bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Cu-ZSM-5 catalysts by chemical vapour deposition for catalytic wet peroxide oxidation of phenol in a fixed bed reactor
Authors: He Donglin , Zhang Huiping , Yan Ying
Published: April 2018

Cu-ZSM-5 catalysts were prepared by chemical vapour deposition for catalytic wet peroxide oxidation (CWPO) of phenol in a fixed bed reactor. Firstly, Cu-ZSM-5 catalysts with Cu loading of 0.5, 2, and 6 wt% were prepared and characterized by X-ray diffraction (XRD), N
2
adsorption–desorption and X-ray photoelectron spectra (XPS). The characterization results demonstrated that CuO was uniformly dispersed on ZSM-5 with slight effect on the structure properties of the support. Then, several variables, such as the copper loading, reaction temperature, catalyst bed height and feed flow rate were investigated in the CWPO of phenol in aqueous solution at high concentration (1000 ppm). Compared with the catalyst prepared by the impregnation method, the Cu-ZSM-5 prepared by chemical vapour deposition has a better capacity of further oxidizing the intermediate organic products into carbon dioxide and water with less metal loading. Based on the Cu-ZSM-5 catalyst with Cu loading of 6 wt%, complete removal of phenol and a high TOC reduction (around 70%) have been achieved at the temperature of 80°C feed flow rate of 2 ml min
−1
and catalyst bed height of 3 cm. Moreover, this catalyst maintained high catalytic activity after three runs with high phenol conversion (94%) under this optimum operating condition. Finally, the reaction mechanism was studied based on the intermediates detected by high-performance liquid chromatography (HPLC).
Stable, high-order computation of impedance–impedance operators for three-dimensional layered medium simulations
Authors: Nicholls David P.
Published: April 2018

The faithful modelling of the propagation of linear waves in a layered, periodic structure is of paramount importance in many branches of the applied sciences. In this paper, we present a novel numerical algorithm for the simulation of such problems which is free of the artificial singularities present in related approaches. We advocate for a surface integral formulation which is phrased in terms of impedance–impedance operators that are immune to the Dirichlet eigenvalues which plague the Dirichlet–Neumann operators that appear in classical formulations. We demonstrate a high-order spectral algorithm to simulate these latter operators based upon a high-order perturbation of surfaces methodology which is rapid, robust and highly accurate. We demonstrate the validity and utility of our approach with a sequence of numerical simulations.
Abundance-dependent effects of neighbourhood dissimilarity and growth rank reversal in a neotropical forest
Authors: Chen Yuxin , Umaña María Natalia , Uriarte María , Yu Shixiao
Published: April 2018

Why tropical forests harbour an exceptional number of species with striking differences in abundances remains an open question. We propose a theoretical framework to address this question in which rare species may have different extirpation risks depending on species ranks in tree growth and sensitivities to neighbourhood interactions. To evaluate the framework, we studied tree growth and its responses to neighbourhood dissimilarity (ND) in traits and phylogeny for 146 species in a neotropical forest. We found that tree growth was positively related to ND, and common species were more strongly affected by ND than rare species, which may help delay dominance of common species. Rare species grew more slowly at the community-wide average ND than common species. But rare species grew faster when common species tended to dominate locally, which may help reduce extirpation risk of rare species. Our study highlights that tree growth rank among species depends on their responses to neighbourhood interactions, which can be important in fostering diversity maintenance in tropical forests.
Distinct evolutionary patterns of Neisseria meningitidis serogroup B disease outbreaks at two universities in the USA
Authors: Hao Li , Holden Matthew T. G. , Wang Xin , Andrew Lubomira , Wellnitz Sabine , Hu Fang , Whaley Melissa , Sammons Scott , Knipe Kristen , Frace Mike , McNamara Lucy A. , Liberator Paul , Anderson Annaliesa S.
Published: April 2018

