scholarly journals Measuring pathway database coverage of the phosphoproteome

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11298
Author(s):  
Hannah Huckstep ◽  
Liam G. Fearnley ◽  
Melissa J. Davis
Keyword(s):  
Pathway Database ◽  
Biological Mechanisms ◽  
Biologically Relevant ◽  
Cellular Processes ◽  
Data Saturation ◽  
Global Coverage ◽  
Using Data ◽  
Translational Mechanisms ◽  
Constant Improvement ◽  
Shed Light

Protein phosphorylation is one of the best known post-translational mechanisms playing a key role in the regulation of cellular processes. Over 100,000 distinct phosphorylation sites have been discovered through constant improvement of mass spectrometry based phosphoproteomics in the last decade. However, data saturation is occurring and the bottleneck of assigning biologically relevant functionality to phosphosites needs to be addressed. There has been finite success in using data-driven approaches to reveal phosphosite functionality due to a range of limitations. The alternate, more suitable approach is making use of prior knowledge from literature-derived databases. Here, we analysed seven widely used databases to shed light on their suitability to provide functional insights into phosphoproteomics data. We first determined the global coverage of each database at both the protein and phosphosite level. We also determined how consistent each database was in its phosphorylation annotations compared to a global standard. Finally, we looked in detail at the coverage of each database over six experimental datasets. Our analysis highlights the relative strengths and weaknesses of each database, providing a guide in how each can be best used to identify biological mechanisms in phosphoproteomic data.

scholarly journals Cooperative subunit dynamics modulate p97 function

2018 ◽  
Vol 116 (1) ◽  
pp. 158-167 ◽  
Author(s):  
Rui Huang ◽  
Zev A. Ripstein ◽  
John L. Rubinstein ◽  
Lewis E. Kay
Keyword(s):  
Bound State ◽  
Nmr Studies ◽  
Biologically Relevant ◽  
Aaa Atpase ◽  
Cellular Processes ◽  
Allosteric Communication ◽  
Functional Dynamics ◽  
Nmr Study ◽  
Wide Range

p97 is an essential hexameric AAA+ ATPase involved in a wide range of cellular processes. Mutations in the enzyme are implicated in the etiology of an autosomal dominant neurological disease in which patients are heterozygous with respect to p97 alleles, containing one copy each of WT and disease-causing mutant genes, so that, in vivo, p97 molecules can be heterogeneous in subunit composition. Studies of p97 have, however, focused on homohexameric constructs, where protomers are either entirely WT or contain a disease-causing mutation, showing that for WT p97, the N-terminal domain (NTD) of each subunit can exist in either a down (ADP) or up (ATP) conformation. NMR studies establish that, in the ADP-bound state, the up/down NTD equilibrium shifts progressively toward the up conformation as a function of disease mutant severity. To understand NTD functional dynamics in biologically relevant p97 heterohexamers comprising both WT and disease-causing mutant subunits, we performed a methyl-transverse relaxation optimized spectroscopy (TROSY) NMR study on a series of constructs in which only one of the protomer types is NMR-labeled. Our results show positive cooperativity of NTD up/down equilibria between neighboring protomers, allowing us to define interprotomer pathways that mediate the allosteric communication between subunits. Notably, the perturbed up/down NTD equilibrium in mutant subunits is partially restored by neighboring WT protomers, as is the two-pronged binding of the UBXD1 adaptor that is affected in disease. This work highlights the plasticity of p97 and how subtle perturbations to its free-energy landscape lead to significant changes in NTD conformation and adaptor binding.

Description of Professional Master's Athletic Training Programs

2015 ◽  
Vol 10 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Thomas G. Bowman ◽  
William A. Pitney ◽  
Stephanie M. Mazerolle ◽  
Thomas M. Dodge
Keyword(s):  
Student Learning ◽  
Athletic Training ◽  
Clinical Education ◽  
Training Programs ◽  
Retention Rate ◽  
Retention Rates ◽  
Athletic Training Student ◽  
Career Placement ◽  
Data Saturation ◽  
Using Data

