bluuebunny/crossref_metadata_2025_split huggingface dataset:
A type 2 diabetes disease module with a high collective influence for Cdk2 and PTPLAD1 is localized in endosomes
Authors: Boutchueng-Djidjou Martial , Belleau Pascal , Bilodeau Nicolas , Fortier Suzanne , Bourassa Sylvie , Droit Arnaud , Elowe Sabine , Faure Robert L. 
Published: June 2018

AbstractDespite the identification of many susceptibility genes our knowledge of the underlying mechanisms responsible for complex disease remains limited. Here, we identified a type 2 diabetes disease module in endosomes, and validate it for functional relevance on selected nodes. Using hepatic Golgi/endosomes fractions, we established a proteome of insulin receptor-containing endosomes that allowed the study of physical protein interaction networks on a type 2 diabetes background. The resulting collated network is formed by 313 nodes and 1147 edges with a topology organized around a few major hubs with Cdk2 displaying the highest collective influence. Overall, 88% of the nodes are associated with the type 2 diabetes genetic risk, including 101 new candidates. The Type 2 diabetes module is enriched with cytoskeleton and luminal acidification –dependent processes that are shared with secretion-related mechanisms. We identified new signaling pathways driven by Cdk2 and PTPLAD1 whose expression regulate the association of the insulin receptor with TUBA, TUBB, the actin component ACTB and the endosomal sorting markers Rab5c and Rab11a. Therefore, the interactome of internalized insulin receptors reveals the presence of a type 2 diabetes disease module enriched in new layers of feedback loops required for insulin signaling, clearance and islet biology.Author SummaryAccording to the local hypothesis each complex disease can be linked to a well-defined network called the disease module. A disease module can be defined by the topological properties of protein interaction networks. Given the complexity of the whole interaction map the existence of such disease modules remains largely to be tested. Here, we found a type 2 diabetes disease module in insulin receptor-containing endosomes. The disease module contains new pathways that are associated with both insulin signaling, clearance and secretion. Its co-functionality with islets biology may provide a mechanistic rationale for the exploration of personalized medicine and elaborate new drugs.
SKEMPI 2.0: An updated benchmark of changes in protein-protein binding energy, kinetics and thermodynamics upon mutation
Authors: Jankauskaitė Justina , Jiménez-García Brian , Dapkūnas Justas , Fernández-Recio Juan , Moal Iain H. 
Published: June 2018

AbstractMotivationUnderstanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein-protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering.ResultsWe present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein-protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations which abolish detectable binding.AvailabilityThe database is available at https://life.bsc.es/pid/skempi2/
Computational enhancement of single-cell sequences for inferring tumor evolution
Authors: Miura Sayaka , Huuki Louise A , Buturla Tiffany , Vu Tracy , Gomez Karen , Kumar Sudhir 
Published: June 2018

AbstractMotivation: Tumor sequencing has entered an exciting phase with the advent of single-cell techniques that are revolutionizing the assessment of single nucleotide variation (SNV) at the highest cellular resolution. However, state-of-the-art single-cell sequencing technologies produce data with many missing bases (MBs) and incorrect base designations that lead to false-positive (FP) and false-negative (FN) detection of somatic mutations. While computational methods are available to make biological inferences in the presence of these errors, the accuracy of the imputed MBs and corrected FPs and FNs remains unknown.Results: Using computer simulated datasets, we assessed the robustness performance of four existing methods (OncoNEM, SCG, SCITE, and SiFit) and one new method (BEAM). BEAM is a Bayesian evolution-aware method that improves the quality of single-cell sequences by using the intrinsic evolutionary information in the single-cell data in a molecular phylogenetic framework. Overall, BEAM and SCITE performed the best. Most of the methods imputed MBs with high accuracy, but effective detection and correction of FPs and FNs require sampling a large number of SNVs. Analysis of an empirical dataset shows that computational methods can improve both the quality of tumor single-cell sequences and their utility for biological inference.Conclusions: Tumor cells descend from pre-existing cells, which creates evolutionary continuity in single-cell sequencing datasets. This information enables BEAM and other methods to correctly impute missing data and incorrect base assignments, but correction of FPs and FNs remains challenging when the number of SNVs sampled is small relative to the number of cells sequenced.Availability:BEAM is available on the web athttps://github.com/SayakaMiura/BEAM.Contact:s.kumar@temple.edu
The Chromatin-binding Protein Spn1 contributes to Genome Instability inSaccharomyces cerevisiae
Authors: Thurston Alison K. , Radebaugh Catherine A. , Almeida Adam R. , Argueso Juan Lucas , Stargell Laurie A. 
Published: June 2018

