bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide Association Studies Reveal Similar Genetic Architecture with Shared and Unique QTL for Bacterial Cold Water Disease Resistance in Two Rainbow Trout Breeding Populations
Authors: Vallejo Roger L. , Gao Guangtu , Liu Sixin , Fragomeni Breno O. , Hernandez Alvaro G. , Parsons James E. , Martin Kyle E. , Evenhuis Jason P. , Welch Timothy J. , Leeds Timothy D. , Wiens Gregory D. , Palti Yniv 
Published: July 2017

ABSTRACTBacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a 57K SNP array and a genome physical map have enabled us to conduct genome-wide association studies (GWAS) that overcome several experimental limitations from our previous work. In the current study, we conducted GWAS for BCWD resistance in two rainbow trout breeding populations using two genotyping platforms, the 57K Affymetrix SNP array and restriction-associated DNA (RAD) sequencing. Overall, we identified 14 moderate-large effect QTL that explained up to 60.8% of the genetic variance in one of the two populations and 27.7% in the other. Four of these QTL were found in both populations explaining a substantial proportion of the variance, although major differences were also detected between the two populations. Our results confirm that BCWD resistance is controlled by the oligogenic inheritance of few moderate-large effect loci and a large-unknown number of loci each having a small effect on BCWD resistance. We detected differences in QTL number and genome location between two GWAS models (weighted single-step GBLUP and Bayes B), which highlights the utility of using different models to uncover QTL. The RAD-SNPs detected a greater number of QTL than the 57K SNP array in one population, suggesting that the RAD-SNPs may uncover polymorphisms that are more unique and informative for the specific population in which they were discovered.
Rapid DNA Replication Origin Licensing Protects Stem Cell Pluripotency
Authors: Matson Jacob Peter , Dumitru Raluca , Coryell Phillip , Baxley Ryan M , Chen Weili , Twaroski Kirk , Webber Beau R. , Tolar Jakub , Bielinsky Anja-Katrin , Purvis Jeremy , Cook Jeanette Gowen 
Published: July 2017

ABSTRACTComplete and robust human genome duplication requires loading MCM helicase complexes at many DNA replication origins, an essential process termed origin licensing. Licensing is restricted to G1 phase of the cell cycle, but G1 length varies widely among cell types. Using quantitative single cell analyses we found that pluripotent stem cells with naturally short G1 phases load MCM much faster than their isogenic differentiated counterparts with long G1 phases. During the earliest stages of differentiation towards all lineages, MCM loading slows concurrently with G1 lengthening, revealing developmental control of MCM loading. In contrast, ectopic Cyclin E overproduction uncouples short G1 from fast MCM loading. Rapid licensing in stem cells is caused by accumulation of the MCM loading protein, Cdt1. Prematurely slowing MCM loading in pluripotent cells not only lengthens G1 but also accelerates differentiation. Thus, rapid origin licensing is an intrinsic characteristic of stem cells that contributes to pluripotency maintenance.
COMPENSATION FOR CHRONIC OXIDATIVE STRESS IN ALADIN NULL MICE
Authors: Jühlen Ramona , Peitzsch Mirko , Gärtner Sebastian , Landgraf Dana , Eisenhofer Graeme , Huebner Angela , Koehler Katrin 
Published: July 2017

ABSTRACTBackgroundMutations in theAAASgene coding for the nuclear pore complex protein ALADIN lead to the autosomal recessive disorder triple A syndrome. Triple A patients present with a characteristic phenotype including alacrima, achalasia and adrenal insufficiency. Patient fibroblasts show increased levels of oxidative stress and severalin vitrostudies demonstrated that the nucleoporin ALADIN is involved in the cellular oxidative stress response and in adrenal steroidogenesis. We showed that ALADIN knock-out mice lack a phenotype resembling human triple A syndrome. Thus, we hypothesized that application of chronic oxidative stress by ingestion of paraquat will generate triple A-like phenotype in ALADIN null mice.ResultsWe demonstrate that ALADIN knock-out mice present with an unexpected compensated glutathione metabolism still lacking a phenotype resembling human triple A syndrome after application of chronic oxidative stress. We could not observe increased levels of oxidative stress and alterations in adrenal steroidogenesis in mice depleted for ALADIN.ConclusionsThis study stresses the species-specific role of the nucleoporin ALADIN presenting a novel compensatory mechanism of the cellular glutathione redox response and shedding light on the role of ALADIN in the cell.
Using mitochondrial genomes to infer phylogenetic relationships among the oldest extant winged insects (Palaeoptera)
Authors: Rutschmann Sereina , Chen Ping , Zhou Changfa , Monaghan Michael T. 
Published: July 2017

