bluuebunny/crossref_metadata_2025_split huggingface dataset:
Realistic vOlumetric-Approach to Simulate Transcranial Electric Stimulation – ROAST – a fully automated open-source pipeline
Authors: Huang Yu , Datta Abhishek , Bikson Marom , Parra Lucas C. 
Published: November 2017

AbstractObjectiveResearch in the area of transcranial electrical stimulation (TES) often relies on computational models of current flow in the brain. Models are built based on magnetic resonance images (MRI) of the human head to capture detailed individual anatomy. To simulate current flow on an individual, the subject’s MRI is segmented, virtual electrodes are placed on this anatomical model, the volume is tessellated into a mesh, and a finite element model (FEM) is solved numerically to estimate the current flow. Various software tools are available for each of these steps, as well as processing pipelines that connect these tools for automated or semi-automated processing. The goal of the present tool – ROAST – is to provide an end-to-end pipeline that can automatically process individual heads with realistic volumetric anatomy leveraging open-source software and custom scripts to improve segmentation and execute electrode placement.ApproachROAST combines the segmentation algorithm of SPM8, a Matlab script for touch-up and automatic electrode placement, the finite element mesher iso2mesh and the solver getDP. We compared its performance with commercial FEM software, and SimNIBS, a well-established open-source modeling pipeline.Main ResultsThe electric fields estimated with ROAST differ little from the results obtained with commercial meshing and FEM solving software. We also do not find large differences between the various automated segmentation methods used by ROAST and SimNIBS. We do find bigger differences when volumetric segmentation are converted into surfaces in SimNIBS. However, evaluation on intracranial recordings from human subjects suggests that ROAST and SimNIBS are not significantly different in predicting field distribution, provided that users have detailed knowledge of SimNIBS.SignificanceWe hope that the detailed comparisons presented here of various choices in this modeling pipeline can provide guidance for future tool development. We released ROAST as an open-source, easy-to-install and fully-automated pipeline for individualized TES modeling.
MODE-TASK: Large-scale protein motion tools
Authors: Ross Caroline , Nizami Bilal , Glenister Michael , Amamuddy Olivier Sheik , Atilgan Ali Rana , Atilgan Canan , Tastan Bishop Özlem 
Published: November 2017

AbstractSummaryMODE-TASK, a novel software suite, comprises Principle Component Analysis, Multidimensional Scaling, and t-Distributed Stochastic Neighbor Embedding techniques using molecular dynamics trajectories. MODE-TASK also includes a Normal Mode Analysis tool based on Anisotropic Network Model so as to provide a variety of ways to analyse and compare large-scale motions of protein complexes for which long MD simulations are prohibitive.Availability and ImplementationMODE-TASK has been open-sourced, and is available for download from https://github.com/RUBi-ZA/MODE-TASK, implemented in Python and C++.Supplementary informationDocumentation available at http://mode-task.readthedocs.io.
EpiGraph: an open-source platform to quantify epithelial organization
Authors: Vicente-Munuera Pablo , Gómez-Gálvez Pedro , Tetley Robert J. , Forja Cristina , Tagua Antonio , Letrán Marta , Tozluoglu Melda , Mao Yanlan , Escudero Luis M. 
Published: November 2017

SUMMARYDuring development, cells must coordinate their differentiation with their growth and organization to form complex multicellular structures such as tissues and organs. Healthy tissues must maintain these structures during homeostasis. Epithelia are packed ensembles of cells from which the different tissues of the organism will originate during embryogenesis. A large barrier to the analysis of the morphogenetic changes in epithelia is the lack of simple tools that enable the quantification of cell arrangements. Here we present EpiGraph, an image analysis tool that quantifies epithelial organization. Our method combines computational geometry and graph theory to measure the degree of order of any packed tissue. EpiGraph goes beyond the traditional polygon distribution analysis, capturing other organizational traits that improve the characterization of epithelia. EpiGraph can objectively compare the rearrangements of epithelial cells during development and homeostasis to quantify how the global ensemble is affected. Importantly, it has been implemented in the open-access platform FIJI. This makes EpiGraph very user friendly, with no programming skills required.
Programming of macrophages by apoptotic cancer cells inhibits cancer progression through exosomal PTEN and PPARγ ligands
Authors: Kim Yong-Bae , Ahn Young-Ho , Lee Jin-Hwa , Kang Jihee Lee 
Published: November 2017

