bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYPT1 O-GlcNAcylation Dictates Timely Disjunction of Centrosomes
Authors: Liu Caifei , Shi Yingxin , Liu Xuewen , Xiahou Zhikai , Li Jie , Tan Zhongping , Chen Xing , Li Jing 
Published: October 2019

ABSTRACTThe role of O-linked N-acetylglucosamine (O-GlcNAc) modification in the cell cycle has been enigmatic. Previously, both O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) disruption have been shown to derail the mitotic centrosome numbers, suggesting that mitotic O-GlcNAc oscillation needs to be in concert with mitotic progression to account for centrosome integrity. Here we attempted to address the underlying molecular mechanism by both chemical approaches and biological assays, and observed that Thiamet-G (OGA inhibitor) incubation strikingly elevated centrosomal distances, suggestive of premature centrosome disjuction. These aberrancies could be overcome by inhibiting Polo-like kinase 1 (Plk1), a mitotic master kinase. Plk1 inactivation is modulated by the Myosin Phosphatase Targeting Subunit 1 (MYPT1)-Protein Phosphatase 1 cβ (PP1cβ) complex. Interestingly, MYPT1 is abundantly O-GlcNAcylated and the modified residues have been detected in a recent O-GlcNAc profiling screen utilizing chemoenzymatic labeling and bioorthogonal conjugation. We demonstrate that MYPT1 is O-GlcNAcylated at T577, S585, S589 and S601, which antagonizes CDK1-dependent phosphorylation at S473, subsequently attenuating the association between MYPT1 and Plk1, and promoting PLK1 activity. Thus under high O-GlcNAc, Plk1 is untimely activated, conducive to inopportune centrosome separation and disrupting the cell cycle. We propose that too much O-GlcNAc is equally deleterious as too little O-GlcNAc, and a fine balance between the OGT/OGA duo is indispensible for successful mitotic divisions.
A topological analysis of difference topology experiments of condensin with Topoisomerases II
Authors: Kim Soojeong , Darcy Isabel K. 
Published: October 2019

ABSTRACTAn experimental technique called difference topology combined with the mathematics of tangle analysis has been used to unveil the structure of DNA bound by the Mu transpososome. However, difference topology experiments can be difficult and time-consuming. We discuss a modification that greatly simplifies this experimental technique. This simple experiment involves using a topoisomerase to trap DNA crossings bound by a protein complex and then running a gel to determine the crossing number of the knotted product(s). We develop the mathematics needed to analyze the results and apply these results to model the topology of DNA bound by 13S condensin and by the condensin MukB.SUMMARY STATEMENTTangles are used to model protein-DNA complexes: A 3-dimensional ball represents protein while strings embedded in this ball represent protein-bound DNA. We use this simple model to analyze experimental results.
Assessment of phylo-functional coherence along the bacterial phylogeny and taxonomy
Authors: Parras-Moltó Marcos , de Cárcer Daniel Aguirre 
Published: October 2019

ABSTRACTIn this report we use available curated phylogenies, taxonomy, and genome annotations to assess the phylogenetic and gene content similarity associated with each different taxa and taxonomic rank. Subsequently, we employ the same data to delimit the frontiers of functional coherence along the bacterial phylogeny. Our results show that within-group phylogenetic and gene content similarity of taxa in the same rank are not homogenous, and that these values show extensive overlap between ranks. Functional coherence along the 16S rRNA gene-based phylogeny was limited to 44 particular nodes presenting large variations in phylogenetic depth. For instance, the deep subtree affiliated to class Actinobacteria presented functional coherence, while the shallower family Enterobacteriaceae-affiliated subtree did not. On the other hand, functional coherence along the genome-based phylogeny delimited deep subtrees affiliated to phyla Actinobacteriota, Deinococcota, Chloroflexota, Firmicutes, and a subtree containing the rest of the bacterial phyla.IMPORTANCEWhile bacterial taxonomy and phylogeny resources as well as related bioinformatic tools continue to improve, the question remains as to how they should best be employed in studies using 16S rRNA gene surveys to assess bacteria-ecosystem relationships, a widespread approach. The results contained herein lead to the recommendation that all ranks from genus to class/phylum be employed if using taxonomic binning in the analysis of 16S rRNA gene surveys. With regards to the use of phylogeny or clustering-based approaches, single or arbitrary tree topology or sequence distance thresholds should not be employed. Instead, the results presented here can be used to obtain more meaningful results in many microbial ecology and evolution research scenarios. Moreover, we provide dedicated scripts and files that can be used to continue the exploration of functional coherence along the bacterial phylogeny employing different parameters or input data.
Mechanism of RPA-Facilitated Processive DNA Unwinding by the Eukaryotic CMG Helicase
Authors: Kose Hazal B. , Xie Sherry , Cameron George , Strycharska Melania S. , Yardimci Hasan 
Published: October 2019

