Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations.

Inferring the 3D structure and conformation of disordered biomolecules, e.g., single stranded nucleic acids (ssNAs), remains challenging due to their conformational heterogeneity in solution. Here, we use escape-time electrometry (ETe) to measure with sub elementary-charge precision the effective electrical charge in solution of short to medium chain length ssNAs in the range of 5-60 bases. We compare measurements of molecular effective charge with theoretically calculated values for simulated molecular conformations obtained from Molecular Dynamics simulations using a variety of forcefield descriptions. We demonstrate that the measured effective charge captures subtle differences in molecular structure in various nucleic acid homopolymers of identical length, and also that the experimental measurements can find agreement with computed values derived from coarse-grained molecular structure descriptions such as oxDNA, as well next generation ssNA force fields. We further show that comparing the measured effective charge with calculations for a rigid, charged rod-the simplest model of a nucleic acid-yields estimates of molecular structural dimensions such as linear charge spacings that capture molecular structural trends observed using high resolution structural analysis methods such as X-ray scattering. By sensitively probing the effective charge of a molecule, electrometry provides a powerful dimension supporting inferences of molecular structural and conformational properties, as well as the validation of biomolecular structural models. The overall approach holds promise for a high throughput, microscopy-based biomolecular analytical approach offering rapid screening and inference of molecular 3D conformation, and operating at the single molecule level in solution.

Far-Field Electrostatic Signatures of Macromolecular 3D Conformation.

In solution as in vacuum, the electrostatic field distribution in the vicinity of a charged object carries information on its three-dimensional geometry. We report on an experimental study exploring the effect of molecular shape on long-range electrostatic interactions in solution. Working with DNA nanostructures carrying approximately equal amounts of total charge but each in a different three-dimensional conformation, we demonstrate that the geometry of the distribution of charge in a molecule has substantial impact on its electrical interactions. For instance, a tetrahedral structure, which is the most compact distribution of charge we tested, can create a far-field effect that is effectively identical to that of a rod-shaped molecule carrying half the amount of total structural charge. Our experiments demonstrate that escape-time electrometry (ETe) furnishes a rapid and facile method to screen and identify 3D conformations of charged biomolecules or molecular complexes in solution.

Fundamentals of Fluorescein Angiography.

In order to provide safe patient care during fluorescein angiography, it is critical that ophthalmic team members understand the use of fluorescein for diagnosing eye-related diseases and conditions, including appropriate doses for adult and pediatric patients. Awareness of side effects, adverse reactions, and complications of the contrast agent allow the ophthalmic health-care team to anticipate, respond quickly, and support the patient during and following the angiographic procedure using fluorescein.

Ophthalmic imaging today: an ophthalmic photographer's viewpoint - a review.

Ophthalmic imaging has changed dramatically since the 1960s with increasingly complex technologies now available. Arguably, the greatest changes have been the development of the digital camera and the speed, processing power and storage of electronic data. Already, ophthalmic practices in many major institutions overseas have paperless medium storage and electronically generated reporting from all equipment that use a computer interface. It is hard to remember the widespread use of photographic film with its attendant costs, or even to remember the days before optical coherence tomography (OCT). These latest technical improvements in ophthalmic imaging are now standard in large Australian institutions and becoming more widespread in smaller private practices. The technicians that operate and maintain this ever-increasing plethora of gadgetry have seen their work practices change from the darkroom to the complexities of data-based imaging and storage. It is a fitting time to examine the contemporary state of ophthalmic imaging and what lies on the horizon as we move towards 2020.

Transient corneal microcysts associated with interferon therapy.

PURPOSE: To report transient corneal epithelial microcysts associated with interferon therapy. METHODS: Case report. RESULTS: Transient corneal epithelial microcysts appeared bilaterally with the onset of therapy with pegylated interferon and ribavirin for the treatment of hepatitis C. These microcysts resolved completely after discontinuation of the pegylated interferon with ribavirin therapy. CONCLUSIONS: Pegylated interferon therapy was associated with transient corneal epithelial microcysts in our patient.