bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic variation in mitochondrial function across New Zealand snail populations
Authors: Greimann Emma S. , Ward Samuel F. , Woodell James D. , Hennessey Samantha , Kline Michael R. , Moreno Jorge A. , Peters Madeline , Cruise Jennifer L. , Montooth Kristi L. , Neiman Maurine , Sharbrough Joel 
Published: December 2017

ABSTRACTMitochondrial function is critical for energy homeostasis and should shape how genetic variation in metabolism is transmitted through levels of biological organization to generate stability in organismal performance. Mitochondrial function is encoded by genes in two distinct and separately inherited genomes – the mitochondrial genome and the nuclear genome – and selection is expected to maintain functional mito-nuclear interactions. Nevertheless, high levels of polymorphism in genes involved in these mito-nuclear interactions and variation for mitochondrial function are nevertheless frequently observed, demanding an explanation for how and why variability in such a fundamental trait is maintained.Potamopyrgus antipodarumis a New Zealand freshwater snail with coexisting sexual and asexual individuals and, accordingly, contrasting systems of separate vs. co-inheritance of nuclear and mitochondrial genomes. As such, this snail provides a powerful means to dissect the evolutionary and functional consequences of mito-nuclear variation. The lakes inhabited byP. antipodarumspan wide environmental gradients, with substantial across-lake genetic structure and mito-nuclear discordance. This situation allows us to use comparisons across reproductive modes and lakes to partition variation in cellular respiration across genetic and environmental axes. Here, we integrated cellular, physiological, and behavioral approaches to quantify variation in mitochondrial function across a diverse set of wildP. antipodarumlineages. We found extensive across-lake variation in organismal oxygen consumption, mitochondrial membrane potential, and behavioral response to heat stress, but few global effects of reproductive mode or sex. Taken together, our data set the stage for applying this important model system for sexual reproduction and polyploidy to dissecting the complex relationships between mito-nuclear variation, performance, plasticity, and fitness in natural populations.
Legionellaprotection and vaccination mediated by Mucosal Associated Invariant T (MAIT) cells
Authors: Wang Huimeng , D’Souza Criselle , Lim Xin Yi , Kostenko Lyudmila , Pediongco Troi J , Eckle Sidonia BG , Meehan Bronwyn S , Wang Nancy , Li Shihan , Liu Ligong , Mak Jeffrey YW , Fairlie David P , Iwakura Yoichiro , Gunnersen Jennifer M , Stent Andrew W , Rossjohn Jamie , Westall Glen P , Kjer-Nielsen Lars , Strugnell Richard A , McCluskey James , Corbett Alexandra J , Hinks Timothy SC , Chen Zhenjun 
Published: December 2017

AbstractMucosal associated invariant T (MAIT) cells recognize conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defense, yet their roles in protection against clinically significant pathogens are unknown. MurineLegionellainfection induced MR1-dependent MAIT cell activation and rapid pulmonary accumulation of MAIT cells associated with immune protection detectable in fully immunocompetent host animals. MAIT cell protection was more evident in mice lacking CD4+ cells, whilst profoundly immunodeficient RAG2−/−γC−/−mice were substantially rescued from uniformly lethalLegionellainfection by adoptively-transferred MAIT cells. This protection was dependent on MR1, IFN-γ and GM-CSF, but not IL-17, TNF-α or perforin. Protection was enhanced and observed earlier post-infection in mice that were Ag-primed to boost MAIT cells before infection. Our findings define a significant role for MAIT cells in protection against a major human pathogen and indicate a potential role for vaccination to enhance MAIT cell immunity.
The role of explicit strategies during reinforcement-based motor learning
Authors: Holland Peter , Codol Olivier 
Published: December 2017

AbstractDespite increasing interest in the role of reward in motor learning, the underlying mechanisms remain ill-defined. In particular, the relevance of explicit strategies to reward-based motor learning is unclear. To address this, we examined subject’s (n=30) ability to learn to compensate for a gradually introduced 25° visuomotor rotation with only reward-based feedback (binary success/failure). Only two-thirds of subjects (n=20) were successful at the maximum angle. The remaining subjects initially follow the rotation but after a variable number of trials begin to reach at an insufficiently large angle and subsequently return to near baseline performance (n=10). Furthermore, those that were successful accomplished this largely via the use of strategies, evidenced by a large reduction in reach angle when asked to remove any strategy they employed. However, both groups display a small degree of remaining retention even after the removal of strategies. All subjects made greater and more variable changes in reach angle following incorrect (unrewarded) trials. However, subjects who failed to learn showed decreased sensitivity to errors, even in the initial period in which they followed the rotation, a pattern previously found in Parkinsonian patients. In a second experiment, the addition of a secondary mental rotation task completely abolished learning (n=10), whilst a control group replicated the results of the first experiment (n=10). These results emphasize a pivotal role of strategy-use during reinforcement-based motor learning and the susceptibility of this form of learning to disruption has important implications for its potential therapeutic benefits.
pytc: a python package for analysis of Isothermal Titration Calorimetry experiments
Authors: Duvvuri Hiranmayi , Wheeler Lucas C. , Harms Michael J. 
Published: December 2017

