Publications by authors named "David Wiley"

59 Publications

Natural dimethyl sulfide gradients would lead marine predators to higher prey biomass.

Commun Biol 2021 Feb 1;4(1):149. Epub 2021 Feb 1.

Applied Ocean Physics and Engineering Department, Woods Hole Oceanographic Institution, Woods Hole, MA, USA.

Finding prey is essential to survival, with marine predators hypothesised to track chemicals such as dimethyl sulfide (DMS) while foraging. Many predators are attracted to artificially released DMS, and laboratory experiments have shown that zooplankton grazing on phytoplankton accelerates DMS release. However, whether natural DMS concentrations are useful for predators and correlated to areas of high prey biomass remains a fundamental knowledge gap. Here, we used concurrent hydroacoustic surveys and in situ DMS measurements to present evidence that zooplankton biomass is spatially correlated to natural DMS concentration in air and seawater. Using agent simulations, we also show that following gradients of DMS would lead zooplankton predators to areas of higher prey biomass than swimming randomly. Further understanding of the conditions and scales over which these gradients occur, and how they are used by predators, is essential to predicting the impact of future changes in the ocean on predator foraging success.
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http://dx.doi.org/10.1038/s42003-021-01668-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851116PMC
February 2021

Open educational resources: undertheorized research and untapped potential.

Authors:
David A Wiley

Educ Technol Res Dev 2020 Nov 30:1-4. Epub 2020 Nov 30.

Lumen Learning and Brigham Young University, Provo, UT USA.

This paper is in response to the manuscript entitled "Open educational resources and college textbook choices: a review of research on efficacy and perceptions" (Hilton in Educ Technol Res Dev 64(4): 573-590, 2016) from a theoretical perspective. The response describes the way many of the papers reviewed by Hilton were undertheorized, limiting their potential for impact. A brief summary of more recent research shows one current direction toward stronger theorization of OER research. Over the short-term, including during the rapid shift to digital learning catalyzed by the COVID-19 pandemic, OER adoption can be expected to save college students money and close the achievement gap between Pell-eligible students and their wealthier peers. Over the longer term, this benefit will likely disappear, and faculty will need to more fully explore the affordances of the 5Rs in order to create dramatic improvements in success for all students.
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http://dx.doi.org/10.1007/s11423-020-09907-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703722PMC
November 2020

Legacy and Novel Per- and Polyfluoroalkyl Substances in Juvenile Seabirds from the U.S. Atlantic Coast.

Environ Sci Technol 2020 10 7;54(20):12938-12948. Epub 2020 Oct 7.

University of Rhode Island Graduate School of Oceanography, Narragansett, Rhode Island 02882, United States.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic, globally distributed chemicals. Legacy PFAS, including perfluorooctane sulfonate (PFOS), have been regularly detected in marine fauna but little is known about their current levels or the presence of novel PFAS in seabirds. We measured 36 emerging and legacy PFAS in livers from 31 juvenile seabirds from Massachusetts Bay, Narragansett Bay, and the Cape Fear River Estuary (CFRE), United States. PFOS was the major legacy perfluoroalkyl acid present, making up 58% of concentrations observed across all habitats (range: 11-280 ng/g). Novel PFAS were confirmed in chicks hatched downstream of a fluoropolymer production site in the CFRE: a perfluorinated ether sulfonic acid (Nafion byproduct 2; range: 1-110 ng/g) and two perfluorinated ether carboxylic acids (PFODA and PFODoDA; PFODoDA range: 5-30 ng/g). PFOS was inversely associated with phospholipid content in livers from CFRE and Massachusetts Bay individuals, while δ C, an indicator of marine versus terrestrial foraging, was positively correlated with some long-chain PFAS in CFRE chick livers. There is also an indication that seabird phospholipid dynamics are negatively impacted by PFAS, which should be further explored given the importance of lipids for seabirds.
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http://dx.doi.org/10.1021/acs.est.0c01951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700771PMC
October 2020

Preface: Reflections on the waves of emerging learning technologies.

Educ Technol Res Dev 2020 Jul 27:1-18. Epub 2020 Jul 27.

204 Highlands Road, Hurricane, WV 25526-8402 USA.

There have been many waves of emerging learning technologies over the past few decades. Some of these waves are extended, some waves are connected, and other waves are repeated. The authors discuss the special journal issue from the standpoint of their personal involvement in many such waves during their careers. They also detail the evolution of this special issue and the potential audiences and stakeholders for it. In the end, they pose several questions and points to ponder in looking toward the future.
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http://dx.doi.org/10.1007/s11423-020-09809-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384554PMC
July 2020

Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways .

Front Physiol 2020 6;11:427. Epub 2020 May 6.

Department of Molecular and Cellular Pharmacology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States.

