bluuebunny/crossref_metadata_2025_split huggingface dataset:
OGT (O-GlcNAc Transferase) selectively modifies multiple residues unique to lamin A
Authors: Simon Dan N. , Wriston Amanda , Fan Qiong , Shabanowitz Jeffrey , Florwick Alyssa , Dharmaraj Tejas , Peterson Sherket B. , Gruenbaum Yosef , Carlson Cathrine R. , Grønning-Wang Line M. , Hunt Donald F , Wilson Katherine L. 
Published: October 2017

AbstractThe LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, chromatin organization, and genome integrity. Mutations in LMNA cause >12 diseases, termed laminopathies. Lamins A and C are identical for their first 566 residues. However, they form distinct filaments in vivo with apparently distinct roles. We report that lamin A is O-GlcNAc modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified OGT enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385-646), with no detectable modification of lamin B1, lamin C, or ‘progerin’ (Δ50) tails. Using mass spectrometry, we identified 11 O-GlcNAc sites in a ‘sweet spot’ unique to lamin A, with up to seven sugars per peptide. Most sites were unpredicted by current algorithms. Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites. By contrast, O-GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson-Gilford progeria syndrome, and greatly reduced by deletion Δ35, suggesting this region is required for substrate recognition or modification by OGT in vitro. These results suggest OGT, an essential protein and master regulator, regulates partners or function(s) unique to lamin A that are lost in progeria.
FERMI: A novel method for sensitive detection of rare mutations in somatic tissue
Authors: Liggett L. Alexander , Sharma Anchal , De Subhajyoti , DeGregori James 
Published: October 2017

AbstractWith growing interest in monitoring mutational processes in normal tissues, tumor heterogeneity, and cancer evolution under therapy, the ability to accurately and economically detect ultra-rare mutations is becoming increasingly important. However, this capability has often been compromised by significant sequencing, PCR and DNA preparation error rates. Here, we describe FERMI (Fast Extremely Rare Mutation Identification) - a novel method designed to eliminate majority of these sequencing and library preparation errors in order to significantly improve rare somatic mutation detection. This method leverages barcoded targeting probes to capture and sequence DNA of interest with single copy resolution. The variant calls from the barcoded sequencing data then further filtered in a position-dependent fashion against an adaptive, context-aware null model in order to distinguish true variants. As a proof of principle, we employ FERMI to probe bone marrow biopsies from leukemia patients, and show that rare mutations and clonal evolution can be tracked throughout cancer treatment, including during historically intractable periods like minimum residual disease. Importantly, FERMI is able to accurately detect nascent clonal expansions within leukemias in a manner that may facilitate the early detection and characterization of cancer relapse.
3D Cell Nuclear Morphology: Microscopy Imaging Dataset and Voxel-Based Morphometry Classification Results
Authors: Kalinin Alexandr A. , Allyn-Feuer Ari , Ade Alex , Fon Gordon-Victor , Meixner Walter , Dilworth David , de Wet Jeffrey R. , Higgins Gerald A. , Zheng Gen , Creekmore Amy , Wiley John W. , Verdone James E. , Veltri Robert W. , Pienta Kenneth J. , Coffey Donald S. , Athey Brian D. , Dinov Ivo D. 
Published: October 2017

AbstractCell deformation is regulated by complex underlying biological mechanisms associated with spatial and temporal morphological changes in the nucleus that are related to cell differentiation, development, proliferation, and disease. Thus, quantitative analysis of changes in size and shape of nuclear structures in 3D microscopic images is important not only for investigating nuclear organization, but also for detecting and treating pathological conditions such as cancer. While many efforts have been made to develop cell and nuclear shape characteristics in 2D or pseudo-3D, several studies have suggested that 3D morphometric measures provide better results for nuclear shape description and discrimination. A few methods have been proposed to classify cell and nuclear morphological phenotypes in 3D, however, there is a lack of publicly available 3D data for the evaluation and comparison of such algorithms. This limitation becomes of great importance when the ability to evaluate different approaches on benchmark data is needed for better dissemination of the current state of the art methods for bioimage analysis. To address this problem, we present a dataset containing two different cell collections, including original 3D microscopic images of cell nuclei and nucleoli. In addition, we perform a baseline evaluation of a number of popular classification algorithms using 2D and 3D voxel-based morphometric measures. To account for batch effects, while enabling calculations of AUROC and AUPR performance metrics, we propose a specific cross-validation scheme that we compare with commonly used k-fold cross-validation. Original and derived imaging data are made publicly available on the project web-page: http://www.socr.umich.edu/projects/3d-cell-morphometry/data.html.
Climatic niche dynamics and its role in the insular endemism ofAnolislizards
Authors: Velasco Julian A. , Martinez-Meyer Enrique , Flores-Villela Oscar 
Published: October 2017