AbstractHere we describe pytc, an open-source Python-package for global fits of thermodynamic models to multiple Isothermal Titration Calorimetry experiments. Key features include simplicity, the ability to implement new thermodynamic models, a robust maximum likelihood fitter, a fast Bayesian Markov-Chain Monte Carlo sampler, rigorous implementation, extensive documentation, and full cross-platform compatibility. pytc can be used as either a programming API or with a GUI. It is available for download at: https://github.com/harmslab/pytc.
Amplicon sequencing of the 16S-ITS-23S rRNA operon with long-read technology for improved phylogenetic classification of uncultured prokaryotes
Authors: Martijn Joran , Lind Anders E. , Spiers Ian , Juzokaite Lina , Bunikis Ignas , Vinnere Pettersson Olga , Ettema Thijs J.G 
Published: December 2017

AbstractAmplicon sequencing of the 16S rRNA gene is the predominant method to quantify microbial compositions of environmental samples and to discover previously unknown lineages. Its unique structure of interspersed conserved and variable regions is an excellent target for PCR and allows for classification of reads at all taxonomic levels. However, the relatively few phylogenetically informative sites prevent confident phylogenetic placements of novel lineages that are deep branching relative to reference taxa. This problem is exacerbated when only short 16S rRNA gene fragments are sequenced. To resolve their placement, it is common practice to gather more informative sites by combining multiple conserved genes into concatenated datasets. This however requires genomic data which may be obtained through relatively expensive metagenome sequencing and computationally demanding analyses. Here we develop a protocol that amplifies a large part of 16S and 23S rRNA genes within the rRNA operon, including the ITS region, and sequences the amplicons with PacBio long-read technology. We tested our method with a synthetic mock community and developed a read curation pipeline that reduces the overall error rate to 0.18%. Applying our method on four diverse environmental samples, we were able to capture near full-length rRNA operon amplicons from a large diversity of prokaryotes. Phylogenetic trees constructed with these sequences showed an increase in statistical support compared to trees inferred with shorter, Illumina-like sequences using only the 16S rRNA gene (250 bp). Our method is a cost-effective solution to generate high quality, near full-length 16S and 23S rRNA gene sequences from environmental prokaryotes.
Migration, acculturation, and the maintenance of between-group cultural variation
Authors: Mesoudi Alex 
Published: December 2017

AbstractHow do migration and acculturation (i.e. psychological or behavioral change resulting from migration) affect within- and between-group cultural variation? Here I answer this question by drawing analogies between genetic and cultural evolution. Population genetic models show that migration rapidly breaks down between-group genetic structure. In cultural evolution, however, migrants or their descendants can acculturate to local behaviors via social learning processes such as conformity, potentially preventing migration from eliminating between-group cultural variation. An analysis of the empirical literature on migration suggests that acculturation is common, with second and subsequent migrant generations shifting, sometimes substantially, towards the cultural values of the adopted society. Yet there is little understanding of the individual-level dynamics that underlie these population-level shifts. To explore this formally, I present models quantifying the effect of migration and acculturation on between-group cultural variation, for both neutral and costly cooperative traits. In the models, between-group cultural variation, measured using F statistics, is eliminated by migration and maintained by conformist acculturation. The extent of acculturation is determined by the strength of conformist bias and the number of demonstrators from whom individuals learn. Acculturation is countered by assortation, the tendency for individuals to preferentially interact with culturally-similar others. Unlike neutral traits, cooperative traits can additionally be maintained by payoff-biased social learning, but only in the presence of strong sanctioning institutions. Overall, the models show that surprisingly little conformist acculturation is required to maintain realistic amounts of between-group cultural diversity. While these models provide insight into the potential dynamics of acculturation and migration in cultural evolution, they also highlight the need for more empirical research into the individual-level learning biases that underlie migrant acculturation.
Application of Atlas of Cancer Signalling Network in pre-clinical studies
Authors: Gomez L. Cristobal Monraz , Kondratova Maria , Ravel Jean-Marie , Barillot Emmanuel , Zinovyev Andrei , Kuperstein Inna 
Published: December 2017

