bluuebunny/crossref_metadata_2025 huggingface dataset:
Sampling strategy optimization to increase statistical power in landscape genomics: a simulation-based approach
Authors: Selmoni Oliver , Vajana Elia , Guillaume Annie , Rochat Estelle , Joost Stéphane
Published: April 2019

An increasing number of studies are using landscape genomics to investigate local adaptation in wild and domestic populations. The implementation of this approach requires the sampling phase to consider the complexity of environmental settings and the burden of logistic constraints. These important aspects are often underestimated in the literature dedicated to sampling strategies.

In this study, we computed simulated genomic datasets to run against actual environmental data in order to trial landscape genomics experiments under distinct sampling strategies. These strategies differed by design approach (to enhance environmental and/or geographic representativeness at study sites), number of sampling locations and sample sizes. We then evaluated how these elements affected statistical performances (power and false discoveries) under two antithetical demographic scenarios.

Our results highlight the importance of selecting an appropriate sample size, which should be modified based on the demographic characteristics of the studied population. For species with limited dispersal, sample sizes above 200 units are generally sufficient to detect most adaptive signals, while in random mating populations this threshold should be increased to 400 units. Furthermore, we describe a design approach that maximizes both environmental and geographical representativeness of sampling sites and show how it systematically outperforms random or regular sampling schemes. Finally, we show that although having more sampling locations (between 40 and 50 sites) increase statistical power and reduce false discovery rate, similar results can be achieved with a moderate number of sites (20 sites). Overall, this study provides valuable guidelines for optimizing sampling strategies for landscape genomics experiments.
Traces of Meaning Itself: Encoding distributional word vectors in brain activity
Authors: Sassenhagen Jona , Fiebach Christian J.
Published: April 2019

How is semantic information stored in the human mind and brain? Some philosophers and cognitive scientists argue for vectorial representations of concepts, where the meaning of a word is represented as its position in a high-dimensional neural state space. At the intersection of natural language processing and artificial intelligence, a class of very successful distributional word vector models has developed that can account for classic EEG findings of language, i.e., the ease vs. difficulty of integrating a word with its sentence context. However, models of semantics have to account not only for context-based word processing, but should also describe how word meaning is represented. Here, we investigate whether distributional vector representations of word meaning can model brain activity induced by words presented without context. Using EEG activity (event-related brain potentials) collected while participants in two experiments (English, German) read isolated words, we encode and decode word vectors taken from the family of prediction-based word2vec algorithms. We find that, first, the position of a word in vector space allows the prediction of the pattern of corresponding neural activity over time, in particular during a time window of 300 to 500 ms after word onset. Second, distributional models perform better than a human-created taxonomic baseline model (WordNet), and this holds for several distinct vector-based models. Third, multiple latent semantic dimensions of word meaning can be decoded from brain activity. Combined, these results suggest that empiricist, prediction-based vectorial representations of meaning are a viable candidate for the representational architecture of human semantic knowledge.
Prevalence of Hepatitis C Virus Genotypes in the Southern Region, Saudi Arabia
Authors: AlKahtani Abdullah M , Alsultan Meaad N , Hakami Abdulrahim R , Alamri Mohammad
Published: April 2019

Aim

The aim of this study was to investigate the prevalence of HCV genotypes in the Southern Region, Saudi Arabia.

Materials & methods

A total of 76 HCV-positive individuals were selected for this study, including 34 males and 42 females, both acute and chronic patients. All HCV isolates were genotyped by direct sequencing of the 5’UTR region. The Chemistry profile, viral load and history of blood transfusion were collected from the hospital record.

Results

The most common genotype was gt 4 (48.7%) followed by gt 1 (34.2%) and gt 3 (14.5%). Genotype 2 (2.6%) was only found in elderly male individuals. Patients with history of blood transfusion showed a high percentage of genotype 1 compared to the total number of all patients with genotype 1 (23% and 11% respectively). Biochemical assay showed high level of ALT particularly in genotype 4. No significant relationship was observed between HCV genotype and AST level between genotypes. The viral load was higher in HCV patients received blood transfusion than other genotypes.