AbstractWe evaluated the tempo and mode of climatic niche evolution in the radiation of CaribbeanAnolislizards and the role of climate in shaping their exceptional insular endemism. Using phylogenetic comparative methods, climatic niche data and a calibrated phylogeny, we reconstructed climatic niche dynamics across time and space for CaribbeanAnolislizards. We found evidence of several instances of niche shifts through the CaribbeanAnolisradiation. Caribbean anole species have diversified mainly along a precipitation rather than a temperature gradient. Only a few lineages have colonized both cold and hot conditions. Furthermore, most of the single-island endemic species are climatically restricted to its native islands and a small set of species might the potential to colonize other islands given its climatic niche requirements. Overall, we found evidence that climate niche conservation has played a role structuring current insularAnolisendemism. The observed climatic dissimilarity across the Greater Antilles likely limit successful population establishment of potential exotic insular species.
Differentiable processing of objects, associations and scenes within the hippocampus
Authors: Dalton Marshall A. , Zeidman Peter , McCormick Cornelia , Maguire Eleanor A. 
Published: October 2017

AbstractThe hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive, with some theories emphasising associative processes and another proposing that scene construction is its primary role. To directly compare these accounts of hippocampal function in human males and females, we devised a novel mental imagery paradigm where different tasks were closely matched for associative processing and mental construction, but either did or did not evoke scene representations, and we combined this with high resolution functional MRI. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. The contrasting patterns of neural engagement could not be accounted for by differences in eye movements, mnemonic processing or the phenomenology of mental imagery. These results inform conceptual debates in the field by showing that the hippocampus does not seem to favour one type of process over another; it is not a story of exclusivity. Rather, there may be different circuits within the hippocampus, each associated with different cortical inputs, which become engaged depending on the nature of the stimuli and the task at hand. Overall, our findings emphasise the importance of considering the hippocampus as a heterogeneous structure, and that a focus on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.Significance statementThe hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive. Here we used a novel mental imagery paradigm and high resolution fMRI to compare accounts of hippocampal function that emphasise associative processes with a theory that proposes scene construction as a primary role. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. We conclude that a greater emphasis on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.
Characterizing the sub-second timescale strategies of fighting in zebrafish
Authors: Laan Andres , Iglesias-Julios Marta , de Polavieja Gonzalo G. 
Published: October 2017

AbstractMost animals fight by repeating complex stereotypic behaviors, yet the internal structure of these behaviors has rarely been dissected in detail. We characterized the internal structure of fighting behaviors by developing a machine learning pipeline that measures and classifies the behavior of individual unmarked animals on a sub-second timescale. This allowed us to quantify several previously hidden features of zebrafish fighting strategies. We found strong correlations between the velocity of the attacker and the defender indicating a dynamic matching of approach and avoidance efforts consistent with the cumulative assessment model of aggression. While velocity matching was ubiquitous, the spatial dynamics of attacks showed phase-specific differences. Contest phase attacks were characterized by a paradoxical side-ways attraction of the retreating animal towards the attacker suggesting that the defender combines avoidance maneuvers with display maneuvers. Post-resolution attacks lacked display-like features and the the defender was avoidance-focused. From the perspective of the winner, game theory modeling further suggested that highly energetically costly post resolution attacks occurred because the winner was trying to increase its relative dominance over the loser. Overall, the rich structure of zebrafish motor coordination during fighting indicates a greater complexity and layering of strategies than has previously been recognized.
Power, false discovery rate and Winner’s Curse in eQTL studies
Authors: Huang Qin Qin , Ritchie Scott C. , Brozynska Marta , Inouye Michael 
Published: October 2017

