Ligify: Automated Genome Mining for Ligand-Inducible Transcription Factors.

Prokaryotic transcription factors can be repurposed into biosensors for the ligand-inducible control of gene expression, but the landscape of chemical ligands for which biosensors exist is extremely limited. To expand this landscape, we developed Ligify, a web application that leverages information in enzyme reaction databases to predict transcription factors that may be responsive to user-defined chemicals. Candidate transcription factors are then incorporated into automatically generated plasmid sequences that are designed to express GFP in response to the target chemical.

Snowprint: a predictive tool for genetic biosensor discovery.

Bioengineers increasingly rely on ligand-inducible transcription regulators for chemical-responsive control of gene expression, yet the number of regulators available is limited. Novel regulators can be mined from genomes, but an inadequate understanding of their DNA specificity complicates genetic design. Here we present Snowprint, a simple yet powerful bioinformatic tool for predicting regulator:operator interactions.

Findings on Repeat Posttraumatic Brain Computed Tomography Scans in Older Patients With Minimal Head Trauma and the Impact of Existing Antithrombotic Use.

Study Objective: Evaluate the utility of routine rescanning of older, mild head trauma patients with an initial negative brain computed tomography (CT), who is on a preinjury antithrombotic (AT) agent by assessing the rate of delayed intracranial hemorrhage (dICH), need for surgery, and attributable mortality.

Methods: Participating centers were trained and provided data collection instruments per institutional review board-approved protocols. Data were obtained from manual chart review and electronic medical record download.

GroovDB: A Database of Ligand-Inducible Transcription Factors.

Genetic biosensors are integral to synthetic biology. In particular, ligand-inducible prokaryotic transcription factors are frequently used in high-throughput screening, for dynamic feedback regulation, as multilayer logic gates, and in diagnostic applications. In order to provide a curated source that users can rely on for engineering applications, we have developed GroovDB (available at https://groov.

The structural basis of fatty acid elongation by the ELOVL elongases.

Very long chain fatty acids (VLCFAs) are essential building blocks for the synthesis of ceramides and sphingolipids. The first step in the fatty acid elongation cycle is catalyzed by the 3-keto acyl-coenzyme A (CoA) synthases (in mammals, ELOVL elongases). Although ELOVLs are implicated in common diseases, including insulin resistance, hepatic steatosis and Parkinson's, their underlying molecular mechanisms are unknown.

Author Correction: A naturally occurring antiviral ribonucleotide encoded by the human genome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mechanistic dissection of the PD-L1:B7-1 co-inhibitory immune complex.

The B7 family represents one of the best-studied subgroups within the Ig superfamily, yet new interactions continue to be discovered. However, this binding promiscuity represents a major challenge for defining the biological contribution of each specific interaction. We developed a strategy for addressing these challenges by combining cell microarray and high-throughput FACS methods to screen for promiscuous binding events, map binding interfaces, and generate functionally selective reagents.

The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K.

Membranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic reticulum (ER) the scramblases have not been identified. Members of the TMEM16 family have either lipid scramblase or chloride channel activity.

Publisher Correction: A naturally occurring antiviral ribonucleotide encoded by the human genome.

Change history: In the HTML version of this Letter, Extended Data Fig. 4 incorrectly corresponded to Fig. 4 (the PDF version of the figure was correct).

A naturally occurring antiviral ribonucleotide encoded by the human genome.

Viral infections continue to represent major challenges to public health, and an enhanced mechanistic understanding of the processes that contribute to viral life cycles is necessary for the development of new therapeutic strategies . Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon-inducible protein implicated in the inhibition of replication of a broad range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus and HIV. Viperin has been suggested to elicit these broad antiviral activities through interactions with a large number of functionally unrelated host and viral proteins.

The effect of damage control laparotomy on major abdominal complications: A matched analysis.

Introduction: Damage control laparotomy (DCL) for trauma is thought to be associated with increased abdominal complications. The purpose of this study is to determine the effect of DCL on abdominal complications by comparing two groups of trauma patients: DCL patients who were prospectively adjudicated to potentially being closed at the primary laparotomy (potential DEF or pDEF) and those who underwent definitive laparotomy (DEF).

Methods: The pDEF group was matched to DEF patients according to mechanism of injury, abdominal injury severity, operating room transfusions, and performance of a colon resection.

Microsomal triglyceride transfer protein contributes to lipid droplet maturation in adipocytes.

Previous studies in our laboratory have established the presence of MTP in both white and brown adipose tissue in mice as well as in 3T3-L1 cells. Additional studies demonstrated an increase in MTP levels as 3T3-L1 cells differentiate into adipocytes concurrent with the movement of MTP from the juxtanuclear region of the cell to the surface of lipid droplets. This suggested a role for MTP in lipid droplet biogenesis and/or maturation.

Monolithic mode-selective few-mode multicore fiber multiplexers.

With the capacity limits of standard single-mode optical fiber fast approaching, new technologies such as space-division multiplexing are required to avoid an Internet capacity crunch. Few-mode multicore fiber (FM-MCF) could allow for a two orders of magnitude increase in capacity by using the individual spatial modes in the different cores as unique data channels. We report the realization of a monolithic mode-selective few-mode multicore fiber multiplexer capable of addressing the individual modes of such a fiber.

Expression of Prokaryotic Integral Membrane Proteins in E. coli.

Production of prokaryotic membrane proteins for structural and functional studies in E. coli can be parallelized and miniaturized. All stages from cloning, expression, purification to detergent selection can be investigated using high-throughput techniques to rapidly and economically find tractable targets.

Safety and Appropriateness of Tourniquets in 105 Civilians.

Background: The United States military considers tourniquets to be effective for controlling bleeding from major limb trauma. The purpose of this study was to assess whether tourniquets are safely applied to the appropriate civilian patient with major limb trauma of any etiology.

Methods: Following IRB approval, patients arriving to a level-1 trauma center between October 2008 and May 2013 with a prehospital (PH) or emergency department (ED) tourniquet were reviewed.

Inhibition of Zinc-Dependent Histone Deacetylases with a Chemically Triggered Electrophile.

Unbiased binding assays involving small-molecule microarrays were used to identify compounds that display unique patterns of selectivity among members of the zinc-dependent histone deacetylase family of enzymes. A novel, hydroxyquinoline-containing compound, BRD4354, was shown to preferentially inhibit activity of HDAC5 and HDAC9 in vitro. Inhibition of deacetylase activity appears to be time-dependent and reversible.

Holey fiber mode-selective couplers.

Directional mode coupling in an asymmetric holey fiber coupler is demonstrated both numerically and experimentally for the first time. The holey fiber mode couplers have interesting spectral characteristics and are also found to exhibit increased dimensional tolerances. Following a design based on numerical investigations, a dual-core polymer holey fiber coupler for LP(01) and LP(11) mode multiplexing was fabricated via a drilling and drawing technique.