The Utilization and Development of Viral Vectors in Vaccines as a Prophylactic Treatment Against Ebola Virus as an Emerging and Zoonotic Infectious Disease.

Alongside the prescription of commonly used antivirals, such as acyclovir, remdesivir, oseltamivir, and ciprofloxacin, the most efficient way to prevent or treat communicable diseases is by vaccination. Vaccines have been the most efficient way to prevent or treat highly transmissible infectious agents, such as Ebola, Anthrax, and Dengue Fever. Most epidemics of these highly transmissible infectious agents occur in places, such as South America, Central America, Tropical Asia, and Africa, where the availability of resources and access to adequate healthcare are limited.

Bringing Plant Immunity to Light: A Genetically Encoded, Bioluminescent Reporter of Pattern-Triggered Immunity in .

Plants rely on innate immune systems to defend against a wide variety of biotic attackers. Key components of innate immunity include cell-surface pattern-recognition receptors (PRRs), which recognize pest- and pathogen-associated molecular patterns (PAMPs). Unlike other classes of receptors that often have visible cell-death immune outputs upon activation, PRRs generally lack rapid methods for assessing function.

Evolutionary gain and loss of a plant pattern-recognition receptor for HAMP recognition.

As a first step in innate immunity, pattern recognition receptors (PRRs) recognize the distinct pathogen and herbivore-associated molecular patterns and mediate activation of immune responses, but specific steps in the evolution of new PRR sensing functions are not well understood. We employed comparative genomic and functional analyses to define evolutionary events leading to the sensing of the herbivore-associated peptide inceptin (In11) by the PRR inceptin receptor (INR) in legume plant species. Existing and de novo genome assemblies revealed that the presence of a functional gene corresponded with ability to respond to In11 across ~53 million years (my) of evolution.

SUMO paralogue-specific functions revealed through systematic analysis of human knockout cell lines and gene expression data.

The small ubiquitin-related modifiers (SUMOs) regulate nearly every aspect of cellular function, from gene expression in the nucleus to ion transport at the plasma membrane. In humans, the SUMO pathway has five SUMO paralogues with sequence homologies that range from 45% to 97%. SUMO1 and SUMO2 are the most distantly related paralogues and also the best studied.

Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds.

Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket.

Catalytic Mechanism of Interfacial Water in the Cycloaddition of Quadricyclane and Diethyl Azodicarboxylate.

"On-water" catalysis, the unusual activity of water molecules at the organic solvent-water interface, has been demonstrated in many organic reactions. However, the catalytic mechanism has remained unclear, largely because of the irreproducibility of the organic-water interface under the common stirring condition. Here, the interfacial area was controlled by employing adsorbed water on mesoporous silica nanoparticles as the catalyst.

Fundamental understanding of millipede morphology and locomotion dynamics.

A detailed model for the locomotory mechanics used by millipedes is provided here through systematic experimentation on the animal and validation of observations through a biomimetic robotic platform. Millipedes possess a powerful gait that is necessary for generating large thrust force required for proficient burrowing. Millipedes implement a metachronal gait through movement of many legs that generates a traveling wave.

Tuning Redox Potential of Gold Nanoparticle Photocatalysts by Light.

Metallic nanoparticle-based photocatalysts have gained a lot of interest in catalyzing oxidation-reduction reactions. In previous studies, the poor performance of these catalysts is partly due to their operation that relies on picosecond-lifetime hot carriers. In this work, electrons that accumulate at a photostationary state, generated by photocharging the catalysts, have a much longer lifetime for catalysis.

Anodic Oxidation of Dithiane Carboxylic Acids: A Rapid and Mild Way to Access Functionalized Orthoesters.

A new electrochemical methodology has been developed for the preparation of a wide variety of functionalized orthoesters under mild and green conditions from easily accessible dithiane derivatives. The new methodology also offers an unprecedented way to access tri(fluorinated) orthoesters, a class of compound that has never been studied before. This provides the community with a rapid and general method to prepare libraries of functionalized orthoesters from simple and readily available starting materials.

Economical, Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals.

A new electrochemical methodology has been developed for the generation of oxycarbonyl radicals under mild and green conditions from readily available hemioxalate salts. Mono- and multi-functionalised γ-butyrolactones were synthesised through exo-cyclisation of these oxycarbonyl radicals with an alkene, followed by the sp -sp capture of the newly formed carbon-centred radical. The synthesis of functionalised valerolactone derivatives was also achieved, demonstrating the versatility of the newly developed methodology.

A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity.

Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance-and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities.

Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition.

Glucokinase phosphorylated a series of C-1 fluorinated α-d-gluco-heptuloses. These phosphorylated products were discovered to be inhibitors of α-phosphomannomutase/phosphoglucomutase (αPMM/PGM) and β-phosphoglucomutase (βPGM). Inhibition potency with both mutases inversely correlated to the degree of fluorination.

Comparing the Effects of Loving-Kindness Meditation (LKM), Music and LKM Plus Music on Psychological Well-Being.

