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Long chain acyl-CoA synthetases (ACSLs), and very long chain acyl-CoA synthetases (ACSVLs) which are also known as fatty acid transporters (FATPs), initiate long chain fatty acid (LCFA) oxidation through activation of LCFA by thiol-esterification. Impaired fatty acid oxidation (FAO) can cause metabolic myopathy; however, the underlying mechanisms by which FAO impairment contributes to the pathogenesis of myopathy remain obscure. Compared to control mice (Acsl1flox/flox), Acsl1M-/- mice had 3.4- and 1.5-fold higher plasma creatine kinase (CK)...


Bacterial β-glucuronidase (GUS) enzymes cause drug toxicity by reversing Phase II glucuronidation in the gastrointestinal tract. While many human gut microbial GUS enzymes have been examined with model glucuronide substrates like p-nitrophenol-β-D-glucuronide (pNPG), the GUS orthologs that are most efficient at processing drug-glucuronides remain unclear. Here we present the crystal structures of GUS enzymes from human gut commensals Lactobacillus rhamnosus, Ruminococcus gnavus, and Faecalibacterium prausnitzii that possess an active site loop (Loop 1; L1) analogous...

Reasons for Increases in Complications of Diabetes

To the Editor Dr Gregg and colleagues identified a resurgence in diabetes complications in the United States beginning in 2010 and analyzed potential underlying contributors and policy implications. However, there may be another underlying mediator of the effect that the authors did not consider.


HIV continues to be an epidemic globally, with approximately 2.1 million incident cases reported in 2015. South Africa contributes a substantial number of these cases, with South African adolescent girls and young women (AGYW) contributing up to an estimated 100,000 a year. Given their high risk, more information is needed about potential risk factors for HIV such as intimate partner violence (IPV), based on mixed conclusions in the literature on the IPV - Incident HIV...

Partial least squares methods for functional regression models

An important class of prediction problems in modern biomedical studies is to use medical images as well as genetic and clinical biomarkers at an earlier time point to predict important clinical outcomes, including continuous, discrete, survival and longitudinal outcomes, at a later time point. Functional regression is one of the statistical models to handle this problem by treating medical images as smooth functions. An appealing way is the functional partial least squares method (FPLS). Delaigle...


The perception of eeriness in old house is part of the experience of fear. I draw from prior work in philosophy and affective science to argue that affect can be experienced as a property of one’s internal state (self-focused) or as a perceived property in the external world (world-focused). As of yet, there has been no published empirical work examining self-focused vs. world-focused affect, nor is there any empirical work examining the mechanisms through which...

3-D Attenuation Model of Sierra Negra Volcano, Galapagos

Rebecca Rodd

Notated FY 2013-2018 USFWS Species Listing Work Plan

Todd BenDor

Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults

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Background & Aims: Functional nausea and vomiting disorders (FNVDs) are classified as chronic nausea and vomiting syndrome (CNVS) or cyclic vomiting syndrome (CVS)—CVS includes cannabinoid hyperemesis syndrome. We investigated the population prevalence of FNVDs, their characteristics, and associated factors. Methods: In the year 2015, an Internet cross-sectional health survey was completed by 5931 adults in the general populations of 3 English-speaking countries; 2100 participants were in the United States, Canada, or the United Kingdom. Quota-based...


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Reply. We thank Drs Siah and Gwee for their interest in our study, in which we reported an exploratory factor analysis of Rome IV symptoms (Clevers et al), which we refer to as the Rome IV exploratory model (R4EM) similar to Siah and Gwee.

Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study

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Background & Aims: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV...

Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria

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Objective: To assess the prevalence of functional gastrointestinal (GI) disorders in children 0-18 years old according to the newly established Rome IV diagnostic criteria as reported by parents in a representative community sample. Study design: A cross-sectional study in which mothers (n = 1255) of children aged 0-18 years old in the US were recruited to complete an online survey about their child's GI symptoms, quality of life (QoL), and other health conditions. Results: Based...

Irritable bowel syndrome: what do the new Rome IV diagnostic guidelines mean for patient management?

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The Rome criteria are universally used as inclusion criteria in pharmaceutical clinical trials and have therefore contributed to testing of several irritable bowel syndrome (IBS)-specific drugs. However, clinicians do not routinely use them because they are complex and consequently difficult to remember. Revised Rome diagnostic criteria for IBS and other functional gastrointestinal disorders (FGIDs) were published in May 2016.

Upward Spirals of Mindfulness and Reappraisal: Testing the Mindfulness-to-Meaning Theory with Autoregressive Latent Trajectory Modeling

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Psychol Inquiry 26(4):377–387, 2015b) proposes that mindfulness generates eudaimonic well-being by promoting positive reappraisal, the positive psychological process through which stressful events are re-construed as benign, meaningful, or growth-promoting. To test this hypothesis, we examined prospective relations between state mindfulness and positive reappraisal in a community sample participating in a mindfulness-based intervention (MBI). At seven weekly time points throughout the MBI, participants (N = 234) engaged in a 10-min mindfulness meditation exercise at home and...