AbstractInitiation and progression of cancer involve multiple molecular mechanisms. The knowledge on these mechanisms is expanding and should be converted into guidelines for tackling the disease. We discuss here formalization of biological knowledge into a comprehensive resource Atlas of Cancer Signalling Network (ACSN) and Google Maps-based tool NaviCell that supports map navigation. The application of maps for omics data visualisation in the context of signalling maps is possible using NaviCell Web Service module and NaviCom tool for generation of network-based molecular portraits of cancer using multi-level omics data. We review how these resources and tools are applied for cancer pre-clinical studies among others for rationalizing synergistic effect of drugs and designing complex disease stage-specific druggable interventions following structural analysis of the maps together with omics data. Modules and maps of ACSN as signatures of biological functions, can help in cancer data analysis and interpretation. In addition, they can also be used to find association between perturbations in particular molecular mechanisms to the risk of a specific cancer type development. These approaches and beyond help to study interplay between molecular mechanisms of cancer, deciphering how gene interactions govern hallmarks of cancer in specific context. We discuss a perspective to develop a flexible methodology and a pipeline to enable systematic omics data analysis in the context of signalling network maps, for stratifying patients and suggesting interventions points and drug repositioning in cancer and other human diseases.
Macrophage-derived granulin drives resistance to immune checkpoint inhibition in metastatic pancreatic cancer
Authors: Quaranta Valeria , Rainer Carolyn , Nielsen Sebastian R. , Raymant Meirion , Ahmed Muhammad Shamsher , Engle Dannielle D. , Taylor Arthur , Murray Trish , Campbell Fiona , Palmer Daniel , Tuveson David A. , Mielgo Ainhoa , Schmid Michael C. 
Published: December 2017

AbstractThe ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumour microenvironment that suppresses and/or excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immuno-protective role of the metastatic tumour microenvironment in pancreatic cancer is not completely understood. In this study we find that macrophage-derived granulin contributes to cytotoxic CD8+ T cell exclusion in metastatic livers. Mechanistically, we find that granulin expression by macrophages is induced in response to colony stimulating factor-1. Genetic depletion of granulin reduces the formation a fibrotic stroma, thereby allowing T cell entry at the metastatic site. While metastatic PDAC tumours are largely resistant to anti-PD-1 therapy, blockade of PD-1 in granulin depleted tumours restored the anti-tumour immune defence and dramatically decreased metastatic tumour burden. These findings suggest that targeting granulin may serve as a potential therapeutic strategy to restore CD8+ T cell infiltration in metastatic PDAC, thereby converting PDAC metastatic tumours, which are refractory to immune checkpoint inhibitors, into tumours that respond to immune checkpoint inhibition therapies.
The IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation
Authors: Pramanik Jhuma , Chen Xi , Kar Gozde , Gomes Tomás , Henriksson Johan , Miao Zhichao , Natarajan Kedar , McKenzie Andrew N. J. , Mahata Bidesh , Teichmann Sarah A. 
Published: December 2017

SummaryThe IRE1a-XBP1 pathway, a conserved adaptive mediator of the unfolded protein response, is indispensable for the development of secretory cells. It maintains endoplasmic reticulum homeostasis by facilitating protein folding and enhancing secretory capacity of the cells. Its role in immune cells is emerging. It is involved in dendritic cell, plasma cell and eosinophil development and differentiation. Using genome-wide approaches, integrating ChIPmentation and mRNA-sequencing data, we have elucidated the regulatory circuitry governed by the IRE1a-XBP1 pathway in type-2 T helper cells (Th2). We show that the XBP1 transcription factor is activated by splicingin vivoin T helper cell lineages. We report a comprehensive repertoire of XBP1 target genes in Th2 lymphocytes. We found that the pathway is conserved across cell types in terms of resolving secretory stress, and has T helper cell-specific functions in controlling activation-dependent Th2 cell proliferation and regulating cytokine expression in addition to secretion. These results provide a detailed picture of the regulatory map governed by the XBP1 transcription factor during Th2 lymphocyte activation.
A mathematical approach to differentiate spontaneous and induced evolution to drug resistance during cancer treatment
Authors: Greene James M. , Gevertz Jana L. , Sontag Eduardo D. 
Published: December 2017

AbstractDrug resistance is a major impediment to the success of cancer treatment. Resistance is typically thought to arise through random genetic mutations, after which mutated cells expand via Darwinian selection. However, recent experimental evidence suggests that the progression to drug resistance need not occur randomly, but instead may be induced by the treatment itself, through either genetic changes or epigenetic alterations. This relatively novel notion of resistance complicates the already challenging task of designing effective treatment protocols. To better understand resistance, we have developed a mathematical modeling framework that incorporates both spontaneous and drug-induced resistance. Our model demonstrates that the ability of a drug to induce resistance can result in qualitatively different responses to the same drug dose and delivery schedule. We have also proven that the induction parameter in our model is theoretically identifiable, and proposed an in vitro protocol which could be used to determine a treatment’s propensity to induce resistance.
Germ layer specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm
Authors: Salinas-Saavedra Miguel , Rock Amber Q. , Martindale Mark Q 
Published: December 2017