AbstractThe DNA double helix is unwound by the Cdc45/Mcm2-7/GINS (CMG) complex at the eukaryotic replication fork. While isolated CMG unwinds duplex DNA very slowly, its fork unwinding rate is stimulated by an order of magnitude by single-stranded DNA binding protein, RPA. However, the molecular mechanism by which RPA enhances CMG helicase activity remained elusive. Here, we demonstrate that engagement of CMG with parental double-stranded DNA (dsDNA) at the replication fork impairs its helicase activity, explaining the slow DNA unwinding by isolated CMG. Using single-molecule and ensemble biochemistry, we show that binding of RPA to the excluded DNA strand prevents duplex engagement by the helicase and speeds up CMG-mediated DNA unwinding. When stalled due to dsDNA interaction, DNA rezipping-induced helicase backtracking re-establishes productive helicase-fork engagement underscoring the significance of plasticity in helicase action. Together, our results elucidate the dynamics of CMG at the replication fork and reveal how other replisome components can mediate proper DNA engagement by the replicative helicase to achieve efficient fork progression.
Clinical extended-spectrum beta-lactamase antibiotic resistance plasmids have diverse transfer rates and can spread in the absence of antibiotic selection
Authors: Benz Fabienne , Huisman Jana S. , Bakkeren Erik , Herter Joana A. , Stadler Tanja , Ackermann Martin , Diard Médéric , Egli Adrian , Hall Alex R. , Hardt Wolf-Dietrich , Bonhoeffer Sebastian 
Published: October 2019

AbstractHorizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global spread of antibiotic resistance. However, the relative contributions of factors that underlie the spread of clinically relevant plasmids are unclear. Here, we quantified conjugative transfer dynamics of Extended Spectrum Beta-Lactamase (ESBL) producing plasmids in the absence of antibiotics. We showed that clinicalEscherichia colistrains natively associated with ESBL-plasmids conjugate efficiently with three distinctE. colistrains and oneSalmonellaenterica serovar Typhimurium strain, reaching final transconjugant frequencies of up to 1% within 24 hoursin vitro. The variation of final transconjugant frequencies varied among plasmids, donors and recipients and was better explained by variation in conjugative transfer efficiency than by variable clonal expansion. We identified plasmid-specific genetic factors, specifically the presence/absence of transfer genes, that influenced final transconjugant frequencies. Finally, we investigated plasmid spread within the mouse intestine, demonstrating qualitative agreement between plasmid spreadin vitroandin vivo.This suggests a potential for the prediction of plasmid spread in the gut of animals and humans, based onin vitrotesting. Altogether, this may allow the identification of resistance plasmids with high spreading potential and help to devise appropriate measures to restrict their spread.
A Study of Association of ABO Blood Group types with Cancer Risk
Authors: Singh Vishal , Yadav Upendra , Rai Vandana , Kumar Pradeep 
Published: October 2019