AbstractPhylogenetic relationships among the basal orders of winged insects remain unclear, in particular the relationship of the Ephemeroptera (mayflies) and the Odonata (dragonflies and damselflies) with the Neoptera. Insect evolution is thought to have followed rapid divergence in the distant past and phylogenetic reconstruction may therefore be susceptible to problems of taxon sampling, choice of outgroup, marker selection, and tree reconstruction method. Here we newly sequenced three mitochondrial genomes representing the two most diverse families of the Ephemeroptera, one of which is a basal lineage of the order. We then used an additional 90 insect mitochondrial genomes to reconstruct their phylogeny using Bayesian and maximum likelihood approaches. Bayesian analysis supported a basal Odonata hypothesis, with Ephemeroptera as sister group to the remaining insects. This was only supported when using an optimized data matrix from which rogue taxa and terminals affected by long-branch attraction were removed. None of our analyses supported a basal Ephemeroptera hypothesis or Ephemeroptera + Odonata as monophyletic clade sister to other insects (i.e., the Palaeoptera hypothesis). Our newly sequenced mitochondrial genomes ofBaetis rutilocylindratus,Cloeon dipterum, andHabrophlebiodes zijinensishad a complete set of protein coding genes and a conserved orientation except for two inverted tRNAs inH. zijinensis.Increased mayfly sampling, removal of problematic taxa, and a Bayesian phylogenetic framework were needed to infer phylogenetic relationships within the three ancient insect lineages of Odonata, Ephemeroptera, and Neoptera. Pruning of rogue taxa improved the number of supported nodes in all phylogenetic trees. Our results add to previous evidence for the Odonata hypothesis and indicate that the phylogenetic resolution of the basal insects can be resolved with more data and sampling effort.
Questioning the role of selected somaticPIK3C2Bmutations in squamous non-small cell lung cancer oncogenesis
Authors: Kind Marcus , Klukowska-Rötzler Jolanta , Berezowska Sabina , Arcaro Alexandre , Charles Roch-Philippe 
Published: July 2017

AbstractPI3K signaling is frequently dysregulated in NSCLC-SQCC. In contrast to well characterized components of the PI3K signaling network contributing to the formation of SQCC, potential oncogenic effects of alterations inPIK3C2Bare poorly understood. Here, a large cohort (n=362) of NSCLC-SQCC was selectively screened for four reported somatic mutations inPIK3C2Bvia Sanger sequencing. In addition, two mutations leading to an amino acid exchange in the kinase domain (C1181, H1208R) were examined on a functional level for their oncogenic potential.None of the mutations were identified in the cohort while well characterized hotspotPIK3CAmutations were observed at the expected frequency. Ultimately, kinase domain mutations in PI3KC2β were found to have no altering effect on downstream signaling. A set of SQCC tumors sequenced by The Cancer Genome Atlas (TCGA) equally indicates a lack of oncogenic potential of the kinase domain mutations orPIK3C2Bin general.Taken together, this study suggests thatPIK3C2Bmight only have a minor role in SQCC oncogenesis.
TASI: A software tool for spatial-temporal quantification of tumor spheroid dynamics
Authors: Hou Yue , Konen Jessica , Brat Daniel J , Marcus Adam I. , Cooper Lee 
Published: July 2017

ABSTRACTSpheroid cultures derived from explanted cancer specimens are an increasingly utilized resource for studying complex biological processes like tumor cell invasion and metastasis, representing an important bridge between the simplicity and practicality of 2D monolayer cultures and the complexity and realism ofin vivoanimal models. Temporal imaging of spheroids can capture the dynamics of cell behaviors and microenvironments, and when combined with quantitative image analysis methods, enables deep interrogation of biological mechanisms. This paper presents a comprehensive open-source software framework forTemporalAnalysis ofSpheroid Imaging (TASI) that allows investigators to objectively characterize spheroid growth and invasion dynamics. TASI performs spatiotemporal segmentation of spheroid cultures, extraction of features describing spheroid morpho-phenotypes, mathematical modeling of spheroid dynamics, and statistical comparisons of experimental conditions. We demonstrate the utility of this tool in an analysis of non-small cell lung cancer spheroids that exhibit variability in metastatic and proliferative behaviors.
Estimating inflation in GWAS summary statistics due to variance distortion from cryptic relatedness
Authors: Holland Dominic , Fan Chun-Chieh , Frei Oleksandr , Shadrin Alexey A. , Smeland Olav B. , Sundar V. S. , Andreassen Ole A. , Dale Anders M. 
Published: July 2017

