A Bio-Polymer Transistor: Electrical Amplification by Microtubules

Microtubules (MTs) are important cytoskeletal structures, engaged in a number of specific cellular activities, including vesicular traffic, cell cyto-architecture and motility, cell division, and information processing within neuronal processes. MTs have also been implicated in higher neuronal functions, including memory, and the emergence of "consciousness". How MTs handle and process electrical information, however, is heretofore unknown. Here we show new electrodynamic properties of MTs. Isolated, taxol-stabilized microtubules behave as bio-molecular transistors capable of amplifying electrical information. Electrical amplification by MTs can lead to the enhancement of dynamic information, and processivity in neurons can be conceptualized as an "ionic-based" transistor, which may impact among other known functions, neuronal computational capabilities.Comment: This is the final submitted version. The published version should be downloaded from Biophysical Journa

Functional single-cell analysis of T-cell activation by supported lipid bilayer-tethered ligands on arrays of nanowells

Supported lipid bilayers are an important biomolecular tool for characterizing immunological synapses. Immobilized bilayers presenting tethered ligands on planar substrates have yielded both spatio-temporal and structural insights into how T cell receptors (TCRs) reorganize during the initial formation of synapses upon recognition of peptide antigens bound to major histocompatibility complex (MHC) molecules. The prototypical configuration of these assays, however, limits the extent to which the kinetics and structure of the supramolecular activation clusters of the synapse (that occur in seconds or minutes) can be related to subsequent complex cellular responses, such as cytokine secretion and proliferation, occurring over hours to days. Here we describe a new method that allows correlative measures of both attributes with single-cell resolution by using immobilized lipid bilayers and tethered ligands on the surface of dense arrays of subnanoliter wells. This modification allows each nanowell to function as an artificial antigen-presenting cell (APC), and the synapses formed upon contact can be imaged by fluorescence microscopy. We show that the lipid bilayers remain stable and mobile on the surface of the PDMS, and that modifying the ligands tethered to the bilayer alters the structure of the resulting synapses in expected ways. Finally, we demonstrate that this approach allows the subsequent characterization of secreted cytokines from the activated human T cell clones by microengraving in both antigen- and pan-specific manners. This new technique should allow detailed investigations on how biophysical and structural aspects of the synapse influence the activation of individual T cells and their complex functional responses.National Institute of Allergy and Infectious Diseases (U.S.) (5P01AI045757)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051

Mutational Analysis of the Nitrogenase Carbon Monoxide Protective Protein CowN Reveals That a Conserved C‑Terminal Glutamic Acid Residue Is Necessary for Its Activity

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work uncovers structural features in CowN that are required for its function and provides new insights into its nitrogenase binding and CO protection mechanism

Element release and reaction-induced porosity alteration during shale-hydraulic fracturing fluid interactions

The use of hydraulic fracturing techniques to extract oil and gas from low permeability shale reservoirs has increased significantly in recent years. During hydraulic fracturing, large volumes of water, often acidic and oxic, are injected into shale formations. This drives fluid-rock interaction that can release metal contaminants (e.g., U, Pb) and alter the permeability of the rock, impacting the transport and recovery of water, hydrocarbons, and contaminants. To identify the key geochemical processes that occur upon exposure of shales to hydraulic fracturing fluid, we investigated the chemical interaction of hydraulic fracturing fluids with a variety of shales of different mineralogical texture and composition. Batch reactor experiments revealed that the dissolution of both pyrite and carbonate minerals occurred rapidly, releasing metal contaminants and generating porosity. Oxidation of pyrite and aqueous Fe drove precipitation of Fe(III)-(oxy)hydroxides that attenuated the release of these contaminants via co-precipitation and/or adsorption. The precipitation of these (oxy)hydroxides appeared to limit the extent of pyrite reaction. Enhanced removal of metals and contaminants in reactors with higher fluid pH was inferred to reflect increased Fe-(oxy)hydroxide precipitation associated with more rapid aqueous Fe(II) oxidation. The precipitation of both Al- and Fe-bearing phases revealed the potential for the occlusion of pores and fracture apertures, whereas the selective dissolution of calcite generated porosity. These pore-scale alterations of shale texture and the cycling of contaminants indicate that chemical interactions between shales and hydraulic fracturing fluids may exert an important control on the efficiency of hydraulic fracturing operations and the quality of water recovered at the surface