ABSTRACTMore than 30 blood group systems have been recognized by International Society of Blood Transfusion (ISBT). ABO blood group is one of the most studied blood group system. ABO blood group system consist of three alleles A, B and O, out which A and B are co-dominant and O is recessive. Many researchers and investigators have found association between ABO blood group and cancer risk. It was found from the recent data that blood group A and AB is associated with increased pancreatic and gastric cancer risk. In the present study data of ABO blood group of 243 patients, both males and females, with confirmed cases of cancer was obtained from Sir Sunderlal hospital, Institute of Medical Science (IMS), Banaras Hindu University (BHU) and Apex hospital, DLW Road, Varanasi. 250 Samples of both males and females were taken as control. Out of 243 cancer patients 117 were males and 126 were females. In 243 cases enrolled in present study, highest number of cases were of breast cancer among women and lowest were rectal cancer. It was found that A blood group was associated with breast cancer, oral cancer, liver cancer and ovarian cancer as compared to other blood group and blood group O was associated with lung cancer, gastric cancer, colon cancer, skin cancer and endometrial cancer.
Comprehensive characterization of the mutational landscape in localized anal squamous cell carcinoma
Authors: Trilla-Fuertes Lucía , Ghanem Ismael , Maurel Joan , G-Pastrián Laura , Mendiola Marta , Peña Cristina , López-Vacas Rocío , Prado-Vázquez Guillermo , López-Camacho Elena , Zapater-Moros Andrea , Heredia Victoria , Cuatrecasas Miriam , García-Alfonso Pilar , Capdevila Jaume , Conill Carles , García-Carbonero Rocío , Heath Karen E. , Ramos-Ruiz Ricardo , Llorens Carlos , Campos-Barros Ángel , Gámez-Pozo Angelo , Feliu Jaime , Vara Juan Ángel Fresno 
Published: October 2019

AbstractPurposeAnal squamous cell carcinoma (ASCC) is a rare neoplasm. Chemo-radiotherapy is the standard of care, with no therapeutic advances achieved over the past three decades. Thus, a deeper molecular characterization of this disease is still necessary.MethodsWe analyzed 46 paraffin-embedded tumor samples from patients diagnosed with primary ASCC by exome sequencing. A bioinformatics approach focused in the identification of high impact genetic variants, which may act as drivers of oncogenesis, was performed. The relation between genetics variant and prognosis was also studied.ResultsThe list of high impact genetic variants was unique for each patient. However, the pathways in which these genes are involved are well-known hallmarks of cancer, such as angiogenesis or immune pathways. Additionally, we determined that genetic variants inBRCA2, ZNF750, FAM208B, ZNF599andZC3H13genes are related with poor disease-free survival in ASCC.ConclusionHigh impact genetic variants in ASCC affect pathways involved in cancer development, and may play a role in the etiology of the disease. Variants inBRCA2, ZNF750, FAM208B, ZNF599andZC3H13genes seem to be related with prognosis in ASCC. Sequencing of ASCC clinical samples appears an encouraging tool for the molecular portrait of this disease.
A proximity-dependent biotinylation map of a human cell: an interactive web resource
Authors: Go Christopher D. , Knight James D.R. , Rajasekharan Archita , Rathod Bhavisha , Hesketh Geoffrey G. , Abe Kento T. , Youn Ji-Young , Samavarchi-Tehrani Payman , Zhang Hui , Zhu Lucie Y. , Popiel Evelyn , Lambert Jean-Philippe , Coyaud Étienne , Cheung Sally W.T. , Rajendran Dushyandi , Wong Cassandra J. , Antonicka Hana , Pelletier Laurence , Palazzo Alexander F. , Shoubridge Eric A. , Raught Brian , Gingras Anne-Claude 
Published: October 2019

ABSTRACTCompartmentalization is a defining characteristic of eukaryotic cells, partitioning cellular processes into discrete subcellular locations. High throughput microscopy1 and biochemical fractionation coupled with mass spectrometry2–6 have helped to define the proteomes of a variety of organelles and macromolecular structures. However, many other intracellular compartments have remained refractory to such approaches, due for example to difficulty in purifying non-membrane bound structures. Proximity-dependent biotinylation techniques such as BioID provide an alternative approach for defining the composition of cellular compartments in living cells7–10. Here we present a BioID-based map of a human cell based on 192 markers from 32 different subcellular compartments, comprising 35,902 high confidence proximity interactions, and defining the intracellular locations of 4,145 unique proteins in HEK 293 cells. Our localization predictions meet or exceed previous-approaches, with higher specificity, and enabled the discovery of proteins at the mitochondrial outer membrane-endoplasmic reticulum (ER) interface that are critical for mitochondrial homeostasis. Based on this dataset, we have established humancellmap.org as a community resource that provides online tools for localization analysis of user BioID data, and demonstrate how this resource can be used to better understand BioID datasets.
Mitogen-independent cell cycle progression in B lymphocytes
Authors: Singh Amit , Spitzer Matthew H. , Joy Jaimy P. , Kaileh Mary , Qiu Xiang , Nolan Garry P. , Sen Ranjan 
Published: October 2019