AbstractCryptic relatedness is inherently a feature of large genome-wide association studies (GWAS), and can give rise to considerable inflation in summary statistics for single nucleotide polymorphism (SNP) associations with phenotypes. It has proven difficult to disentangle these inflationary effects from true polygenic effects. Here we present results of a model that enables estimation of polygenicity, mean strength of association, and residual inflation in GWAS summary statistics. We show that there is substantial residual inflation in recent large GWAS of height and schizophrenia; correcting for this reduces the number of independent genome-wide significant loci from the reported values of 697 for height and 108 for schizophrenia to 368 and 61, respectively. In contrast, a larger GWAS of educational attainment shows no residual inflation. Additionally, we find that height has a relatively low polygenicity, with approximately 8k SNPs having causal association, more than an order of magnitude less than has been reported. The residual inflation in GWAS summary statistics can be corrected using the standard genomic control procedure with the estimated residual inflation factor.
A Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels
Authors: Ghovanloo Mohammad-Reza , Abdelsayed Mena , Peters Colin H. , Ruben Peter C. 
Published: July 2017

ABSTRACTSkeletal muscle channelopathies, many of which are inherited as autosomal dominant mutations, include both myotonia and periodic paralysis. Myotonia is defined by a delayed relaxation after muscular contraction, whereas periodic paralysis is defined by episodic attacks of weakness. One sub-type of periodic paralysis, known as hypokalemic periodic paralysis (hypoPP), is associated with low potassium levels. Interestingly, the P1158S missense mutant, located in the third domain S4-S5 linker of the ‘‘skeletal muscle’’ voltage-gated sodium channel, Nav1.4, has been implicated in causing both myotonia and hypoPP. A common trigger for these conditions is physical activity. We previously reported that Nav1.4 is relatively insensitive to changes in extracellular pH compared to Nav1.2 and Nav1.5. Given that intense exercise is often accompanied by blood acidosis, we decided to test whether changes in pH would push gating in P1158S towards either phenotype. Our results indicate that, unlike in WT Nav1.4, low pH depolarizes the voltage-dependence of activation and steady-state fast inactivation, decreases current density, and increases late currents in P1185S. Thus, P1185S turns the normally pH-insensitive Nav1.4 into a proton-sensitive channel. Using action potential modeling we also predict a pH-to-phenotype correlation in patients with P1158S. We conclude that activities which alter blood pH may trigger myotonia or periodic paralysis in P1158S patients.SIGNIFICANCE STATEMENTVoltage-gated sodium channels (Nav) contribute to the physiology and pathophysiology of electrical signaling in excitable cells. Nav subtypes are expressed in a tissue-specific manner, thus they respond differently to physiological modulators. For instance, the cardiac subtype, Nav1.5, can be modified by changes in blood pH; however, the skeletal muscle subtype, Nav1.4, is mostly pH-insensitive. Nav1.4 mutants can mostly cause either hyper-or hypo-excitability in skeletal muscles, leading to conditions such as myotonia or periodic paralysis. P1158S uniquely causes both phenotypes. This study investigates pH-sensitivity in P1158S, and describes how physiological pH changes can push P1158S to cause myotonia and periodic paralysis.
Community pharmacists as vaccine providers
Authors: Rhodes Laura A. , Williams Dennis M. , Marciniak Macary W. , Weber David Jay 
Published: July 2017

Purpose
The purpose of this paper is to describe the history of pharmacist involvement as vaccine providers in the USA and discuss examples of growing interests in other parts of the world.

Design/methodology/approach
Literature searches were performed in PubMed as well as pharmacy-related journals.

Findings
Pharmacists have been involved with the storage and management of vaccines for more than a century. Based on the unmet needs in meeting national goals for vaccination rates among adults in the USA, efforts led to training and recognizing pharmacists as vaccine providers which is now within the scope of practice for a pharmacist in all US states and territories. Pharmacists complete a comprehensive training program in vaccine sciences, regulatory considerations, as well as demonstration of skills in administering vaccines. Over 300,000 pharmacists have been trained in vaccine delivery and this represents the majority of the pharmacist workforce in the USA. There are examples of the beneficial impact of pharmacist involvement as vaccine providers in community pharmacy settings.

Research limitations/implications
This review is based on a thorough review of the literature but was not conducted in a systematic fashion.

Originality/value
This review provides a historical perspective and evidence of the benefit of pharmacists as vaccine providers.
Does lean cure variability in health care?
Authors: Roemeling Oskar , Land Martin , Ahaus Kees 
Published: July 2017

Purpose
The purpose of this paper is to investigate the roles that employee-initiated Lean improvement projects play in health care. Lean ideas are introduced to improve flow in health care. Although variability is detrimental to flow performance, it is unclear whether Lean initiatives set out to reduce this variability and the associated buffers.

Design/methodology/approach
Longitudinal field research is combined with an exploratory field-quasi-experiment. First, a large set of Lean interventions were explored and their focus classified. Semi-structured interviews with practitioners supported the initial findings regarding the focus. Second, this study investigated whether a knowledge deficiency could explain the identified focus through a quasi-experiment in which the authors’ stimulated knowledge on the roles of variability and buffers and then classified subsequent interventions.

