescence imaging). Two concepts facilitate efforts to observe population neural code with single-cell recordings. First, even the highest quality single-cell recording studies find a fraction of the stimulus information in high-dimensional population recordings. Finding any of this missing information provides proof of principle. Second, neurons and neural populations are understood as coupled nonlinear differential equations. Therefore, fitted ordinary differential equations provide a basis for single-trial single-cell stimulus decoding. We obtained intracellular recordings of fluctuating transmembrane current and potential in mouse visual cortex during stimulation with drifting gratings. We use mean deflection from baseline when comparing to prior single-cell studies because action potentials are too sparse and the deflection response to drifting grating stimuli (e.g. tuning curves) are well studied. Equation-based decoders allowed more precise single-trial stimulus discrimination than tuning-curve-base decoders. Performance varied across recorded signal types in a manner consistent with population recording studies and both classification bases evinced distinct stimulus-evoked phases of population dynamics, providing further corroboration. Naturally and deeply integrated observations of population dynamics would be invaluable. We offer proof of principle and a versatile framework.

A Novel Small Molecule Targets Androgen Receptor and Its Splice Variants in Castration-Resistant Prostate Cancer.

Reactivation of androgen receptor (AR) appears to be the major mechanism driving the resistance of castration-resistant prostate cancer (CRPC) to second-generation antiandrogens and involves AR overexpression, AR mutation, and/or expression of AR splice variants lacking ligand-binding domain. There is a need for novel small molecules targeting AR, particularly those also targeting AR splice variants such as ARv7. A high-throughput/high-content screen was previously reported that led to the discovery of a novel lead compound, 2-(((3,5-dimethylisoxazol-4-yl)methyl)thio)-1-(4-(2,3-dimethylphenyl)piperazin-1-yl)ethan-1-one (IMTPPE), capable of inhibiting nuclear AR level and activity in CRPC cells, including those resistant to enzalutamide. A novel analogue of IMTPPE, JJ-450, has been investigated with evidence for its direct and specific inhibition of AR transcriptional activity via a pulldown assay and RNA-sequencing analysis, PSA-based luciferase, qPCR, and chromatin immunoprecipitation assays, and xenograft tumor model 22Rv1. JJ-450 blocks AR recruitment to androgen-responsive elements and suppresses AR target gene expression. JJ-450 also inhibits ARv7 transcriptional activity and its target gene expression. Importantly, JJ-450 suppresses the growth of CRPC tumor xenografts, including ARv7-expressing 22Rv1. Collectively, these findings suggest JJ-450 represents a new class of AR antagonists with therapeutic potential for CRPC, including those resistant to enzalutamide.

Advanced Filtration Membranes for the Removal of Perfluoroalkyl Species from Water.

Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are two perfluoroalkyl substances that have been shown to result in several adverse health effects, including birth defects, kidney/testicular cancer, as well as liver and thyroid damage. The surfactant nature of PFOS and PFOA in water makes these compounds extremely difficult to remove from drinking water. In this paper, an efficient method to remove PFOS and PFOA from drinking water using linear fluorinated silane-functionalized aluminum oxide hydroxide (γ-AlOOH) nanowhiskers was developed. Filters functionalized with linear fluorinated silanes containing 13-17 fluorine atoms were able to remove >90% of the PFOS/PFOA at a very high flux of 1223 L/m2·h. However, due to the hydrophobicity of these linear fluorinated silanes, high pressure drop was also noted across the membrane thickness during the filtration process. To reduce the back-pressure drop, linear fluorinated silanes with appended hydrophilic poly(ethylene glycol) units were synthesized, and it was further demonstrated that the new hydrophilic linear fluorinated silane dramatically reduced the pressure drop of the γ-AlOOH filter while maintaining 99.9% PFOS and PFOA reduction. Adsorption tests were performed to understand the removal mechanism.

Single-Cell Membrane Potential Fluctuations Evince Network Scale-Freeness and Quasicriticality.