Conclusion

The prevalence of genotypes in this study confirmed the observation of other investigations, but no link was found between sex and genotype. There might be an association between blood donation in the past and infections with genotype 1.
Induced expression of Xerophyta viscosa XvSap1 gene greatly impacts tolerance to drought stress in transgenic sweetpotato
Authors: Mbinda Wilton , Dixelius Christina , Oduor Richard
Published: April 2019

Key message Drought stress in sweetpotato could be overcome by introducing XvSap1 gene from Xerophyta viscosa.

Drought stress often leads to reduced yields and is perilous delimiter for expanded cultivation and increased productivity of sweetpotato. Cell wall stabilization proteins have been identified to play a pivotal role in mechanical stabilization during desiccation stress mitigation. They are involved in myriad cellular processes that modify the cell wall properties to tolerate the mechanical stress during dehydration in plants. This provides a possible approach to engineer crops for enhanced stable yields under adverse climatic conditions. In this study, we introduced the XvSap1 gene isolated from Xerophyta viscosa, a resurrection plant into sweetpotato by Agrobacterium-mediated transformation. Detection of the transgene by PCR coupled with Southern blot revealed the integration of XvSap1 in the three independent events. Sweetpotato plants expressing the XvSap1 gene exhibited superior growth performance such as shoot length, number of leaves and yield than the wild type plants under drought stress. Quantitative real time-PCR results confirmed higher expression of the XvSap1 gene in XSP1 transgenic plants imposed with drought stress. In addition, the transgenic plants had increased levels of chlorophyll, free proline and relative water content but malonaldehyde content was decreased under drought stress compared to wild type plants. Conjointly, our findings show that XvSap1 can enhance drought resilience without causing deleterious phenotypic and yield changes, thus providing a promising candidate target for improving the drought tolerance of sweetpotato cultivars through genetic engineering. The transgenic drought tolerant sweetpotato line provides a valuable resource as drought tolerant crop on arid lands of the world.
Tissue-specific changes in the RNA structurome mediate salinity response inArabidopsis
Authors: Tack David C. , Su Zhao , Yu Yunqing , Bevilacqua Philip C. , Assmann Sarah M.
Published: April 2019

RNA structures are influenced by their physico-chemical environment. Few studies have assessed genome-wide impacts of abiotic stresses onin vivoRNA structure, however, and none have investigated tissue-specificity. We applied our Structure-seq method to assessin vivomRNA secondary structure in Arabidopsis shoots and roots under control and salt stress conditions. Structure-seq utilizes dimethyl sulfate (DMS) forin vivotranscriptome-wide covalent modification of accessible As and Cs, i.e. those lacking base pairing and protection. Tissue type was a strong determinant of DMS reactivity, indicating tissue-specificity of RNA structuromes. Both tissues exhibited a significant inverse correlation between salt stress-induced changes in transcript reactivity and changes in transcript abundance, implicating changes in RNA structure and accessibility in transcriptome regulation. In mRNAs wherein the 5’UTR, CDS and 3’UTR concertedly increased or decreased in mean reactivity under salinity, this inverse correlation was more pronounced, suggesting that concordant structural changes across the mRNA have the greatest impact on abundance. Transcripts with the greatest and least salt stress-induced changes in DMS reactivity were enriched in genes encoding stress-related functions and included housekeeping functions, respectively. We conclude that secondary structure regulates mRNA abundance, thereby contributing to tissue specificity of the transcriptome and its dynamic adjustment under stress.

One Sentence Summary:Transcriptome-wide methods reveal dynamic tissue-specific and salt stress-dependent modulation of mRNA accessibility and structure, and correlated mRNA abundance changes.
Drosophilaadult muscle precursor cells contribute to motor axon pathfinding and proper innervation of embryonic muscles
Authors: Lavergne Guillaume , Jagla Krzysztof
Published: April 2019