Neisseria meningitidis serogroup B (MnB) was responsible for two independent meningococcal disease outbreaks at universities in the USA during 2013. The first at University A in New Jersey included nine confirmed cases reported between March 2013 and March 2014. The second outbreak occurred at University B in California, with four confirmed cases during November 2013. The public health response to these outbreaks included the approval and deployment of a serogroup B meningococcal vaccine that was not yet licensed in the USA. This study investigated the use of whole-genome sequencing(WGS) to examine the genetic profile of the disease-causing outbreak isolates at each university. Comparative WGS revealed differences in evolutionary patterns between the two disease outbreaks. The University A outbreak isolates were very closely related, with differences primarily attributed to single nucleotide polymorphisms/insertion-deletion (SNP/indel) events. In contrast, the University B outbreak isolates segregated into two phylogenetic clades, differing in large part due to recombination events covering extensive regions (>30 kb) of the genome including virulence factors. This high-resolution comparison of two meningococcal disease outbreaks further demonstrates the genetic complexity of meningococcal bacteria as related to evolution and disease virulence.
Fusarium graminearum-induced shoot elongation and root reduction in maize seedlings correlate with later seedling blight severity
Authors: Zhou Shaoqun , Bae Justin S. , Bergstrom Gary C. , Jander Georg
Published: April 2018

Fusarium graminearum seedling blight is a common disease of maize (Zea mays). Development of genetic resistance to seedling blight in maize germplasm requires efficient and accurate quantitative assessment of disease severity. Through artificial inoculation experiments under controlled growth conditions, we determined that host genotype, pathogen genotype, and infection dose influence the extent to which F. graminearum induces shoot elongation and inhibits root growth in maize seedlings. A comparison of fifteen maize inbred lines showed independent variation of these two fungus-induced effects on seedling growth. In a broader survey with nine commercial maize hybrids and three field-collected fungal isolates, there was significant correlation between these seedling growth responses, as well as with later seedling blight severity. Analysis of variance suggested that this variation and the observed correlative relationships were primarily driven by differing pathogenicity of the three fungal isolates. Together, our results indicate that F. graminearum-induced shoot elongation and root reduction in maize seedlings have distinct underlying physiological mechanisms, and that early observations of seedling growth responses can serve as a proxy for investigating natural variation in host resistance and pathogen aggressiveness at later growth stages.
A unifying framework for joint trait analysis under a non-infinitesimal model
Authors: Johnson Ruth , Shi Huwenbo , Pasaniuc Bogdan , Sankararaman Sriram
Published: April 2018

Motivation

A large proportion of risk regions identified by genome-wide association studies (GWAS) are shared across multiple diseases and traits. Understanding whether this clustering is due to sharing of causal variants or chance colocalization can provide insights into shared etiology of complex traits and diseases.

Results

In this work, we propose a flexible, unifying framework to quantify the overlap between a pair of traits called UNITY (Unifying Non-Infinitesimal Trait analYsis). We formulate a Bayesian generative model that relates the overlap between pairs of traits to GWAS summary statistic data under a non-infinitesimal genetic architecture underlying each trait. We propose a Metropolis-Hastings sampler to compute the posterior density of the genetic overlap parameters in this model. We validate our method through comprehensive simulations and analyze summary statistics from height and BMI GWAS to show that it produces estimates consistent with the known genetic makeup of both traits.

Availability

The UNITY software is made freely available to the research community at: https://github.com/bogdanlab/UNITY

Contact

ruthjohnson@ucla.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
A common genomic code for chromatin architecture and recombination landscape
Authors: Jabbari Kamel , Wirtz Johannes , Rauscher Martina , Wiehe Thomas
Published: April 2018