Arginyltransferase1 (ATE1) is a conserved enzyme in eukaryotes mediating posttranslational arginylation, the addition of an extra arginine to an existing protein. In mammals, the dysregulations of the ATE1 gene () is shown to be involved in cardiovascular abnormalities, cancer, and aging-related diseases. Although biochemical evidence suggested that arginylation may be involved in stress response and/or protein degradation, the physiological role of ATE1 has never been systematically determined. This gap of knowledge leads to difficulties for interpreting the involvements of ATE1 in diseases pathogenesis. Since is highly conserved between human and the unicellular organism (), we take advantage of the gene-knockout library of , to investigate the genetic interactions between and other genes in a systematic and unbiased manner. By this approach, we found that has a surprisingly small and focused impact size. Among the 3659 tested genes, which covers nearly 75% of the genome of , less than 5% of them displayed significant genetic interactions with . Furthermore, these -interacting partners can be grouped into a few discrete clustered categories based on their functions or their physical interactions. These categories include translation/transcription regulation, biosynthesis/metabolism of biomolecules (including histidine), cell morphology and cellular dynamics, response to oxidative or metabolic stress, ribosomal structure and function, and mitochondrial function. Unexpectedly, inconsistent to popular belief, very few genes in the global ubiquitination or degradation pathways showed interactions with . Our results suggested that ATE1 specifically regulates a handful of cellular processes , which will provide critical mechanistic leads for studying the involvements of ATE1 in normal physiologies as well as in diseased conditions.
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http://dx.doi.org/10.3389/fphys.2020.00427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218141PMC
May 2020

From a calf's perspective: humpback whale nursing behavior on two US feeding grounds.

PeerJ 2020 4;8:e8538. Epub 2020 Mar 4.

Vertebrate Ecology Lab, Moss Landing Marine Laboratories, Moss Landing, CA, United States of America.

Nursing influences growth rate and overall health of mammals; however, the behavior is difficult to study in wild cetaceans because it occurs below the surface and can thus be misidentified from surface observations. Nursing has been observed in humpback whales on the breeding and calving grounds, but the behavior remains unstudied on the feeding grounds. We instrumented three dependent calves (four total deployments) with combined video and 3D-accelerometer data loggers (CATS) on two United States feeding grounds to document nursing events. Two associated mothers were also tagged to determine if behavior diagnostic of nursing was evident in the mother's movement. Animal-borne video was manually analyzed and the average duration of successful nursing events was 23 s (±7 sd,  = 11). Nursing occurred at depths between 4.1-64.4 m (along the seafloor) and in close temporal proximity to foraging events by the mothers, but could not be predicted solely by relative positions of mother and calf. When combining all calf deployments, successful nursing was documented eleven times; totaling only 0.3% of 21.0 hours of video. During nursing events, calves had higher overall dynamic body acceleration (ODBA) and increased fluke-stroke rate (FSR) compared to non-nursing segments (Mixed effect models, ODBA: F1,107 = 13.57756,  = 0.0004, FSR: F1,107 = 32.31018,  < 0.0001). In contrast, mothers had lower ODBA and reduced FSR during nursing events compared to non-nursing segments. These data provide the first characterization of accelerometer data of humpback whale nursing confirmed by animal-borne video tags and the first analysis of nursing events on feeding grounds. This is an important step in understanding the energetic consequences of lactation while foraging.
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http://dx.doi.org/10.7717/peerj.8538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060748PMC
March 2020

Energetic and physical limitations on the breaching performance of large whales.

Elife 2020 03 11;9. Epub 2020 Mar 11.

Hopkins Marine Station of Stanford University, Pacific Grove, United States.

The considerable power needed for large whales to leap out of the water may represent the single most expensive burst maneuver found in nature. However, the mechanics and energetic costs associated with the breaching behaviors of large whales remain poorly understood. In this study we deployed whale-borne tags to measure the kinematics of breaching to test the hypothesis that these spectacular aerial displays are metabolically expensive. We found that breaching whales use variable underwater trajectories, and that high-emergence breaches are faster and require more energy than predatory lunges. The most expensive breaches approach the upper limits of vertebrate muscle performance, and the energetic cost of breaching is high enough that repeated breaching events may serve as honest signaling of body condition. Furthermore, the confluence of muscle contractile properties, hydrodynamics, and the high speeds required likely impose an upper limit to the body size and effectiveness of breaching whales.
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http://dx.doi.org/10.7554/eLife.51760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065846PMC
March 2020

High sensitivity of a keystone forage fish to elevated CO and temperature.

Conserv Physiol 2019 21;7(1):coz084. Epub 2019 Nov 21.

Department of Marine Sciences, University of Connecticut, 1080 Shennecossett Road, Avery Point, CT 06340, USA.