AbstractCells expend a large amount of energy to maintain their DNA sequence. DNA repair pathways, cell cycle checkpoint activation, proofreading polymerases, and chromatin structure are ways in which the cell minimizes changes to the genome. During replication, the DNA damage tolerance pathway allows the replication forks to bypass damage on the template strand. This avoids prolonged replication fork stalling, which can contribute to genome instability. The DNA damage tolerance pathway includes two sub-pathways: translesion synthesis and template switch. Post-translational modification of PCNA and the histone tails, cell cycle phase, and local DNA structure have all been shown to influence sub-pathway choice. Chromatin architecture contributes to maintaining genome stability by providing physical protection of the DNA and by regulating DNA processing pathways. As such, chromatin-binding factors have been implicated in maintaining genome stability. UsingSaccharomyces cerevisiae, we examined the role of Spn1, a chromatin binding and transcription elongation factor, in DNA damage tolerance. Expression of a mutant allele ofSPN1results in increased resistance to the DNA damaging agent methyl methanesulfonate, lower spontaneous and damage-induced mutation rates, along with increased chronological lifespan. We attribute these effects to an increased usage of the template switch branch of the DNA damage tolerance pathway in thespn1strain. This provides evidence for a role of wild type Spn1 in promoting genome instability, as well as having ties to overcoming replication stress and contributing to chronological aging.
A fast mrMLM algorithm for multi-locus genome-wide association studies
Authors: Tamba Cox Lwaka , Zhang Yuan-Ming 
Published: June 2018

AbstractBackgroundRecent developments in technology result in the generation of big data. In genome-wide association studies (GWAS), we can get tens of million SNPs that need to be tested for association with a trait of interest. Indeed, this poses a great computational challenge. There is a need for developing fast algorithms in GWAS methodologies. These algorithms must ensure high power in QTN detection, high accuracy in QTN estimation and low false positive rate.ResultsHere, we accelerated mrMLM algorithm by using GEMMA idea, matrix transformations and identities. The target functions and derivatives in vector/matrix forms for each marker scanning are transformed into some simple forms that are easy and efficient to evaluate during each optimization step. All potentially associated QTNs with P-values ≤ 0.01 are evaluated in a multi-locus model by LARS algorithm and/or EM-Empirical Bayes. We call the algorithm FASTmrMLM. Numerical simulation studies and real data analysis validated the FASTmrMLM. FASTmrMLM reduces the running time in mrMLM by more than 50%. FASTmrMLM also shows high statistical power in QTN detection, high accuracy in QTN estimation and low false positive rate as compared to GEMMA, FarmCPU and mrMLM. Real data analysis shows that FASTmrMLM was able to detect more previously reported genes than all the other methods: GEMMA/EMMA, FarmCPU and mrMLM.ConclusionsFASTmrMLM is a fast and reliable algorithm in multi-locus GWAS and ensures high statistical power, high accuracy of estimates and low false positive rate.Author SummaryThe current developments in technology result in the generation of a vast amount of data. In genome-wide association studies, we can get tens of million markers that need to be tested for association with a trait of interest. Due to the computational challenge faced, we developed a fast algorithm for genome-wide association studies. Our approach is a two stage method. In the first step, we used matrix transformations and identities to quicken the testing of each random marker effect. The target functions and derivatives which are in vector/matrix forms for each marker scanning are transformed into some simple forms that are easy and efficient to evaluate during each optimization step. In the second step, we selected all potentially associated SNPs and evaluated them in a multi-locus model. From simulation studies, our algorithm significantly reduces the computing time. The new method also shows high statistical power in detecting significant markers, high accuracy in marker effect estimation and low false positive rate. We also used the new method to identify relevant genes in real data analysis. We recommend our approach as a fast and reliable method for carrying out a multi-locus genome-wide association study.
Nonlinear processing of shape information in rat lateral extrastriate cortex
Authors: Matteucci Giulio , Marotti Rosilari Bellacosa , Riggi Margherita , Rosselli Federica B. , Zoccolan Davide 
Published: June 2018

