bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancestral diet leads to dynamic transgenerational plasticity for five generations in Drosophila melanogaster
Authors: Emborski Carmen , Mikheyev Alexander S 
Published: March 2018

AbstractAncestral exposures can influence phenotypic expression in subsequent generations, which influence diverse biological processes ranging from phenotypic plasticity to obesity. Currently, most transgenerational studies work under the assumption of transgenerational response stability and reproducibility through time and across exposure differences, relying on short-term (i.e. 2-3 generations) single-exposure experiments. Yet, little evidence exists in the literature to validate this assumption, leaving the consistency and reliability of interpretations in question. Additionally, as most studies have focused on proximal mechanistic (‘how’) rather than ultimate evolutionary (‘why’) questions, the interpretations of observed responses and broader evolutionary implications remain unclear. In the current study, we begin to address these gaps by analyzing the transgenerational effects of three dietary sugar concentrations (i.e. no, low, and high) relative to controls on body composition (i.e. whole body fat and sugar concentrations) and reproduction (i.e. lifetime fitness) over five generations in both males and females. We found that the changes in ancestral diet led to complex transgenerational body composition and fitness fluctuations relative to control offspring responses, despite the conformity of the treatments to a control diet in the F1-F5 generations. Interestingly, the direction of response frequently changed from generation to generation, and as a function of ancestral exposures and sex. These fluctuating response findings have not been documented previously, and were broadly consistent in both our pilot and main experiments. Our results highlight the dynamic and multifaceted nature of transgenerational plasticity, and provide some of the first evidence that transgenerational response stability may not be universally valid.Summary StatementAlterations in ancestral dietary sugar transgenerationally influences body composition and fitness in Drosophila melanogaster, leading to fluctuating responses relative to controls over five generations following exposure.
Blimp-1 mediates tracheal lumen maturation in Drosophila melanogaster
Authors: Öztürk-Çolak Arzu , Stephan-Otto Attolini Camille , Casanova Jordi , Araújo Sofia J. 
Published: March 2018

AbstractThe specification of tissue identity during embryonic development requires precise spatiotemporal coordination of gene expression. Many transcription factors required for the development of organs have been identified and their expression patterns are known; however, the mechanisms through which they coordinate gene expression in time remain poorly understood. Here we show that hormone-induced transcription factor Blimp-1 participates in the temporal coordination of tubulogenesis in Drosophila melanogaster by regulating the expression of many genes involved in tube maturation. In particular, we demonstrate that Blimp-1 regulates the expression of genes involved in chitin deposition and F-actin organization. We show that Blimp-1 is involved in the temporal control of lumen maturation by regulating the beginning of chitin deposition. We also report that Blimp-1 represses a variety of genes involved in tracheal maturation. Finally, we reveal that the kinase Btk29A serves as a link between Blimp-1 transcriptional repression and apical extra-cellular matrix organization.
The Mathematics of Descriptions in Descriptive Epidemiology
Authors: Ozonoff David , Pogel Alex 
Published: March 2018

AbstractIdentifying patterns of disease distribution in a population is the task of descriptive epidemiology, where the patterns are descriptions of how the disease is distributed in the population. In everyday public health practice it is descriptive epidemiology that is hard at work when we inform the public about health problems, monitor its health status, gather information for planning and administrative purposes, or generate hypotheses to be tested by further analytic investigations. In this paper we pursue a formalization of the population descriptions that are the heart of descriptive epidemiology. We call attention to a fact, so far unrecognized by epidemiologists, that the set of (complete) population descriptions, suitably defined, has an associated relational and algebraic structure. This formalization allows us to access mathematical properties of this structure of an epidemiologic dataset with methods developed over the past 30 years.
A Sentence Supramodal Areas Atlas (Sensaas) Based on Multiple Task-Induced Activation Mapping and Graph Analysis of Intrinsic Connectivity in 144 Healthy Right-Handers
Authors: Labache L , Joliot M , Saracco J , Jobard G , Hesling I , Zago L , Mellet E , Petit L , Crivello F , Mazoyer B , Tzourio-Mazoyer N 
Published: March 2018