AbstractThe canonical view of the cell cycle posits that G1 progression signals are essential after each mitosis to enter S phase. A subset of tumor cells bypass this requirement and progress to the next cell division in the absence of continued signaling. B and T lymphocytes of the adaptive immune system undergo a proliferative burst, termed clonal expansion, to generate pools of antigen specific cells for effective immunity. There is evidence that rules for lymphocyte cell division digress from the canonical model. Here we show that B lymphocytes sustain several rounds of mitogen-independent cell division following the first mitosis. Such division is driven by unique characteristics of the post mitotic G1 phase and limited by extensive cell death that can be circumvented by appropriate anti-apoptotic signals. An essential component for continued cell division is Birc5 (survivin), a protein associated with chromosome segregation in G2/M. Our observation provides direct evidence for Pardee’s hypothesis that retention of features of G2M in post-mitotic cells could trigger further cell cycle progression. The partially active G1 phase and propensity for apoptosis that is inherited after each division may permit rapid burst of proliferation and cell death that are hallmarks of immune responses.
Supply chain innovation research: content analysis based review
Authors: Jajja Muhammad Shakeel Sadiq , Asif Muhammad , Shah Syed Aamir Ali , Chatha Kamran Ali 
Published: October 2019

PurposeThe purpose of this paper is to analyze research methodologies and publication trends across geographical regions in the field of supply chain innovation (SCI) and provide a discussion of future research in the SCI.Design/methodology/approachUsing a content analysis approach, this paper investigates 26 years of SCI research based on a sample of 473 journal articles published in 77 peer-reviewed international journals.FindingsThere has been an increasing focus on empirical quantitative research design as compared to empirical qualitative, conceptual quantitative and conceptual qualitative designs in the field of SCI. Continued research interest in SCI from all parts of the world including North America, Europe and Asia illustrates the importance of SCI in the broader field of management.Research limitations/implicationsThe inclusion of a large number of journals provides greater confidence in the identified trends. However, as the top-tier journals publish only the most rigorous studies, considering all journals as equally weighted will give rise to a mixed pool of studies. Identifying trends from this mixed pool may provide more comprehensiveness at the cost of inclusion of non-core journals of the field.Originality/valueThe current study builds a holistic view of the methodological progress made so far in the field of SCI.
Time, island and ambulance type characteristics of patient transfers from two Turkish islands
Authors: Caliskan Cuneyt , Altintas K. Hakan 
Published: October 2019

Purpose
The purpose of this paper is to evaluate the time, place and ambulance types specified on the ambulance patient registry forms for cases transferred through 112 EMS in the Bozcaada and Gökçeada island districts of the province of Çanakkale.

Design/methodology/approach
The universe of the descriptive – cross-sectional epidemiological study was composed of the ambulance patient registration forms of the cases which were transferred from Bozcaada and Gökçeada islands between January 1, 2009 and December 31, 2013.

Findings
Of the transfers made, 28.1 percent were in the year 2012, 39.5 percent were in summer, 16.6 percent were in July, 17.9 percent were on Monday, 37.1 percent were between 12.00 and 17.59 h and 61.5 percent were from Gökçeada island. Ground ambulances were more common in the transfers from Bozcaada island, while ambulance boat and helicopter ambulance were more common for transfers from Gökçeada island. Helicopter-Emergency Medical Service (HEMS) (p<0.001), which is commonly preferred for patient transfers, inversely affects the use of Ambulance Boat-Emergency Medical Service (BEMS) and ground ambulances. Transfers from Bozcaada island were found to be shorter in duration, and the number of transfers from Bozcaada island between 00.00 and 05.59 h were found to be higher than from Gökçeada island (p<0.001), while the number of transfers via ground ambulance between 00.00 and 05.59 h were found to be higher than the other ambulance types (p<0.001).

