bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accurate prediction of orthologs in the presence of divergence after duplication
Authors: Lafond Manuel , Miardan Mona Meghdari , Sankoff David 
Published: April 2018

AbstractMotivationWhen gene duplication occurs, one of the copies may become free of selective pressure and evolve at an accelerated pace. This has important consequences on the prediction of orthology relationships, since two orthologous genes separated by divergence after duplication may differ in both sequence and function. In this work, we make the distinction between the primary orthologs, which have not been affected by accelerated mutation rates on their evolutionary path, and the secondary orthologs, which have. Similarity-based prediction methods will tend to miss secondary orthologs, whereas phylogeny-based methods cannot separate primary and secondary orthologs. However, both types of orthology have applications in important areas such as gene function prediction and phylogenetic reconstruction, motivating the need for methods that can distinguish the two types.ResultsWe formalize the notion of divergence after duplication, and provide a theoretical basis for the inference of primary and secondary orthologs. We then put these ideas to practice with the HyPPO (Hybrid Prediction of Paralogs and Orthologs) framework, which combines ideas from both similarity and phylogeny approaches. We apply our method to simulated and empirical datasets, and show that we achieve superior accuracy in predicting primary orthologs, secondary orthologs and paralogs.AvailabilityHyPPO is a modular framework with a core developed in Python, and is provided with a variety of C++ modules. The source code is available at https://github.com/manuellafond/HyPPO.Contactmlafond2@uOttawa.ca, mmegh021@uottawa.ca, sankoff@uottawa.ca
PinMol: Python application for designing molecular beacons for live cell imaging of endogenous mRNAs
Authors: Bayer Livia V. , Omar Omar S. , Bratu Diana P. , Catrina Irina E. 
Published: April 2018

ABSTRACTMolecular beacons are nucleic acid oligomers labeled with a fluorophore and a quencher that fold in a hairpin-shaped structure, which fluoresce only when bound to their target RNA. They are used for the visualization of endogenous mRNAs in live cells. Here, we report a Python program (PinMol) that designs molecular beacons best suited for live cell imaging by using structural information from secondary structures of the target RNA, predicted via energy minimization approaches. PinMol takes into account the accessibility of the targeted regions, as well as the inter- and intramolecular interactions of each selected probe. To demonstrate its applicability, we synthesized an oskar mRNA-specific molecular beacon (osk1236), which is selected by PinMol to target a more accessible region than a manually designed oskar-specific molecular beacon (osk2216). We previously demonstrated osk2216 to be efficient in detecting oskar mRNA in in vivo experiments. Here, we show that osk1236 outperformed osk2216 in live cell imaging experiments.
Dissection of yeast pleiotropic drug resistance regulation reveals links between cell cycle regulation and control of drug pump expression
Authors: Li Jian , Kolberg Kristen , Schlecht Ulrich , St.Onge Robert P. , Aparicio Ana Maria , Horecka Joe , Davis Ronald W. , Hillenmeyer Maureen E. , Harvey Colin J.B. 
Published: April 2018

SummaryEukaryotes utilize a highly-conserved set of drug efflux transporters to confer pleiotropic drug resistance (PDR). Despite decades of effort interrogating this process, multiple aspects of the PDR process, in particular PDR regulation, remain mysterious. In order to interrogate the regulation of this critical process, we have developed a small-molecule responsive biosensor that couples PDR transcriptional induction to growth rate inSaccharomyces cerevisiae. We applied this system to genome-wide screens for potential PDR regulators using the homozygous diploid deletion collection. These screens identified and characterized a series of genes with significant but previously uncharacterized roles in the modulation of the yeast PDR in addition to recapitulating previously-known factors involved in PDR regulation. Furthermore, we demonstrate that disruptions of the mitotic spindle checkpoint assembly lead to elevated PDR response in response to exposure to certain compounds. These results not only establish our biosensor system as a viable tool to investigate PDR in high-throughput, but also uncovers novel control mechanisms governing PDR response and a previously uncharacterized link between this process and cell cycle regulation.SignificancePleiotropic drug resistance (PDR) is a conserved mechanism by which cells utilize membrane bound pumps to transport chemicals out of the cell. Here, we develop a growth-based biosensor system in yeast that enables high-throughput identification of factors that transcriptionally regulate PDR. Among the novel PDR regulators identified here, we show that spindle assembly checkpoint (SAC) proteins, which are important for cell cycle regulation, inhibit hyperactivation of PDR upon drug treatment. This result provides insights into PDR regulation, as well as potential targets for therapeutic intervention, particularly in chemoresistant cancers where the cell cycle regulation is often disrupted.
Colonization of phosphate-solubilizingPseudomonassp. strain P34-L in the wheat rhizosphere and its effects on wheat growth and the expression of phosphate transporter geneTaPT4in wheat
Authors: Liu Xixi , Jiang Xiaoxun , Zhao Weirong , Cao Yuanyuan , Guo Tingting , He Xiangyi , Ni Haiting , Tang Xinyun 
Published: April 2018