AbstractWe herein propose an atlas of 32 sentence-related areas based on a 3-step method combining the analysis of activation and asymmetry during multiple language tasks with hierarchical clustering of resting-state connectivity and graph analyses. 144 healthy right-handers performed fMRI runs based on language production, reading and listening, both with sentences and lists of over-learned words. Sentence minus word-list BOLD contrast and left-minus-right BOLD asymmetry for each task were computed in pairs of homotopic regions of interest (hROIs) from the AICHA atlas. Thirty-two hROIs were identified that were conjointly activated and leftward asymmetrical in each of the 3 language contrasts. Analysis of resting- state temporal correlations of BOLD variations between these 32 hROIs allowed the segregation of a core network, SENT_CORE including 18 hROIs. Resting-state graph analysis applied to SENT_CORE hROIs revealed that the pars triangularis of the inferior frontal gyrus and the superior temporal sulcus were hubs based on their degree centrality, betweenness, and participation values, corresponding to epicentres of sentence processing. Positive correlations between DC and BOLD activation values for SENT_CORE hROIs were observed across individuals and across regions regardless of the task: the more a SENT_CORE area is connected at rest the stronger it is activated during sentence processing. DC measurements in SENT_CORE may thus be a valuable index for the evaluation of inter-individual variations in language areas functional activity in relation to anatomical or clinical patterns in large populations. SENSAAS (SENtence Supramodal Areas AtlaS), comprising the 32 supramodal sentence areas, including SENT-CORE network, can be downloaded at http://www.gin.cnrs.fr/en/tools/.
MicroRNAs as potential therapeutics to enhance chemosensitivity in advanced prostate cancer
Authors: Lin Hui-Ming , Nikolic Iva , Yang Jessica , Castillo Lesley , Deng Niantao , Chan Chia-Ling , Yeung Nicole K. , Dodson Eoin , Elsworth Benjamin , Spielman Calan , Lee Brian Y. , Boyer Zoe , Simpson Kaylene J. , Daly Roger J. , Horvath Lisa G. , Swarbrick Alexander 
Published: March 2018

AbstractDocetaxel and cabazitaxel are taxane chemotherapy treatments for metastatic castration-resistant prostate cancer (CRPC). However, therapeutic resistance remains a major issue. MicroRNAs are short non-coding RNAs that can silence multiple genes, regulating several signalling pathways simultaneously. Therefore, synthetic microRNAs may have therapeutic potential in CRPC by regulating genes involved in taxane response and minimise compensatory mechanisms that cause taxane resistance. To identify microRNAs that can improve the efficacy of taxanes in CRPC, we performed a genome-wide screen of 1280 microRNAs in the CRPC cell lines PC3 and DU145 in combination with docetaxel or cabazitaxel treatment. Mimics of miR-217 and miR-181b-5p enhanced apoptosis significantly in PC3 cells in the presence of these taxanes. These mimics downregulated at least a thousand different transcripts, which were enriched for genes with cell proliferation and focal adhesion functions. Individual knockdown of a selection of 46 genes representing these transcripts resulted in toxic or taxane sensitisation effects, indicating that these genes may be mediating the effects of the microRNA mimics. A range of these genes are expressed in CRPC metastases, suggesting that these microRNA mimics may be functional in CRPC. With further development, these microRNA mimics may have therapeutic potential to improve taxane response in CRPC patients.
Dazl regulates germ cell survival through a network of polyA-proximal mRNA interactions
Authors: Zagore Leah L. , Sweet Thomas J. , Hannigan Molly M. , Weyn-Vanhentenryck Sebastien M. , Jobava Raul , Hatzoglou Maria , Zhang Chaolin , Licatalosi Donny D. 
Published: March 2018

