bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual reality as a tool for environmental conservation and fundraising
Authors: Nelson Katherine M. , Anggraini Eva , Schlüter Achim 
Published: October 2019

AbstractAnecdotal evidence from philanthropic fundraisers shows that virtual reality (VR) technology increases empathy and can influence people toward pro-environmental behavior. Non-profit organizations are increasingly marketing their causes using virtual reality and they report increased donations when VR technology is employed. In VR, users are immersed in situations intended to feel more like the real world through technology, such as 360° video screened through 3D headsets that block out visual and auditory distractions. The framing of the message as either positive or negative has long shown to have an effect on behavior, although consensus on the impact of framing has not been reached in relation to encouraging contributions to public goods. This paper focuses on field experiments used to investigate the effects of varying degrees of visual immersion and positive versus negative message framing on respondents’ contributions to a conservation charity. Participants were exposed to a five-minute underwater film about coral reefs and the importance of protecting them. We employed a 2×2 experimental design using 3D head-mounted displays comparing 360° film footage vs. unidirectional film and a positive message vs. a negative message. After watching the film, each participant completed a short questionnaire and had the opportunity to donate to a marine conservation charity. In addition, we tested a control treatment where no video was observed. The video was filmed in Indonesia which is host to some of the world’s most biodiverse reefs that are under great threat from human activity. We also conducted the study in Indonesia, sampling a total of 1006 participants from the Bogor city area and tourists on the island of Gili Trawangan - which is popular for scuba diving and snorkeling. We find significant differences in observed behavior and reported emotions between all treatments compared to the control condition. Among the tourist sample, we find significant differences between the 360° film with a negative message which garnered significantly larger average donation amounts compared to the unidirectional film with both positive and negative framing. Overall, we can infer from these studies that virtual reality is an effective way to raise awareness of environmental threats and encourage behavioral action, especially when tailored to target groups. New technology, such as the VR head-mounted display, is highly effective at attracting interest which is an important point to encourage organizations to invest in new technologies.
Target-responsive vasoactive probes for ultrasensitive molecular imaging
Authors: Ohlendorf Robert , Wiśniowska Agata , Desai Mitul , Barandov Ali , Slusarczyk Adrian L. , Jasanoff Alan 
Published: October 2019

ABSTRACTThe ability to monitor molecules volumetrically throughout the body could provide valuable biomarkers for studies of healthy function and disease, but noninvasive detection of molecular targets in living subjects often suffers from poor sensitivity or selectivity. Here we describe a family of potent imaging probes that can be activated by molecules of interest in deep tissue, providing a basis for mapping nanomolar-scale analytes without the radiation or heavy metal content associated with traditional molecular imaging agents. The probes are reversibly-caged vasodilators that induce responses detectable by hemodynamic imaging; they are constructed by combining vasoactive peptides with synthetic chemical appendages and protein blocking domains. We use this architecture to create ultrasensitive biotin-responsive imaging agents, which we apply for wide-field mapping of targets in rat brains using functional magnetic resonance imaging. We also adapt the sensor design for detecting the neurotransmitter dopamine, illustrating versatility of this approach for addressing biologically important molecules.
Membrane stiffness is a key determinant of E coli MscS channel mechanosensitivity
Authors: Xue Feng , Cox Charles D. , Bavi Navid , Rohde Paul R , Nakayama Yoshitaka , Martinac Boris 
Published: October 2019