Hypnosis and upper digestive function and disease

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Hypnosis is a therapeutic technique that primarily involves attentive receptive concentration. Even though a small number of health professionals are trained in hypnosis and lingering myths and misconceptions associated with this method have hampered its widespread use to treat medical conditions, hypnotherapy has gained relevance as an effective treatment for irritable bowel syndrome not responsive to standard care. More recently, a few studies have addressed the potential influence of hypnosis on upper digestive function and...

Role of the Linker Domain and the 203–214 N-Terminal Residues in the Human Topoisomerase I DNA Complex Dynamics

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The influence of the N-terminal residues 203–214 and the linker domain on motions in the human topoisomerase I-DNA complex has been investigated by comparing the molecular dynamics simulations of the system with (topo70) or without (topo58/6.3) these regions. Topo58/6.3 is found to fluctuate more than topo70, indicating that the presence of the N-terminal residues and the linker domain dampen the core and C-terminal fluctuations. The simulations also show that residues 203–207 and the linker domain...

Total Internal Reflection with Fluorescence Correlation Spectroscopy: Nonfluorescent Competitors

Total internal reflection with fluorescence correlation spectroscopy is a method for measuring the surface association/dissociation rate constants and absolute densities of fluorescent molecules at the interface of a planar substrate and solution. This method can also report the apparent diffusion coefficient and absolute concentration of fluorescent molecules very close to the surface. Theoretical expressions for the fluorescence fluctuation autocorrelation function when both surface association/dissociation kinetics and diffusion through the evanescent wave, in solution, contribute to...

Analysis Method for Measuring Submicroscopic Distances with Blinking Quantum Dots

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A method is described that takes advantage of the intermittency (“blinking”) in the fluorescence of quantum dots (QDs) to measure absolute positions of closely spaced QDs. The concept is that even if two QDs are separated by only tens of nanometers, the position of each QD is resolvable if the point spread function of each can be imaged independently of the other. In the case of QDs, this is possible if each QD separately blinks...

Bistability, Stochasticity, and Oscillations in the Mitogen-Activated Protein Kinase Cascade

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Signaling pathways respond to stimuli in a variety of ways, depending on the magnitude of the input and the physiological status of the cell. For instance, yeast can respond to pheromone stimulation in either a binary or graded fashion. Here we present single cell transcription data indicating that a transient binary response in which all cells eventually become activated is typical. Stochastic modeling of the biochemical steps that regulate activation of the mitogen-activated protein kinase...

Neuronal SNAREs Do Not Trigger Fusion between Synthetic Membranes but Do Promote PEG-Mediated Membrane Fusion

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At low surface concentrations that permit formation of impermeable membranes, neuronal soluble N-ethyl maleimide sensitive factor attachment protein receptor (SNARE) proteins form a stable, parallel, trans complex when vesicles are brought into contact by a low concentration of poly(ethylene glycol) (PEG). Surprisingly, formation of a stable SNARE complex does not trigger fusion under these conditions. However, neuronal SNAREs do promote fusion at low protein/lipid ratios when triggered by higher concentrations of PEG. Promotion of PEG-triggered...

Seeing Is Believing: The Stalk Intermediate

Membrane biophysicists have sought the molecular nature of biomembrane fusion for more than 30 years. In this time, two conflicting hypotheses have evolved to explain very different observations. One, based on electrophysiological measurements on patch-clamped cells (1), is the proteinacious pore hypothesis. This model, popular among neurobiologists, contends that the initial fusion pore consists of a single proteinacious channel that later opens into a full fusion pore due to dissipation of the initial protein pore...

Analysis of Membrane Fusion as a Two-State Sequential Process: Evaluation of the Stalk Model

We propose a model that accounts for the time courses of PEG-induced fusion of membrane vesicles of varying lipid compositions and sizes. The model assumes that fusion proceeds from an initial, aggregated vesicle state ((A) membrane contact) through two sequential intermediate states (I1 and I2) and then on to a fusion pore state (FP). Using this model, we interpreted data on the fusion of seven different vesicle systems. We found that the initial aggregated state...

Mechanical and Biochemical Modeling of Cortical Oscillations in Spreading Cells

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Actomyosin-based cortical contractility is a common feature of eukaryotic cells and is involved in cell motility, cell division, and apoptosis. In nonmuscle cells, oscillations in contractility are induced by microtubule depolymerization during cell spreading. We developed an ordinary differential equation model to describe this behavior. The computational model includes 36 parameters. The values for all but two of the model parameters were taken from experimental measurements found in the literature. Using these values, we demonstrate...

Versatile Horizontal Force Probe for Mechanical Tests on Pipette-Held Cells, Particles, and Membrane Capsules

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We present a multipurpose nanomechanical force probe that combines a sideways-mounted elastic cantilever and an optical-lever detection module with automated micropipette manipulation. It allows us to apply and measure compression, stretching, adhesion, and dissociation forces in the horizontal direction while providing a “side view” of ongoing experiments. The integrated micropipette setup facilitates the easy manipulation and mechanical interrogation of individual cells, functionalized particles, and synthetic membrane capsules. Pipette-held test objects are translated perpendicularly to and...

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  • University of North Carolina at Chapel Hill
  • University of Minnesota