Context Professional master's (PM) athletic training programs (ATPs) are becoming more popular as the profession debates what the entry-level degree should be for athletic training. More information is needed related to the potential benefits of PM ATPs. Objective Describe the Commission on Accreditation of Athletic Training Education (CAATE) accredited PM ATPs including athletic training student retention rates and career placement rates as well as strengths and areas for improvement. Design Mixed-method study. Setting Professional master's ATPs. Patients or Other Participants We surveyed directors of all accredited PM ATPs and obtained responses from 15 out of the 25 directors (60.0%). Main Outcome Measure(s) We sent a link to an electronic survey to all directors. The survey asked background questions about the ATP, the institution, and the director. Using data saturation as a guide, we also performed follow-up telephone interviews with 8 directors to expand upon the data gathered in the survey, specifically related to aspects of their PM ATPs. We analyzed the data using grounded theory and maintained trustworthiness through multiple analyst triangulation, member checks, and a peer review. Results Our findings indicate an 88.7% retention rate and an 88.5% career placement rate for PM athletic training students. The directors responded very positively about their ATPs, particularly didactic education. The participants also felt they provide a positive environment which fosters student learning, excellent clinical education opportunities, and unique experiences beyond those typically offered at the undergraduate level. Many directors also noted they wanted to make personnel modifications to strengthen their ATPs. Conclusions We were able to provide descriptive information on PM ATPs. The participants described the didactic and clinical education experiences, social experiences, and overall ATP atmosphere as overwhelmingly positive. The small class sizes and involvement from faculty, staff, and preceptors helped create an environment, which fosters athletic training student learning.

scholarly journals Current and Future Perspectives on Children’s Genetic- and Endophenotype-Based Differential Susceptibility to Parenting

2019 ◽  
Vol 29 (3) ◽  
pp. 773-779
Author(s):  
Karen Fischer ◽  
Joyce Weeland ◽  
Patty Leijten ◽  
Alithe van den Akker ◽  
Geertjan Overbeek
Keyword(s):  
Externalizing Behavior ◽  
Differential Susceptibility ◽  
Positive Parenting ◽  
Future Perspectives ◽  
Biological Mechanisms ◽  
Methodological Issues ◽  
Susceptibility Factors ◽  
Enriched Environments ◽  
Study Designs ◽  
Shed Light

Abstract Objectives Accumulating research provides support for differential susceptibility, which holds that the same children who are most vulnerable to adversity, such as negative parenting, may also benefit most from enriched environments, such as positive parenting. This “for better and for worse” phenomenon is believed to be rooted in endogenous, biological susceptibility factors such as genes, and cognitive and physiological endophenotypes (e.g., heart rate variability and skin conductance). The goal of this paper is to discuss the effect of this biological perspective on children’s susceptibility, and the inclusion of genetic and endophenotypical data in parenting research to shed light on the differential effects of parenting behavior We discuss a number of conceptual and methodological issues related to prior studies that have aimed to assess this. Methods We review and discuss current and future perspectives on children’s genetic- and endophenotype-based differential susceptibility to parenting, and experimental study designs that can adequately assess the within-person phenomenon of differential susceptibility. Results We summarize our call for research in an experimental paradigm to test children’s gene- and endophenotype-based differential susceptibility to parenting in their development of externalizing behavior. Conclusions Hereby we aim to advance our understanding of the biological mechanisms underlying children’s differential susceptibility to negative and positive parenting.

Shrouded Prices and Firm Reputation: Evidence from the U.S. Hotel Industry

2020 ◽  
Author(s):  
Bennett Chiles
Keyword(s):  
Rating Scale ◽  
Causal Effect ◽  
Hotel Industry ◽  
Firm Characteristics ◽  
Firm Reputation ◽  
Using Data ◽  
Online Travel ◽  
The Impact ◽  
Shed Light ◽  
The U.S

Firms in many industries engage in price obfuscation—tactics that intentionally make prices more difficult for consumers to discern. Although existing research has focused on the short-term financial gains that motivate firms to obfuscate, reputational concerns may at least partially counteract these incentives if consumers punish deceptive firms via loss of loyalty in future transactions and/or publicly observable negative feedback. This paper addresses the latter possibility, exploring the impact of mandatory shrouded surcharges on firm reputation in the U.S. hotel industry. Using data collected from two major online travel sites, I exploit differences in surcharge disclosure across booking channels to identify the causal effect of hidden “resort fees” on traveler ratings. I find that hidden fees decrease ratings by roughly 0.15 points (on a rating scale ranging from 1 to 5). The magnitude of this effect varies based on firm characteristics, and this variation is consistent with observed heterogeneity in resort fee adoption patterns: when the expected punishment is more severe, firms are substantially less likely to adopt shrouded surcharges. Results shed light on the extent to which reputational mechanisms may act as a check against price obfuscation and other similar practices intended to exploit boundedly rational consumers. This paper was accepted by Eric Anderson, marketing.

scholarly journals Glycan-decorated protocells: novel features for rebuilding cellular processes