Sand lances of the genus are keystone forage fish in coastal ecosystems across the northern hemisphere. Because they directly support populations of higher trophic organisms such as whales, seabirds or tuna, the current lack of empirical data and, therefore, understanding about the climate sensitivity of sand lances represent a serious knowledge gap. Sand lances could be particularly susceptible to ocean warming and acidification because, in contrast to other tested fish species, they reproduce during boreal winter months, and their offspring develop slowly under relatively low and stable CO conditions. Over the course of 2 years, we conducted factorial CO × temperature exposure experiments on offspring of the northern sand lance , a key forage species on the northwest Atlantic shelf. Wild, spawning-ripe adults were collected from Stellwagen Bank National Marine Sanctuary (Cape Cod, USA), and fertilized embryos were reared at three CO conditions (400, 1000 and 2100 μatm) crossed with three temperatures (5, 7 and 10 ˚C). Exposure to future CO conditions consistently resulted in severely reduced embryo survival. Sensitivity to elevated CO was highest at 10 ˚C, resulting in up to an 89% reduction in hatching success between control and predicted end-of-century CO conditions. Moreover, elevated CO conditions delayed hatching, reduced remaining endogenous energy reserves at hatch and reduced embryonic growth. Our results suggest that the northern sand lance is exceptionally CO-sensitive compared to other fish species. Whether other sand lance species with similar life history characteristics are equally CO-sensitive is currently unknown. But the possibility is a conservation concern, because many boreal shelf ecosystems rely on sand lances and might therefore be more vulnerable to climate change than currently recognized. Our findings indicate that life history, spawning habitat, phenology and developmental rates mediate the divergent early life CO sensitivities among fish species.
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http://dx.doi.org/10.1093/conphys/coz084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868386PMC
November 2019

Scaling of swimming performance in baleen whales.

J Exp Biol 2019 10 23;222(Pt 20). Epub 2019 Oct 23.

Hopkins Marine Station, Stanford University, Pacific Grove, CA 93950, USA.

The scale dependence of locomotor factors has long been studied in comparative biomechanics, but remains poorly understood for animals at the upper extremes of body size. Rorqual baleen whales include the largest animals, but we lack basic kinematic data about their movements and behavior below the ocean surface. Here, we combined morphometrics from aerial drone photogrammetry, whale-borne inertial sensing tag data and hydrodynamic modeling to study the locomotion of five rorqual species. We quantified changes in tail oscillatory frequency and cruising speed for individual whales spanning a threefold variation in body length, corresponding to an order of magnitude variation in estimated body mass. Our results showed that oscillatory frequency decreases with body length (∝length) while cruising speed remains roughly invariant (∝length) at 2 m s We compared these measured results for oscillatory frequency against simplified models of an oscillating cantilever beam (∝length) and an optimized oscillating Strouhal vortex generator (∝length). The difference between our length-scaling exponent and the simplified models suggests that animals are often swimming non-optimally in order to feed or perform other routine behaviors. Cruising speed aligned more closely with an estimate of the optimal speed required to minimize the energetic cost of swimming (∝length). Our results are among the first to elucidate the relationships between both oscillatory frequency and cruising speed and body size for free-swimming animals at the largest scale.
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http://dx.doi.org/10.1242/jeb.204172DOI Listing
October 2019

Identifying the Inclusion of National Sexuality Education Standards Utilizing a Systematic Analysis of Teen Dating Violence Prevention Curriculum.

J Sch Health 2019 02;89(2):106-114

Department of Health and Human Performance, Texas State University, 601 University Drive, San Marcos, TX 78666.

Background: Violent behaviors have devastating impacts on youth and adolescents. National standards offer a framework for age and developmentally appropriate health education expectations. This study provides findings from a systematic review and analysis of teen dating violence (TDV) prevention curricula using National Sexuality Education Standards (NSES) and National Health Education Standards (NHES).

Methods: Evidence-based and/or practice informed interventions for TDV prevention were compiled and analyzed. We used a standardized review instrument to analyze each curriculum (N = 11); each curriculum was reviewed independently and results met inter-rater agreement requirements. Data were analyzed to determine NSES and NHES inclusion.

Results: This study provides findings from the TDV prevention curriculum analysis using the NSES. Five NSES topic areas were addressed in the TDV prevention curriculum and included personal safety, healthy relationships, identity, sexually transmitted diseases and human immunodeficieny virus, and pregnancy and reproduction. Personal safety was the most included topic and ranged from 37% to 77%. Healthy relationships were the second most included NSES and ranged from 11% to 53%. Inclusions of NHES skills, as they are embedded within the NSES, are identified.

Conclusions: Curricula decision-makers gain insight by conducting reviews before recommendations are made or the adoption process is complete. The NSES and NHES support expectations for TDV prevention and can guide curricula adoption for a school or district. School professionals should work together to ensure TDV prevention curricula complements sexuality education units. While TDV curricula may cover critical topics, a singular focus on one content area cannot replace comprehensive sexuality education.
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http://dx.doi.org/10.1111/josh.12718DOI Listing
February 2019

Identification of an oncogenic network with prognostic and therapeutic value in prostate cancer.

Mol Syst Biol 2018 08 14;14(8):e8202. Epub 2018 Aug 14.

Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA

Identifying critical pathways governing disease progression is essential for accurate prognosis and effective therapy. We developed a broadly applicable and novel systems-level gene discovery strategy. This approach focused on constitutively active androgen receptor (AR) splice variant-driven pathways as representative of an intractable mechanism of prostate cancer (PC) therapeutic resistance. We performed a meta-analysis of human prostate samples using weighted gene co-expression network analysis combined with experimental AR variant transcriptome analyses. An AR variant-driven gene module that is upregulated during human PC progression was identified. We filtered this module by identifying genes that functionally interacted with AR variants using a high-throughput synthetic genetic array screen in This strategy identified seven AR variant-regulated genes that also enhance AR activity and drive cancer progression. Expression of the seven genes predicted poor disease-free survival in large independent PC patient cohorts. Pharmacologic inhibition of interacting members of the gene set potently and synergistically decreased PC cell proliferation. This unbiased and novel gene discovery strategy identified a clinically relevant, oncogenic, interacting gene hub with strong prognostic and therapeutic potential in PC.
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http://dx.doi.org/10.15252/msb.20188202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684952PMC
August 2018

A Novel Treatment Approach to Over-Pronation Dysfunction .