Recent investigation established a link between DNA sequences and chromatin architecture and explained the evolutionary conservation of TADs (Topologically Associated Domains) and LADs (Lamina Associated Domains) in mammals. This prompted us to analyse the relationship between chromatin architecture and recombination landscapes of human and mouse. The results revealed that: (1) Blocks of elevated linkage disequilibrium tend to coincide with TADs and isochores, indicating co-evolving regulatory elements and genes in insulated neighbourhood; (2) double strand break (DSB) and recombination frequencies increase in GC-rich TADs, whereas recombination cold spots are typical of LADs; (3) binding and loading of proteins which are critical for DSB and meiotic recombination (Spo11, DMC1, H3K4me3 and PRMD9) are higher in GC-rich TADs. One explanation for these observations is that the occurrence of DSB and recombination in meiotic cells are associated to compositional and epigenetic features (genomic code) that are similar to those guiding the architecture of chromosomes in the interphase nucleus of pre-leptotene spermatocytes.
Dynamics of Plasma Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes – Type 1 Diabetes Prediction and Prevention Study (DIPP)
Authors: Lamichhane Santosh , Ahonen Linda , Dyrlund Thomas Sparholt , Kemppainen Esko , Siljander Heli , Hyöty Heikki , Ilonen Jorma , Toppari Jorma , Veijola Riitta , Hyötyläinen Tuulia , Knip Mikael , Oresic Matej
Published: April 2018

Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that children who progressed to islet autoimmunity or overt T1D are characterized by distinct lipidomic signatures, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.
Single-cell analysis identifies EpCAM+/CDH6+/TROP-2−cells as human liver progenitors
Authors: Segal Joe M , Wesche Daniel J , Serra Maria Paola , Oulès Bénédicte , Kent Deniz , Ng Soon Seng , Kar Gozde , Emerton Guy , Blackford Samuel J I , Darmanis Spyros , Miquel Rosa , Vinh Tu , Yamamoto Ryo , Bonham Andrew , Vigilante Alessandra , Teichmann Sarah , Quake Stephen R. , Nakauchi Hiromitsu , Rashid S Tamir
Published: April 2018

The liver is largely composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists as to whether a liver stem/progenitor cell capable of renewing both hepatocytes and BECs exists. Single cell RNA sequencing of freshly isolated human foetal and healthy adult liver identified hepatocyte, hepatoblast and liver progenitor cell (hLPC) populations. hLPCs, found at the interface between hepatocytes and bile ducts in both foetal and adult tissue, were distinguishable from BECs by their negative expression of TROP-2. Prospective isolation followed by in vitro culture demonstrated their potential for expansion and bi-lineage differentiation. The hLPC expression signature was also conserved within expanded cell populations specific to certain cases of liver injury and cancer. These data support the idea of a true progenitor existing within healthy adult liver that can be activated upon injury. Further work to define the mechanisms regulating hLPC behaviour could advance understanding of human development and disease.
Robust single-cell DNA methylome profiling with snmC-seq2
Authors: Luo Chongyuan , Rivkin Angeline , Zhou Jingtian , Sandoval Justin P. , Kurihara Laurie , Lucero Jacinta , Castanon Rosa , Nery Joseph R. , Pinto-Duarte António , Bui Brian , Fitzpatrick Conor , O’Connor Carolyn , Ruga Seth , van Eden Marc E. , Davis David A. , Mash Deborah C. , Behrens M.Margarita , Ecker Joseph R.
Published: April 2018

Single-cell DNA methylome profiling has enabled the study of epigenomic heterogeneity in complex tissues and during cellular reprogramming. However, broader applications of the method have been impeded by the modest quality of sequencing libraries. Here we report snmC-seq2, which provides improved read mapping, reduced artifactual reads, enhanced throughput, as well as increased library complexity and coverage uniformity compared to snmC-seq. snmC-seq2 is an efficient strategy suited for large scale single-cell epigenomic studies.
An ultralight head-mounted camera system integrates detailed behavioral monitoring with multichannel electrophysiology in freely moving mice
Authors: Meyer Arne F. , Poort Jasper , O’Keefe John , Sahani Maneesh , Linden Jennifer F.
Published: April 2018

