bluuebunny/crossref_metadata_2025_split huggingface dataset:
FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics
Authors: Nune Melesse , Morgan Michael , Connell Zaily , McCullough Laura , Jbara Muhammad , Sun Hao , Brik Ashraf , Formosa Tim , Wolberger Cynthia 
Published: August 2018

AbstractMonoubiquitination of histone H2B (H2B-Ub) plays a role in transcription and DNA replication, and is required for normal localization of the histone chaperone, FACT. In yeast, H2B-Ub is deubiquitinated by Ubp8, a subunit of SAGA, and Ubp10. Although they target the same substrate, loss of Ubp8 and Ubp10 causes different phenotypes and alters the transcription of different genes. We show that Ubp10 has poor activity on yeast nucleosomes, but that addition of FACT stimulates Ubp10 activity on nucleosomes and not on other substrates. Consistent with a role for FACT in deubiquitinating H2Bin vivo, a FACT mutant strain shows elevated levels of H2B-Ub. Combination of FACT mutants with deletion of Ubp10, but not Ubp8, confers increased sensitivity to hydroxyurea and activates a cryptic transcription reporter, suggesting that FACT and Ubp10 may coordinate nucleosome assembly during DNA replication and transcription. Our findings reveal unexpected interplay between H2B deubiquitination and nucleosome dynamics.
Early Life Trauma Predicts Affective Phenomenology and the Effects are Partly Mediated by Staging Coupled with Lowered Lipid-Associated Antioxidant Defences
Authors: Maes Michael , Congio Ana , Moraes Juliana Brum , Bonifacio Kamila Landucci , Barbosa Decio Sabbatini , Vargas Heber Odebrecht , Morris Gerwyn , Puri Basant K. , Michelin Ana Paula , Vargas Nunes Sandra Odebrecht 
Published: August 2018

AbstractBackgroundEarly life trauma (ELT) may drive mood disorder phenomenology, neuro-oxidative and neuro-immune pathways and impairments in semantic memory. Nevertheless, there are no data regarding the impact of ELT on affective phenomenology and whether these pathways are mediated by staging or lowered lipid-associated antioxidant defences.MethodsThis study examined healthy controls (n=54) and patients with affective disorders including major depression, bipolar disorder and anxiety disorders (n=118). ELT was assessed using the Child Trauma Questionnaire. In addition, we measured affective phenomenology and assayed advanced oxidation protein products; malondialdehyde, paraoxonase 1 (CMPAase) activity, high-sensitivity C-reactive protein (hsCRP), and high-density lipoprotein (HDL) cholesterol.ResultsELT was associated with increased risk for mood and comorbid anxiety disorders and a more severe phenomenology, including staging characteristics (number of mood episodes), severity of depression and anxiety, suicide attempts, suicidal ideation, type of treatments received, disabilities, body mass index, smoking behaviour and hsCRP, as well as lowered health-related quality of life, socio-economic status, antioxidant defences and semantic memory. The number of mood episodes and CMPAase/HDL-cholesterol levels could be reliably combined into a new vulnerability staging-biomarker index, which mediates in part the effects of ELT on affective phenomenology, while lowered antioxidant defences are associated with increased oxidative stress. Moreover, the effects of female sex on mood disorders and affective phenomenology are mediated by ELT.DiscussionThe cumulative effects of different types of ELT drive many aspects of affective phenomenology either directly or indirectly through effects of staging and/or lipid–associated antioxidant defences. The results show that children, especially girls, with ELT are at great risk to develop mood disorders and more severe phenotypes of affective disorders.
Learning 2-in-1: Towards Integrated EEG-fMRI-Neurofeedback
Authors: Perronnet Lorraine , Lécuyer Anatole , Mano Marsel , Fleury Mathis , Lioi Giulia , Cury Claire , Clerc Maureen , Lotte Fabien , Barillot Christian 
Published: August 2018