AbstractApoptotic cell clearance by phagocytes is essential in tissue homeostasis. We demonstrated that conditioned medium (CM) from macrophages exposed to apoptotic cancer cells inhibits epithelial-mesenchymal transition (EMT), migration, and invasion of cancer cells with the acquisition of cancer-stem–like traits. Apoptotic 344SQ (ApoSQ) cell-induced PPARγ activity in macrophages caused increased PTEN levels, secreted in exosomes. ApoSQ-exposed CM from PTEN knockdown cells failed to enhance PTEN in recipient 344SQ cells, restore cellular polarity, and exert anti-EMT and anti-invasive effects. The CM which deficient of PPARγ ligands could not reverse the suppression of PPARγ activity and PTEN and consequently failed to the prevent EMT process. Moreover, single injection of ApoSQ cells inhibited lung metastasis in syngeneic mice with enhanced PPARγ/PTEN signaling both in tumor-associated macrophages and tumor cells. PPARγ antagonist GW9662 reversed PTEN signaling and anti-metastatic effect. Thus, apoptotic cancer cell therapy may offer a new strategy for the prevention of metastasis.
Eco-evolutionary dynamics in metacommunities: ecological inheritance, helping within- and harming between-species
Authors: Mullon Charles , Lehmann Laurent 
Published: November 2017

AbstractUnderstanding selection on intra- and inter-specific interactions that take place in dispersal-limited communities is a challenge for ecology and evolutionary biology. The problem is that local demographic stochasticity generates eco-evolutionary dynamics that are generally too complicated to make tractable analytical investigations. Here, we circumvent this problem by approximating the selection gradient on a quantitative trait that influences local community dynamics, assuming that such dynamics are deterministic with a stable fixed point. We nonetheless incorporate unavoidable kin selection effects arising from demographic stochasticity. Our approximation reveals that selection depends on how an individual expressing a trait-change influences: (1) its own fitness and the fitness of its current relatives; and (2) the fitness of its downstream relatives through modifications of local ecological conditions (i.e., through ecological inheritance). Mathematically, the effects of ecological inheritance on selection are captured by dispersal-limited versions of press-perturbations of community ecology. We use our approximation to investigate the evolution of helping within- and harming between-species when these behaviours influence demography. We find that individually costly helping evolves more readily when intra-specific competition is for material resources rather than for space because in this case, the costs of kin competition are paid by downstream relatives. Similarly, individually costly harming between species evolves when it alleviates downstream relatives from inter-specific competition. Beyond these examples, our approximation can help better understand the influence of ecological inheritance on a variety of eco-evolutionary dynamics in metacommunities, from consumer-resource and predator-prey coevolution to selection on mating systems with demographic feedbacks.
Diversification of heart progenitor cells by EGF signaling and differential modulation of ETS protein activity
Authors: Schwarz Benjamin , Hollfelder Dominik , Scharf Katharina , Hartmann Leonie , Reim Ingolf 
Published: November 2017