AbstractIn rodents, the progression of extrastriate areas located laterally to primary visual cortex (V1) has been assigned to a putative object-processing pathway (homologous to the primate ventral stream), based on anatomical considerations. Recently, we found functional support for such attribution (Tafazoli et al., 2017), by showing that this cortical progression is specialized for coding object identity despite view changes – the hallmark property of a ventral-like pathway. Here, we sought to clarify what computations are at the base of such specialization. To this aim, we performed multi-electrode recordings from V1 and laterolateral area LL (at the apex of the putative ventral-like hierarchy) of male adult rats, during the presentation of drifting gratings and noise movies. We found that the extent to which neuronal responses were entrained to the phase of the gratings sharply dropped from V1 to LL, along with the quality of the receptive fields inferred through reverse correlation. Concomitantly, the tendency of neurons to respond to different oriented gratings increased, while the sharpness of orientation tuning declined. Critically, these trends are consistent with the nonlinear summation of visual inputs that is expected to take place along the ventral stream, according to the predictions of hierarchical models of ventral computations and a meta-analysis of the monkey literature. This suggests an intriguing homology between the mechanisms responsible for building up shape selectivity and transformation tolerance in the visual cortex of primates and rodents, reasserting the potential of the latter as models to investigate ventral stream functions at the circuitry level.Significance StatementDespite the growing popularity of rodents as models of visual functions, it remains unclear whether their visual cortex contains specialized modules for processing shape information. To addresses this question, we compared how neuronal tuning evolves from rat primary visual cortex (V1) to a downstream visual cortical region (area LL) that previous work has implicated in shape processing. In our experiments, LL neurons displayed a stronger tendency to respond to drifting gratings with different orientations, while maintaining a sustained response across the whole duration of the drift cycle. These trends match the increased complexity of pattern selectivity and the augmented tolerance to stimulus translation found in monkey visual temporal cortex, thus revealing a homology between shape processing in rodents and primates.
Perception of environmental polypeptides inC. elegansactivates insulin/IGF signaling and alters lipid metabolism
Authors: Kaplan Rebecca E. W. , Webster Amy K. , Chitrakar Rojin , Dent Joseph A. , Ryan Baugh L. 
Published: June 2018

AbstractFood perception affects animal physiology in complex ways. We uncoupled the effects of food perception and ingestion in the roundwormC. elegans. Perception was not sufficient to promote development, but larvae exposed to food without ingestion failed to develop upon return to normal culture conditions. Inhibition of gene expression during perception rescued subsequent development, demonstrating the response to perception without feeding is deleterious. Perception altered DAF-16/FOXO localization, reflecting activation of insulin/IGF signaling (IIS). The insulin-like peptidedaf-28was specifically required, suggesting perception in chemosensory neurons directly regulates peptide secretion. Gene expression and Nile Red staining suggest that perception alters lipid metabolism. Environmental polypeptides are sensed by starved larvae and promote dauer diapause recovery. We conclude that polypeptides are perceived as a food-associated cue, initiating a signaling and gene regulatory cascade that alters metabolism in anticipation of feeding and development, but that this response is detrimental if feeding does not occur.
RNA Binding Motif Protein 48 is required for U12 splicing and maize endosperm differentiation
Authors: Bai Fang , Corll Jacob , Shodja Donya N. , Davenport Ruth , Feng Guanqiao , Mudunkothge Janaki , Brigolin Christian J. , Martin Federico , Spielbauer Gertraud , Tseung Chi-Wah , Siebert Amy E. , Barbazuk W. Brad , Lal Shailesh , Settles A. Mark 
Published: June 2018