ABSTRACTNeurofeedback (NF) allows to exert self-regulation over specific aspects of one’s own brain activity by returning information extracted in real-time from brain activity measures. These measures are usually acquired from a single modality, most commonly electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). EEG-fMRI-neurofeedback (EEG-fMRI-NF) is a new approach that consists in providing a NF based simultaneously on EEG and fMRI signals. By exploiting the complementarity of these two modalities, EEG-fMRI-NF opens a new spectrum of possibilities for defining bimodal NF targets that could be more robust, flexible and effective than unimodal ones. Since EEG-fMRI-NF allows for a richer amount of information to be fed back, the question arises of how to represent the EEG and fMRI features simultaneously in order to allow the subject to achieve better self-regulation. In this work, we propose to represent EEG and fMRI features in a single bimodal feedback (integrated feedback). We introduce two integrated feedback strategies for EEG-fMRI-NF and compare their early effects on a motor imagery task with a between-group design. The BiDim group (n=10) was shown a two-dimensional (2D) feedback in which each dimension depicted the information from one modality. The UniDim group (n=10) was shown a one-dimensional (1D) feedback that integrated both types of information even further by merging them into one. Online fMRI activations were significantly higher in the UniDim group than in the BiDim group, which suggests that the 1D feedback is easier to control than the 2D feedback. However subjects from the BiDim group produced more specific BOLD activations with a notably stronger activation in the right superior parietal lobe (BiDim > UniDim, p < 0.001, uncorrected). These results suggest that the 2D feedback encourages subjects to explore their strategies to recruit more specific brain patterns. To summarize, our study shows that 1D and 2D integrated feedbacks are effective but also appear to be complementary and could therefore be used in a bimodal NF training program. Altogether, our study paves the way to novel integrated feedback strategies for the development of flexible and effective bimodal NF paradigms that fully exploits bimodal information and are adapted to clinical applications.
A 3-fold kernel approach for characterizing Late Onset Alzheimer’s Disease
Authors: Squillario Margherita , Tomasi Federico , Tozzo Veronica , Barla Annalisa , Uberti Daniela ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2018

SummaryThe purpose of this study is to identify a global and robust signature characterizing Alzheimer’s Disease (AD). Two public GWAS datasets were analyzed considering a 3-fold kernel approach, based on SNPs, Genes and Pathways analysis, and two binary classifications tasks were addressed: cases@controls and APOE4 task. In the SNP signature of the ADNI-1 and ADNI-2 datasets, chromosome 19 and 20 reached high classification accuracy. In addition, the functional characterization of ADNI-1 and ADNI-2 SNP signatures found enriched the same pathway (i.e., Neuroactive ligand-receptor interaction), with GRM7 gene in common with both. TOMM40 was confirmed linked to AD pathology by SNP, gene and pathway-based analyses in ADNI-1. Using this 3-fold kernel approach, a peculiar signature of SNPs, genes and pathways has been highlighted in both datasets. Based on these significant results, we retain such approach a valuable tool to elucidate the heritable susceptibility to AD but also to other similar complex diseases.
Mining ancient microbiomes using selective enrichment of damaged DNA molecules
Authors: Weiß Clemens L. , Gansauge Marie-Theres , Aximu-Petri Ayinuer , Meyer Matthias , Burbano Hernán A. 
Published: August 2018

AbstractBackgroundThe identification of bona fide microbial taxa in microbiomes derived from ancient and historical samples is complicated by the unavoidable mixture between DNA from ante- and post-mortem microbial colonizers. One possibility to distinguish between these sources of microbial DNA is querying for the presence of age-associated degradation patterns typical of ancient DNA (aDNA). The presence of uracils, resulting from cytosine deamination, has been detected ubiquitously in aDNA retrieved from diverse sources, and used as an authentication criterion. Here, we employ a library preparation method that separates molecules that carry uracils from those that do not for a set of samples that includes Neandertal remains, herbarium specimens and archaeological plant remains.ResultsWe show that sequencing DNA libraries enriched in molecules carrying uracils effectively amplifies age associated degradation patterns in microbial mixtures of ancient and historical origin. This facilitates the discovery of authentic ancient microbial taxa in cases where degradation patterns are difficult to detect due to large sequence divergence in microbial mixtures. Additionally, the relative enrichment of taxa in the uracil enriched fraction can help to identify bona fide ancient microbial taxa that could be missed using a more targeted approach.ConclusionsOur experiments show, that in addition to its use in enriching authentic endogenous DNA of organisms of interest, the selective enrichment of damaged DNA molecules can be a valuable tool in the discovery of ancient microbial taxa.
Reward revaluation biases hippocampal replay content away from the preferred outcome
Authors: Carey Alyssa A. , Tanaka Youki , van der Meer Matthijs A. A. 
Published: August 2018