SummaryThe RNA binding protein Dazl is essential for gametogenesis, but its direct in vivo functions, RNA targets, and the molecular basis for germ cell loss in DAZL null mice are unknown. Here, we mapped transcriptome-wide Dazl-RNA interactions in vivo, revealing Dazl binding to thousands of mRNAs via polyA-proximal 3’UTR interactions. In parallel, fluorescence activated cell sorting and RNA-Seq identified mRNAs sensitive to Dazl deletion in male germ cells. Despite binding a broad set of mRNAs, integrative analyses indicate that Dazl post-transcriptionally controls only a subset of its mRNA targets, namely those corresponding to a network of genes critical for germ cell proliferation and survival. Additionally, we provide evidence that polyA sequences have key roles in specifying Dazl-RNA interactions across the transcriptome. Altogether, our results reveal a mechanism for Dazl-RNA binding, and illustrate that Dazl functions as a master regulator of a post-transcriptional mRNA program essential for germ cell survival.
Transcription factor TAp73 and microRNA-449 complement each other to support multiciliogenesis
Authors: Wildung Merit , Esser Tilman Uli , Grausam Katie Baker , Wiedwald Cornelia , Volceanov-Hahn Larisa , Riedel Dietmar , Beuermann Sabine , Li Li , Zylla Jessica , Guenther Ann-Kathrin , Wienken Magdalena , Ercetin Evrim , Han Zhiyuan , Bremmer Felix , Shomroni Orr , Andreas Stefan , Zhao Haotian , Lizé Muriel 
Published: March 2018

AbstractMotile cilia serve vital functions in development, homeostasis and regeneration. We recently demonstrated that TAp73 is an essential transcriptional regulator of respiratory multiciliogenesis. Here, we show that TAp73 is expressed in multiciliated cells (MCCs) of diverse tissues. Analysis of TAp73 mutant animals revealed that TAp73 regulates Foxj1, Rfx2, Rfx3, axonemal dyneins Dnali1 and Dnai1, plays a pivotal role in the generation of MCCs in male and female reproductive ducts, and contributes to fertility. However, the function of MCCs in the brain appears to be preserved despite the loss of TAp73, and robust activity of cilia-related networks is maintained in the absence of TAp73. Notably, TAp73 loss leads to distinct changes in ciliogenic microRNAs: miR34bc expression is reduced, whereas the miR449 cluster is induced in diverse multiciliated epithelia. Among different MCCs, choroid plexus (CP) epithelial cells in the brain display prominent miR449 expression, whereas brain ventricles exhibit significant increase in miR449 levels along with an increase in the activity of ciliogenic E2F4/MCIDAS circuit in TAp73 mutant animals. Conversely, E2F4 induces robust transcriptional response from miR449 genomic regions. To address whether increased miR449 levels in the brain maintain the multiciliogenesis program in the absence of TAp73, we deleted both TAp73 and miR449 in mice. Although loss of miR449 alone led to a mild ciliary defect in the CP, more pronounced ciliary defects and hydrocephalus were observed in the brain lacking both TAp73 and miR449. In contrast, miR449 loss in other MCCs failed to enhance ciliary defects associated with TAp73 loss. Together, our study shows that, in addition to the airways, TAp73 is essential for generation of MCCs in male and female reproductive ducts, whereas miR449 and TAp73 complement each other to support multiciliogenesis and CP development in the brain.
A Comprehensive Mathematical Model of Surface Electromyography and Force Generation
Authors: Petersen Eike , Rostalski Philipp 
Published: March 2018

The purpose of this article is to provide a unified description of a comprehensive mathematical model of surface electromyographic (EMG) measurements and the corresponding force signal in skeletal muscles. The model comprises motor unit pool organization, recruitment and rate coding, intracellular action potential generation and the resulting EMG measurements, as well as the generated muscular force during voluntary isometric contractions. It consolidates and extends the results of several previous publications that proposed mathematical models for the individual model components. A parameterization of the electrical and mechanical components of the model is proposed that ensures a physiologically meaningful EMG-force relation in the simulated signals. Moreover, a novel nonlinear transformation of the excitation model input is proposed, which ensures that the model force output equals the desired target force. Finally, an alternative analytical formulation of the EMG model is proposed, which renders the physiological meaning of the model more clear and facilitates a mathematical proof that muscle fibers in this model at no point in time represent a net current source or sink.Neuromuscular physiology is a vibrant research field that has recently seen exciting advances. Many previous publications have focused on thorough analyses of particular aspects of neuromuscular physiology, yet an integration of the various novel findings into a single, comprehensive model is missing. A consistent description of a complete physiological model as presented here, including thorough justification of model component choices, will facilitate the use of these advanced models in future research. Results of a numerical simulation highlight the model’s capability to reproduce many physiological effects observed in experimental measurements, and to produce realistic synthetic data that are useful for the validation of signal processing algorithms. The model is based on recent advances in the understanding of muscular physiology and hence also applicable for analyzing the influence of various physiological and measurement setup parameters on the measured force and EMG signals.
DoesBorrelia burgdorferisensu lato facilitate the colonisation of marginal habitats byIxodes ricinus? A correlative study in the Swiss Alps
Authors: Lemoine Mélissa , Cornetti Luca , Tschirren Barbara 
Published: March 2018