AbstractThe last eukaryotic common ancestor had two classes of introns that are still found in most eukaryotic lineages. Common U2-type and rare U12-type introns are spliced by the major and minor spliceosomes, respectively. Relatively few splicing factors have been shown to be specific to the minor spliceosome. We found that the maize RNA Binding Motif Protein48 (RBM48) is a U12 splicing factor that functions to promote cell differentiation and repress cell proliferation. RBM48 is coselected with the U12 splicing factor, ZRSR2/RGH3. Protein-protein interactions between RBM48, RGH3, and U2 Auxiliary Factor (U2AF) subunits suggest major and minor spliceosome factors may form complexes during intron recognition. Human RBM48 interacts with ARMC7. Maize RBM48 and ARMC7 have a conserved protein-protein interaction. These data predict that RBM48 is likely to function in U12 splicing throughout eukaryotes and that U12 splicing promotes endosperm cell differentiation in maize.
Soluble CD93 is an Apoptotic Cell Opsonin Recognized by the αxβ2Integrin
Authors: Blackburn Jack W.D. , Lau Darius H.C. , Ellins Jessica , Kipp Angela , Pawlak Emily N. , Dikeakos Jimmy D. , Heit Bryan 
Published: June 2018

AbstractEfferocytosis – the phagocytic removal of apoptotic cells – is essential for the maintenance of homeostasis and prevention of the inflammatory and autoimmune diseases which can follow the lysis of uncleared apoptotic cells. CD93 is a transmembrane glycoprotein previously implicated in efferocytosis and angiogenesis, and upon mutation, results in the onset of efferocytosis-associated diseases such as atherosclerosis and rheumatoid arthritis. CD93 is produced as a cell surface protein which is shed as soluble CD93, but it is unknown how CD93 mediates efferocytosis or whether its efferocytic activity is mediated by the soluble or membrane-bound form. Herein, we demonstrate that the membrane bound form of CD93 has no phagocytic, efferocytic, or tethering activity, whereas soluble CD93 potently opsonizes apoptotic cells but not a broad range of Gram-Negative, Gram-Positive or fungal microorganisms. Using mass spectrometry, we identified the αxβ2integrin as the receptor required for soluble CD93-mediated efferocytosis, and via deletion mutagenesis determined that soluble CD93 binds to apoptotic cells via its C-Type Lectin-Like domain, and to αxβ2by its EGF-like repeats. This bridging of apoptotic cells to the αxβ2integrin markedly enhanced efferocytosis by macrophages, and could be abrogated by knockdown of αxβ2integrin. Combined, these data elucidate the mechanism by which CD93 regulates efferocytosis and identify a previously unreported opsonin-receptor system utilized by the immune system for the efferocytic clearance of apoptotic cells.
Challenging the difference between white and brown Agaricus bisporus mushrooms
Authors: Vunduk Jovana , Djekic Ilija , Petrović Predrag , Tomašević Igor , Kozarski Maja , Despotović Saša , Nikšić Miomir , Klaus Anita 
Published: June 2018

Purpose
The purpose of this paper is to examine compositional differences between brown and white varieties of Agaricus bisporus during shelf life and to determine if the growing demand for the brown variety is scientifically justified.

Design/methodology/approach
Field research enabled analyzing consumers’ perceptions on intrinsic, extrinsic and quality characteristics of mushrooms. A total of 275 consumers participated in the survey. Obtained results were used for comparing white and brown varieties of A. bisporus over a period of 22 days. Mushrooms were packed in air and in modified atmosphere packaging (MAP) at 4°C. Samples were analyzed for their nutritional, antioxidative and microbiological characteristics.