AbstractThe ability to colonize the rhizosphere is an important basics requirement for field application of plant growth-promoting rhizobacteria (PGPR) strains. There are complex signal exchanges and mutual recognition between microbes and plants. In this study, phosphate-solubilizingPseudomonassp. P34, a PGPR strain with affinity to wheat, was isolated from the wheat rhizosphere by wheat germ agglutinin (WGA). The plasmid pTR102 harboring the luciferaseluxAB gene was transferred into P34 to create P34-L. The labeled strain was used to track the temporal and spatial characteristics of colonization in wheat rhizosphere and its effects on wheat development. The transcript level of phosphate transporter geneTaPT4, a phosphorus deficiency indicator gene, in wheat roots was monitored by quantitative reverse-transcription PCR. The experimental results indicated that there was a high density of stain P34-L within the top 8-cm depth of the wheat rhizosphere on day 36 of wheat growth. The strain could survive in the wheat rhizosphere for a long time, and colonize new spaces in wheat rhizosphere following the extension of wheat roots. Compared with uninoculated wheat plants, those inoculated with P34-L showed significantly increased phosphorus accumulation in leaves, seedling fresh and dry weight, root fresh and dry weight, total root length, and number of root tips, forks, crossings, which showed a great value of application of the strain on wheat production by promoting the root growth and dry matter accumulation. Strain P34-L down-regulated the transcript level ofTaPT4in wheat roots, which means a well phosphorus supplementation environment was established by P34-L.ImportanceMany PGPR strains often failed to achieve the desired effects when applied in the field. One major reason for the failure is lack of a special affinity between a certain strain and the target host plant, so those strains have low competitive ability with the indigenous microorganism, and unable to survive constantly in rhizosphere. In this work, a new technique to isolate wheat-specific phosphate-solubilizing PGPR strain by WGA was established. The isolate P34 was confirmed can colonize the wheat rhizosphere, and have significantly ability in promoting phosphorus absorption and wheat growth by luminescence labeling techniques. Furthermore, the phosphate-solubilizing ability of this affinity PGPR strain was verified in gene level by quantitative reverse-transcription PCR. These results lay a firm foundation for further research on the relationships between PGPR and their host plants. Meanwhile, this work supplied a potential ideal biofertilizer producing strain for sustainable agriculture.
Maintenance of Cell Fates by Regulation of the Histone Variant H3.3 inCaenorhabditis elegans
Authors: Shibata Yukimasa , Nishiwaki Kiyoji 
Published: April 2018

HighlightsTLK-1 maintains cell fates by repression of selector genesTLK-1 and downstream H3 chaperone CAF1 inhibit H3.3 depositionLoss ofsin-3suppresses the defect in cell-fate maintenance oftlk-1mutantsAcH4-binding protein BET-1 is necessary forsin-3suppressionSummaryCell-fate maintenance is important to preserve the variety of cell types that are essential for the formation and function of tissues. We previously showed that the acetylated histone H4-binding protein BET-1 maintains cell fate by recruiting the histone variant H2A.z. Here, we report thatCaenorhabditis eleganstousled-like kinase TLK-1 and the histone H3 chaperone CAF1 maintain cell fate by preventing the incorporation of histone variant H3.3 into nucleosomes, thereby repressing ectopic expression of transcription factors that induce cell-fate specification. Genetic analyses suggested that TLK-1 and BET-1 act in parallel pathways. Intlk-1mutants, the loss of SIN-3, which promotes histone acetylation, suppressed a defect in cell-fate maintenance in a manner dependent on MYST family histone acetyltransferase MYS-2 and BET-1.sin-3mutation also suppressed abnormal H3.3 incorporation. Thus, we propose that the regulation and interaction of histone variants play crucial roles in cell-fate maintenance through the regulation of selector genes.
Mettl14 is required for mouse post-implantation development by facilitating epiblast maturation
Authors: Meng Tie-Gang , Lu Xukun , Guo Lei , Hou Guan-Mei , Ma Xue-Shan , Li Qian-Nan , Huang Lin , Fan Li-Hua , Zhao Zheng-Hui , Ou Xiang-Hong , OuYang Ying-Chun , Schatten Heide , Li Lei , Wang Zhen-Bo , Sun Qing-Yuan 
Published: April 2018

