Parallelized identification of on- and off-target protein interactions.

Genetic selection combined with next-generation sequencing enables the simultaneous interrogation of the functionality and stability of large numbers of naturally occurring, engineered, or computationally designed protein variants in parallel. We display hundreds of engineered proteins on the surface of yeast cells, select for binding to a set of target molecules by flow cytometry, and sequence the starting pool as well as selected pools to obtain enrichment values for each displayed protein with each target. We show that this high-throughput workflow of multiplex genetic selections followed by large-scale sequencing and comparative analysis allows not only the determination of relative affinities, but also the monitoring of specificity profiles for hundreds to thousands of protein-protein and protein-small molecule interactions in parallel.

Profiling epigenetic changes in human cell line induced by atrazine exposure.

How environmental chemicals can affect and exert their toxic effect at a molecular level has gained significant interest in recent years, not only for understanding their immediate health implications over exposed individuals, but also for their subsequent progeny. Atrazine (ATZ) is a commonly used herbicide in the U.S.

The impact of clinical pharmacy services on pneumococcal vaccine frequency and appropriateness in a family medicine clinic.

Objective: To evaluate the impact of an ambulatory clinical pharmacy service (inclusive of immunization needs assessments) on the frequency and appropriateness of pneumococcal vaccine administration in a family medicine clinic.

Methods: This cohort study had an observational and retrospective design and included patients who received pneumococcal vaccines at a family medicine clinic in a medically underserved area in Southwestern Pennsylvania across a 42-month period from January 1, 2015, to June 30, 2018. The outcome measures included the administration and appropriateness of pneumococcal 13-valent conjugate (PCV13) and pneumococcal 23-valent polysaccharide (PPSV23) vaccines across 3 time cohorts including before, during, and after the establishment of a clinical pharmacy service.

Replicator degrees of freedom allow publication of misleading failures to replicate.

In recent years, the field of psychology has begun to conduct replication tests on a large scale. Here, we show that "replicator degrees of freedom" make it far too easy to obtain and publish false-negative replication results, even while appearing to adhere to strict methodological standards. Specifically, using data from an ongoing debate, we show that commonly exercised flexibility at the experimental design and data analysis stages of replication testing can make it appear that a finding was not replicated when, in fact, it was.

Total Syntheses of the 3-Pyrrolo[2,3-]quinolone-Containing Alkaloids Marinoquinolines A-F, K, and Aplidiopsamine A Using a Palladium-Catalyzed Ullmann Cross-Coupling/Reductive Cyclization Pathway.

Compounds - and representing key members of the marinoquinoline family of natural products, together with the related marine alkaloid aplidiopsamine A (), have been synthesized using various combinations of palladium-catalyzed Ullmann cross-coupling and reductive cyclization processes involving a C3-arylated pyrrole as the common intermediate. These natural products have been characterized by single-crystal X-ray analyses and evaluated as inhibitors of acetylcholinesterase (AChE) with congener proving to be the most active.

Molecular dynamics simulation of zirconium tungstate amorphization and the amorphous-crystalline interface.

Classical molecular dynamics (MD) simulations were performed to provide a conceptual understanding of the amorphous-crystalline interface for a candidate negative thermal expansion (NTE) material, ZrWO. Simulations of pressure-induced amorphization at 300 K indicate that an amorphous phase forms at pressures of 10 GPa and greater, and this phase persists when the pressure is subsequently decreased to 1 bar. However, the crystalline phase is recovered when the slightly distorted 5 GPa phase is relaxed to 1 bar.

Predicting response to cognitive processing therapy: Does trauma history matter?

Objective: Cognitive processing therapy (CPT) has reliably demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD) for most patients, however, not all patients derive the same benefit from CPT. The aim of the present study is to identify trauma-related variables that predict differential response to CPT in a sample of treatment-seeking veterans in order to improve individual responses to CPT.

Method: The present study evaluated demographic, therapy, and trauma-related variables as possible predictors of variable response to CPT in a sample of 259 treatment-seeking veterans who received treatment in an outpatient clinic.

Intra-tracheal administration of a naked plasmid expressing stromal derived factor-1 improves lung structure in rodents with experimental bronchopulmonary dysplasia.