What information single neurons receive about general neural circuit activity is a fundamental question for neuroscience. Somatic membrane potential (Vm) fluctuations are driven by the convergence of synaptic inputs from a diverse cross-section of upstream neurons. Furthermore, neural activity is often scale-free, implying that some measurements should be the same, whether taken at large or small scales. Together, convergence and scale-freeness support the hypothesis that single Vm recordings carry useful information about high-dimensional cortical activity. Conveniently, the theory of "critical branching networks" (one purported explanation for scale-freeness) provides testable predictions about scale-free measurements that are readily applied to Vm fluctuations. To investigate, we obtained whole-cell current-clamp recordings of pyramidal neurons in visual cortex of turtles with unknown genders. We isolated fluctuations in Vm below the firing threshold and analyzed them by adapting the definition of "neuronal avalanches" (i.e., spurts of population spiking). The Vm fluctuations which we analyzed were scale-free and consistent with critical branching. These findings recapitulated results from large-scale cortical population data obtained separately in complementary experiments using microelectrode arrays described previously (Shew et al., 2015). Simultaneously recorded single-unit local field potential did not provide a good match, demonstrating the specific utility of Vm Modeling shows that estimation of dynamical network properties from neuronal inputs is most accurate when networks are structured as critical branching networks. In conclusion, these findings extend evidence of critical phenomena while also establishing subthreshold pyramidal neuron Vm fluctuations as an informative gauge of high-dimensional cortical population activity.SIGNIFICANCE STATEMENT The relationship between membrane potential (Vm) dynamics of single neurons and population dynamics is indispensable to understanding cortical circuits. Just as important to the biophysics of computation are emergent properties such as scale-freeness, where critical branching networks offer insight. This report makes progress on both fronts by comparing statistics from single-neuron whole-cell recordings with population statistics obtained with microelectrode arrays. Not only are fluctuations of somatic Vm scale-free, they match fluctuations of population activity. Thus, our results demonstrate appropriation of the brain's own subsampling method (convergence of synaptic inputs) while extending the range of fundamental evidence for critical phenomena in neural systems from the previously observed mesoscale (fMRI, LFP, population spiking) to the microscale, namely, Vm fluctuations.

Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer.

After a high-throughput screening campaign identified thioether 1 as an antagonist of the nuclear androgen receptor, a zone model was developed for structure-activity relationship (SAR) purposes and analogues were synthesized and evaluated in a cell-based luciferase assay. A novel thioether isostere, cyclopropane (1S,2R)-27, showed the desired increased potency and structural properties (stereospecific SAR response, absence of a readily oxidized sulfur atom, low molecular weight, reduced number of flexible bonds and polar surface area, and drug-likeness score) in the prostate-specific antigen luciferase assay in C4-2-PSA-rl cells to qualify as a new lead structure for prostate cancer drug development.

Developing and assessing curriculum on the physics of medical instruments.

Undergraduate educational settings often struggle to provide students with authentic biologically or medically relevant situations and problems that simultaneously improve their understanding of physics. Through exercises and laboratory activities developed in an elective Physics in Biomedicine course for upper-level biology or pre-health majors at Portland State University, we aim to teach fundamental physical concepts, such as light absorption and emission and atomic energy levels, through analysis of biological systems and medical devices. The activities address the properties of electromagnetic waves as they relate to the interaction with biological tissue and make links between physics and biomedical applications such as microscopy or laser eye surgery. We report on the effect that engaging students in tasks with actual medical equipment has had on their conceptual understanding of light and spectroscopy. These initial assessments indicate that students' understanding improves in some areas as a result of taking the course, but gains are not uniform and are relatively low for other topics. We also find a promising "nonshift" in student attitudes toward learning science as a result of taking the course. A long-term goal of this work is to develop these materials to the extent that they can eventually be imported into an introductory curriculum for life sciences majors.