Authors:
David Wiley

J Am Podiatr Med Assoc 2017 11;107(6):568-572

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http://dx.doi.org/10.7547/16-181DOI Listing
November 2017

Functional characterizations of rare variants in X-linked Spinal Muscular Atrophy.

F1000Res 2017 4;6:1636. Epub 2017 Sep 4.

Translational Genomics Research Institute (TGen), Phoenix, Arizona, 85004, USA.

X-linked spinal muscular atrophy (XL-SMA) results from mutations in the Ubiquitin-Like Modifier Activating Enzyme 1 ( ). Previously, four novel closely clustered mutations have been shown to cause this fatal infantile disorder affecting only males. These mutations, three missense and one synonymous, all lie within Exon15 of the gene, which contains the active adenylation domain (AAD). In this study, our group characterized the three known missense variants . Using a novel Uba1 assay and other methods, we investigated Uba1 adenylation, thioester, and transthioesterification reactions to determine possible biochemical effects of the missense variants. Our data revealed that only one of the three XL-SMA missense variants impairs the Ubiquitin-adenylating ability of Uba1. Additionally, these missense variants retained Ubiquitin thioester bond formation and transthioesterification rates equal to that found in the wild type. Our results demonstrate a surprising shift from the likelihood of these XL-SMA mutations playing a damaging role in Uba1's enzymatic activity with Ubiquitin, to other roles such as altering  mRNA splicing via the disruption of splicing factor binding sites, similar to a mechanism in traditional SMA, or disrupting binding to other important binding partners.  These findings help to narrow the search for the areas of possible dysfunction in the Ubiquitin-proteasome pathway that ultimately result in XL-SMA. Moreover, this investigation provides additional critical understanding of the mutations' biochemical mechanisms, vital for the development of future effective diagnostic assays and therapeutics.
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http://dx.doi.org/10.12688/f1000research.11878.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615770PMC
September 2017

Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension.

Circulation 2017 Jun 29;135(23):2288-2298. Epub 2017 Mar 29.

From Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT (C.H., H.-W.L., H.K., H.J., I.P., J.H., J.-D.K., W.P.D., X.H., S.L., O.E.-H., A.S., H.J.C., S.-W.J.); Department of Biology, University of North Carolina, Chapel Hill (D.S.W., V.L.B.); School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology, Korea (B.P., S.-W.J.); Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, OH (L.P., S.C., S.C.E.); Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul (E.M.H., J.-Y.P.); School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul (J.-Y.P.); Department of Neurology, Yale University School of Medicine, New Haven, CT (J.-L.T.); and Université Pierre and Marie Curie-Paris 6, CRICM, Groupe Hospitalier Pitié-Salpètrière, France; INSERM, UMRS 975, Groupe Hospitalier Pitié-Salpètrière, Paris, France; APHP, Groupe Hospitalier Pitié-Salpètrière, Paris, France (J.-L.T.).

Background: Bone morphogenetic protein (BMP) signaling has multiple roles in the development and function of the blood vessels. In humans, mutations in BMP receptor type 2 (BMPR2), a key component of BMP signaling, have been identified in the majority of patients with familial pulmonary arterial hypertension (PAH). However, only a small subset of individuals with mutation develops PAH, suggesting that additional modifiers of BMPR2 function play an important role in the onset and progression of PAH.

Methods: We used a combination of studies in zebrafish embryos and genetically engineered mice lacking endothelial expression of to determine the interaction between vascular endothelial growth factor receptor 3 (VEGFR3) and BMPR2. Additional in vitro studies were performed by using human endothelial cells, including primary lung endothelial cells from subjects with PAH.

Results: Attenuation of Vegfr3 in zebrafish embryos abrogated Bmp2b-induced ectopic angiogenesis. Endothelial cells with disrupted VEGFR3 expression failed to respond to exogenous BMP stimulation. Mechanistically, VEGFR3 is physically associated with BMPR2 and facilitates ligand-induced endocytosis of BMPR2 to promote phosphorylation of SMADs and transcription of genes. Conditional, endothelial-specific deletion of in mice resulted in impaired BMP signaling responses, and significantly worsened hypoxia-induced pulmonary hypertension. Consistent with these data, we found significant decrease in VEGFR3 expression in pulmonary arterial endothelial cells from human PAH subjects, and reconstitution of VEGFR3 expression in PAH pulmonary arterial endothelial cells restored BMP signaling responses.

Conclusions: Our findings identify VEGFR3 as a key regulator of endothelial BMPR2 signaling and a potential determinant of PAH penetrance in humans.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.025390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523010PMC
June 2017

Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6.

Nat Commun 2016 11 11;7:13247. Epub 2016 Nov 11.

Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation. Endothelial cell responsiveness to these pro-angiogenic BMP ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression. Thus, we reveal a paradigm for Notch-dependent regulation of angiogenesis: Notch regulates SMAD6 expression to affect BMP responsiveness of endothelial cells and new vessel branch formation.
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http://dx.doi.org/10.1038/ncomms13247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114582PMC
November 2016

Evidence for ship noise impacts on humpback whale foraging behaviour.

Biol Lett 2016 Aug;12(8)

Syracuse University, Syracuse, NY, USA.

Noise from shipping activity in North Atlantic coastal waters has been steadily increasing and is an area of growing conservation concern, as it has the potential to disrupt the behaviour of marine organisms. This study examines the impacts of ship noise on bottom foraging humpback whales (Megaptera novaeangliae) in the western North Atlantic. Data were collected from 10 foraging whales using non-invasive archival tags that simultaneously recorded underwater movements and the acoustic environment at the whale. Using mixed models, we assess the effects of ship noise on seven parameters of their feeding behaviours. Independent variables included the presence or absence of ship noise and the received level of ship noise at the whale. We found significant effects on foraging, including slower descent rates and fewer side-roll feeding events per dive with increasing ship noise. During 5 of 18 ship passages, dives without side-rolls were observed. These findings indicate that humpback whales on Stellwagen Bank, an area with chronically elevated levels of shipping traffic, significantly change foraging activity when exposed to high levels of ship noise. This measureable reduction in within-dive foraging effort of individual whales could potentially lead to population-level impacts of shipping noise on baleen whale foraging success.
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http://dx.doi.org/10.1098/rsbl.2016.0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014013PMC
August 2016

Spatial control of translation repression and polarized growth by conserved NDR kinase Orb6 and RNA-binding protein Sts5.

Elife 2016 07 30;5. Epub 2016 Jul 30.

Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, United States.

RNA-binding proteins contribute to the formation of ribonucleoprotein (RNP) granules by phase transition, but regulatory mechanisms are not fully understood. Conserved fission yeast NDR (Nuclear Dbf2-Related) kinase Orb6 governs cell morphogenesis in part by spatially controlling Cdc42 GTPase. Here we describe a novel, independent function for Orb6 kinase in negatively regulating the recruitment of RNA-binding protein Sts5 into RNPs to promote polarized cell growth. We find that Orb6 kinase inhibits Sts5 recruitment into granules, its association with processing (P) bodies, and degradation of Sts5-bound mRNAs by promoting Sts5 interaction with 14-3-3 protein Rad24. Many Sts5-bound mRNAs encode essential factors for polarized cell growth, and Orb6 kinase spatially and temporally controls the extent of Sts5 granule formation. Disruption of this control system affects cell morphology and alters the pattern of polarized cell growth, revealing a role for Orb6 kinase in the spatial control of translational repression that enables normal cell morphogenesis.
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http://dx.doi.org/10.7554/eLife.14216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011436PMC
July 2016

Novel 3-dimensional analysis to evaluate temporomandibular joint space and shape.

Am J Orthod Dentofacial Orthop 2016 Mar;149(3):416-28

Professor, Division of Orthodontics, Department of Orofacial Sciences, School of Dentistry, University of California at San Francisco; private practice, DDI Imaging Center, Sacramento, Calif.

Introduction: The purpose of this study was to present and validate a novel semiautomated method for 3-dimensional evaluation of the temporomandibular joint (TMJ) space and condylar and articular shapes using cone-beam computed tomographic data.

Methods: The protocol for 3-dimensional analysis with the Checkpoint software (Stratovan, Davis, Calif) was established by analyzing cone-beam computed tomographic images of 14 TMJs representing a range of TMJ shape variations. Upon establishment of the novel method, analysis of 5 TMJs was further repeated by several investigators to assess the reliability of the analysis.

Results: Principal components analysis identified 3 key components that characterized how the condylar head shape varied among the 14 TMJs. Principal component analysis allowed determination of the minimum number of landmarks or patch density to define the shape variability in this sample. Average errors of landmark placement ranged from 1.15% to 3.65%, and none of the 121 landmarks showed significant average errors equal to or greater than 5%. Thus, the mean intraobserver difference was small and within the clinically accepted margin of error. Interobserver error was not significantly greater than intraobserver error, indicating that this is a reliable methodology.

Conclusions: This novel semiautomatic method is a reliable tool for the 3-dimensional analysis of the TMJ including both the form and the space between the articular eminence and the condylar head.
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http://dx.doi.org/10.1016/j.ajodo.2015.10.017DOI Listing
March 2016

Attitudes about partner communication regarding contraceptive use among hispanic male college students.

J Am Coll Health 2016 May-Jun;64(4):279-87. Epub 2016 Jan 5.

c Department of Sociology , Texas State University , San Marcos , Texas , USA.

Objective: The purpose of this exploratory study was to examine cultural factors that influence Hispanic male college students' intention to communicate with partners about contraception use.

Participants: A sample of 239 self-identified Hispanic participants enrolled in at least 1 college course participated in this study in the spring 2014 semester.

Methods: Students completed a 47-item paper survey. Data were analyzed with multiple regression and descriptive methods.

