Enhanced Sequence-Specific DNA Recognition Using Oligodeoxynucleotide-Benzimidazole Conjugates.

Synthetic modification of oligodeoxynucleotides (ODNs) via conjugation to nucleic acid binding small molecules can improve hybridization and pharmacokinetic properties. In the present study, five Hoechst 33258 derived benzimidazoles were conjugated to T rich ODNs and their hybridization effectiveness was tested. Thermal denaturation studies revealed significant stabilization of complementary duplexes by ODN-benzimidazole conjugates, with the extent of stabilization being highly dependent on the length of the linker between DNA and benzimidazole.

Noninvasive measurement of tracer extraction efficiency in tissue, illustrated with Tc-99m-MAG3.

Objective: The aim of this study is to develop a noninvasive technique for measuring tissue tracer extraction efficiency ( E ) and illustrate it for Tc-99m-mercaptoacetyltriglycine (MAG3) and kidney.

Methods: E was measured in 10 patients with normal MAG3 renography. E is the ratio of tissue clearance-to-blood flow ( Ki/F ).

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.

Evaluation of the contamination droplet model used for the assessment of skin dose during the manipulation of radiopharmaceuticals.

The manipulation of radiopharmaceuticals in nuclear medicine can result in the droplet contamination of operators resulting in the accumulation of a significant skin dose. Current methods to estimate this skin dose often utilise a 50l cylindrical droplet model, which can lead to unrealistically high estimated skin doses for some radiopharmaceuticals. By conducting experiments to measure the volume of real droplets arising from simulating the manipulation of radiopharmaceuticals, this work found that 50l is an overestimation of a realistic contamination droplet.

Probing Bioactive Chemical Space to Discover RNA-Targeted Small Molecules.

Small molecules have become increasingly recognized as invaluable tools to study RNA structure and function and to develop RNA-targeted therapeutics. To rationally design RNA-targeting ligands, a comprehensive understanding and explicit testing of small molecule properties that govern molecular recognition is crucial. To date, most studies have primarily evaluated properties of small molecules that bind RNA , with little to no assessment of properties that are distinct to selective and bioactive RNA-targeted ligands.

R-BIND 2.0: An Updated Database of Bioactive RNA-Targeting Small Molecules and Associated RNA Secondary Structures.

Discoveries of RNA roles in cellular physiology and pathology are increasing the need for new tools that modulate the structure and function of these biomolecules, and small molecules are proving useful. In 2017, we curated the NA-targeted oactive ligad atabase (R-BIND) and discovered distinguishing physicochemical properties of RNA-targeting ligands, leading us to propose the existence of an "RNA-privileged" chemical space. Biennial updates of the database and the establishment of a website platform (rbind.

ClinicalTrials.Gov: Pitfalls for pregnant women looking to enroll in studies.

The common exclusion of pregnant women from clinical HIV research warrants inquiry into those few studies that do include pregnant women. This commentary highlights some of the pitfalls of the ClinicalTrials.gov platform for its intended users--study participants, particularly pregnant women--and investigators looking to use its data for study.

The Pathway Forward: Insights on Factors that Facilitate Research with Pregnant Women.

The near-routine exclusion of pregnant women from clinical research has resulted in evidence gaps that endanger the health of pregnant women and their future offspring. Although existing literature documents numerous obstacles along the clinical trial pathway that can stymie research involving pregnant women, there is little guidance on how to facilitate such research. This qualitative study aims to fill that void by examining the experiences of individuals involved in conducting, approving, or overseeing research involving pregnant women at one academic institution.

Administration of aspirin tablets using a novel gel-based swallowing aid: an open-label randomised controlled cross-over trial.

Introduction: To ease administration of medicines to people with dysphagia we developed and patented a gel formulation within which whole tablets could be inserted. The aim was to determine whether the gel would affect bioequivalence of uncoated aspirin tablet.

Method: A gel containing gelatin, hydroxypropylmethylcellulose, citric acid, potassium sorbate and water was developed to maintain structure on tablet insertion and increase saliva production to lubricate the swallow.

Fluorescent indicator displacement assays to identify and characterize small molecule interactions with RNA.

Fluorescent indicator displacement (FID) assays are an advantageous approach to convert receptors into optical sensors that can detect binding of various ligands. In particular, the identification of ligands that bind to RNA receptors has become of increasing interest as the roles of RNA in cellular processes and disease pathogenesis continue to be discovered. Small molecules have been validated as tools to elucidate unknown RNA functions, underscoring the critical need to rapidly identify and quantitatively characterize RNA:small molecule interactions for the development of chemical probes.

Gold nanoparticles loaded with cullin-5 DNA increase sensitivity to 17-AAG in cullin-5 deficient breast cancer cells.

HSP90 inhibitors have the potential to treat many types of cancer due to the dependence of tumor cells on HSP90 for cell growth and proliferation. The Cullin-5 (Cul5) E3 ubiquitin ligase is required for HSP90 inhibitors to induce client protein degradation and subsequent cell death. Cul5 is expressed at low levels in breast cancer cells compared to patient matched controls.

It's how I am . . . it's what I am . . . it's a part of who I am: A narrative exploration of the impact of adolescent-onset chronic illness on identity formation in young people.

In Western society, identity formation is argued to be one of the key developmental tasks of adolescence. Despite implications for adolescent development, research into chronic illness (CI) onset during this period has been notably sparse. This study aimed to explore how diagnosis impacts on the developmental tasks of adolescence, what role adolescent-onset CI plays in identity formation, and how adolescents incorporate the diagnosis into their identity using a narrative analysis.