Findings
The results reflected a narrow application of Lean, with most interventions directed at reducing direct waste. A quasi-experiment demonstrated that a small investment in knowledge enables the focus to shift toward buffers and variability issues – i.e. toward a more complete Lean approach.

Research limitations/implications
This research supports the commonly held view that there is a tendency to focus on waste. Furthermore, a lengthy experience of Lean does not guarantee interventions will focus on buffers and variability, issues with arguably a higher complexity compared to obvious waste. However, small investments in knowledge can broaden the focus of practitioners’ interventions.

Originality/value
This study is one of the first to research the focus of Lean interventions through a data set spanning several years. The results are based on a unique data set covering a large number of documented Lean interventions.
How performance measurement influences stakeholders in not-for-profit organizations
Authors: Beer Haley Allison , Micheli Pietro 
Published: July 2017

Purpose
The purpose of this paper is to examine the influences of performance measurement (PM) on not-for-profit (NFP) organizations’ stakeholders by studying how PM practices interact with understandings of legitimate performance goals. This study invokes institutional logics theory to explain interactions between PM and stakeholders.

Design/methodology/approach
An in-depth case study is conducted in a large NFP organization in the UK. Managers, employees, and external partners are interviewed and observed, and performance-related documents analyzed.

Findings
Both stakeholders and PM practices are found to have dominant institutional logics that portray certain goals as legitimate. PM practices can reinforce, reconcile, or inhibit stakeholders’ understandings and propensity to act toward goals, depending on the extent to which practices share the dominant logic of the stakeholders they interact with.

Research limitations/implications
A theoretical framework is proposed for how PM practices first interact with stakeholders at a cognitive level and second influence action. This research is based on a single case study, which limits generalizability of findings; however, results may be transferable to other environments where PM is aimed at balancing competing stakeholder objectives and organizational priorities.

Practical implications
PM affects the experience of stakeholders by interacting with their understanding of legitimate performance goals. PM systems should be designed and implemented on the basis of both their formal ability to represent organizational aims and objectives, and their influence on stakeholders.

Originality/value
Findings advance PM theory by offering an explanation for how PM influences attention and actions at an individual micro level.
ESD professional development of university educators in Serbia, Croatia and Macedonia
Authors: Nikolic Vesna , Milutinovic Slobodan , Nedanovski Pece , Mrnjaus Kornelija 
Published: July 2017

PurposeThe paper aims to deal with the education for sustainable development (ESD) competences of university educators. The purpose of this paper is to provide a comparative analysis of opportunities for the development of ESD competences in higher education (HE) institutions in Serbia, Croatia and Macedonia. In addition, the paper explores the drivers and barriers experienced in this area using a process-oriented approach.Design/methodology/approachFor the purpose of collecting data, internet and desktop research was carried out, which was then followed by interviews with key respondents and experts in HE. The interviews were carried out face-to-face or via telephone. In addition, information collected from the interviews was compared with both data found in the literature and official documents.FindingsThe comparative analysis indicated how specific institutional and cultural contexts affect the development of ESD competences in HE in the region. There were differences but also common opportunities for developing the ESD competences of university educators in the countries analysed. For each country, the drivers and barriers, as well as their relevance, were manifested differently and specific key constructs were identified to explain the implementation process for developing ESD competences of university educators.Practical implicationsThis paper tried to respond to this diversity of perspectives, contexts and initiatives and attempted to extract the benefits of different approaches to the ESD professional development of university educators in Serbia, Croatia and Macedonia. It is hoped that this paper will provide valuable insights into the development of ESD in HE and support the development of ESD competences in the region.Originality/valueThis is one of the first papers that provide a comparative analysis of the ESD professional development of university educators in Balkan countries. The value of the paper lies in its potential to help us to understand the role that different drivers and barriers play in different patterns of implementation for developing the ESD competences of university educators.
A collaborative action research project towards embedding ESD within the higher education curriculum
Authors: Cebrián Gisela 
Published: July 2017

Purpose
This paper aims to present a collaborative action research project conducted at the University of Southampton with the aim to promote curriculum and professional development in education for sustainable development (ESD) and learn from everyday practices of academics.

Design/methodology/approach
An action research approach guided by participatory and emancipatory approaches was used. An interdisciplinary group of five academic staff members from different subject areas (education; archaeology; electronics and computer sciences; biology; and health sciences) was created with the aim to support the group’s critical reflection and action towards embedding ESD in their teaching practice.

Findings
The main outcomes of delivery of sustainability teaching achieved through the project and evidences of the impact of the facilitator role are outlined. The facilitator role has enabled reflection and action, together with the identification of specific needs of academics and the factors influencing their engagement and action.

Originality/value
This research demonstrates the potential of using action research to rethink current practice in embedding ESD and to lead to new practices and actions of communities of practice. The facilitator role and second-order action research can contribute to better decision-making of sustainability as it questions practice, current assumptions and worldviews.