AbstractThe rodent hippocampus spontaneously generates bursts of neural activity (“replay”) which can depict spatial trajectories to reward locations, suggesting a role in model-based behavioral control. A largely separate literature emphasizes reward revaluation as the litmus test for such control, yet the content of hippocampal replay under revaluation conditions is unknown. We report that the content of awake hippocampal sharp wave-ripple events is biased away from the preferred outcome following reward revaluation, challenging the idea that such sequences reflect recent experience or trajectories toward the preferred goal.
Allele-specific genome editing using CRISPR-Cas9 causes off-target mutations in diploid yeast
Authors: Gorter de Vries Arthur R. , Couwenberg Lucas G. F. , van den Broek Marcel , de la Torre Cortés Pilar , Horst Jolanda ter , Pronk Jack T. , Daran Jean-Marc G. 
Published: August 2018

ABSTRACTTargeted DNA double-strand breaks (DSBs) with CRISPR-Cas9 have revolutionized genetic modification by enabling efficient genome editing in a broad range of eukaryotic systems. Accurate gene editing is possible with near-perfect efficiency in haploid or (predominantly) homozygous genomes. However, genomes exhibiting polyploidy and/or high degrees of heterozygosity are less amenable to genetic modification. Here, we report an up to 99-fold lower gene editing efficiency when editing individual heterozygous loci in the yeast genome. Moreover, Cas9-mediated introduction of a DSB resulted in large scale loss of heterozygosity affecting DNA regions up to 360 kb that resulted in introduction of nearly 1700 off-target mutations, due to replacement of sequences on the targeted chromosome by corresponding sequences from its non-targeted homolog. The observed patterns of loss of heterozygosity were consistent with homology directed repair. The extent and frequency of loss of heterozygosity represent a novel mutagenic side-effect of Cas9-mediated genome editing, which would have to be taken into account in eukaryotic gene editing. In addition to contributing to the limited genetic amenability of heterozygous yeasts, Cas9-mediated loss of heterozygosity could be particularly deleterious for human gene therapy, as loss of heterozygous functional copies of anti-proliferative and pro-apoptotic genes is a known path to cancer.
Transcription activity contributes to the firing of non-constitutive origins in Trypanosoma brucei
Authors: da Silva Marcelo S. , Cayres-Silva Gustavo R. , Vitarelli Marcela O. , Marin Paula A. , Hiraiwa Priscila M. , Araújo Christiane B. , Ávila Andrea R. , Reis Marcelo S. , Elias Maria Carolina 
Published: August 2018

ABSTRACTThe cosynthesis of DNA and RNA potentially generates conflicts between replication and transcription, which can lead to genomic instability. In trypanosomatids, eukaryotic parasites that perform polycistronic transcription, this phenomenon and its consequences have not yet been investigated. Here, using equations and computational analysis we demonstrated that the number of constitutive origins mapped in the Trypanosoma brucei genome is close to the minimum required to complete replication within S phase duration. However, taking into account the location of these origins in the genome, the replication in due time becomes virtually impossible, making it necessary to activate non-constitutive origins. Moreover, computational and biological assays pointed to transcription being responsible for activating non-constitutive origins. Together, our results suggest that transcription action through conflicts with replication contributes to the firing of non-constitutive origins, maintaining the robustness of S phase duration. The usage of this entire pool of origins seems to be of paramount importance for the survival of this parasite that infects million people around the world since it contributes to the maintenance of the replication of its DNA.
Fitness Landscape of the Fission Yeast Genome
Authors: Grech Leanne , Jeffares Daniel Charlton , Sadée Christoph Yves , Rodríguez-López María , Bitton Danny Asher , Hoti Mimoza , Biagosch Carolina , Aravani Dimitra , Speekenbrink Maarten , Illingworth Christopher J. R. , Schiffer Philipp H. , Pidoux Alison L. , Tong Pin , Tallada Victor A. , Allshire Robin , Levin Henry L. , Bähler Jürg 
Published: August 2018