AbstractProkaryotic mechanosensitive (MS) channels have an intimate relationship with membrane lipids. Membrane lipids may influence channel activity by directly interacting with bacterial MS channels or by influencing the global properties of the membrane such as area stretch and bending moduli. Previous work has implicated membrane stiffness as a key determinant of the mechanosensitivity of E. coli (Ec)MscS. Here we systematically tested this hypothesis using patch fluorometry of azolectin liposomes doped with lipids of increasing area stretch moduli. Increasing DOPE content of azolectin liposomes causes a rightward shift in the tension response curve of EcMscS. These rightward shifts are further magnified by the addition of stiffer forms of PE such as the branched chain lipid DPhPE and the fully saturated lipid DSPE. Furthermore, a comparison of the branched chain lipid DPhPC to the stiffer DPhPE showed a rightward shift in the tension response curve in the presence of the stiffer DPhPE. We show that these changes are not due to changes in membrane bending rigidity as the tension threshold of EcMscS in membranes doped with PC18:1 and PC18:3 are the same, despite a two-fold difference in their bending rigidity. We also show that after prolonged pressure application sudden removal of force in softer membranes causes a rebound reactivation of EcMscS and we discuss the relevance of this phenomenon to bacterial osmoregulation. Collectively, our data demonstrate that membrane stiffness is a key determinant of the mechanosensitivity of EcMscS.
Assembly of novel, nuclear dimers of the PI3-Kinase regulatory subunits underpins the pro-proliferative activity of the Cdc42-activated tyrosine kinase, ACK
Authors: Clayton Natasha S. , Fox Millie , Vicenté-Garcia Jose J. , Schroeder Courtney M. , Littlewood Trevor D. , Wilde Jonathan I. , Corry Jessica , Krishnan Kadalmani , Zhang Qifeng , Wakelam Michael J. O. , Brown Murray J. B. , Crafter Claire , Mott Helen R. , Owen Darerca 
Published: October 2019

AbstractThe tyrosine kinase ACK is an oncogene associated with poor prognosis in human cancers. ACK promotes proliferation, in part, by contributing to the activation of Akt, the major PI3-Kinase effector. We show that ACK also regulates PI3-Kinase directly, via interactions with the PI3-Kinase regulatory subunits. ACK interacts with all five regulatory subunit isoforms and directly phosphorylates p85α, p85β, p55α and p50α on Tyr607 (or equivalent). Phosphorylation of p85β at this residue promotes cell proliferation but, counterintuitively, ACK does not stimulate PI3-Kinase catalytic activity. We show that ACK stabilizes p85α levels by promoting an interaction between the p85 nSH2 domain and pTyr607, protecting p85 from ubiquitination. We demonstrate that ACK interacts with p85α exclusively in nuclear-enriched cell fractions where the increased levels of the regulatory subunits, together with the nSH2-pTyr607 interaction, promote formation of dimeric p85. We postulate that these novel dimers undertake nuclear functions that contribute to Cdc42-ACK driven oncogenesis. We propose that ACK shapes PI3-Kinase signalling by dampening the PIP3response, whilst continuing to drive cell proliferation through Akt activation and hereto unexplored but crucial functions of nuclear dimeric p85. These new regulatory subunit dimers represent a previously undescribed mode of regulation for PI3-Kinase and potentially reveal additional avenues for therapeutic intervention.
White matter hyperintensities and neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment
Authors: Misquitta Karen , Dadar Mahsa , Collins D. Louis , Tartaglia Maria Carmela ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

AbstractBackground and Purpose: Neuropsychiatric symptoms (NPS) are frequently encountered in patients with Alzheimer’s disease (AD). Focal grey matter atrophy has been linked to NPS development. Cerebrovascular disease can cause focal lesions and is common among AD patients. As cerebrovascular disease can be detected on MRI as white matter hyperintensities (WMH), this study evaluated WMH burden in mild cognitive impairment (MCI), AD and normal controls and determined their relationship with NPS. Methods: NPS were assessed using the Neuropsychiatric Inventory and grouped into subsyndromes. WMH were measured using an automatic segmentation technique and mean deformation-based morphometry was used to measure atrophy of grey matter regions. Results: WMHs and grey matter atrophy both contributed significantly to NPS subsyndromes in MCI and AD subjects, however, WMH burden played a greater role. Conclusions: This study could provide a better understanding of the pathophysiology of NPS in AD.
Widespread dysregulation of long non-coding genes associated with fatty acid metabolism, cell division, and immune response gene networks in xenobiotic-exposed rat liver
Authors: Karri Kritika , Waxman David J. 
Published: October 2019