AbstractFor coordinated circulation, vertebrate and invertebrate hearts require stereotyped arrangements of diverse cell populations. This study explores the process of cardiac cell diversification in theDrosophilaheart, focusing on the two major cardioblast subpopulations: generic working myocardial cells and inflow valve-forming ostial cardioblasts. By screening a large collection of randomly induced mutants we identified several genes involved in cardiac patterning. Further analysis revealed an unexpected, specific requirement of EGF signaling for the specification of generic cardioblasts and a subset of pericardial cells. We demonstrate that the Tbx20 ortholog Midline acts as a direct target of the EGFR effector Pointed to repress ostial fates. Furthermore, we identified Edl/Mae, an antagonist of the ETS factor Pointed, as a novel cardiac regulator crucial for ostial cardioblast specification. Combining these findings we propose a regulatory model in which the balance between activation of Pointed and its inhibition by Edl controls cardioblast subtype-specific gene expression.
A repetitive mutation and selection system for bacterial evolution to increase the specific affinity to pancreatic cancer cells
Authors: Osawa Masaki 
Published: November 2017

AbstractIt is difficult to target and kill cancer cells. One possible approach is to mutate bacteria to enhance their binding to cancer cells. In this study, Gram-negative bacteria Escherichia coli and Gram-positive bacteria Bacillus subtilis were randomly mutated, and then were positively and negatively selected for binding cancer and normal cells. With repetitive mutation and selection both bacteria successfully evolved to increase affinity to the pancreatic cancer cell line (Mia PaCa-2) but not normal cells (HPDE: immortalized human pancreatic ductal epithelial cell line). The mutant E. coli and B. subtilis strains could bind to Mia PaCa-2 cells about 10 and 25 times more than to HPDE cells. The selected E. coli, strain had mutations in biofilm-related genes and the regulatory region for a type I pilus gene. Consistent with type I pili involvement, mannose could inhibit the binding to cells. However, the results suggest that weak but specific binding is involved in the initial step of adhesion. To kill Mia PaCa-2 cells, hemolysin was expressed in the mutant strain. The hemolysin that was released from the mutant strain could kill Mia PaCa-2 cells. This type of mutation/selection strategy may be applicable to other combinations of cancer cells and bacterial species.
L-tyrosine supplementation is not therapeutic for skeletal muscle dysfunction in zebrafish and mouse models of dominant skeletal muscle α-actin nemaline myopathy
Authors: Messineo Adriana M. , Gineste Charlotte , Sztal Tamar E. , McNamara Elyshia L. , Vilmen Christophe , Ogier Augustin C. , Hahne Dorothee , Bendahan David , Laing Nigel G. , Bryson-Richardson Robert J. , Gondin Julien , Nowak Kristen J. 
Published: November 2017

ABSTRACTNemaline myopathy (NM) is a skeletal muscle disorder with no curative treatment. Although L-tyrosine administration has been indicated to provide benefit to patients, previous studies have been limited due to sample size or not testing for raised L-tyrosine levels. We evaluated the efficacy of L-tyrosine treatment to improve skeletal muscle function in three animal models of NM caused by skeletal muscle α-actin (ACTA1) mutations. Firstly we determined the maximum safest L-tyrosine concentration for inclusion in the water of wildtype zebrafish. We then treated NM TgACTA1D286G-eGFPzebrafish from 24 hours post fertilization with the highest safe L-tyrosine dose (10 µM). At 6 days post fertilization, no significant improvement was detected in skeletal muscle function (swimming distance). We also determined the highest safe L-tyrosine dose for dietary L-tyrosine supplementation to wildtype mice. Next we treated the NM TgACTA1D286Gmouse model continuously from preconception with 2% L-tyrosine supplemented to regular feed. We examined skeletal muscles at 6–7 weeks using indicators of skeletal muscle integrity: bodyweight, voluntary running wheel and rotarod performance, all parameters previously shown to be reduced in TgACTA1D286Gmice. The L-tyrosine treatment regime did not result in any improvement of these parameters, despite significant elevation of free L-tyrosine levels in sera (57%) and quadriceps muscle (45%) of treated TgACTA1D286Gmice. Additionally, we assessed the effects of 4 weeks of 2% L-tyrosine dietary supplementation on skeletal muscle function of older (6-7 month old) NM TgACTA1D286Gand KIActa1H40Ymice. This dosing regime did not improve decreased bodyweight, nor the mechanical properties, energy metabolism, or atrophy of skeletal muscles in these NM models. Together these findings demonstrate that with the treatment regimes and doses evaluated, L-tyrosine does not therapeutically modulate dysfunctional skeletal muscles in NM animal models with dominantACTA1mutations. Therefore this study yields important information on aspects of the clinical utility of L-tyrosine forACTA1NM.Summary statementDespite previous encouraging reports, this study utilising zebrafish and mouse models of nemaline myopathy shows no therapeutic benefit on skeletal muscle functionality in response to L-tyrosine supplementation.
A synergistic transcriptional regulation of olfactory genes derives complex behavioral responses in the mosquito Anopheles culicifacies
Authors: De Tanwee Das , Thomas Tina , Verma Sonia , Singla Deepak , Rawal Charu , Srivastava Vartika , Sharma Punita , Kumari Seena , Tevatiya Sanjay , Rani Jyoti , Hasija Yasha , Pandey Kailash C , Dixit Rajnikant 
Published: November 2017