AbstractParasites can alter host and vector phenotype and thereby affect ecological processes in natural populations. Laboratory studies have shown thatBorrelia burgdorferisensu lato, the causative agent of human Lyme borreliosis, induces physiological alterations in its main tick vector in Europe,Ixodes ricinus, which increase its survival under challenging conditions. We hypothesise that these phenotypic alterations may allowI. ricinusto colonise marginal habitats, thereby fuelling the ongoing range expansion ofI. ricinustowards higher elevations and latitudes induced by climate change. To explore the potential for such an effect under natural conditions, we studied the prevalence ofB. burgdorferis.l. in questingI. ricinusand its variation with elevation in the Swiss Alps. We screened forB. burgdorferis.l. infection in questing nymphs ofI. ricinus(N = 411) from 15 sites between 528 and 1774 m.a.s.l to test ifB. burgdorferis.l. prevalence is higher at high elevations (i.e. in marginal habitats). We found thatB. burgdorferis.l. prevalence inI. ricinusnymphs decreased linearly with increasing elevation and that it was 12.6% lower inI. ricinusnymphs collected at high elevations compared to nymphs in the core range. Thus, we found no evidence that theB. burgdorferis.l.-induced alterations ofI. ricinusphenotype facilitate the colonisation of marginal habitats in the wild. These findings have implications for a better understanding of eco-evolutionary processes in natural host-parasite systems, as well as the assessment of Lyme borreliosis risk in regions whereI. ricinusis newly emerging.
How optimal foragers should respond to habitat changes? On the consequences of habitat conversion
Authors: Calcagno Vincent , Hamelin Frédéric , Mailleret Ludovic , Grognard Frédéric 
Published: March 2018

AbstractThe Marginal Value Theorem (MVT) provides a framework to predict how habitat modifications related to the distribution of resources over patches should impact the realized fitness of individuals and their optimal rate of movement (or patch residence times) across the habitat. Most MVT theory has focused on the consequences of changing the shape of the gain functions in some patches, describing for instance patch enrichment. However an alternative form of habitat modification is habitat conversion, whereby patches are converted from one existing type to another (e.g. closed habitat to open habitat). In such a case the set of gain functions existing in the habitat does not change, only their relative frequencies does. This has received comparatively very little attention in the context of the MVT. Here we analyze mathematically the consequences of habitat conversion under the MVT. We study how realized fitness and the average rate of movement should respond to changes in the frequency distribution of patch-types, and how they should covary. We further compare the response of optimal and non-plastic foragers. We find that the initial pattern of patch-exploitation in a habitat, characterized by the regression slope of patch yields over residence times, can help predict the qualitative responses of fitness and movement rate following habitat conversion. We also find that for some habitat conversion patterns, optimal and non-plastic foragers exhibit qualitatively different responses, and that adaptive foragers can have opposite responses in the early and late phases following habitat conversion. We suggest taking into account behavioral responses may help better understand the ecological consequences of habitat conversion.
SpiceRx: an integrated resource for the health impacts of culinary spices and herbs
Authors: Nk Rakhi , Tuwani Rudraksh , Garg Neelansh , Mukherjee Jagriti , Bagler Ganesh 
Published: March 2018