Breakthroughs in understanding the neural basis of natural behavior require neural recording and intervention to be paired with high-fidelity multimodal behavioral monitoring. An extensive genetic toolkit for neural circuit dissection, and well-developed neural recording technology, make the mouse a powerful model organism for systems neuroscience. However, methods for high-bandwidth acquisition of behavioral signals in mice remain limited to fixed-position cameras and other off-animal devices, complicating the monitoring of animals freely engaged in natural behaviors. Here, we report the development of an ultralight head-mounted camera system combined with head-movement sensors to simultaneously monitor eye position, pupil dilation, whisking, and pinna movements along with head motion in unrestrained, freely behaving mice. The power of the combined technology is demonstrated by observations linking eye position to head orientation; whisking to non-tactile stimulation; and, in electrophysiological experiments, visual cortical activity to volitional head movements.
Accurate prediction of orthologs in the presence of divergence after duplication
Authors: Lafond Manuel , Miardan Mona Meghdari , Sankoff David
Published: April 2018

Motivation

When 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.

Results

We 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.

Availability

HyPPO 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.

Contact

mlafond2@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

Molecular 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

Eukaryotes 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.

Significance

Pleiotropic 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

The 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.

Importance

Many 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

Highlights

TLK-1 maintains cell fates by repression of selector genes

TLK-1 and downstream H3 chaperone CAF1 inhibit H3.3 deposition

Loss ofsin-3suppresses the defect in cell-fate maintenance oftlk-1mutants

AcH4-binding protein BET-1 is necessary forsin-3suppression

Cell-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.
Functional selectivity and specific connectivity of inhibitory neurons in primary visual cortex
Authors: Znamenskiy Petr , Kim Mean-Hwan , Muir Dylan R. , Iacaruso Maria Florencia , Hofer Sonja B. , Mrsic-Flogel Thomas D.
Published: April 2018

In the cerebral cortex, the interaction of excitatory and inhibitory synaptic inputs shapes the responses of neurons to sensory stimuli, stabilizes network dynamics1 and improves the efficiency and robustness of the neural code2–4. Excitatory neurons receive inhibitory inputs that track excitation5–8. However, how this co-tuning of excitation and inhibition is achieved by cortical circuits is unclear, since inhibitory interneurons are thought to pool the inputs of nearby excitatory cells and provide them with non-specific inhibition proportional to the activity of the local network9–13. Here we show that although parvalbumin-expressing (PV) inhibitory cells in mouse primary visual cortex make connections with the majority of nearby pyramidal cells, the strength of their synaptic connections is structured according to the similarity of the cells’ responses. Individual PV cells strongly inhibit those pyramidal cells that provide them with strong excitation and share their visual selectivity. This fine-tuning of synaptic weights supports co-tuning of inhibitory and excitatory inputs onto individual pyramidal cells despite dense connectivity between inhibitory and excitatory neurons. Our results indicate that individual PV cells are preferentially integrated into subnetworks of inter-connected, co-tuned pyramidal cells, stabilising their recurrent dynamics. Conversely, weak but dense inhibitory connectivity between subnetworks is sufficient to support competition between them, de-correlating their output. We suggest that the history and structure of correlated firing adjusts the weights of both inhibitory and excitatory connections, supporting stable amplification and selective recruitment of cortical subnetworks.
(In)exhaustible suppliers for evolution? Epistatic selection tunes the adaptive potential of non-genetic inheritance
Authors: Rajon Etienne , Charlat Sylvain
Published: April 2018

Non-genetic inheritance media, from methyl-accepting cytosines to culture, tend to ‘mutate’ more frequently than DNA sequences. Whether or not this makes them inexhaustible suppliers for adaptive evolution will depend on the effect of non-genetic mutations (hereafter epimutations) on fitness-related traits. Here we investigate how the magnitude of these effects might themselves evolve. More specifically, we examine the hypothesis that natural selection could set boundaries to the adaptive potential of non-genetic inheritance media due to their higher mutability. In our model, the genetic and epigenetic contributions to a non-neutral phenotype are controlled by an epistatic modifier locus, which we let evolve under the combined effects of drift and selection, in stable and in variable environments. We show that a pure genetic control evolves when the environment is stable, provided that the population is large enough, such that the phenotype becomes robust to frequent epimutations. When the environment fluctuates, however, the direction of selection on the modifier locus also fluctuates and can overall produce a large non-genetic contribution to the phenotype, especially when the epimutation rate matches the rate of environmental variation. We further show that selection on the modifier locus is mostly direct –i.e.it does not rely on subsequent effects in future generations – as our results are generally insensitive to recombination. These results suggest that unstable inheritance media might significantly contribute to fitness variation of traits subject to highly variable selective pressures, but little to traits responding to scarcely variable aspects of the environment, which likely represent a majority. More generally, our study demonstrates that the rate of mutation and the adaptive potential of any inheritance media should not be seen as independent properties.
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

