Plasmonic Sensor Could Enable Label-Free DNA Sequencing.

We demonstrated a proof-of-principle concept of a label-free platform that enables nucleic acid sequencing by binding methodology. The system utilizes gold surfaces having high fidelity plasmonic nanohole arrays which are very sensitive to minute changes of local refractive indices. Our novel surface chemistry approach ensures accurate identification of correct bases at individual positions along a targeted DNA sequence on the gold surface.

Redesigning Recombinase Specificity for Safe Harbor Sites in the Human Genome.

Site-specific recombinases (SSRs) are valuable tools for genetic engineering due to their ability to manipulate DNA in a highly specific manner. Engineered zinc-finger and TAL effector recombinases, in particular, are two classes of SSRs composed of custom-designed DNA-binding domains fused to a catalytic domain derived from the resolvase/invertase family of serine recombinases. While TAL effector and zinc-finger proteins can be assembled to recognize a wide range of possible DNA sequences, recombinase catalytic specificity has been constrained by inherent base requirements present within each enzyme.

Improved cell-penetrating zinc-finger nuclease proteins for precision genome engineering.

Safe, efficient, and broadly applicable methods for delivering site-specific nucleases into cells are needed in order for targeted genome editing to reach its full potential for basic research and medicine. We previously reported that zinc-finger nuclease (ZFN) proteins have the innate capacity to cross cell membranes and induce genome modification via their direct application to human cells. Here, we show that incorporation of tandem nuclear localization signal (NLS) repeats into the ZFN protein backbone enhances cell permeability nearly 13-fold and that single administration of multi-NLS ZFN proteins leads to genome modification rates of up to 26% in CD4(+) T cells and 17% in CD34(+) hematopoietic stem/progenitor cells.

Enhancing the specificity of recombinase-mediated genome engineering through dimer interface redesign.

Despite recent advances in genome engineering made possible by the emergence of site-specific endonucleases, there remains a need for tools capable of specifically delivering genetic payloads into the human genome. Hybrid recombinases based on activated catalytic domains derived from the resolvase/invertase family of serine recombinases fused to Cys2-His2 zinc-finger or TAL effector DNA-binding domains are a class of reagents capable of achieving this. The utility of these enzymes, however, has been constrained by their low overall targeting specificity, largely due to the formation of side-product homodimers capable of inducing off-target modifications.

Highly active zinc-finger nucleases by extended modular assembly.

Zinc-finger nucleases (ZFNs) are important tools for genome engineering. Despite intense interest by many academic groups, the lack of robust noncommercial methods has hindered their widespread use. The modular assembly (MA) of ZFNs from publicly available one-finger archives provides a rapid method to create proteins that can recognize a very broad spectrum of DNA sequences.

Reducing patient restraints: a pilot approach using clinical case review.

Purpose: This study aims to reduce the incidents of restraints by applying a nontraditional consultation process in which a university-based team focused on patient consultations to collect data on treatment interventions and milieu approaches and conditions, as well as staff interactions.

Conclusions: The efforts resulted in restraint reduction from 36 episodes per month to 0 episodes per month as well as precipitating a change in unit climate and care approaches on a specialized unit for patients with developmental disabilities and mental illness.

Practice Implications: Reducing the use of restraints involving multiple restraint incident patients is possible with a team-based approach and a specific intervention plan.

Combined buprenorphine and chlonidine for short-term opiate detoxification: patient perspectives.

The approval in 2003 for the use of buprenorphine in opiate addiction treatment has provided physicians with a new pharmacological tool to combat opiate addiction. We surveyed a sample of 100 inpatients who completed short-term opiate detoxification treatment utilizing a combination of buprenorphine and clonidine to assess patient perspectives regarding the usefulness and tolerability of this medication regimen and to compare it to their past opiate detox experiences, if any. Patients identified pain (63%), sleep problems (57%), and anxiety (56%) as the symptoms they perceived to be most helped with buprenorphine.