ABSTRACTN6-methyladenosine (m6A) is the most prevalent and reversible internal modification of mammalian messenger and noncoding RNAs mediated by specific m6A writer, reader, and eraser proteins. As an m6A writer, the METTL3–METTL14-WTAP complex dynamically regulates m6A modification and plays important roles in diverse biological processes. However, our knowledge about the complete functions of this RNA methyltransferase complex, the contributions of each component to the methylation and their impacts on different biological pathways, are still very limited. Here, by employing both in vivo and in vitro models, we report that METTL14 was indispensable for post-implantation embryonic development by facilitating the conversion from naïve to primed state of the epiblast. Depletion of Mettl14 lead to conspicuous embryonic growth retardation from E6.5 mainly as a result of resistance to differentiation, which further lead to embryonic lethality early in gestation. Our data highlight the critical function of METTL14, as an m6A modification regulator, in orchestrating early mouse embryogenesis.
Open Universities: the next phase
Authors: Tait Alan 
Published: April 2018

Purpose
The purpose of this paper is to report on research on the views of Presidents and Vice Chancellors of Open Universities of current threats and opportunities for their institutions as the author marks the 50th anniversary of the first Open University in the UK established in 1969. The paper offers a historical account of the development of the Open University model, and assesses the extent to which it remains in the key position as owner of innovation in the higher education sector.

Design/methodology/approach
Interviews were conducted with leaders of Open Universities or distance teaching universities. They covered a total of 14 universities.

Findings
The replies from institutional leaders reveal the current developments, opportunities and strategic challenges of the universities. It is suggested that the digital revolution along with a wider range of environmental changes for higher education have substantially eroded the first-mover advantage that Open Universities had undoubtedly enjoyed in the first 25 years.

Originality/value
The paper concludes that there are significant concerns that innovation in Open Universities is not sufficiently embedded to ensure that their contribution to the UN Sustainable Development Goals will be maximised, or even in some cases their survival, and that a key but undervalued element is leadership development for innovation and change.
Supply chain collaboration and firm’s performance
Authors: Panahifar Farhad , Byrne P.J. , Salam Mohammad Asif , Heavey Cathal 
Published: April 2018

PurposeThe purpose of this paper is to identify and assess the interrelationships between various characteristics of information sharing and trust and their criticality for effective information-centred supply chain collaboration initiatives and, in turn, its criticality to overall firm’s performance.Design/methodology/approachA survey of 189 executives from different firms was conducted and the resulting data were analysed to investigate how collaboration enablers affect effective collaboration and to determine its impacts on organisational performance. Structural equation modelling through partial least squares is used to study the relationships between four enablers (trust, information readiness, information accuracy and information security), perceived collaboration success, and two outcomes (sales growth and overall operational performance).FindingsThe empirical results indicate that three collaboration enablers including trust, information readiness and secure sharing of information improve supply chain collaboration. The present study finds that “secure sharing of information” was the most important factor in fostering information sharing-centred collaboration. The present study also demonstrates that effective collaboration positively and significantly influences on firm’s performance.Practical implicationsThis study provides researchers and practitioners with a more comprehensive understanding about the information sharing-centred collaboration, its enablers and effects on firms’ performance in a supply chain context. Future research should focus on developing additional constructs that may capture other drivers of effective collaboration.Originality/valueThe present study makes an empirical contribution to the body of knowledge by investigating an integrated framework focussing on the enablers of collaboration through information sharing and its impact on firms’ performance.
Workplace spirituality and employee commitment
Authors: Jena Lalatendu Kesari , Pradhan Sajeet 
Published: April 2018