Adult Muscle Precursors (AMPs), theDrosophilamuscle stem cells, arise from the asymmetric cell divisions of a subset of muscle progenitors ([1]) and are characterized by the persistent expression of the myogenic transcription factor Twist ([2]) and activation of the Notch pathway ([3]; [4]). They occupy stereotyped positions in the vicinity of developing body wall muscles, stay quiescent and undifferentiated during embryonic life and are reactivated during second larval instar ([5]; [6]) to generate muscles of the adult fly. Strikingly, AMPs are also located in the path of intersegmental (ISN) and segmental (SN) motor neuron branches ([2]; [7]). However, their role and interactions with the motor neurons have not yet been analyzed in details. Here, using AMP sensor line revealing cell membrane extensions we show that the navigating ISN first contacts the dorso-lateral (DL-AMPs) and then the dorsal AMP (D-AMP) marking the end of its trajectory. In parallel, the segmental nerve SNa innervating lateral muscles targets the lateral AMPs (L-AMPs).In vivoanalyses of AMPs behavior highlight an active filopodial dynamic of AMPs toward the ISN and SNa suggesting they could guide motor axons and contribute to muscle innervations. Indeed, our data show that loss or mispositioning of L-AMPs affect the SNa motor axons pathfinding and branching, leading to loss or aberrant muscle innervation. The finding of a transient expression of the guidance molecule Sidestep in L-AMPs suggests its implication in this process. Thus, proper muscle innervation does not only rely on the dialogue between the motor neurons and the muscles, but also on the AMP cells. AMPs represent spatial landmarks for navigating motor neurons and their positioning is critical for the muscles innervation in the lateral region.
B cells suppress medullary granulopoiesis by an extracellular glycosylation-dependent mechanism
Authors: Irons Eric E. , Lee-Sundlov Melissa M. , Hoffmeister Karin M. , Lau Joseph T.Y.
Published: April 2019

The immune response relies on the timely integration of cell-intrinsic processes with cell-extrinsic cues. During infection, B cells vacate the bone marrow for the emergency generation of granulocytes. However, it is unclear if cross-talk between B cells and neutrophils also encourages the return to homeostasis. Here, we report that B cells remodel glycans on hematopoietic progenitors to suppress granulopoiesis. Human B cells secrete active ST6Gal-1 sialyltransferase to modify the sialylation and Gr-1 expression of co-cultured hematopoietic progenitors. After adoptive transfer, total hematopoietic and B cells modified the sialylation of non-self cells and elevated blood ST6Gal-1. Mature IgD+ B cells co-localized with megakaryocytes to sialylated bone marrow niches, suggesting their role in medullary extrinsic sialylation. Finally, ST6Gal-1 expression in multiple myeloma cells negatively correlated with neutrophil abundance in human patients. Our results highlight the growing significance of extracellular glycoslytransferases as mediators of a novel glycan-dependent interaction between B cells and granulocytes.
RNA polymerases as moving barriers to condensin loop extrusion
Authors: Brandão Hugo B. , Wang Xindan , Paul Payel , van den Berg Aafke A. , Rudner David Z. , Mirny Leonid A.
Published: April 2019

To separate replicated sister chromatids during mitosis, eukaryotes and prokaryotes have structural maintenance of chromosome (SMC) condensin complexes that were recently shown to organize chromosomes by a process known as DNA loop extrusion. In rapidly dividing bacterial cells, the process of separating sister chromatids occurs concomitantly with ongoing transcription. How transcription interferes with the condensin loop extrusion process is largely unexplored, but recent experiments show that sites of high transcription may directionally affect condensin loop extrusion. We quantitatively investigate different mechanisms of interaction between condensin and elongating RNA polymerases (RNAP) and find that RNAPs are likely steric barriers that can push and interact with condensins. Supported by new Hi-C and ChIP-seq data for cells after transcription inhibition and RNAP degradation, we argue that translocating condensins must bypass transcribing RNAPs within ~2 seconds of an encounter at rRNA genes and within ~10 seconds at protein coding genes. Thus, while individual RNAPs have little effect on the progress of loop extrusion, long, highly transcribed operons can significantly impede the extrusion process. Our data and quantitative models further suggest that bacterial condensin loop extrusion occurs by two independent, uncoupled motor activities; the motors translocate on DNA in opposing directions and function together to enlarge chromosomal loops, each independently bypassing steric barriers in their path. Our study provides a quantitative link between transcription and 3D genome organization and proposes a mechanism of interactions between SMC complexes and elongating transcription machinery relevant from bacteria to higher eukaryotes.
Transcription amplification by nuclear speckle association
Authors: Kim Jiah , Khanna Nimish , Belmont Andrew S.
Published: April 2019