AbstractXenobiotic exposure activates or inhibits transcription of hundreds of protein-coding genes in mammalian liver, impacting many physiological processes and inducing diverse toxicological responses. Little is known about the effects of xenobiotic exposure on long noncoding RNAs (lncRNAs), many of which play critical roles in regulating gene expression. Objective: to develop a computational framework to discover liver-expressed, xenobiotic-responsive lncRNAs (xeno-lncs) with strong functional, gene regulatory potential and elucidate the impact of xenobiotic exposure on their gene regulatory networks. We analyzed 115 liver RNA-seq data sets from male rats treated with 27 individual chemicals representing seven mechanisms of action (MOAs) to assemble the long non-coding transcriptome of xenobiotic-exposed rat liver. Ortholog analysis was combined with co-expression data and causal inference methods to infer lncRNA function and deduce gene regulatory networks, including causal effects of lncRNAs on protein-coding gene expression and biological pathways. We discovered >1,400 liver-expressed xeno-lncs, many with human and/or mouse orthologs. Xenobiotics representing different MOAs were often regulated common xeno-lnc targets: 123 xeno-lncs were dysregulated by at least 10 chemicals, and 5 xeno-lncs responded to at least 20 of the 27 chemicals investigated. 81 other xeno-lncs served as MOA-selective markers of xenobiotic exposure. Xeno-lnc–protein-coding gene co-expression regulatory network analysis identified xeno-lncs closely associated with exposure-induced perturbations of hepatic fatty acid metabolism, cell division, and immune response pathways. We also identified hub and bottleneck lncRNAs, which are expected to be key regulators of gene expression incisor intrans. This work elucidates extensive networks of xeno-lnc–protein-coding gene interactions and provides a framework for understanding the extensive transcriptome-altering actions of diverse foreign chemicals in a key responsive mammalian tissue.
CircFOXK2 Promotes Tumor Growth and Metastasis of Pancreatic Ductal Adenocarcinoma via Complexing with RNA Binding Proteins and Sponging MiR-942
Authors: Wong Chi Hin , Lou Ut Kei , Li Youjia , Chan Stephen Lam , Tong Joanna Hung-Man , To Ka-Fai , Chen Yangchao 
Published: October 2019

AbstractObjectiveCircular RNA (circRNA) is a novel class of non-coding RNAs that regulate gene expression. However, the role of circRNAs in pancreatic ductal adenocarcinoma (PDAC) is largely unknown.DesignWe performed circRNA sequencing of non-tumor HPDE and PDAC cells. We investigated the functions of circFOXK2 in PDAC by gain-of-function and loss-of-function assays. Bioinformatics analysis, luciferase assay and microRNA pulldown assays were performed to identify circFOXK2 interacting-miRNAs. To further investigate the mechanism, we performed circRNA-pulldown and mass spectrometry to identify circFOXK2-interacting proteins in PDAC.ResultsWe identified 169 differentially expressed circRNAs in PDAC cells. We validated that one of the circRNAs circFOXK2 was significantly up-regulated in PDAC cells and in 63 % of primary tumor (53 out of 84). Gain-of-function and loss-of-function assays demonstrated that circFOXK2 promoted PDAC cell growth, migration and invasion. CircFOXK2 was also involved in cell cycle progression and apoptosis. circFOXK2 functioned as sponge for miR-942, and in turn promoted the expression of miR-942 targets ANK1, GDNF and PAX6. Furthermore, circFOXK2 interacted with 94 proteins, which were involved in cell adhesion and mRNA splicing. Among these circFOXK2-interacting proteins, YBX1 and hnRNPK were validated by RNA immunoprecipitation. Importantly, circFOKX2 interacted with YBX1 and hnRNPK targets NUF2 and PDXK in PDAC cells. Knockdown of circFOXK2 reduced the binding of YBX1 and hnRNPK to NUF2 and PDXK, and in turn decreased their expressions in PDAC cells.ConclusionWe identified that circFOXK2 promoted PDAC cells growth and metastasis. Also, circFOXK2 complexed with YBX1 and hnRNPK to promote the expressions of oncogenic proteins.Significance of this studyWhat is already known on this subject?Differentially expressed circRNAs are involved in carcinogenesis of many cancers.CircRNAs function as microRNA sponges to regulate gene expression.The roles of circRNAs in PDAC progression is largely unknown.What are the new findings?circFOXK2 is upregulated in PDAC primary tumors.circFOXK2 promotes PDAC tumor growth and liver metastasis.circFOXK2 functions as sponges for miR-942 to promote the expressions of oncogenic ANK1, GDNF and PAX6.circFOXK2 complexes with YBX1 and hnRNPK to promote the expressions of oncogenic proteins in PDAC.How might it impact on clinical practice in the foreseeable future?circFOXK2 upregulation in PDAC may function as a novel biomarker for diagnosis.circFOXK2 may be a novel therapeutic target in treating PDAC.
GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs to Assist Ribosome-Associated Quality Control
Authors: Hickey Kelsey L. , Dickson Kimberley , Cogan J. Zachery , Replogle Joseph M. , Schoof Michael , D’Orazio Karole N. , Sinha Niladri K. , Frost Adam , Green Rachel , Weissman Jonathan S. , Kostova Kamena K. 
Published: October 2019