AbstractInvestigation of the genetic architecture of gene expression traits has aided interpretation of disease and trait-associated genetic variants, however key aspects of expression quantitative trait (eQTL) study design and analysis remain understudied. We used extensive, empirically-driven simulations to explore eQTL study design and the performance of various analysis strategies. Across multiple testing correction methods, false discoveries of genes with eQTLs (eGenes) were substantially inflated when false discovery rate (FDR) control was applied to all tests, and only appropriately controlled using hierarchical procedures. All multiple testing correction procedures had low power and inflated FDR for eGenes whose causal SNPs had small allele frequencies using small sample sizes (e.g. frequency <10% in 100 samples), indicating that even moderately low frequency eQTL SNPs (eSNPs) in these studies are enriched for false discoveries. In scenarios with ≥80% power, the top eSNP was the true simulated eSNP 90% of the time, but substantially less frequently for very common eSNPs (minor allele frequencies >25%). Overestimation of eQTL effect sizes, so-called “Winner’s Curse”, was common in low and moderate power settings. To address this, we developed a bootstrap method (BootstrapQTL) which led to more accurate effect size estimation. These insights provide a foundation for future eQTL studies, especially those with sampling constraints and subtly different conditions.
A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer
Authors: Liu Zhixian , Li Mengyuan , Jiang Zehang , Wang Xiaosheng 
Published: October 2017

AbstractBackgroundTriple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed a comprehensive portrait of immunologic landscape of TNBC based on 2 large-scale breast cancer genomic data.MethodsWe compared expression levels of immune-related genes and gene-sets among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features. Moreover, we explored the association of immune-related genes or gene-sets expression and survival prognosis in TNBC patients.ResultsWe found that almost all analyzed immune-related gene-sets had significantly higher expression levels in TNBC than non-TNBC. These highly expressed gene-sets in TNBC included 15 immune cell type and function, human leukocyte antigen (HLA), cancer testis (CT), tumor-infiltrating lymphocytes (TILs), immune cell infiltrate, regulatory T (Treg) cells, immune checkpoint, cytokine and cytokine receptor, metastasis-promoting, pro-inflammatory and parainflammation (PI) gene-sets. Moreover, TP53-mutated, TNBC had significantly higher expression levels of the immune checkpoint, Treg, PI, and CT gene-sets, and lower expression levels of the immune cell infiltrate gene-set than TP53-wildtype TNBC. Furthermore, we found that elevated expression of most of the immune-related genes in TNBC was associated with the ER-status, while some were associated with both ER-and HER2-status. Elevated expression of the immune-related genes in TNBC was also associated with the high tumor mutation burden (TMB) in TNBC. Finally, elevated expression of the immune-related gene-sets was likely to be associated with better survival prognosis in TNBC.ConclusionsOur findings suggest that TNBC is a breast cancer subtype with particularly strong immunogenicity, and therefore could be propitious to immunotherapeutic options.
Pathway-based polygenic risk implicates GO: 17144 drug metabolism in recurrent depressive disorder
Authors: Docherty Anna R. , Moscati Arden , Bigdeli T. Bernard , Edwards Alexis K. , Peterson Roseann , Yang Fuzhong , Adkins Daniel E. , Anderson John S. , Flint Jonathan , Kendler Kenneth S. , Bacanu Silviu-Alin 
Published: October 2017

AbstractThe Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic, with any top risk loci conferring a very small proportion of variance in case-control status (1). Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways have proved successful in treating MDD. However, it is possible that with information from PGC analyses, examining specific molecular pathway(s) implicated in MDD can further inform our study of molecular drug targets. Using a large case-control GWAS based on low-coverage whole genome sequencing (N = 10,640), we derived polygenic risk scores for MDD and for MDD specific to each of over 300 molecular pathways. We then used these data to identify sets of scores significantly predictive of case status, accounting for critical covariates. Over and above global polygenic risk for MDD, polygenic risk within the GO: 17144 drug metabolism pathway significantly predicted recurrent depression. In transcriptomic analyses, two pathway genes yielded suggestive signals at FDR q-values = .054: CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1). Because the neuroleptic carbamazepine is a known inducer of CYP2C19, future research might examine whether drug metabolism PRS has any influence on clinical presentation and treatment response. Overall, results indicate that pathway-based risk might inform treatment of severe depression. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.
Searching to bridge the gaps: a new typology of university-industry interaction
Authors: Schaeffer Paola Rücker , Dullius Andréia Cristina , Maldonado Rodrigues Rodrigo , Zawislak Paulo Antonio 
Published: October 2017

Purpose
The purpose of this paper is to propose a new typology to leverage the different knowledge gaps existing between universities and industries. This new typology classifies interactions into training-oriented, diffusion-oriented, service-oriented, development-oriented, and research-oriented.