A significant fraction of active chromosome regions and genes reproducibly position near nuclear speckles, but the functional significance of this positioning is unknown. Here we show that Hsp70 BAC transgenes and endogenous genes turn on 2-4 mins after heat shock irrespective of their distance to nuclear speckles. However, we observe 12-56-fold and 3-7-fold higher transcription levels for speckle-associated Hsp70 transgenes and endogenous genes, respectively, after 1-2 hrs heat shock. Several fold higher transcription levels for several genes flanking the Hsp70 locus also correlate with speckle-association at 37 °C. Live-cell imaging reveals this modulation of Hsp70 transcription temporally correlates with speckle association/disassociation. Our results demonstrate stochastic gene expression dependent on positioning relative to a liquid-droplet nuclear compartment through a “transcriptional amplification” mechanism distinct from transcriptional bursting.
Anex vivocystic fibrosis model recapitulates key clinical aspects of chronicStaphylococcus aureusinfection
Authors: Sweeney Esther , Hassan Marwa M. , Harrington Niamh E. , Smyth Alan R. , Hurley Matthew N. , Tormo-Mas María Ángeles , Harrison Freya
Published: April 2019

Staphylococcus aureusis one of the most prevalent organisms isolated from the airways of people with cystic fibrosis (CF), predominantly early in life. Yet its role in the pathology of lung disease is poorly understood. Clinical studies are limited in scope by age and health of participants andin vitrostudies are not always able to accurately recapitulate chronic disease characteristics such as the development of small colony variants. Further, animal models also do not fully represent features of clinical disease: in particular, mice are not readily colonized byS. aureusand when infection is established it leads to the formation of abscesses, a phenomenon almost never observed in the human CF lung. Here, we present details of the development of an existingex vivopig lung model of CF infection to investigate the growth ofS. aureus. We show thatS. aureusis able to establish infection and demonstrates clinically significant characteristics including small colony variant phenotype, increased antibiotic tolerance and preferential localisation in mucus. Tissue invasion and the formation of abscesses were not observed, in line with clinical data.
Transcriptome Surveys in Silverfish Suggest a Multistep Origin of the Insect Odorant Receptor Gene Family
Authors: Thoma Michael , Missbach Christine , Jordan Melissa D. , Grosse-Wilde Ewald , Newcomb Richard D. , Hansson Bill S.
Published: April 2019

The insect odorant receptor (Or) gene family is among the largest multigene families in insect genomes, but its evolutionary origin and mode of expansion is still a matter of debate. We performed transcriptomic surveys of two wingless insect species, the silverfishLepisma saccharinaandTricholepidion gertschi, and identified multiple Or gene family members in both species. A phylogenetic analysis suggests that the silverfish Ors do not fall into the clade comprised of more derived flying insect ligand-binding Ors, but, along with bristletail, firebrat and some mayfly Ors, are consistently resolved as a distinct set of genes that may constitute an evolutionary intermediate between gustatory receptors and the more derived Ors of flying insects. We propose to consider these “primitive Ors” separately from higher insect Ors until their cellular expression patterns and function are resolved and suggest a multistep evolutionary scenario ultimately leading to the highly sensitive, rapidly evolving and physiologically diverse Or gene family observed in higher insects.
tagPAINT: covalent labelling of genetically encoded protein tags for DNA-PAINT imaging
Authors: Nieves Daniel J. , Hilzenrat Geva , Tran Jason , Yang Zhengmin , MacRae Hugh H. , Baker Matthew A. B. , Gooding J Justin , Gaus Katharina
Published: April 2019

Recently, DNA-PAINT single molecule localisation microscopy (SMLM) has shown great promise for quantitative imaging. However, labelling strategies so far have relied on approaches that are multivalent or affinity-based. Here, we demonstrate tagPAINT - the covalent labelling of expressed protein tags (SNAP tag and Halo tag) with single DNA docking strands for single molecule localisation microscopy via DNA-PAINT. We utilised tagPAINT for T-cell receptor signalling proteins at the immune synapse as a proof of principle.
CRISPR/Cas9 Treatment Causes Extended TP53-Dependent Cell Cycle Arrest In Human Cells
Authors: Geisinger Jonathan M. , Stearns Tim
Published: April 2019