Background: Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification and disordered angiogenesis. Stromal derived factor-1 (SDF-1) is a chemokine which modulates cell migration, proliferation, and angiogenesis. Here we tested the hypothesis that intra-tracheal (IT) administration of a naked plasmid DNA expressing SDF-1 would attenuate neonatal hyperoxia-induced lung injury in an experimental model of BPD, by promoting angiogenesis.

Spatial and temporal disease dynamics of the parasite Hematodinium sp. in shore crabs, Carcinus maenas.

Background: The parasitic dinoflagellates of the genus Hematodinium represent the causative agent of so-called bitter or pink crab disease in a broad range of shellfish taxa. Outbreaks of Hematodinium-associated disease can devastate local fishing and aquaculture efforts. The goal of our study was to examine the potential role of the common shore (green) crab Carcinus maenas as a reservoir for Hematodinium.

LongAxis: A MATLAB-based program for 3D quantitative analysis of epithelial cell shape and orientation.

Epithelial morphogenesis, a fundamental aspect of development, generates 3-dimensional tissue structures crucial for organ function. Underlying morphogenetic mechanisms are, in many cases, poorly understood, but mutations that perturb organ development can affect epithelial cell shape and orientation - difficult features to quantify in three dimensions. The basic structure of the eye is established via epithelial morphogenesis: in the embryonic optic cup, the retinal progenitor epithelium enwraps the lens.

Sir William Osler (1849-1919) and the paternity of William Willoughby Francis (1878-1959): Review of the evidence.

It has been suggested that beneath the sunny personality and enormous productivity of Sir William Osler (1849-1919) lurked a deep sorrow. A longstanding rumor suggests this sorrow was a prolonged affair with an older first cousin, Marian Osler (Bath) Francis (1841-1915), which resulted in Osler's paternity of William Willoughby Francis (1878-1959). Osler treated W.

New observations support William Osler's rationale for systemic bloodletting.

Bloodletting has been called William Osler's "blind spot," especially with respect to pneumonia. Also puzzling has been his endorsement of bleeding in selected cases of heatstroke. Recent clinical observations on pneumonia and, to a lesser extent, heatstroke lend support to Osler's rationale for bloodletting in these conditions.

Measurement of the Antineutrino Spectrum from ^{235}U Fission at HFIR with PROSPECT.

This Letter reports the first measurement of the ^{235}U ν[over ¯]_{e} energy spectrum by PROSPECT, the Precision Reactor Oscillation and Spectrum experiment, operating 7.9 m from the 85  MW_{th} highly enriched uranium (HEU) High Flux Isotope Reactor. With a surface-based, segmented detector, PROSPECT has observed 31678±304(stat) ν[over ¯]_{e}-induced inverse beta decays, the largest sample from HEU fission to date, 99% of which are attributed to ^{235}U.

Structural characterization of β-ketoacyl ACP synthase I bound to platencin and fragment screening molecules at two substrate binding sites.

The bacterial fatty acid pathway is essential for membrane synthesis and a range of other metabolic and cellular functions. The β-ketoacyl-ACP synthases carry out the initial elongation reaction of this pathway, utilizing acetyl-CoA as a primer to elongate malonyl-ACP by two carbons, and subsequent elongation of the fatty acyl-ACP substrate by two carbons. Here we describe the structures of the β-ketoacyl-ACP synthase I from Brucella melitensis in complex with platencin, 7-hydroxycoumarin, and (5-thiophen-2-ylisoxazol-3-yl)methanol.

Anthropogenic remediation of heavy metals selects against natural microbial remediation.

In an era of unprecedented environmental change, there have been increasing ecological and global public health concerns associated with exposure to anthropogenic pollutants. While there is a pressing need to remediate polluted ecosystems, human intervention might unwittingly oppose selection for natural detoxification, which is primarily carried out by microbes. We test this possibility in the context of a ubiquitous chemical remediation strategy aimed at targeting metal pollution: the addition of lime-containing materials.

Shipboard Global Health Engagement Missions: Essential Lessons for Military Healthcare Personnel.

Introduction: Global health engagement missions are conducted to improve and protect the health of populations worldwide. Recognizing the strong link between health and security, the Armed Forces have increased the number of global health engagement missions over the last decade to support force health protection, medical readiness, enhance interoperability, improve host nation capacity building, combat global health threats (i.e.