Practical implications
This study reveals the current state of the various referral routes from the islands.

Originality/value
This paper is the first study to demonstrate the characteristics of patients referred from the island belongs to Turkey.
The European Union’s multi-level impact on member state projectification in light of neoinstitutional theory
Authors: Jałocha Beata 
Published: October 2019

PurposeThe purpose of this paper is to understand how has the European Union (EU) funding influenced projectification of the Polish public sector. The projectification of the public sector is analysed in relation to three levels: mega (state level), macro (sector level) and mezo (organisation level). Hence, it is understood as a multidimensional phenomenon that permeates different social structures. The study also applies elements of neoinstitutional theory and Europeanisation concept to the research on projectification.Design/methodology/approachThe research is based on the mixed methods approach. The adopted methods (document analysis, quantitative analysis and in-depth interviews) are both qualitative and quantitative in nature and were used sequentially to address the research question, while securing the triangulation of the data.FindingsThe Polish public sector was projectified as a result of the implementation of hundreds of thousands of projects co-financed by the EU, which among other things, effected in legal regulations that support the project implementation of public tasks and changes in organisational structures towards a project-oriented direction. At public organisation level, it causes changes in the scope of organisational structures, strategic management processes and methods of work. On the basis of the assumptions that explain the mechanism of organisational isomorphism and Europeanisation, the paper may conclude that the public sector projectification process was triggered by a misfit between the projectified EU structures and the low degree of projectification in the Polish public sector.Originality/valueThe study is the first step to try to understand how the massification of project activities can affect the activities of the public sector of the particular country and the shaping of public policies at home. Because Poland has been the largest beneficiary of EU funds in Europe for over ten years, it can be assumed that these processes in this country are particularly intense. An attempt was also made to identify the scale of the public sector projectification process in Poland by not only describing, but also quantifying the phenomenon.
The phenomena of overtourism: a review
Authors: Dodds Rachel , Butler Richard 
Published: October 2019

PurposeThe purpose of this paper is to examine the emergence of overtourism, outline the issues and contributing factors, as it relates to cities, and to suggest possible mitigation measures that might be taken by policy makers.Design/methodology/approachThis paper draws from a review of literature looking at longitudinal issues of tourism development overtime and what has contributed to the phenomena of overtourism. A discussion of implications is provided from this review.FindingsAs tourism is an industry which has historically been poorly managed, greater political will and actual acknowledgement of the problem, as well as action by all levels of government are the necessary first steps to address overtourism.Practical implicationsThis paper outlines key elements that contribute to overtourism and provides global examples which may help practitioners identify key critical issues in their own destinations and identify appropriate actions.Social implicationsThis paper identifies issues raised by local resident populations and possible responses.Originality/valueThis paper provides a critical overview of overtourism issues, as it relates to cities and discusses potential mitigation and reduction efforts, thereby providing an explanation of why overtourism has become so prevalent.
The significance of the contribution of children to conceptualising the destination of the future
Authors: Seraphin Hugues , Green Sarah 
Published: October 2019

PurposeAs there is a growing demand of cutting-edge technology as part of the tourism experience from the digital native population and because little is known about this group as tourism consumers despite the fact they will be the core tourism spender of tomorrow, the purpose of this paper is to give children an opportunity to share their vision of the destination of the future.Design/methodology/approachFrom a methodological point of view, a qualitative approach is adopted. Children were asked to draw, communicate and display their view on their Winchester of the future. The data collected are used to formulate an innovative, smart-based future-fit management approach for products and services design.FindingsTo fully meet the needs and expectation of the coming generation of tourists, Winchester (city located in the South of England, and surrounded by some of the most visited UK destinations, namely London, Oxford and Cambridge) will have to adopt an ambidextrous management approach when developing products and services for customers of the future. This ambidextrous management approach will balance metaphorical thinking and objective thinking in product and service design.Originality/valueThere is a scarcity of studies on children in tourism research despite the fact the industry and academics recognise the value and impact of children, and more specifically, their role in purchase decisions. Equally important, this research is also going to contribute to the body of knowledge on smart management of destinations.