While the mechanism of CRISPR/Cas9 cleavage is understood, the large variation in mutant recovery for a given target sequence between cell lines is much less clear. We hypothesized that this variation may be due to differences in how the DNA damage response affects cell cycle progression. We used incorporation of EdU as a marker of cell cycle progression to analyze the response of several human cell lines to CRISPR/Cas9 treatment with a single guide directed to a unique locus. Cell lines with functionally wild-type TP53 exhibited higher levels of cell cycle arrest compared to lines without. Chemical inhibition of TP53 protein combined with TP53 and RB1 transcript silencing alleviated induced arrest in TP53+/+ cells. This arrest is driven in part by Cas9 binding to DNA. Additionally, wild-type Cas9 induced fewer 53BP1 foci in TP53+/+ cells compared to TP53−/− cells, suggesting that differences in break sensing are responsible for cell cycle arrest variation. We conclude that CRISPR/Cas9 treatment induces a cell cycle arrest dependent on functional TP53 as well as Cas9 DNA binding and cleavage. Our findings suggest that transient inhibition of TP53 may increase genome editing efficiency in primary and TP53+/+ cell lines.
Pentamycin biosynthesis in PhilippineStreptomycessp. S816: Cytochrome P450-catalysed installation of the C-14 hydroxyl group
Authors: Zhou Shanshan , Song Lijiang , Masschelein Joleen , Sumang Felaine A.M. , Papa Irene A. , Zulaybar Teofila O. , Custodio Aileen B. , Zabala Daniel , Alcantara Edwin P. , de los Santos Emmanuel L.C. , Challis Gregory L.
Published: April 2019

Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomo-niasis and mixed infections. Chemical instability has hindered its wide-spread application and development as a drug. Here we report the identification ofStreptomycessp. S816, isolated from Philippine mangrove soil, as a pentamycin producer. Genome sequence analysis identified the putative pentamycin biosynthetic gene cluster, which shows a high degree of similarity to the gene cluster responsible for filipin III biosynthesis. TheptnJgene, which is absent from the filipin III biosynthetic gene cluster, was shown to encode a cytochrome P450 capable of converting filipin III to pentamycin. This confirms that the cluster directs pentamycin biosynthesis, paving the way for biosynthetic engineering approaches to the production of pentamycin analogues. Several otherStreptomycesgenomes were found to containptnJorthologues clustered with genes encoding polyketide synthases that appear to have similar architectures to those responsible for the assembly of filipin III and pentamycin, suggesting pentamycin production may be common inStreptomycesspecies.
Vulnerable species interactions are important for the stability of mutualistic networks
Authors: Simmons Benno I. , Wauchope Hannah S. , Amano Tatsuya , Dicks Lynn V. , Sutherland William J. , Dakos Vasilis
Published: April 2019

Species are central to ecology and conservation. However, it is the interactions between species that generate the functions on which ecosystems and humans depend. Despite the importance of interactions, we lack an understanding of the risk that their loss poses to ecological communities. Here, we quantify risk as a function of the vulnerability (likelihood of loss) and importance (contribution to network stability in terms of species coexistence) of 4330 mutualistic interactions from 41 empirical pollination and seed dispersal networks across six continents. Remarkably, we find that more vulnerable interactions are also more important: the interactions that contribute most to network stability are those that are most likely to be lost. Furthermore, most interactions tend to have more similar vulnerability and importance across networks than expected by chance, suggesting that vulnerability and importance may be intrinsic properties of interactions, rather than only a function of ecological context. These results provide a starting point for prioritising interactions for conservation in species interaction networks and, in areas lacking network data, could allow interaction properties to be inferred from taxonomy alone.
The hypoxic ventilatory response is facilitated by the activation of Lkb1-AMPK signalling pathways downstream of the carotid bodies
Authors: Mahmoud Amira D. , Holmes Andrew P. , MacMillan Sandy , Ogunbayo Oluseye A. , Wyatt Christopher N. , Dallas Mark L. , Kumar Prem , Foretz Marc , Viollet Benoit , Evans A. Mark
Published: April 2019

