Subunit Communication within Dimeric SF1 DNA Helicases.

Monomers of the Superfamily (SF) 1 helicases, E. coli Rep and UvrD, can translocate directionally along single stranded (ss) DNA, but must be activated to function as helicases. In the absence of accessory factors, helicase activity requires Rep and UvrD homo-dimerization.

A Model for Competency-Based Grading and Its Effect on Student Outcomes in a Biomechanics Course.

Competency-based grading (CBG) can take different forms in different subject areas. We present a method for implementing CBG in a biomechanics course with nine primary learning objectives. Competency in each learning objective is measured by the student's ability to correctly answer knowledge questions and solve analytical problems in the field of biomechanics.

Safety Factors and Patterns of Bicycle Trauma in a Tertiary Level 1 Trauma Center in Boston, Massachusetts: A Retrospective Review and Survey Study.

Objectives: Increasing bicycle ridership is accompanied by ongoing bicycle-related accidents in many urban cities. There is a need for improved understanding of patterns and risks of urban bicycle usage. We describe the injuries and outcomes of bicycle-related trauma in Boston, Massachusetts, and determine accident-related factors and behaviors associated with injury severity.

Kinetics of ATP/ADP binding to the gp16 ATPase.

The gp16 ATPase is the constituent subunit of the pentameric dsDNA (double-stranded deoxyribonucleic acid) translocation motor of the Bacillus subtilis Φ29 bacteriophage. Although recent single-molecule studies have provided tantalizing clues about the activity of this motor, the mechanism by which the gp16 subunits couple the energy obtained from the binding and hydrolysis of ATP to the mechanical work of dsDNA translocation remains unknown. To address this need, we have characterized the binding of fluorophore-labeled ATP and ADP to monomeric gp16 using a stopped-flow fluorescence assay.

Elasmobranch microbiomes: emerging patterns and implications for host health and ecology.

Elasmobranchs (sharks, skates and rays) are of broad ecological, economic, and societal value. These globally important fishes are experiencing sharp population declines as a result of human activity in the oceans. Research to understand elasmobranch ecology and conservation is critical and has now begun to explore the role of body-associated microbiomes in shaping elasmobranch health.

Remodeler Catalyzed Nucleosome Repositioning: Influence of Structure and Stability.

The packaging of the eukaryotic genome into chromatin regulates the storage of genetic information, including the access of the cell's DNA metabolism machinery. Indeed, since the processes of DNA replication, translation, and repair require access to the underlying DNA, several mechanisms, both active and passive, have evolved by which chromatin structure can be regulated and modified. One mechanism relies upon the function of chromatin remodeling enzymes which couple the free energy obtained from the binding and hydrolysis of ATP to the mechanical work of repositioning and rearranging nucleosomes.

Analysis of the Fire Behavior of Polymers (PP, PA 6 and PE-LD) and Their Improvement Using Various Flame Retardants.

The fire behavior of polymers is examined primarily with the time-dependent heat release rate (HRR) measured with a cone calorimeter. The HRR is used to examine the fire behavior of materials with and without flame retardants, especially Polypropylene (PP-Copo) and Polyethylene (PE-LD). Polypropylene is stored for up to 99 days under normal conditions and the heat release rate shows especially changes about 100 s after irradiation with cone calorimeter, which may be caused by aging effects.

Movement patterns and habitat use of tiger sharks (Galeocerdo cuvier) across ontogeny in the Gulf of Mexico.

The tiger shark (Galeocerdo cuvier) is globally distributed with established coastal and open-ocean movement patterns in many portions of its range. While all life stages of tiger sharks are known to occur in the Gulf of Mexico (GoM), variability in habitat use and movement patterns over ontogeny have never been quantified in this large marine ecosystem. To address this data gap we fitted 56 tiger sharks with Smart Position and Temperature transmitting tags between 2010 and 2018 and examined seasonal and spatial distribution patterns across the GoM.

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study.

Purpose: Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC.

First insights into the movements of young-of-the-year white sharks (Carcharodon carcharias) in the western North Atlantic Ocean.

In recent years, white sharks (Carcharodon carcharias) have become more accessible to researchers off the northeastern U.S. as feeding aggregation sites have emerged and the population has increased.

Anisotropy-Based Nucleosome Repositioning Assay.

Most eukaryotic DNA is tightly packaged into nucleosomes that render these sequences largely inaccessible for transcription or repair. Molecular motors called chromatin remodelers use an ATP-dependent mechanism to relieve the inhibition of these processes by sliding or disassembling the nucleosomes. This allows them to serve an essential role in the regulation of gene expression and genomic integrity.

Effects of nucleosome stability on remodeler-catalyzed repositioning.

Chromatin remodelers are molecular motors that play essential roles in the regulation of nucleosome positioning and chromatin accessibility. These machines couple the energy obtained from the binding and hydrolysis of ATP to the mechanical work of manipulating chromatin structure through processes that are not completely understood. Here we present a quantitative analysis of nucleosome repositioning by the imitation switch (ISWI) chromatin remodeler and demonstrate that nucleosome stability significantly impacts the observed activity.