Loving-kindness meditation (LKM), a meditative practice directing caring feelings toward self and others, is a popular, evidence-base approach to increasing well-being. Music listening is also a popular form of emotion regulation used to enhance well-being. This interdisciplinary study evaluated a novel intervention called Convergence-combining LKM with accompanying classical guitar music-and its effects on adults' well-being, mindfulness, compassion and self-compassion outcomes.

Interferon-γ ablation exacerbates myocardial hypertrophy in diastolic heart failure.

Diastolic heart failure (HF) accounts for up to 50% of all HF admissions, with hypertension being the major cause of diastolic HF. Hypertension is characterized by left ventricular (LV) hypertrophy (LVH). Proinflammatory cytokines are increased in LVH and hypertension, but it is unknown if they mediate the progression of hypertension-induced diastolic HF.

Effect of wall-molecule interactions on electrokinetic transport of charged molecules in nanofluidic channels during FET flow control.

The interactions between charged molecules and channel surfaces are expected to significantly influence the electrokinetic transport of molecules and their separations in nanochannels. This study reports the effect of wall-molecule interactions on flow control of negatively charged Alexa 488 and positively charged Rhodamine B dye molecules in an array of nanochannels (100 nm wx 500 nm dx 14 mm l) embedded in fluidic field effect transistors (FETs). For FET flow control, a third electrical potential, known as a gate bias, is applied to the channel walls to manipulate their zeta-potential.

Formation and dynamics of supported phospholipid membranes on a periodic nanotextured substrate.

We have studied and modeled the morphology and dynamics of fluid planar lipid bilayer membranes supported on a textured silicon substrate. The substrate is fabricated to have channels on its surface that are a few hundred nanometers across, with a channel depth of a few hundred nanometers perpendicular to the plane of observation. Using atomic force microscopy and quantitative fluorescence microscopy, we have shown that the bilayer assemblies conform to the underlying nanostructured substrate.

Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms.

Aldosterone induces extracellular signal-regulated kinase (ERK)-dependent cardiac remodeling. Fenofibrate improves cardiac remodeling in adult rat ventricular myocytes (ARVM) partly via inhibition of aldosterone-induced ERK1/2 phosphorylation and inhibition of matrix metalloproteinases. We sought to determine whether aldosterone caused apoptosis in cultured ARVM and whether fenofibrate ameliorated the apoptosis.

Electrokinetic transport and separations in fluidic nanochannels.

This article presents a summary of theory, experimental studies, and results for the electrokinetic transport in small fluidic nanochannels. The main focus is on the effect of the electric double layer on the EOF, electric current, and electrophoresis of charged analytes. The double layer thickness can be of the same order as the width of the nanochannels, which has an impact on the transport by shaping the fluid velocity profile, local distributions of the electrolytes, and charged analytes.

Electrokinetic molecular separation in nanoscale fluidic channels.

This report presents a study of electrokinetic transport in a series of integrated macro- to nano-fluidic chips that allow for controlled injection of molecular mixtures into high-density arrays of nanochannels. The high-aspect-ratio nanochannels were fabricated on a Si wafer using interferometric lithography and standard semiconductor industry processes, and are capped with a transparent Pyrex cover slip to allow for experimental observations. Confocal laser scanning microscopy was used to examine the electrokinetic transport of a negatively charged dye (Alexa 488) and a neutral dye (rhodamine B) within nanochannels that varied in width from 35 to 200 nm with electric field strengths equal to or below 2000 V m-1.

The ethics of capping non-economic damages to control rising healthcare costs.

Purpose: To explore from an ethical paradigm the current research in support of and opposition to imposing caps on non-economic damages as a means of addressing the healthcare crisis.

Design/methodology/approach: A review of peer- and non-peer-reviewed articles primarily covering the period from 2001-2004, which addresses the rationale articulated in support of and in opposition to imposing caps on non-economic damages. The articles are sorted into sections and critiqued: rationale for imposing caps, arguments against caps, ethical paradigms impacting caps, and conclusions.

Tumor necrosis factor alpha leads to increased cell surface expression of CXCR4 in SK-N-MC cells.

Both host and viral factors play an important role in the pathogenesis of human immunodeficiency virus (HIV)-associated bran injury. In this study, the authors examined the interactions between tumor necrosis factor (TNF)-alpha, CXCR4, the alpha chemokine receptor, and three HIV isolates, including the T-tropic viruses, HIV-1(MN) and HIV-1(IIIB), and the dual tropic virus, HIV-1(89.6).

Software and methods for oligonucleotide and cDNA array data analysis.

Two HTML-based programs were developed to analyze and filter gene-expression data: 'Bullfrog' for Affymetrix oligonucleotide arrays and 'Spot' for custom cDNA arrays. The programs provide intuitive data-filtering tools through an easy-to-use interface. A background subtraction and normalization program for cDNA arrays was also built that provides an informative summary report with data-quality assessments.