Results: Participants with more siblings were more likely to intend to communicate with partners about contraception use than those with fewer siblings. Participants who received contraceptive information exclusively from fathers exhibited a more favorable attitude toward partner communication. Mother's education level was positively correlated with participants' contraceptive knowledge.

Conclusions: These results emphasize the importance of support from family members to this sample's intentions to communicate with partners about contraceptive use. Parental involvement and male responsibility, in regards to contraceptive use, should be integrated into Hispanic-focused sexual health improvement efforts.
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http://dx.doi.org/10.1080/07448481.2015.1117467DOI Listing
June 2017

Phosphorylation-dependent inhibition of Cdc42 GEF Gef1 by 14-3-3 protein Rad24 spatially regulates Cdc42 GTPase activity and oscillatory dynamics during cell morphogenesis.

Mol Biol Cell 2015 Oct 5;26(19):3520-34. Epub 2015 Aug 5.

Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101 Marine Biological Laboratory, Woods Hole, MA 02543.

Active Cdc42 GTPase, a key regulator of cell polarity, displays oscillatory dynamics that are anticorrelated at the two cell tips in fission yeast. Anticorrelation suggests competition for active Cdc42 or for its effectors. Here we show how 14-3-3 protein Rad24 associates with Cdc42 guanine exchange factor (GEF) Gef1, limiting Gef1 availability to promote Cdc42 activation. Phosphorylation of Gef1 by conserved NDR kinase Orb6 promotes Gef1 binding to Rad24. Loss of Rad24-Gef1 interaction increases Gef1 protein localization and Cdc42 activation at the cell tips and reduces the anticorrelation of active Cdc42 oscillations. Increased Cdc42 activation promotes precocious bipolar growth activation, bypassing the normal requirement for an intact microtubule cytoskeleton and for microtubule-dependent polarity landmark Tea4-PP1. Further, increased Cdc42 activation by Gef1 widens cell diameter and alters tip curvature, countering the effects of Cdc42 GTPase-activating protein Rga4. The respective levels of Gef1 and Rga4 proteins at the membrane define dynamically the growing area at each cell tip. Our findings show how the 14-3-3 protein Rad24 modulates the availability of Cdc42 GEF Gef1, a homologue of mammalian Cdc42 GEF DNMBP/TUBA, to spatially control Cdc42 GTPase activity and promote cell polarization and cell shape emergence.
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http://dx.doi.org/10.1091/mbc.E15-02-0095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591695PMC
October 2015

A multi-institutional study of the impact of open textbook adoption on the learning outcomes of post-secondary students.

J Comput High Educ 2015 22;27(3):159-172. Epub 2015 Sep 22.

3Lumen Learning, Portland, OR USA.

In some educational settings, the cost of textbooks approaches or even exceeds the cost of tuition. Given limited resources, it is important to better understand the impacts of free open educational resources (OER) on student outcomes. Utilizing digital resources such as OER can substantially reduce costs for students. The purpose of this study was to analyze whether the adoption of no-cost open digital textbooks significantly predicted students' completion of courses, class achievement, and enrollment intensity during and after semesters in which OER were used. This study utilized a quantitative quasi-experimental design with propensity-score matched groups to examine differences in outcomes between students that used OER and those who did not. The demographics of the initial sample of 16,727 included 4909 students in the treatment condition with a pool of 11,818 in the control condition. There were statistically significant differences between groups, with most favoring students utilizing OER.
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http://dx.doi.org/10.1007/s12528-015-9101-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115070PMC
September 2015

Evidence for acoustic communication among bottom foraging humpback whales.

Sci Rep 2014 Dec 16;4:7508. Epub 2014 Dec 16.

Stellwagen Bank National Marine Sanctuary, NOAA National Ocean Service, Scituate, MA 02066, U.S.A.

Humpback whales (Megaptera novaeangliae), a mysticete with a cosmopolitan distribution, demonstrate marked behavioural plasticity. Recent studies show evidence of social learning in the transmission of specific population level traits ranging from complex singing to stereotyped prey capturing behaviour. Humpback whales have been observed to employ group foraging techniques, however details on how individuals coordinate behaviour in these groups is challenging to obtain. This study investigates the role of a novel broadband patterned pulsed sound produced by humpback whales engaged in bottom-feeding behaviours, referred to here as a 'paired burst' sound. Data collected from 56 archival acoustic tag deployments were investigated to determine the functional significance of these signals. Paired burst sound production was associated exclusively with bottom feeding under low-light conditions, predominantly with evidence of associated conspecifics nearby suggesting that the sound likely serves either as a communicative signal to conspecifics, a signal to affect prey behaviour, or possibly both. This study provides additional evidence for individual variation and phenotypic plasticity of foraging behaviours in humpback whales and provides important evidence for the use of acoustic signals among foraging individuals in this species.
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http://dx.doi.org/10.1038/srep07508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267198PMC
December 2014

Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases.

F1000Res 2014 2;3:121. Epub 2014 Jun 2.

Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

Genetic interaction networks that underlie most human diseases are highly complex and poorly defined. Better-defined networks will allow identification of a greater number of therapeutic targets. Here we introduce our Yeast Augmented Network Analysis (YANA) approach and test it with the X-linked spinal muscular atrophy (SMA) disease gene UBA1. First, we express UBA1 and a mutant variant in fission yeast and use high-throughput methods to identify fission yeast genetic modifiers of UBA1. Second, we analyze available protein-protein interaction network databases in both fission yeast and human to construct UBA1 genetic networks. Third, from these networks we identified potential therapeutic targets for SMA. Finally, we validate one of these targets in a vertebrate (zebrafish) SMA model. This study demonstrates the power of combining synthetic and chemical genetics with a simple model system to identify human disease gene networks that can be exploited for treating human diseases.
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http://dx.doi.org/10.12688/f1000research.4188.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097366PMC
July 2014

Intrinsic expression of a multiexon type 3 deiodinase gene controls zebrafish embryo size.

Endocrinology 2014 Oct 8;155(10):4069-80. Epub 2014 Jul 8.

State Key Laboratory of Medical Genomics (C.G., X.C., H.S.), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025 China; Thyroid Program of the Division of Endocrinology (C.G., X.C., H.S., M.A.M., R.H.J., N.Y.L., L.A.C., S.A.H.) and Clinical Research Center (H.A.F.), Boston Children's Hospital; Stem Cell Program and Division of Hematology/Oncology (Y.Z., J.J.G., D.W., L.I.Z.), Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, and Howard Hughes Medical Institute; Department of Medicine (A.V.L., V.N.G., S.A.H.), Brigham and Women's Hospital; Dana Farber Cancer Institute (V.N.G., L.I.Z., S.A.H.), Boston, Massachusetts 02115; and Departments of Physiology and Pharmacology (T.S.S.), Oregon Health and Science University, Portland, Oregon 97239.

Thyroid hormone is a master regulator of differentiation and growth, and its action is terminated by the enzymatic removal of an inner-ring iodine catalyzed by the selenoenzyme type 3 deiodinase (dio3). Our studies of the zebrafish reveal that the dio3 gene is duplicated in this species and that embryonic deiodination is an important determinant of embryo size. Although both dio3 paralogs encode enzymatically active proteins with high affinity for thyroid hormones, their anatomic patterns of expression are markedly divergent and only embryos with knockdown of dio3b, a biallelically expressed selenoenzyme expressed in the developing central nervous system, manifest severe thyroid hormone-dependent growth restriction at 72 hours post fertilization. This indicates that the embryonic deficiency of dio3, once considered only a placental enzyme, causes microsomia independently of placental physiology and raises the intriguing possibility that fetal abnormalities in human deiodination may present as intrauterine growth retardation. By mapping the gene structures and enzymatic properties of all four zebrafish deiodinases, we also identify dio3b as the first multiexon dio3 gene, containing a large intron separating its open reading frame from its selenocysteine insertion sequence (SECIS) element.
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http://dx.doi.org/10.1210/en.2013-2029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164935PMC
October 2014

Individual differences in transcranial electrical stimulation current density.

J Biomed Res 2013 Nov 25;27(6):495-508. Epub 2013 Oct 25.

Aaken Research Institute, Inc. Davis, CA 95616, USA;

Transcranial electrical stimulation (TCES) is effective in treating many conditions, but it has not been possible to accurately forecast current density within the complex anatomy of a given subject's head. We sought to predict and verify TCES current densities and determine the variability of these current distributions in patient-specific models based on magnetic resonance imaging (MRI) data. Two experiments were performed. The first experiment estimated conductivity from MRIs and compared the current density results against actual measurements from the scalp surface of 3 subjects. In the second experiment, virtual electrodes were placed on the scalps of 18 subjects to model simulated current densities with 2 mA of virtually applied stimulation. This procedure was repeated for 4 electrode locations. Current densities were then calculated for 75 brain regions. Comparison of modeled and measured external current in experiment 1 yielded a correlation of r = .93. In experiment 2, modeled individual differences were greatest near the electrodes (ten-fold differences were common), but simulated current was found in all regions of the brain. Sites that were distant from the electrodes (e.g. hypothalamus) typically showed two-fold individual differences. MRI-based modeling can effectively predict current densities in individual brains. Significant variation occurs between subjects with the same applied electrode configuration. Individualized MRI-based modeling should be considered in place of the 10-20 system when accurate TCES is needed.
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http://dx.doi.org/10.7555/JBR.27.20130074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841475PMC
November 2013

Sequencing and comparative analysis of the gorilla MHC genomic sequence.

Database (Oxford) 2013 15;2013:bat011. Epub 2013 Apr 15.

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1HH, UK.

Major histocompatibility complex (MHC) genes play a critical role in vertebrate immune response and because the MHC is linked to a significant number of auto-immune and other diseases it is of great medical interest. Here we describe the clone-based sequencing and subsequent annotation of the MHC region of the gorilla genome. Because the MHC is subject to extensive variation, both structural and sequence-wise, it is not readily amenable to study in whole genome shotgun sequence such as the recently published gorilla genome. The variation of the MHC also makes it of evolutionary interest and therefore we analyse the sequence in the context of human and chimpanzee. In our comparisons with human and re-annotated chimpanzee MHC sequence we find that gorilla has a trimodular RCCX cluster, versus the reference human bimodular cluster, and additional copies of Class I (pseudo)genes between Gogo-K and Gogo-A (the orthologues of HLA-K and -A). We also find that Gogo-H (and Patr-H) is coding versus the HLA-H pseudogene and, conversely, there is a Gogo-DQB2 pseudogene versus the HLA-DQB2 coding gene. Our analysis, which is freely available through the VEGA genome browser, provides the research community with a comprehensive dataset for comparative and evolutionary research of the MHC.
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http://dx.doi.org/10.1093/database/bat011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626023PMC
June 2013

Preformed vs intraoperative bending of titanium mesh for orbital reconstruction.