Evaluation of Esophageal Motility Utilizing the Functional Lumen Imaging Probe

© 2016 by the American College of Gastroenterology. Objectives:Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia.Methods:In all, 145 patients (aged 18-85 years, 54% female) with dysphagia that completed up per endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered "abnormal". FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered "abnormal" if EGJ-DI was < 2.8 mm 2 /mm Hg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions.Results:HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, and 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was "normal" in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. In all, 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI.Conclusions:FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia.Link_to_subscribed_fulltex

Gaps in Patient Education on Safe Handling and Disposal of Oral Chemotherapy Drugs: A Pilot Prospective Cohort Survey Study

Background Oral anticancer chemotherapy (OC) has been misperceived as being safer than intravenous chemotherapy, leading to its increased risk of improper handling and disposal. This survey study assessed the knowledge, practices and attitudes of pharmacists and patients regarding OC handling and disposal, gaps in knowledge and barriers to patient education. Methods Surveys were developed based on literature review and pilot study validation results. Patients completed a 33-item paper or electronic survey whereas pharmacists completed a 38-item electronic survey. Descriptive statistics and Fisher’s exact test computed using the R Project were used for analyses. Results Pharmacist group (16/25, 62.5%) and patient group (14/29, 48.3%) believed that the oral route is safer than IV. Average overall correct response rates for pharmacist and patient groups were 78.3% and 61.9%, respectively. Significant gaps in knowledge between groups were observed in three sections (p \u3c 0.05). Common barriers to providing patient education were insufficient training (70.8%) and insufficient time (50%). Conclusion Pharmacist and patient knowledge, awareness and practices of OC safe handling and disposal are suboptimal. Areas of knowledge gaps and barriers to patient education were identified. Enhanced supports are needed to empower pharmacists to assume an active role in patient education on safe handling and disposal of OC

The road to deterministic matrices with the restricted isometry property

The restricted isometry property (RIP) is a well-known matrix condition that provides state-of-the-art reconstruction guarantees for compressed sensing. While random matrices are known to satisfy this property with high probability, deterministic constructions have found less success. In this paper, we consider various techniques for demonstrating RIP deterministically, some popular and some novel, and we evaluate their performance. In evaluating some techniques, we apply random matrix theory and inadvertently find a simple alternative proof that certain random matrices are RIP. Later, we propose a particular class of matrices as candidates for being RIP, namely, equiangular tight frames (ETFs). Using the known correspondence between real ETFs and strongly regular graphs, we investigate certain combinatorial implications of a real ETF being RIP. Specifically, we give probabilistic intuition for a new bound on the clique number of Paley graphs of prime order, and we conjecture that the corresponding ETFs are RIP in a manner similar to random matrices.Comment: 24 page

Intravascular Immune Surveillance by CXCR6(+) NKT Cells Patrolling Liver Sinusoids

We examined the in vivo behavior of liver natural killer T cells (NKT cells) by intravital fluorescence microscopic imaging of mice in which a green fluorescent protein cDNA was used to replace the gene encoding the chemokine receptor CXCR6. NKT cells, which account for most CXCR6(+) cells in liver, were found to crawl within hepatic sinusoids at 10–20 μm/min and to stop upon T cell antigen receptor activation. CXCR6-deficient mice exhibited a selective and severe reduction of CD1d-reactive NKT cells in the liver and decreased susceptibility to T-cell-dependent hepatitis. CXCL16, the cell surface ligand for CXCR6, is expressed on sinusoidal endothelial cells, and CXCR6 deficiency resulted in reduced survival, but not in altered speed or pattern of patrolling of NKT cells. Thus, NKT cells patrol liver sinusoids to provide intravascular immune surveillance, and CXCR6 contributes to liver-based immune responses by regulating their abundance

Anesthetic Concerns in Psychiatric Disease

As the prevalence of mental health illnesses rises worldwide, the use of psychotropic medications follows. Undoubtedly, many patients using psychotropic medications will undergo procedures requiring anesthesia both in the operating room and outside of it. This chapter focuses on psychotropic medications that may complicate the surgical and postoperative course of patients undergoing anesthesia. Toward this aim, we performed a literature review using targeted key terms. Relevant articles were cited, and findings are summarized in this narrative review. We begin with discussing psychotropic medication pharmacology, drug-drug interactions, and side effects, emphasizing their interaction with anesthetic agents. We summarize the current recommendations for managing these medications in the perioperative period. In the discussion section, we focus on highlighting future directions for the intersection between psychotropic medications and anesthesia. Overall, we provide insight into the perioperative management of patients taking psychotropic medications, the point of intersection between the fields of psychiatry and anesthesia