Purpose
The purpose of this paper is to provide an empirical investigation of workplace spirituality (WS) and employee commitment (EC). EC is presumed as a mindset which is generally influenced by spiritual culture and the prospective outcomes are in the form of sense of calling and sense of membership with one’s profession and organisation. Drawing on the proposition of Tepper’s (2003), organisational citizenship behaviour (OCB) was proposed as a mediator between spirituality and commitment. The study also tests whether emotional intelligence (EI) moderates the relations among them.

Design/methodology/approach
Data were collected from 761 executives working in Indian manufacturing and service organisations. SPSS 20.0 and AMOS 18.0 were used to analyse the data.

Findings
The results confirmed that an insignificant mediation of OCB and moderation of EI among WS and EC. However, WS is found to be a strong and consistent predictor of EC. The findings highlight the necessity of suitable HR intervention for instrumentalizing personal role-organisational goal fitment to create an engaging and committed workforce.

Originality/value
The study is among the few to empirically investigate the role of WS on employee commitment at work. The study is first of its kind to explore the mediating role of OCB and interactive role of EI at work in explaining the relationship between WS and EC.
Framework analysis: a whole paradigm approach
Authors: Kiernan Matthew D. , Hill Mick 
Published: April 2018

Purpose
Students of social research methods in search of a “Haynes manual” type set of instructions are often, if not invariably, thwarted in their ambitions and are either confronted with an abstract description which remains firmly at the level of methodology or, alternatively, an uncritical mechanical template for application. The purpose of this paper is not to rectify these deficits, but rather to make the interplay between epistemological and methodological concerns and those relating to method visible to inspection.

Design/methodology/approach
To illustrate this interplay, the authors present one example of a piece of applied policy research which employed a process of framework analysis.

Findings
It is argued that rhetorical transparency in the creation of any qualitative account enhances its authenticity, and in part, this article demonstrates that it remains possible to maintain reflexive awareness of epistemological and methodological concerns whilst at the same time pursuing clear and practical methodical guidelines.

Originality/value
This article provides unique approach to providing researchers with a practical guide to framework analysis with theoretical reflection on the wider methodological concerns.
Unraveling determinants of inferred and stated attribute nonattendance: Effects on farmers’ willingness to accept to join agri‐environmental schemes
Authors: Rodríguez‐Entrena Macario , Villanueva Anastasio J. , Gómez‐Limón José A. 
Published: April 2018

AbstractAttribute nonattendance (ANA) has received very little attention in the context of willingness to accept (WTA), although an increasing number of studies analyze the preferences of ecosystem service providers toward incentive‐based schemes. We add to the understanding of ANA behavior by analyzing stated and inferred ANA in a choice experiment investigating farmers’ WTA for participating in agri‐environmental schemes (AES) in southern Spain. We use mixed logit models, following Hess and Hensher for the inferred ANA approach. Evidence is found of ANA behavior for both stated and inferred approaches, with models accounting for ANA clearly outperforming those that do not account for it; however, we produce no conclusive results as to which ANA approach is best. WTA estimates are only moderately affected, which to some extent is consistent with the low level of non‐attendance found for the monetary attribute. Stated and inferred approaches show very similar WTA estimates. Additionally, we investigate sources of observed heterogeneity related to ANA behavior by using a sequence of bivariate probit models for each attribute. Overall, our results hint at a positive relationship between ease of scheme adoption and nonattendance to attributes. However, further research is still needed in this field.
Efficacy and safety of rivaroxaban compared to enoxaparin in treatment of cancer‐associated venous thromboembolism
Authors: Simmons Benjamin , Wysokinski Waldemar , Saadiq Rayya A. , Bott‐Kitslaar Dalene , Henkin Stanislav , Casanegra Ana , Lenz Charles , Daniels Paul , Bjarnason Haraldur , Vargas Emily , Hodge David , Holton Sara J. , Cerhan James R. , Loprinzi Charles , McBane Robert 
Published: April 2018

