Nucleic Acid Specificity, Cellular Localization and Reduced Toxicities of Thiazole Orange-Neomycin Conjugates.

Selective binding of small molecule ligands to nucleic acids with high affinity and limited toxicity remains an important goal in the development of compounds that can probe DNA or RNA in cells. Thiazole orange is a cell semi-permeant, fluorescent cyanine dye, with low background noise, that binds several forms of nucleic acids. However, thiazole orange can exhibit cytotoxicity when used at high concentration and/or with prolonged exposure.

A Cell-Based Screening Assay for rRNA-Targeted Drug Discovery.

Worldwide, bacterial antibiotic resistance continues to outpace the level of drug development. One way to counteract this threat to society is to identify novel ways to rapidly screen and identify drug candidates in living cells. Developing fluorescent antibiotics that can enter microorganisms and be displaced by potential antimicrobial compounds is an important but challenging endeavor due to the difficulty in entering bacterial cells.

Understanding Antisense Oligonucleotide Efficiency in Inhibiting Prokaryotic Gene Expression.

Oligonucleotides offer a unique opportunity for sequence specific regulation of gene expression in bacteria. A fundamental question to address is the choice of oligonucleotide, given the large number of options available. Different modifications varying in RNA binding affinities and cellular uptake are available but no comprehensive comparisons have been performed.

A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient.

With the recent success of lipid nanoparticle (LNP) based SARS-CoV-2 mRNA vaccines, the potential for RNA therapeutics has gained widespread attention. LNPs are promising non-viral delivery vectors to protect and deliver delicate RNA therapeutics, which are ineffective and susceptible to degradation alone. While food and drug administration (FDA) approved formulations have shown significant promise, benchmark lipid formulations still require optimization and improvement.

Development and Validation of the Protocol for Administering Telehealth Home (PATH) Assessments.

Home safety assessments and subsequent modifications can prevent hospitalization, institutionalization, and death among older adults. Telehealth has been shown to be an effective means to administer home safety assessments. However, a structured approach to synchronous telehealth home assessments has not been examined.

Multi-scale habitat assessment of pronghorn migration routes.

We studied the habitat selection of pronghorn (Antilocapra americana) during seasonal migration; an important period in an animal's annual cycle associated with broad-scale movements. We further decompose our understanding of migration habitat itself as the product of both broad- and fine-scale behavioral decisions and take a multi-scale approach to assess pronghorn spring and fall migration across the transboundary Northern Sagebrush Steppe region. We used a hierarchical habitat selection framework to assess a suite of natural and anthropogenic features that have been shown to influence selection patterns of pronghorn at both broad (migratory neighborhood) and fine (migratory pathway) scales.

Aggregation morphology of planar engineered nanomaterials.

In this investigation, the utility of a static light scattering (SLS) technique to characterize aggregate morphology of two-dimensional engineered nanomaterials (2D ENMs) was systematically evaluated. The aggregation of graphene oxide (GO) and lithiated-molybdenum disulfide (Li-MoS) were measured and compared to that of a spherical reference colloid, carboxylate-modified latex (CML) nanoparticles. The critical coagulation concentration (CCC) for all dispersions was determined via analysis of aggregation kinetics using time-resolved dynamic light scattering.

Gram-negative synergy and mechanism of action of alkynyl bisbenzimidazoles.

Bisbenzimidazoles with terminal alkynyl linkers, selective inhibitors of bacterial topoisomerase I, have been evaluated using bacterial cytological profiling (BCP) to ascertain their mechanism of action and screened for synergism to improve Gram-negative bacterial coverage. Principal component analysis of high throughput fluorescence images suggests a dual-mechanism of action affecting DNA synthesis and cell membrane integrity. Fluorescence microscopy of bacteria challenged with two of the alkynyl-benzimidazoles revealed changes in the cellular ultrastructure that differed from topoisomerase II inhibitors including induction of spheroplasts and membrane lysis.

Corvus: a framework for interfacing scientific software for spectroscopic and materials science applications.

Corvus, a Python-based package designed for managing workflows of physical simulations that utilize multiple scientific software packages, is presented. Corvus can be run as an executable script with an input file and automatically generated or custom workflows, or interactively, in order to build custom workflows with a set of Corvus-specific tools. Several prototypical examples are presented that link density functional, vibrational and X-ray spectroscopy software packages and are of interest to the synchrotron community.

Synthesis, antimicrobial activity, attenuation of aminoglycoside resistance in MRSA, and ribosomal A-site binding of pyrene-neomycin conjugates.

The development of new ligands that have comparable or enhanced therapeutic efficacy relative to current drugs is vital to the health of the global community in the short and long term. One strategy to accomplish this goal is to functionalize sites on current antimicrobials to enhance specificity and affinity while abating resistance mechanisms of infectious organisms. Herein, we report the synthesis of a series of pyrene-neomycin B (PYR-NEO) conjugates, their binding affinity to A-site RNA targets, resistance to aminoglycoside-modifying enzymes (AMEs), and antibacterial activity against a wide variety of bacterial strains of clinical relevance.

Targeting miRNA by tunable small molecule binders: peptidic aminosugar mediated interference in miR-21 biogenesis reverts epithelial to mesenchymal transition.

Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose cell polarity and cell-cell adhesion and gain migratory and invasive properties to become mesenchymal cells that are very vital for development, wound healing and stem cell behavior and contribute pathologically to fibrosis and cancer progression. miR21, a potent regulator of the tumor suppressor gene PTEN, can be silenced to reverse EMT, thereby providing an attractive target for abrogating the malignant behavior of breast cancer. Here, we report the design, synthesis and binding of a peptidic-aminoglycoside (PA) based chemical library against pre-miR21 that led to the identification of a group of small molecules that bind to pre-miR21 with high affinities and antagonize miR-21 maturation and function, thereby reversing EMT.