AbstractDecoding the molecular basis of host seeking and blood feeding behavioral evolution/adaptation in the adult female mosquito may provide an opportunity to design new molecular strategy to disrupt human-mosquito interactions. However, despite the great progress in the field of mosquito olfaction and chemo-detection, little is known that how the sex-specific specialization of the olfactory system enables adult female mosquitoes to derive and manage complex blood feeding associated behavioral responses. A comprehensive RNAseq analysis of prior and post blood meal olfactory system of An. culicifacies mosquito revealed that a minor but unique change in the nature and regulation of key olfactory genes play a pivotal role in managing diverse behavioral responses. Age dependent transcriptional profiling demonstrated that adult female mosquito’s chemosensory system gradually learned and matured to drive the host-seeking and blood feeding behavior at the age of 5-6 days. A zeitgeber time scale expression analysis of Odorant Binding Proteins (OBPs) unravels unique association with a late evening to midnight peak biting time. Blood meal-induced switching of unique sets of OBP genes and Odorant Receptors (ORs) expression coincides with the change in the innate physiological status of the mosquitoes. Blood meal follows up experiments provide enough evidence that how a synergistic and concurrent action of OBPs-ORs may drive ‘prior and post blood meal’ complex behavioral events. Finally, tissue-specific gene expression analysis and molecular modelling predicted two uncharacterized novel sensory appendages proteins (SAP-1 & SAP2) unique to An. culicifacies mosquito and may play a central role in the host-seeking behavior.SignificanceEvolution and adaptation of blood feeding behavior not only favored the reproductive success of adult female mosquito but also make them an important disease vectors. Immediately after emergence, an environmental exposure may favor the broadly tuned olfactory system of mosquitoes to derive complex behavioral responses. But, how these olfactory derived genetic factors manage female specific ‘pre and post’ blood meal associated complex behavioral responses are not well known. We unraveled synergistic actions of olfactory factors governs an innate to prime learning strategy to facilitate rapid blood meal acquisition and downstream behavioral activities. A species-specific transcriptional profiling and an in-silico analysis predict novel ‘sensory appendages protein’, as a unique target to design disorientation strategy against the mosquito Anopheles culicifacies.
Microglia dysfunction caused by the loss of Rhoa disrupts neuronal physiology and leads to neurodegeneration
Authors: Socodato Renato , Portugal Camila C. , Canedo Teresa , Rodrigues Artur , Almeida Tiago O. , Henriques Joana F. , Vaz Sandra H. , Magalhães João , Silva Cátia M. , Baptista Filipa I. , Alves Renata L. , Coelho-Santos Vanessa , Silva Ana Paula , Paes-de-Carvalho Roberto , Magalhães Ana , Brakebusch Cord , Sebastião Ana M. , Summavielle Teresa , Ambrósio António F. , Relvas João B. 
Published: November 2017