Findings
Two weeks from harvest, white variety showed higher amount of essential nutrients, while during the third week, brown mushrooms were more nutritionally valuable. Brown variety had better antioxidative ability for all 22 days of storage. Aerobic plate count (APC) was as expected for the mushrooms. MAPs significantly lowered APC in both varieties. The number of Enterobacteriaceae was equal for both varieties at the beginning, but later on they developed much faster in the case of brown variety. Field research combined with specific analyses clarified that there are no nutritive or microbiological reasons for the precedence of brown variety over white.

Research limitations/implications
Sensory aspect of the quality of mushrooms was not analyzed.

Originality/value
Market trend toward brown variety was scientifically challenged.
Internet-based digitalmarketing strategies fordata-rich environments
Authors: Kiran Faiqa , Zubair Ahsan , Shahzadi Irum , Abbas Aamir 
Published: June 2018

Purpose
The purpose of this paper is to first bring to light the essential digital strategies to study organizations. Second, how businesses can improve their strategic capabilities by using the information gathered from internet sources or networks. Third, this study investigates how employees in an organization tend to engage in positive and/or negative gossip and how gossips affect coworker-rated informal influence in organization and supervisor-rated performance. Social network analysis is used to find the underlying relationships between gossips, coworker-rated influence and supervisor-rated performance.

Design/methodology/approach
This research paper is divided into two parts. The first study based on profound synthesis of literature. Major digital sources to study organizations are identified. The strategies requirement for each channel is identified. Suggestions are given to managers to improve strategic decision-making based on big data. The second study is a cross-sectional study where questionnaires (survey) are used to elicit data. Social network analysis is used to analyze the data using ucinet 6 software.

Findings
The findings of the study pinpoint the skills required to analyze large data, available in organizations. The second study finds out that close friends are more engaged in gossips than coworkers who have only working relationships. The friends having high structural embeddedness are more likely to be involved in negative gossips. Coworker perceives those employees who are engaged in negative gossips as having high informal influence. However, there is negative relationship between negative gossips and supervisor-rated influence.

Research limitations/implications
The research study is cross-sectional in design; however, longitudinal design can be used to gain more insights about negative gossips and their effects. Second, a very small sample is used in this study.

Practical implications
This study can be used to understand informal communication network in the organization. Managers can use this channel to pass information quickly, as informal channels are faster than formal communication channels. This research can be used to understand the underling relationships between the coworkers in organizations

Originality/value
This paper provides guidelines to organizational life and information on how the informal networks within organization can be studied.
Collaborative innovation in tourism and hospitality: a systematic review of the literature
Authors: Marasco Alessandra , De Martino Marcella , Magnotti Fabio , Morvillo Alfonso 
Published: June 2018

Purpose
The purpose of this study is to provide a synthesis of the state of research on collaborative innovation in tourism and hospitality. It presents a systematic review of the academic literature, and provides insights into the specific issues addressed by studies in this area.

Design/methodology/approach
A search of major research databases with multiple keywords was performed to identify relevant articles up to 2017. A total of 79 articles were identified and analyzed according to the following criteria: location of the study, perspective of analysis, methodology, level of analysis and specific themes addressed.

Findings
Based on a qualitative thematic analysis, five groups of articles were identified: cooperative behavior of innovating firms, co-creation, collaborative networks for innovation, knowledge transfer and innovation policies.

Research limitations/implications
This study contributes to making the current body of knowledge on collaborative innovation in tourism and hospitality more organized. The analysis of the different issues addressed by the literature could build the foundation for future research.

Originality/value
This study presents a comprehensive review of literature on collaborative innovation in tourism and hospitality. It can serve as a roadmap of literature for both academicians and practitioners, and help stimulate further interest.