High-throughput protein binder discovery by rapid in vivo selection.

Proteins that selectively bind to a target of interest are foundational components of research pipelines , diagnostics , and therapeutics . Current immunization-based , display- based , and computational approaches for discovering binders are laborious and time- consuming - taking months or more, suffer from high false positives - necessitating extensive secondary screening, and have a high failure rate, especially for disordered proteins and other challenging target classes. Here we establish Phage-Assisted Non-Continuous Selection of Protein Binders (PANCS-binders), an selection platform that links the life cycle of M13 phage to target protein binding though customized proximity-dependent split RNA polymerase biosensors, allowing for complete and comprehensive high-throughput screening of billion-plus member protein variant libraries with high signal-to-noise.

Biodesign: Engineering an aortic endograft explantation tool.

Endovascular aortic repair (EVAR) graft failure can be as high as 16% to 30% owing to endoleak, graft migration, or infection, often necessitating explantation, leading to potential morbidity (31%) and mortality (6.3%). Graft prongs frequently tear through the endothelium during explantation, leading to endothelial damage and subsequent fatal bleeding.

RNA-based translation activators for targeted gene upregulation.

Technologies capable of programmable translation activation offer strategies to develop therapeutics for diseases caused by insufficient gene expression. Here, we present "translation-activating RNAs" (taRNAs), a bifunctional RNA-based molecular technology that binds to a specific mRNA of interest and directly upregulates its translation. taRNAs are constructed from a variety of viral or mammalian RNA internal ribosome entry sites (IRESs) and upregulate translation for a suite of target mRNAs.

Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression.

Background: Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.

Methods: In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period.

Ester modification at the 3' end of anti-microRNA oligonucleotides increases potency of microRNA inhibition.

MicroRNAs (miRNAs) are short noncoding RNAs that play a fundamental role in gene regulation. Deregulation of miRNA expression has a strong correlation with disease and antisense oligonucleotides that bind and inhibit miRNAs associated with disease have therapeutic potential. Current research on the chemical modification of anti-miRNA oligonucleotides (anti-miRs) is focused on alterations of the phosphodiester-ribose backbone to improve nuclease resistance and binding affinity to miRNA strands.

The Path to U.S. Neurosurgical Residency for Foreign Medical Graduates: Trends from a Decade 2007-2017.

Objective: The increasing competitiveness of the neurosurgical residency match has made it progressively difficult for foreign medical graduates (FMGs) to match in neurosurgery. We compared FMG to U.S.