AbstractIn triploblastic animals, Par-proteins regulate cell-polarity and adherens junctions of both ectodermal and endodermal epithelia. But, in embryos of the diploblastic cnidarian Nematostella vectensis, Par-proteins are degraded in all cells in the bifunctional gastrodermal epithelium. Using immunohistochemistry, CRISPR/Cas9 mutagenesis, and overexpression of specific mRNAs, we describe the functional association between Par-proteins, ß-catenin, and snail transcription factor genes in N. vectensis embryos. We demonstrate that the aPKC/Par complex regulates the localization of ß-catenin in the ectoderm by stabilizing its role in cell-adhesion, and that endomesodermal epithelial cells are organized by a different cell-adhesion system than that of overlying ectoderm. We also show that ectopic expression of snail genes, which are expressed in mesodermal derivatives in bilaterians, are sufficient to downregulate Par-proteins and translocate ß-catenin from the junctions to the cytoplasm in ectodermal cells. These data provide molecular insight into the evolution of epithelial structure and distinct mesodermal tissue in metazoan embryos.
The research landscape of school-based sexuality education
Authors: Roien Line Anne , Graugaard Christian , Simovska Venka 
Published: December 2017

Purpose
The purpose of this paper is to map and discuss the overall characteristics of international research on school-based sexuality education, published in academic journals, with a particular focus on the framing of non-conservative approaches including sexuality education research targeting young pupils 6-12 years of age.

Design/methodology/approach
The paper draws upon the methodology of systematic research mapping and presents a broad overview of research on sexuality education in a school setting for pupils aged 6-16. The authors searched the leading bibliographic databases in the field, i.e., ERIC, PsycINFO, PubMed, Scopus, Australian Education Index, British Education Index and Education Research Complete, using the search terms “sexuality education” and “school” and “children” or “adolescents.” The mapping focused on articles published in peer-reviewed journals in English, German, Danish, Swedish or Norwegian, in the period 2000-2016.

Findings
Out of 3,769 papers identified in the search process, a total of 576 papers were found to meet the inclusion criteria of the mapping. The mapping portrays a research landscape that is diverse and nuanced in terms of contextual, theoretical and methodological approaches, but also characterized by limitations. The findings point to the clear dominance of research on schools in English-speaking countries, conceptual research is scarce, and school-based sexuality education aimed at the youngest children seems to be neglected. The mapping identifies gaps in the literature that justify a call for more research from diverse sociocultural, political and geographical contexts, more conceptual research using social theory, and more research focusing on the potentials and challenges linked to sexuality education for younger pupils.

Originality/value
This paper offers a rare, if not the first, comprehensive overview of research on school-based sexuality education including a focus on younger school children 6-12 years of age.
Six Sigma learning evaluation model using Bloom’s Taxonomy
Authors: Fonseca Amorim Gabriela , Balestrassi Pedro Paulo , Sawhney Rapinder , de Oliveira-Abans Mariângela , Ferreira da Silva Diogo Leonardo 
Published: December 2017

Purpose
This paper aims to propose a learning evaluation model for Green Belts and Black Belts at the training level. A question bank has been developed on the basis of Bloom’s learning classification and applied to a group of employees who were being trained in Six Sigma (SS). Their results were then used to decide on the students’ approval and to guide the instructor’s plan of teaching for the next classes.

Design/methodology/approach
An action research has been conducted to develop a question bank of 310 questions based on the revised Bloom’s Taxonomy, to implement the evaluation model, and to apply it during the SS training.

Findings
The evaluation model has been designed so that the students do not proceed unless they have acquired the conceptual knowledge at each step of the DMAIC (Define, Measure, Analyze, Improve and Control) roadmap. At the end of the evaluation process, the students’ results have been analyzed. The number of mistakes in all stages of DMAIC was equal, implying that the training was uniform the entire roadmap. However, the opposite happened in each of the Bloom’s Taxonomy levels, showing that some skills need to be better stimulated by the instructor than others.

Research limitations/implications
The learning evaluation model proposed in this paper has been applied to a group of 70 employees who were being trained in SS at a Brazilian aircraft manufacturer. The data have been analyzed using Microsoft Excel® and Minitab® 17 Statistical Software.

Originality/value
Despite the abundance of courses offering the SS Green Belt and Black Belt certifications, there is no standard evaluation to ensure the training quality. Thus, this paper proposes an innovative learning evaluation model.