AbstractSpices and herbs are key dietary ingredients used in cuisines across the world. They have been reported to be of medicinal value for a wide variety of diseases through a large body of biomedical investigations. Bioactive phytochemicals in these plant products form the basis of their therapeutic potential as well as adverse effects. A systematic compilation of empirical data involving these aspects of culinary spices and herbs could help unravel molecular mechanisms underlying their effects on health.SpiceRx provides a platform for exploring the health impact of spices and herbs used in food preparations through a structured database of tripartite relationships with their phytochemicals and disease associations. Starting with an extensive dictionary of culinary spices and herbs, their disease associations were text mined from MEDLINE, the largest database of biomedical abstracts, assisted with manual curation. This information was further combined with spice-phytochemical and phytochemical-disease associations. SpiceRx is an integrated repertoire of evidence-based knowledge pertaining to the health impacts of culinary spices and herbs, and facilitates their disease-specific culinary recommendations as well as exploration of molecular mechanisms underlying their health effects.Availability and ImplementationSpiceRx is available at http://cosylab.iiitd.edu.in/spicerx and supports all modern browsers. SpiceRx is implemented with Python web development framework Django and relational database PostgreSQL; the front-end was built using HTML, CSS, JavaScript, AJAX, jQuery, JSME Molecular Editor, Bootstrap, Jmol, DataTables and Google Charts.Supplementary informationSupplementary data are available at Bioinformatics online.
Mapping Local Conformational Landscapes of Proteins in Solution
Authors: ElGamacy M. , Riss M. , Zhu H. , Truffault V. , Coles M. 
Published: March 2018

SummaryThe ability of proteins to adopt multiple conformational states is essential to their function and elucidating the details of such diversity under physiological conditions has been a major challenge. Here we present a generalized method for mapping protein population landscapes by NMR spectroscopy. Experimental NOESY spectra are directly compared to a set of expectation spectra back-calculated across an arbitrary conformational space. Signal decomposition of the experimental spectrum then directly yields the relative populations of local conformational microstates. In this way, averaged descriptions of conformation can be eliminated. As the method quantitatively compares experimental and expectation spectra, it inherently delivers an R-factor expressing how well structural models explain the input data. We demonstrate that our method extracts sufficient information from a single 3D NOESY experiment to perform initial model building, refinement and validation, thus offering a complete de novo structure determination protocol.
IFNβ and TNFα cooperate to induce a STAT1-independent antiviral and immunoregulatory program via non-canonical STAT2 and IRF9 pathways
Authors: Mariani Mélissa K. , Dasmeh Pouria , Fortin Audray , Caron Elise , Kalamujic Mario , Harrison Alexander N. , Kasumba Dacquin M. , Cervantes-Ortiz Sandra , Mukawera Espérance , Serohijos Adrian W.R. , Grandvaux Nathalie 
Published: March 2018

ABSTRACTIFNβ typically induces an antiviral and immunoregulatory transcriptional program through the activation of ISGF3 (STAT1, STAT2 and IRF9) transcriptional complexes. The response to IFNβ is context-dependent and is prone to crosstalk with other cytokines, such as TNFα IFNβ and TNFα synergize to drive a specific delayed transcriptional program. Previous observation led to the hypothesis that an alternative STAT1-independent pathway involving STAT2 and IRF9 might be involved in gene induction by the combination of IFNβ and TNFα. Using genome wide transcriptional profiling by RNASeq, we found that the costimulation with IFNβ and TNFα induces a broad antiviral and immunoregulatory transcriptional program independently of STAT1. Additionally, STAT2 and IRF9 are involved in the regulation of only a subset of these STAT1-independent genes. Consistent with the growing literature, STAT2 and IRF9 act in concert to regulate a subgroup of these genes. Unexpectedly, STAT2 and IRF9 were also engaged in specific independent pathways to regulate distinct sets of IFNβ and TNFα-induced genes. Altogether these observations highlight the existence of distinct previously unrecognized non-canonical STAT1-independent, but STAT2 and/or IRF9-dependent pathways in the establishment of a delayed antiviral and immunoregulatory transcriptional program in conditions where elevated levels of both IFNβ and TNFα are present.
GiraFFe Browse: A lightweight web based tool for inspecting GFF and FASTA data
Authors: Garland Owen , Clare Amanda , Aubrey Wayne 
Published: March 2018

AbstractSummaryGiraFFe Browse is a tool aimed at making GFF and FASTA data more useful and accessible to researchers. Existing solutions are large in scope and difficult to maintain without specialist knowledge of computer systems. GiraFFe Browse is a lightweight alternative, built using modern software engineering practices with a focus on being developer and user friendly.Availability and implementationGiraFFe Browse is open source (GPL) software that is available from the Github repository: https://github.com/bag-man/giraffe-browseDemo versionAn example installation of the application is available at http://giraffe.owen.cymru, using a GFF and FASTA file of Escherichia coli from the European Nucleotide Archive.Contactgarland.owen@gmail.com