2019 ◽  
Vol 9 (2) ◽  
pp. 20180084 ◽  
Author(s):  
Ramin Omidvar ◽  
Winfried Römer
Keyword(s):  
Synthetic Biology ◽  
Membrane Fusion ◽  
Molecular Mechanisms ◽  
Lipid Vesicles ◽  
Cross Linking ◽  
Membrane Systems ◽  
Biophysical Characterization ◽  
Characterization Methods ◽  
Cellular Processes ◽  
Shed Light

In synthetic biology approaches, lipid vesicles are widely used as protocell models. While many compounds have been encapsulated in vesicles (e.g. DNA, cytoskeleton and enzymes), the incorporation of glycocalyx components in the lipid bilayer has attracted much less attention so far. In recent years, glycoconjugates have been integrated in the membrane of giant unilamellar vesicles (GUVs). These minimal membrane systems have largely contributed to shed light on the molecular mechanisms of cellular processes. In this review, we first introduce several preparation and biophysical characterization methods of GUVs. Then, we highlight specific applications of protocells investigating glycolipid-mediated endocytosis of toxins, viruses and bacteria. In addition, we delineate how prototissues have been assembled from glycan-decorated protocells by using lectin-mediated cross-linking of opposed glycoreceptors (e.g. glycolipids and glycopeptides). In future applications, glycan-decorated protocells might be useful for investigating cell–cell interactions (e.g. adhesion and communication). We also speculate about the implication of lectin–glycoreceptor interactions in membrane fusion processes.

scholarly journals When Private Information Settles the Bill: Money and Privacy in Google’s Market for Smartphone Applications

2019 ◽  
Vol 65 (8) ◽  
pp. 3470-3494 ◽  
Author(s):  
Michael Kummer ◽  
Patrick Schulte
Keyword(s):  
Private Information ◽  
Personal Information ◽  
Supply And Demand ◽  
User Group ◽  
Smartphone Applications ◽  
Difference In Differences ◽  
Android Market ◽  
Using Data ◽  
Google Play ◽  
Shed Light

We shed light on a money-for-privacy trade-off in the market for smartphone applications (“apps”). Developers offer their apps at lower prices in return for greater access to personal information, and consumers choose between low prices and more privacy. We provide evidence for this pattern using data from 300,000 apps obtained from the Google Play Store (formerly Android Market) in 2012 and 2014. Our findings show that the market’s supply and demand sides both consider an app’s ability to collect private information, measured by the apps’s use of privacy-sensitive permissions: (1) cheaper apps use more privacy-sensitive permissions; (2) given price and functionality, demand is lower for apps with sensitive permissions; and (3) the strength of this relationship depends on contextual factors, such as the targeted user group, the app’s previous success, and its category. Our results are robust and consistent across several robustness checks, including the use of panel data, a difference-in-differences analysis, “twin” pairs of apps, and various measures of privacy-sensitivity and app demand. This paper was accepted by Anandhi Bharadwaj, information systems.

scholarly journals Supraphysiological Concentrations of Bisphenol A Alter the Expression of Extracellular Vesicle-Enriched miRNAs From Human Primary Granulosa Cells

2019 ◽  
Vol 169 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Rodosthenis S Rodosthenous ◽  
Andrea A Baccarelli ◽  
Abdallah Mansour ◽  
Michal Adir ◽  
Ariel Israel ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Granulosa Cells ◽  
Target Genes ◽  
Quantitative Polymerase Chain Reaction ◽  
Extracellular Vesicle ◽  
Biological Mechanisms ◽  
Expression Levels ◽  
Biologically Relevant ◽  
Reproductive Effects ◽  
Polymerase Chain

Abstract Bisphenol A (BPA) is a widely used chemical that has been detected in follicular fluid and associated with adverse reproductive effects. Granulosa cells have an important role in follicular growth and oocyte maturation, however, little is known about the biological mechanisms of BPA toxicity on human granulosa cells. In this study, we exposed primary granulosa cells to different concentrations of BPA (0, 20, 200, 2000, and 20 000 ng/ml) and used quantitative polymerase chain reaction to measure the expression levels of miRNAs enriched in extracellular vesicles (EV-enriched miRNAs), and cellular levels of selected target genes of differentially expressed EV-enriched miRNAs. We found that exposure to 20 000 ng/ml BPA was associated with decreased levels of EV-miR-27b-3p (FC = 0.58, p = .04) and increased levels of its biologically relevant target genes FADD (FC = 1.22, p = .01), IGF1 (FC = 1.59, p = .06), and PPARG (FC = 1.73, p = .001) as compared with the control. In addition, we observed that under the same exposure conditions, the expression levels of miR-27b-3p in granulosa cells were also downregulated (FC = 0.65, p = .03) as compared with the control. Our findings suggest that both cellular and extracellular changes in gene expression may mediate BPA toxicity in granulosa cells.