AbstractBackgroundNon-protein-coding regions of eukaryotic genomes remain poorly understood. Diversity studies, comparative genomics and biochemical outputs of genomic sites can be indicators of functional elements, but none produce fine-scale genome-wide descriptions of all functional elements.ResultsTowards the generation of a comprehensive description of functional elements in the haploid Schizosaccharomyces pombe genome, we generated transposon mutagenesis libraries to a density of one insertion per 13 nucleotides of the genome. We applied a five-state hidden Markov model (HMM) to characterise insertion-depleted regions at nucleotide-level resolution. HMM-defined functional constraint was consistent with genetic diversity, comparative genomics, gene-expression data and genome annotation.ConclusionsWe infer that transposon insertions lead to fitness consequences in 90% of the genome, including 80% of the non-protein-coding regions, reflecting the presence of numerous non-coding elements in this compact genome that have functional roles. Display of this data in genome browsers provides fine-scale views of structure-function relationships within specific genes.
High-order epistasis in catalytic power of dihydrofolate reductase gives rise to a rugged fitness landscape in the presence of trimethoprim selection
Authors: Tamer Yusuf Talha , Gaszek Ilona K. , Abdizadeh Haleh , Batur Tugce Altinusak , Reynolds Kimberly , Atilgan Ali Rana , Atilgan Canan , Toprak Erdal 
Published: August 2018

ABSTRACTEvolutionary fitness landscapes of certain antibiotic target enzymes have been comprehensively mapped showing strong high order epistasis between mutations, but understanding these effects at the biochemical and molecular levels remained open. Here, we carried out an extensive experimental and computational study to quantitatively understand the evolutionary dynamics of Escherichia coli dihydrofolate reductase (DHFR) enzyme in the presence of trimethoprim induced selection. Biochemical and structural characterization of resistance-conferring mutations targeting a total of ten residues spanning the substrate binding pocket of DHFR revealed distinct resistance mechanisms. Next, we experimentally measured biochemical parameters (Km, Ki, and kcat) for a mutant library carrying all possible combinations of six resistance-conferring DHFR mutations and quantified epistatic interactions between them. We found that the epistasis between DHFR mutations is high-order for catalytic power of DHFR (kcat and Km), but less prevalent for trimethoprim affinity (Ki). Taken together our data provide a concrete illustration of how epistatic coupling at the level of biochemical parameters can give rise to complex fitness landscapes, and suggest new strategies for developing mutant specific inhibitors.
Gut microbial features can predict host phenotype response to protein deficiency
Authors: Navarro Guadalupe , Sharma Anukriti , Dugas Lara R. , Forrester Terrence , Gilbert Jack A. , Layden Brian T. 
Published: August 2018

AbstractMalnutrition remains a major health problem in low and middle income countries. During low protein intake, < 0.67 g/kg/day, there is a loss of nitrogen (N2) balance, due to the unavailability of amino acid for metabolism and unbalanced protein catabolism results. However, there are individuals, who consume the same low protein intake, and preserve N2 balance for unknown reasons. A novel factor, the gut microbiota, may account for these N2 balance differences. To investigate this, we correlated gut microbial profiles with the growth of four murine strains (C57Bl6/J, CD-1, FVB, and NIH-Swiss) on protein deficient (PD) diet. Results show that a PD diet exerts a strain-dependent impact on growth and N2 balance as determined through analysis of urinary urea, ammonia and creatinine excretion. Bacterial alpha diversity was significantly (p < 0.05, FDR) lower across all strains on a PD diet compared to normal chow (NC). Multi-group analyses of the composition of microbiomes (ANCOM) revealed significantly differential microbial signatures between the four strains independent of diet. However, mice on a PD diet demonstrated differential enrichment of bacterial genera including, Allobaculum (C57Bl6/J), Parabacteroides (CD-1), Turicibacter (FVB), and Mucispirillum (NIH-Swiss) relative to NC. Additionally, statistical model fitting revealed that the relative abundance of genera such as Bifidobacterium, Ruminococcus, and Lactobacillus were significantly positively correlated with body weight, while Anaerofustis, Roseburia, and Bilophila were significantly positively correlated with ammonia excretion. Taken together, these results suggest a potential relationship between the specific gut microbiota, N2 balance and animal response to malnutrition.
Accountants’ proactivity in intra-organisational networks: a strong structuration perspective
Authors: Daff Lyn , Jack Lisa 
Published: August 2018