Preference for tap, bottled, and recycled water: Relations to PTC taste sensitivity and personality.

This study investigated people's preferences for different water sources and factors that predict such preferences using a blind taste test. Water preferences of 143 participants for one name-brand bottled water, one groundwater-sourced tap water, and one indirect potable reuse (IDR) water were assessed. For predictors of water preference, we measured each participant's PTC taste sensitivity and assessed two personality traits (Neuroticism, Openness to Experience).

Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase I by Hoechst 33258 Derived Mono- and Bisbenzimidazoles.

A series of Hoechst 33258 based mono- and bisbenzimidazoles have been synthesized and their Escherichia coli DNA topoisomerase I inhibition, binding to B-DNA duplex, and antibacterial activity has been evaluated. Bisbenzimidazoles with alkynyl side chains display excellent E. coli DNA topoisomerase I inhibition properties with IC values <5.

Role of pH and ionic strength in the aggregation of TiO nanoparticles in the presence of extracellular polymeric substances from Bacillus subtilis.

Increased use of commercial titanium dioxide nanoparticles (TiO NPs) in consumer products most likely leads to their additional environmental release. Aggregation and disaggregation processes are expected to play an important role in the fate and transport of TiO NPs in natural aquatic ecosystems. Therefore, in this work, we have studied the colloidal stability of TiO NPs in the presence of extracellular polymeric substances (EPS) from Bacillus subtilis and the adsorption behavior of EPS on TiO NPs in aqueous solutions at different pH values and ionic strengths (IS).

Antimicrobial Activity, AME Resistance, and A-Site Binding Studies of Anthraquinone-Neomycin Conjugates.

The antibacterial effects of aminoglycosides are based on their association with the A-site of bacterial rRNA and interference with the translational process in the bacterial cell, causing cell death. The clinical use of aminoglycosides is complicated by resistance and side effects, some of which arise from their interactions with the human mitochondrial 12S rRNA and its deafness-associated mutations, C1494U and A1555G. We report a rapid assay that allows screening of aminoglycoside compounds to these classes of rRNAs.

Influence of triethyl phosphate on phosphatase activity in shooting range soil: Isolation of a zinc-resistant bacterium with an acid phosphatase.

Phosphatase-mediated hydrolysis of organic phosphate may be a viable means of stabilizing heavy metals via precipitation as a metal phosphate in bioremediation applications. We investigated the effect of triethyl phosphate (TEP) on soil microbial-phosphatase activity in a heavy-metal contaminated soil. Gaseous TEP has been used at subsurface sites for bioremediation of organic contaminants but not applied in heavy-metal contaminated areas.

Successful desensitization to brentuximab vedotin after hypersensitivity reaction.

Monoclonal antibodies (mAb) have become the standard of care for numerous diseases. However, side effects including infusion and hypersensitivity reactions experienced by patients continue to be a limiting factor in their use. In the therapy of cancer, treatment choices are frequently limited and minimizing side effects of a life-saving or life-prolonging therapy becomes of the utmost importance.

DNA-Templated Molecular Silver Fluorophores.

Conductive and plasmon-supporting noble metals exhibit an especially wide range of size-dependent properties, with discrete electronic levels, strong optical absorption, and efficient radiative relaxation dominating optical behavior at the ~10-atom cluster scale. In this Perspective, we describe the formation and stabilization of silver clusters using DNA templates and highlight the distinct spectroscopic and photophysical properties of the resulting hybrid fluorophores. Strong visible to near-IR emission from DNA-encapsulated silver clusters ranging in size from 5-11 atoms has been produced and characterized.

Probing Maxwell's demon with a nanoscale thermometer.

A precise definition for a quantum electron thermometer is given, as an electron reservoir coupled locally (e.g., by tunneling) to a sample, and brought into electrical and thermal equilibrium with it.

Preemptive leucovorin administration minimizes pralatrexate toxicity without sacrificing efficacy.

Balancing efficacy and safety of drugs is key for successful cancer therapy, as adverse reactions can prohibit the use of efficacious treatments. Pralatrexate (PDX) is a novel antifolate with a higher affinity for tumor cells than methotrexate, Food and Drug Administration (FDA) approved for use in relapsed and refractory peripheral T-cell lymphoma (PTCL) and transformed mycosis fungoides (T-MF). Patients with T-MF have a higher incidence of adverse events than patients with other lymphomas, necessitating a lower recommended dose of 15 mg/m(2) (vs.

Breast implant-associated ALCL: a unique entity in the spectrum of CD30+ lymphoproliferative disorders.

CD30(+) lymphoproliferative disorders represent a spectrum of diseases with distinct clinical phenotypes ranging from reactive conditions to aggressive systemic anaplastic lymphoma kinase (ALK)(-) anaplastic large cell lymphoma (ALCL). In January 2011, the U.S.

Silver clusters as both chromophoric reporters and DNA ligands.

Molecular silver clusters conjugated with DNA act as analyte sensors. Our studies evaluate a type of cluster-laden DNA strand whose structure and silver stoichiometry change with hybridization. The sensor strand integrates two functions: the 3' region binds target DNA strands through base recognition while the 5' sequence C(3)AC(3)AC(3)TC(3)A favors formation of a near-infrared absorbing and emitting cluster.