AbstractBackgroundLow molecular weight heparin (LMWH) is the guideline‐endorsed treatment for cancer‐associated venous thromboembolism (cVTE). Study objectives were to compare the efficacy and safety of rivaroxaban and enoxaparin in cVTE.MethodsUsing a cohort study design, consecutive patients with cVTE (3/1/2013‐7/31/2016), enrolled in the Mayo Thrombophilia Clinic Direct Oral Anticoagulants Registry, were compared to contemporary cancer patients receiving enoxaparin. The cumulative incidence of venous thromboembolism (VTE) recurrence, major and clinically relevant non‐major bleeding, and survival were assessed at 3 and 12 months.ResultsNinety‐eight patients received rivaroxaban (51% female, mean age 63 ± 12 years) and 168 enoxaparin (34.5% female, mean age 62 ± 15 years). The most common cancers included gastrointestinal/pancreatic, genitourinary and hematologic cancers. More than half of patients had pulmonary emboli at presentation. More than half had metastases, and two‐thirds were receiving chemotherapy. At 3 months, there were no differences in VTE recurrence (rivaroxaban 1.0% vs enoxaparin 4.2%; P = .15), major bleeding (rivaroxaban 5.1% vs enoxaparin 3.6%; P = .55), or all‐cause mortality (rivaroxaban 4.1% vs enoxaparin 8.9%; P = .14). At 12 months, these outcomes did not differ by treatment strategy.ConclusionThe results of this “real‐world” experience with cVTE suggest that rivaroxaban may offer a safe and effective alternative to LMWH.
Seasonal associations with novel climates for North American migratory bird populations
Authors: La Sorte Frank A. , Fink Daniel , Johnston Alison 
Published: April 2018

AbstractDetermining the implications of global climate change for highly mobile taxa such as migratory birds requires a perspective that is spatiotemporally comprehensive and ecologically relevant. Here, we document how passerine bird species that migrate within the Western Hemisphere (n = 77) are associated with projected novel climates across the full annual cycle. Following expectations, highly novel climates occurred on tropical non‐breeding grounds and the least novel climates occurred on temperate breeding grounds. Contrary to expectations, highly novel climates also occurred within temperate regions during the transition from breeding to autumn migration. This outcome was caused by lower inter‐annual climatic variability occurring in combination with stronger warming projections. Thus, migrants are projected to encounter novel climates across the majority of their annual cycle, with a pronounced peak occurring when juveniles are leaving the nest and preparing to embark on their first migratory journey, which may adversely affect their chances of survival.
Recombinant protein susceptibility to proteolysis in the plant cell secretory pathway is pH‐dependent
Authors: Jutras Philippe V. , Goulet Marie‐Claire , Lavoie Pierre‐Olivier , D'Aoust Marc‐André , Sainsbury Frank , Michaud Dominique 
Published: April 2018

SummaryCellular engineering approaches have been proposed to mitigate unintended proteolysis in plant protein biofactories, involving the design of protease activity‐depleted environments by gene silencing or in situ inactivation with accessory protease inhibitors. Here, we assessed the impact of influenza virus M2 proton channel on host protease activities and recombinant protein processing in the cell secretory pathway of Nicotiana benthamiana leaves. Transient co‐expression assays with M2 and GFP variant pHluorin were first conducted to illustrate the potential of proton export from the Golgi lumen to promote recombinant protein yield. A fusion protein‐based system involving protease‐sensitive peptide linkers to attach inactive variants of tomato cystatin SlCYS8 was then designed to relate the effects of M2 on protein levels with altered protease activities in situ. Secreted versions of the cystatin fusions transiently expressed in leaf tissue showed variable ‘fusion to free cystatin’ cleavage ratios, in line with the occurrence of protease forms differentially active against the peptide linkers in the secretory pathway. Variable ratios were also observed for the fusions co‐expressed with M2, but the extent of fusion cleavage was changed for several fusions, positively or negatively, as a result of pH increase in the Golgi. These data indicating a remodelling of endogenous protease activities upon M2 expression confirm that the stability of recombinant proteins in the plant cell secretory pathway is pH‐dependent. They suggest, in practice, the potential of M2 proton channel to modulate the stability of protease‐susceptible secreted proteins in planta via a pH‐related, indirect effect on host resident proteases.