SummaryRibosome-associated Quality Control (RQC) pathways protect cells from toxicity caused by incomplete protein products resulting from translation of damaged or problematic mRNAs. Extensive work in yeast has identified highly conserved mechanisms that lead to the degradation of the faulty mRNA and partially synthesized polypeptide. Here, we used CRISPR-Cas9-based screening to search for additional RQC strategies in mammals. We found that failed translation leads to specific silencing of translation initiation on that message. This negative feedback loop is mediated by two translation inhibitors, GIGYF2 and 4EHP. Their recruitment to defective messages can be mediated by different factors, including potentially the collision sensor ZNF598. Both model substrates and growth-based assays established that inhibition of additional rounds of translation acts in concert with known RQC pathways to prevent buildup of toxic proteins. Inability to block translation of faulty mRNAs, and subsequent accumulation of partially synthesized polypeptides, could explain the neurodevelopmental and neuropsychiatric disorders observed in mice and humans with compromised GIGYF2 function.
Strain-Dependent Kinetic Properties of KIF3A and KIF3C Tune the Mechanochemistry of the KIF3AC Heterodimer
Authors: Bensel Brandon M. , Woody Michael S. , Pyrpassopoulos Serapion , Goldman Yale E. , Gilbert Susan P. , Ostap E. Michael 
Published: October 2019

AbstractKIF3AC is a mammalian neuron-specific kinesin-2 implicated in intracellular cargo transport. It is a heterodimer of KIF3A and KIF3C motor polypeptides which have distinct biochemical and motile properties as engineered homodimers. Single-molecule motility assays show that KIF3AC moves processively along microtubules at a rate faster than expected given the motility rates of the KIF3AA and much slower KIF3CC homodimers. To resolve the stepping kinetics of KIF3A and KIF3C motors in homo-and heterodimeric constructs, and to determine their transport potential under mechanical load, we assayed motor activity using interferometric scattering (iSCAT) microscopy and optical trapping. The distribution of stepping durations of KIF3AC molecules is described by a rate (k1 = 11 s−1) without apparent kinetic asymmetry in stepping. Asymmetry was also not apparent under hindering or assisting mechanical loads of 1 pN in the optical trap. KIF3AC shows increased force sensitivity relative to KIF3AA, yet is more capable of stepping against mechanical load than KIF3CC. Microtubule gliding assays containing 1:1 mixtures of KIF3AA and KIF3CC result in speeds similar to KIF3AC, indicating the homodimers mechanically impact each other’s motility to reproduce the behavior of the heterodimer. We conclude that the stepping of KIF3C can be activated by KIF3A in a strain-dependent manner which is similar to application of an assisting load, and the behavior of KIF3C mirrors prior studies of kinesins with increased interhead compliance. These results suggest that KIF3AC-based cargo transport likely requires multiple motors, and its mechanochemical properties arise due to the strain-dependences of KIF3A and KIF3C.Significance StatementKinesins are important long-range intracellular transporters in neurons required by the extended length of the axon and dendrites and selective cargo transport to each. The mammalian kinesin-2, KIF3AC, is a neuronal heterodimer of fast and slow motor polypeptides. Our results show that KIF3AC has a single observed stepping rate in the presence and absence of load and detaches from the microtubule rapidly under load. Interestingly, both KIF3A and assisting loads accelerate the kinetics of KIF3C. These results suggest that KIF3AC is an unconventional cargo transporter and its motile properties do not represent a combination of alternating fast and slow step kinetics. We demonstrate that the motile properties of KIF3AC represent a mechanochemistry that is specific to KIF3AC and may provide functional advantages in neurons.
RCy3: Network Biology using Cytoscape from within R
Authors: Gustavsen Julia A. , Pai Shraddha , Isserlin Ruth , Demchak Barry , Pico Alexander R. 
Published: October 2019