Otolaryngol Head Neck Surg 2013 Jul 12;149(1):60-6. Epub 2013 Mar 12.

Department of Otolaryngology, University of California, Davis, California 95817, USA.

Objective: The most accurate orbital reconstructions result from an anatomic repair of the premorbid orbital architecture. Many different techniques and materials have been used; unfortunately, there is currently no optimal method. This study compares the use of preformed vs intraoperative bending of titanium mesh for orbital reconstruction in 2-wall orbital fractures.

Study Design: Cadaver-based study.

Setting: University hospital.

Subjects And Methods: Preinjury computed tomography scans were obtained in 15 cadaveric heads (30 orbits). Stereolithographic (STL) models were fabricated for 5 of the specimens (10 orbits). Two wall fractures (lamina papyracea and floor) were then generated in all orbits. Surgical reconstruction was performed in all orbits using 1 of 3 techniques (10 orbits each): (1) patient-specific implant molded from the preinjury STL model, (2) titanium mesh sheet bent freehand, and (3) preformed titanium mesh. Each technique was evaluated for orbital volume correction, contour accuracy, ease of use, and cost.

Results: No difference in volume restoration was found between the 3 techniques. Patient-specific implants had the greatest contour accuracy, poor ease of use, and highest cost. Freehand bending implants had the poorest contour accuracy, acceptable ease of use, and lowest cost. Preformed mesh implants had intermediate contour accuracy, excellent ease of use, and low cost.

Conclusion: All 3 techniques provide equivalent orbital volume correction. However, preformed mesh implants have many advantages based on contour accuracy, ease of use, and relative cost.
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http://dx.doi.org/10.1177/0194599813481430DOI Listing
July 2013

Eukaryotic initiation factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion.

J Biol Chem 2012 Aug 2;287(34):28738-44. Epub 2012 Jul 2.

Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

In eukaryotic cells, there are two well characterized pathways that regulate translation initiation in response to stress, and each have been shown to be targeted by various viruses. We recently showed in a yeast-based model that the bacterial virulence factor YopJ disrupts one of these pathways, which is centered on the α-subunit of the translation factor eIF2. Here, we show in mammalian cells that induction of the eIF2 signaling pathway occurs following infection with bacterial pathogens and that, consistent with our yeast-based findings, YopJ reduces eIF2 signaling in response to endoplasmic reticulum stress, heavy metal toxicity, dsRNA, and bacterial infection. We demonstrate that the well documented activities of YopJ, inhibition of NF-κB activation and proinflammatory cytokine expression, are both dependent on an intact eIF2 signaling pathway. Unexpectedly, we found that cells with defective eIF2 signaling were more susceptible to bacterial invasion. This was true for pathogenic Yersinia, a facultative intracellular pathogen, as well as for the intracellular pathogens Listeria monocytogenes and Chlamydia trachomatis. Collectively, our data indicate that the highly conserved eIF2 signaling pathway, which is vitally important for antiviral responses, plays a variety of heretofore unrecognized roles in antibacterial responses.
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http://dx.doi.org/10.1074/jbc.M112.375915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436510PMC
August 2012

Oscillatory dynamics of Cdc42 GTPase in the control of polarized growth.

Science 2012 Jul 17;337(6091):239-43. Epub 2012 May 17.

Department of Molecular and Cellular Pharmacology (R-189), University of Miami Miller School of Medicine, Post Office Box 016189, Miami, FL 33101, USA.

Cells promote polarized growth by activation of Rho-family protein Cdc42 at the cell membrane. We combined experiments and modeling to study bipolar growth initiation in fission yeast. Concentrations of a fluorescent marker for active Cdc42, Cdc42 protein, Cdc42-activator Scd1, and scaffold protein Scd2 exhibited anticorrelated fluctuations and oscillations with a 5-minute average period at polarized cell tips. These dynamics indicate competition for active Cdc42 or its regulators and the presence of positive and delayed negative feedbacks. Cdc42 oscillations and spatial distribution were sensitive to the amounts of Cdc42-activator Gef1 and to the activity of Cdc42-dependent kinase Pak1, a negative regulator. Feedbacks regulating Cdc42 oscillations and spatial self-organization appear to provide a flexible mechanism for fission yeast cells to explore polarization states and to control their morphology.
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http://dx.doi.org/10.1126/science.1218377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681419PMC
July 2012

Using science to improve the sexual health of America's youth.

Authors:
David C Wiley

Am J Prev Med 2012 Mar;42(3):308-10

Department of Health and Human Performance, Texas State University, San Marcos, Texas 78666, USA.

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http://dx.doi.org/10.1016/j.amepre.2011.11.005DOI Listing
March 2012