A Pilot Study to Explore Novice Debriefers’ Post-Simulation Debriefing Experiences

2020 ◽  
pp. 104687812097099
Author(s):  
Grace Ng ◽  
Daniel M. Lugassy
Keyword(s):  
Faculty Development ◽  
Skill Acquisition ◽  
Health Professions ◽  
Structured Interviews ◽  
Roles And Responsibilities ◽  
Learner Participation ◽  
Simulation Based ◽  
Data Saturation ◽  
Study Participants ◽  
Shed Light

Introduction. Effective debriefing of simulation-based experiences is critical for learning. Approximately 33% of health professions instructors are debriefing novices. However, specific faculty development needs of novice debriefers has not been studied. This study examines how health professions instructors approach debriefing when they are new to debriefing simulation-based experiences. Methods. This pilot qualitative study used a thematic analysis approach to explore novice debriefers’ experiences in conducting post-simulation debriefings. Eligible participants engaged in one-hour semi-structured interviews. Recruitment continued until data saturation was reached. We reviewed verbatim interview transcripts, hand-coded the data, and formed codes into themes. Results. Nine novice debriefers participated. The overarching theme “I’m on my own…and they’re on their own,” reflects debriefers’ view that they are on their own, without resources. Debriefers also believe learners should identifying their own errors. Three main themes emerged: “Deep divide between me and the learners” portrays a separation between debriefers and learners in terms of expectations, roles, and responsibilities. “Winging it” depicts debriefers’ making-up their own debriefing approaches. “Debriefing quality: missing pieces of the puzzle” portrays novice debriefers unaware of criteria for effective debriefing. Conclusions. Novice debriefers in this study perceived that they were on their own, having little to no debriefing training and mentorship. Study participants expressed debriefing struggles in several areas including discussing errors, facilitating learner participation, and assessing debriefing quality. Our findings shed light on simulation as a growing specialty by health profession educators and it is critical that resources are devoted to faculty development for debriefing skill acquisition. These findings can serve as a basis for future studies on debriefer skill acquisition.

scholarly journals Null subjects in Middle English

2016 ◽  
Vol 21 (3) ◽  
pp. 439-473 ◽  
Author(s):  
GEORGE WALKDEN ◽  
KRISTIAN A. RUSTEN
Keyword(s):  
Middle English ◽  
Old English ◽  
Complete Disappearance ◽  
English Poetry ◽  
Limited Extent ◽  
Null Subjects ◽  
Null Subject ◽  
Middle English Poetry ◽  
Using Data ◽  
Shed Light

This article investigates the occurrence and distribution of referential null subjects in Middle English. Whereas Modern English is the textbook example of a non-null-subject language, the case has recently been made that Old English permits null subjects to a limited extent, which raises the question of what happens in the middle period. In this article we investigate Middle English using data drawn from thePenn–Helsinki Parsed Corpus of Middle English Proseand the newParsed Corpus of Middle English Poetry, aiming to shed light on the linguistic and extralinguistic factors conditioning the alternation between null and overt subjects. Generalized mixed-effects logistic regression and random forests are used to assess the importance of the variables included. We show that the set of factors at play is similar to that found for Old English, and we document a near-complete disappearance of the null subject option by the end of the Middle English period.

scholarly journals Measuring the repertoire of age-related behavioral changes in Drosophila melanogaster

2021 ◽  
Author(s):  
Katherine E. Overman ◽  
Daniel M. Choi ◽  
Kawai Leung ◽  
Joshua W. Shaevitz ◽  
Gordon J. Berman
Keyword(s):  
Drosophila Melanogaster ◽  
Energy Budget ◽  
Behavioral Changes ◽  
Sexually Dimorphic ◽  
Behavioral Repertoire ◽  
Biological Mechanisms ◽  
Age Related ◽  
Using Data ◽  
Almost All ◽  
And Behavior

Aging affects almost all aspects of an organism – its morphology, its physiology, its behavior. Isolating which biological mechanisms are regulating these changes, however, has proven difficult, potentially due to our inability to characterize the full repertoire of an animal’s behavior across the lifespan. Using data from fruit flies (D. melanogaster) we measure the full repertoire of behaviors as a function of age. We observe a sexually dimorphic pattern of changes in the behavioral repertoire during aging. Although the stereotypy of the behaviors and the complexity of the repertoire overall remains relatively unchanged, we find evidence that the observed alterations in behavior can be explained by changing the fly’s overall energy budget, suggesting potential connections between metabolism, aging, and behavior.

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