Purpose
The purpose of this paper is to provide insights into the importance of accountants’ networks inside organisations, the parties who comprise those networks and how accountants go about building and maintaining their networks. It also illustrates the use of strong structuration theory, which specifically considers the networks that surround agents. The theoretical discussion highlights the significance of communication as agency in the context of accounting practice through a strong structuration perspective.

Design/methodology/approach
A qualitative approach to the inquiry was adopted. Interviews were conducted with 30 Australian accountants from 22 not-for-profit organisations. A thematic approach was used to analyse the transcripts. Structuration theory, supplemented by strong structuration, informed the study.

Findings
The interviewees attested to the importance of communication and developing networks within their organisations. They actively sought to expand and enhance their networks. The accountants played a pivotal role in networks and they pursued both horizontal and vertical relations. The accountants’ knowledge of organisational positions and perceptions of their own roles were used strategically in attempts to alter the internal structures of networked others.

Research limitations/implications
The interviewed accountants worked in not-for-profit organisations and this may influence the findings. Future research might consider accountants working in for-profit organisations. The study provides insights into strategies to develop intra-organisational networks.

Originality/value
The study contributes to the meagre literature regarding accountants’ networks within organisations. It provides insights that may assist accountants in enhancing their own networks. Although structuration theory is well-established in accounting research, the enrichments offered by strong structuration are illustrated in this study.
Are we ready?
Authors: Shrivastava Archana , Naik Asha 
Published: August 2018

Subject area
Human Resource Management and Business Strategy.

Study level/applicability
Postgraduate.

Case overview
The case provides a holistic perspective of organizational transformation, management of change impact on employees and leader behavior. The challenge at Govind Milk and Milk Products Pvt. Ltd. a mid-size company, in the dairy industry was to transform itself into a pan India and global company from a regional organization. The case study outlines how the organization took on the transformation journey under a strong leadership and managed change by focusing on creating a brand, implementing technology and creating a culture of meritocracy. Having made the successful transition from being a family run business to a professionally managed company and having built significant internal capacity the big question is – Can the company strive and thrive in the VUCA business environment?

Expected learning outcomes
To highlight the process and management of organizational change. To highlight the role of leadership in the process of organizational change. To understand how the environmental factors or the VUCA environment impacts the performance of an organization. To highlight internal capacity building as a strategy to deal with the VUCA environment.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS: 6: Human Resource Management.
Wonder Pedicabs: leisure rickshaw rides
Authors: Jain Vranda , Srivastava Vinita 
Published: August 2018

Subject area
Marketing Management and Economics.

Study level/applicability
Management courses (MBA level), Courses on Tourism

Case overview
When in India (WII) is a tour company serving the niche segment of Heritage tourism. WII was incorporated in 2011 with the aim to enable foreign and domestic tourists to experience the deeply embedded cultural ethos and heritage of Old Delhi. Their unique tourism product, “the Wonder Pedicabs”, provides leisure rickshaw rides through the Old Delhi lanes. This teaching case focuses on various managerial dimensions of the operations of WII. The case can be used in courses on Marketing as well as Economics. The case discusses the macro and micro environmental forces operating on WII. It deliberates on the economics of various tours offered by WII. It also educates the participants about the process of decision-making that goes into the selection of a tour operator and a tourism product. Hence, it appreciates the significance of need recognition, search for information, evaluation of alternatives and purchase decision as pillars in the process of decision-making process. The case also attempts to educate the participants about the Indian Tourism Sector.

Expected learning outcomes
Comprehend what constitutes a tourism product and types of tourism. Understand consumer decision-making for a tourism product. Highlight the importance of the tourism sector in the Indian economy. Discuss economic concepts pertaining to cost and volume, enabling managerial decision-making.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 12: Tourism and Hospitality.