N6-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.
Integrated analysis sheds light on evolutionary trajectories of young transcription start sites in the human genome
Authors: Li Cai , Lenhard Boris , Luscombe Nicholas M.
Published: April 2018

Understanding the molecular mechanisms and evolution of the gene regulatory system remains a major challenge in biology. Transcription start sites (TSSs) are especially interesting because they are central to initiating gene expression. Previous studies revealed widespread transcription initiation and fast turnover of TSSs in mammalian genomes. Yet, how new TSSs originate and how they evolve over time remain poorly understood. To address these questions, we analyzed ∼200,000 human TSSs by integrating evolutionary (inter- and intra-species) and functional genomic data, particularly focusing on evolutionarily young TSSs that emerged in the primate lineage. TSSs were grouped according to their evolutionary age using sequence alignment information as a proxy. Comparisons of young and old TSSs revealed that (1) new TSSs emerge through a combination of intrinsic factors, like the sequence properties of transposable elements and tandem repeats, and extrinsic factors such as their proximity to existing regulatory modules; (2) new TSSs undergo rapid evolution that reduces the inherent instability of repeat sequences associated with a high propensity of TSS emergence; and (3) once established, the transcriptional competence of surviving TSSs is gradually enhanced, with evolutionary changes subject to temporal (fewer regulatory changes in younger TSSs) and spatial constraints (fewer regulatory changes in more isolated TSSs). These findings advance our understanding of how regulatory innovations arise in the genome throughout evolution and highlight the genomic robustness and evolvability in these processes.
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

Purpose

The 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/approach

A 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).

Findings

The 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 implications

This 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/value

The 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

Attribute 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

Background

Low 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.

Methods

Using 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.

Results

Ninety‐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.

Conclusion

The 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

Determining 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.
Closure of gastrointestinal incisions using skin staples alone and in combination with suture in 29 cats
Authors: Schwartz Z. , Coolman B. R.
Published: April 2018

Objective

To report the use of skin staples alone, and in combination with sutures, for closure of gastrointestinal incisions in cats and to describe outcomes.

Materials and Methods

Retrospective study of cats that underwent gastrotomy, jejunotomy, jejunal or colonic anastomosis using skin staples alone or in combination with sutures to close the enteric wounds at one referral hospital between 2001 and 2016. Data regarding patient signalment, duration of clinical signs, indication for surgery, diagnosis, haematological and biochemical values, surgical time, procedure, complications and outcome were collected. All the gastrotomies and some of the large intestine incisions were closed in a hybrid technique using two layers (monofilament suture and skin staples). All the small intestine and some of the large intestinal incisions were closed in a single layer using skin staples.

Results

Twenty‐nine cats were included in the study. Indications for surgery included foreign body (14/29), neoplasia (6/29) and idiopathic megacolon (9/29). Overall, 26 of 29 (~90%) of cases survived to discharge. One cat had postoperative cardiopulmonary arrest, and 2/29 cats were euthanased at the owner's request. There was no evidence of incisional dehiscence in any case.

Clinical Significance

Skin staplers are safe, reliable, affordable and effective for closure of gastrointestinal incisions in cats. We found skin staples can be a useful tool in closure of gastrotomies and large intestinal resection and anastomosis procedures in cats.
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

Cellular 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.