Design/methodology/approach
The Brazilian 2010 Census data available from the CNPq Research Group Directory were used to test the typology.

Findings
It was found that, among the five types of interactions proposed, the most frequent were the development-oriented (39 per cent), diffusion-oriented (23 per cent), and research-oriented (16 per cent) ones. These findings indicate that it is likely that university-industry (U-I) interactions have improved in terms of quality in an attempt to attain a joint higher technological development.

Originality/value
The paper provides the U-I interaction debate with a new perspective about the kinds of interactions that could effectively bridge the knowledge gaps between universities and industries, especially in a developing country context.
Managing innovation in the Argentinian nuclear sector
Authors: Cantero Javier , Gonzalez Natalia Lorena , Diaz Daiana 
Published: October 2017

PurposeThe design, construction, and operation of a nuclear power plant (NPP) pose technological and R&D challenges for the organisations concerned. The purpose of this paper is to analyse the sources of innovation and the technological developments throughout the construction and commissioning processes for Atucha II NPP.Design/methodology/approachStudying a high-risk organisation that is reliable in practice poses several research questions the authors consider in this work. What kind of R&D processes can take place in a mature industry like the nuclear sector in Argentina? How have technological challenges been overcome since the restart of the completion phase of Atucha II NPP? Primary data were mostly gathered through semi-structured interviews. Grounded theory was the methodological approach adopted.FindingsMultiple sources of technological developments arise, an incremental R&D pattern being the most salient. Atucha II NPP seems to be a case of network innovation in a triple helix innovation scheme led by the Argentinian state. In effect, one of the outcomes of the construction of the Atucha II NPP was the development of the Argentinian nuclear sector together with the development of organisational capabilities. In this sense, the third Argentine NPP follows the socio-technical path of the Argentine nuclear industry.Originality/valueToo little is known about R&D processes in high reliability organisations (HROs), especially in the nuclear sector of a Latin American country such as Argentina as there seem to be no organisational studies analysing HROs’ impact on innovation, reliability, and economic development.
Mediation effect of quality of worklife, job involvement, and organizational citizenship behavior in relationship between transglobal leadership to employee performance
Authors: Hermawati Adya , Mas Nasharuddin 
Published: October 2017

PurposeThe purpose of this paper is to obtain empirical evidence, analyze and explain the mediating effect of the quality of work life (QWL), job-retention engagement and organizational citizenship behavior (OCB) on the relationship between transglobal leadership and employee performance.Design/methodology/approachThe population in this research is all employees of the most outstanding cooperatives in East Java Province. The method used to analyze the data in this study is generalized structural component analysis.FindingsThe main findings of this research show that the effects of mediation variables of QWL, job involvement and OCB in transglobal leadership influence employee performance in cooperatives in East Java. These findings are not in line with the Theory of Leadership by Sharkey et al. (2012), and explains the link between behaviors of transglobal leadership and employee performance. The study finds a need for attention in intervening/mediating variables such as QWL, job involvement and OCB as regard the relationship between transglobal leadership and employee performance.Research limitations/implicationsTransglobal leadership directly affects the QWL, job involvement and OCB: the higher the transglobal leadership, the higher the effect on QWL, job involvement and OCB. However, transglobal leadership has no direct effect on employee performance. Then, QWL, job involvement and OCB are mediating variables between the effects of transglobal leadership on full-mediation employee performance.Social implicationsTo improve the performance of employees of cooperatives, some improvements are needed such as an increase in the quality of a leader’s cooperative approach, especially with transglobal leadership style. However, particularly in the approach, factor of quality of work life, job involvement and OCB cannot be ignored or overriden. Improved leadership capacity, priority for improved business intelligence main factor, while the quality of work-life priorities take precedence in the growth and development factors. Job involvement of preferred priority on self-esteem factor performances, while the main priority organizational citizenship behavior on altruism factor. Employee performance will be improved with the aforementioned ideal conditions, especially on the work factor result.Originality/valueMediation effect of job involvement and OCB, using Sobel test, for assessing the relationship between translgobal leadership and employee performance has not been studied before.