AbstractRCy3 is an R package in Bioconductor that communicates with Cytoscape via its REST API, providing access to the full feature set of Cytoscape from within the R programming environment. RCy3 has been redesigned to streamline its usage and future development as part of a broader Cytoscape Automation effort. Over 100 new functions have been added, including dozens of helper functions specifically for intuitive data overlay operations. Over 40 Cytoscape apps have implemented automation support so far, making hundreds of additional operations accessible via RCy3. Two-way conversion with networks from igraph and graph ensures interoperability with existing network biology workflows and dozens of other Bioconductor packages. These capabilities are demonstrated in a series of use cases involving public databases, enrichment analysis pipelines, shortest path algorithms and more. With RCy3, bioinformaticians will be able to quickly deliver reproducible network biology workflows as integrations of Cytoscape functions, complex custom analyses and other R packages.
Optimal bang–bang feedback for bursty gene expression
Authors: Zabaikina Iryna , Bokes Pavol , Singh Abhyudai 
Published: October 2019

AbstractStochasticity in gene expression poses a critical challenge to the precise control of cellular function. In this paper we examine how precisely can a stochastically expressed protein attain a given target expression level. We consider a protein which is produced in bursts and which is able to control its expression via a negative feedback loop; we specifically focus on feedback of a bang–bang type which turns off the production of the protein whenever its concentration exceeds a given threshold. Using a piecewise deterministic mathematical formalism, we derive explicit expressions for the probabilistic distribution of the protein concentration, and for the mean square deviation from the target level. Employing a combination of analytic and numerical optimization, we identify the optimal value of the bang–bang threshold, in terms of minimising the deviation, and examine the dependence of the optimal value on the target level and the sub-threshold burst frequency. The systematic analysis allows us to formulate a number of quantitative and qualitative conclusions about the controllability of burst like gene expression. Finally, we outline directions for future research into the topic.
Fractal characteristics of AC corrosion morphology of X80 pipeline steel in coastal soil solution
Authors: Fu Yu , Kou Jie , Du Cuiwei 
Published: October 2019

Purpose
Pipelines are seriously corroded due to the close distance between pipelines and high voltage transmission lines. The purpose of this paper is to study the influence of alternating current (AC) on corrosion behavior of X80 pipeline steel in coastal soil solution.

Design/methodology/approach
The corrosion behavior of X80 steel under different AC densities in coastal soil solution was investigated by electrochemical measurements and image processing technology. Furthermore, a quantitative description model of AC corrosion through fractal dimension of corrosion image was established.

Findings
The results show that under low AC density the X80 steel is mainly uniform corrosion, and once AC density reaches 150 A/m2, the corrosion morphology gradually turns to pitting corrosion with irregular circle. For another aspect, the fractal dimension of corrosion images shows that the two/three-dimensional fractal dimension increase with the increase of AC density, presenting a linear and an exponential relationship respectively. In addition, the variation of the three-dimensional fractal dimension is the same as that of average corrosion rate. The threshold of the increasing trend of fractal dimension as well as corrosion type is 150 A/m2.

Originality/value
The investigation provides a quantitative method to describe AC corrosion morphology through fractal dimension. Furthermore, the method is of benefit to process corrosion images automatically.