Molecular motor translocation kinetics: Application of Monte Carlo computer simulations to determine microscopic kinetic parameters.

Methods for studying the translocation of motor proteins along a filament (e.g., nucleic acid and polypeptide) typically monitor the total production of ADP, the arrival/departure of the motor protein at/from a particular location (often one end of the filament), or the dissociation of the motor protein from the filament.

Factitious Disorder in a Patient Claiming to be a Sexually Sadistic Serial Killer.

Factitious disorder involves the conscious simulation of psychological or physiological symptoms of illness, for the purpose of fulfilling the unconscious desire to be taken care of or to assume the "sick role." Typically patients with factitious disorder simulate conditions that are designed to arouse feelings of empathy in care providers with the intention to engage them in caretaking. However, patients might also simulate conditions that arouse revulsion or rejection and still meet full diagnostic criteria for factitious disorder.

A 3D paper-based enzymatic fuel cell for self-powered, low-cost glucose monitoring.

In this work, we demonstrate a novel low-cost, self-powered paper-based biosensor for glucose monitoring. The device operating mechanism is based on a glucose/oxygen enzymatic fuel cell using an electrochemical energy conversion as a transducing element for glucose monitoring. The self-powered glucose biosensor features (i) a 3D origami paper-based structure for easy system integration onto paper, (ii) an air-cathode on paper for low-cost production and easy operation, and (iii) a screen printed chitosan/glucose oxidase anode for stable current generation as an analytical signal for glucose monitoring.

Mitotic-dependent phosphorylation of leukemia-associated RhoGEF (LARG) by Cdk1.

Rho GTPases are integral to the regulation of actin cytoskeleton-dependent processes, including mitosis. Rho and leukemia-associated Rho guanine-nucleotide exchange factor (LARG), also known as ARHGEF12, are involved in mitosis as well as diseases such as cancer and heart disease. Since LARG has a role in mitosis and diverse signaling functions beyond mitosis, it is important to understand the regulation of the protein through modifications such as phosphorylation.

Genome-wide association study of colorectal cancer identifies six new susceptibility loci.

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.

Low processivity for DNA translocation by the ISWI molecular motor.

The motor protein ISWI (Imitation SWItch) is the conserved catalytic ATPase domain of the ISWI family of chromatin remodelers. Members of the ISWI family are involved in regulating the structure of cellular chromatin during times of transcription, translation, and repair. Current models for the nucleosome repositioning activity of ISWI and other chromatin remodelers require the translocation of the remodeling protein along double-stranded DNA through an ATP-dependent mechanism.

Trapping of intermediates with substrate analog HBOCoA in the polymerizations catalyzed by class III polyhydroxybutyrate (PHB) synthase from Allochromatium vinosum.

Polyhydroxybutyrate (PHB) synthases (PhaCs) catalyze the formation of biodegradable PHB polymers that are considered as an ideal alternative to petroleum-based plastics. To provide strong evidence for the preferred mechanistic model involving covalent and noncovalent intermediates, a substrate analog HBOCoA was synthesized chemoenzymatically. Substitution of sulfur in the native substrate HBCoA with an oxygen in HBOCoA enabled detection of (HB)nOCoA (n = 2-6) intermediates when the polymerization was catalyzed by wild-type (wt-)PhaECAv at 5.

Waiting for triage: unmeasured time in patient flow.

Introduction: The Centers for Medicare and Medicaid Services (CMS) requires reporting of multiple time-sensitive metrics. Most facilities use triage time as the time of arrival. Little is known about how long patients wait prior to triage.

All motors have to decide is what to do with the DNA that is given them.

DNA translocases are a diverse group of molecular motors responsible for a wide variety of cellular functions. The goal of this review is to identify common aspects in the mechanisms for how these enzymes couple the binding and hydrolysis of ATP to their movement along DNA. Not surprisingly, the shared structural components contained within the catalytic domains of several of these motors appear to give rise to common aspects of DNA translocation.

Quantitative determination of binding of ISWI to nucleosomes and DNA shows allosteric regulation of DNA binding by nucleotides.

The regulation of chromatin structure is controlled by a family of molecular motors called chromatin remodelers. The ability of these enzymes to remodel chromatin structure is dependent on their ability to couple ATP binding and hydrolysis into the mechanical work that drives nucleosome repositioning. The necessary first step in determining how these essential enzymes perform this function is to characterize both how they bind nucleosomes and how this interaction is regulated by ATP binding and hydrolysis.

ISWI remodels nucleosomes through a random walk.

The chromatin remodeler ISWI is capable of repositioning clusters of nucleosomes to create well-ordered arrays or moving single nucleosomes from the center of DNA fragments toward the ends without disrupting their integrity. Using standard electrophoresis assays, we have monitored the ISWI-catalyzed repositioning of different nucleosome samples each containing a different length of DNA symmetrically flanking the initially centrally positioned histone octamer. We find that ISWI moves the histone octamer between distinct and thermodynamically stable positions on the DNA according to a random walk mechanism.