AbstractNervous tissue homeostasis requires regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation of the small GTPase Rhoa in adult microglia is sufficient to trigger spontaneous microglia activation producing a neurological phenotype (including synapse and neuron loss, impairment of LTP, formation of ß-amyloid plaques and memory deficits). Mechanistically, loss of Rhoa in microglia triggers Src activation and Src-mediated Tnf production, leading to excitotoxic glutamate secretion. Inhibiting Src in microglia Rhoa-deficient mice attenuates microglia dysregulation and the ensuing neurological phenotype. We also found that the Rhoa/Src signaling pathway was disrupted in microglia of the APP/PS1 mouse model of Alzheimer’s disease and that low doses of Aß oligomers triggered microglia neurotoxic polarization through the disruption of Rhoa-to-Src signaling. Overall, our results indicate that disturbing RhoGTPase signaling in microglia can directly cause neurodegeneration.
Robustness of early warning signals for catastrophic and non-catastrophic transitions
Authors: Dutta Partha Sharathi , Sharma Yogita , Abbott Karen C. 
Published: November 2017

AbstractEarly warning signals (EWS) are statistical indicators that a rapid regime shift may be forthcoming. Their development has given ecologists hope of predicting rapid regime shifts before they occur. Accurate predictions, however, rely on the signals being appropriate to the system in question. Most of the EWS commonly applied in ecology have been studied in the context of one specific type of regime shift (the type brought on by a saddle-node bifurcation, at which one stable equilibrium point collides with an unstable equilibrium and disappears) under one particular perturbation scheme (temporally uncorrelated noise that perturbs the net population growth rate in a density independent way). Whether and when these EWS can be applied to other ecological situations remains relatively unknown, and certainly underappreciated. We study a range of models with different types of dynamical transitions (including rapid regime shifts) and several perturbation schemes (density-dependent uncorrelated or temporally-correlated noise) and test the ability of EWS to warn of an approaching transition. We also test the sensitivity of our results to the amount of available pre-transition data and various decisions that must be made in the analysis (i.e. the rolling window size and smoothing bandwidth used to compute the EWS). We find that EWS generally work well to signal an impending saddle-node bifurcation, regardless of the autocorrelation or intensity of the noise. However, EWS do not reliably appear as expected for other types of transition. EWS were often very sensitive to the length of the pre-transition time series analyzed, and usually less sensitive to other decisions. We conclude that the EWS perform well for saddle-node bifurcation in a range of noise environments, but different methods should be used to predict other types of regime shifts. As a consequence, knowledge of the mechanism behind a possible regime shift is needed before EWS can be used to predict it.
High fidelity lineage tracing in mouse pre-implantation embryos using primed conversion of photoconvertible proteins
Authors: Welling Maaike , Mohr Manuel Alexander , Ponti Aaron , Sabater Lluc Rullan , Boni Andrea , Liberali Prisca , Pelczar Pawel , Pantazis Periklis 
Published: November 2017

AbstractAccurate lineage reconstruction of mammalian pre-implantation development is essential for inferring the earliest cell fate decisions of mammalian development. Lineage tracing using global labeling techniques is complicated by increasing cell density and rapid embryo rotation, impeding automatic alignment and rendering accurate cell tracking of obtained four-dimensional imaging data sets highly challenging. Here, we exploit the advantageous properties of primed convertible fluorescent proteins (pr-pcFPs) to simultaneously visualize the global green and the photoconverted red population to minimize tracking uncertainties over prolonged time windows. Confined primed conversion of H2B-pr-mEosFP labeled nuclei combined with light-sheet imaging greatly facilitates segmentation, classification, and tracking of individual nuclei from the 4-cell stage up to the blastocyst. Using green and red labels as fiducial markers, we computationally correct for rotational and translational drift and accomplish high fidelity lineage tracing combined with a reduced data size – addressing majors concerns in the field of volumetric embryo imaging.