We recently demonstrated that the role of the AMP-activated protein kinase (AMPK), a ubiquitously expressed enzyme that governs cell-autonomous metabolic homeostasis, has been extended to system-level control of breathing and thus oxygen and energy (ATP) supply to the body. Here we assess the contribution to the hypoxic ventilatory response (HVR) of two upstream kinases that govern the activities of AMPK. Lkb1, which activates AMPK in response to metabolic stress and CaMKK2 which mediates the alternative Ca2+-dependent mechanism of AMPK activation. HVRs remained unaffected in mice with global deletion of the CaMKK2 gene. By contrast, HVRs were markedly attenuated in mice with conditional deletion of LKB1 in catecholaminergic cells, including carotid body type I cells and brainstem respiratory networks. In these mice hypoxia evoked hypoventilation, apnoea and Cheyne-Stokes-like breathing, rather than hyperventilation. Attenuation of HVRs, albeit less severe, was also conferred in mice carrying ∼90% knockdown of Lkb1 expression. Carotid body afferent input responses were retained following either ∼90% knockdown of Lkb1 or AMPK deletion. In marked contrast, LKB1 deletion virtually abolished carotid body afferent discharge during normoxia, hypoxia and hypercapnia. We conclude that Lkb1 and AMPK, but not CaMKK2, facilitate HVRs at a site downstream of the carotid bodies.
A spatiotemporal ventricular myocyte model incorporating mitochondrial calcium cycling
Authors: Song Z. , Xie L-H , Weiss J. N. , Qu Z.
Published: April 2019

Intracellular calcium (Ca2+) cycling dynamics in cardiac myocytes are spatiotemporally generated by stochastic events arising from a spatially distributed network of coupled Ca2+ release units (CRUs) that interact with an intertwined mitochondrial network. In this study, we developed a spatiotemporal ventricular myocyte model that integrates mitochondria-related Ca2+ cycling components into our previously developed ventricular myocyte model consisting of a 3-dimensional CRU network. Mathematical formulations of mitochondrial membrane potential, mitochondrial Ca2+ cycling, mitochondrial permeability transition pore (MPTP) stochastic opening and closing, intracellular reactive oxygen species (ROS) signaling, and oxidized Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling were incorporated into the model. We then used the model to simulate the effects of mitochondrial depolarization on mitochondrial Ca2+ cycling, Ca2+ spark frequency and amplitude, which agree well with experimental data. We also simulated the effects of the strength of mitochondrial Ca2+ uniporters and their spatial localization on intracellular Ca2+ cycling properties, which substantially affected diastolic and systolic Ca2+ levels in the mitochondria but exhibited only a small effect on sarcoplasmic reticulum and cytosolic Ca2+ levels under normal conditions. We show that mitochondrial depolarization can cause Ca2+ waves and Ca2+ alternans, which agrees with previous experimental observations. We propose that this new spatiotemporal ventricular myocyte model, incorporating properties of mitochondrial Ca2+ cycling and ROS-dependent signaling, will be useful for investigating the effects of mitochondria on intracellular Ca2+ cycling and action potential dynamics in ventricular myocytes.
Comparing within- and between-family polygenic score prediction
Authors: Selzam Saskia , Ritchie Stuart J. , Pingault Jean-Baptiste , Reynolds Chandra A. , O’Reilly Paul F. , Plomin Robert
Published: April 2019

Polygenic scores are a popular tool for prediction of complex traits. However, prediction estimates in samples of unrelated participants can include effects of population stratification, assortative mating and environmentally mediated parental genetic effects, a form of genotype-environment correlation (rGE). Comparing genome-wide polygenic score (GPS) predictions in unrelated individuals with predictions between siblings in a within-family design is a powerful approach to identify these different sources of prediction. Here, we compared within- to between-family GPS predictions of eight life outcomes (anthropometric, cognitive, personality and health) for eight corresponding GPSs. The outcomes were assessed in up to 2,366 dizygotic (DZ) twin pairs from the Twins Early Development Study from age 12 to age 21. To account for family clustering, we used mixed-effects modelling, simultaneously estimating within- and between-family effects for target- and cross-trait GPS prediction of the outcomes. There were three main findings: (1) DZ twin GPS differences predicted DZ differences in height, BMI, intelligence, educational achievement and ADHD symptoms; (2) target and cross-trait analyses indicated that GPS prediction estimates for cognitive traits (intelligence and educational achievement) were on average 60% greater between families than within families, but this was not the case for non-cognitive traits; and (3) this within- and between-family difference for cognitive traits disappeared after controlling for family socio-economic status (SES), suggesting that SES is a source of between-family prediction through rGE mechanisms. These results provide novel insights into the patterns by which rGE contributes to GPS prediction, while ruling out confounding due to population stratification and assortative mating.
Mechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: a QM/MM study
Authors: Recabarren Rodrigo , Osorio Edison H. , Caballero Julio , Tuñón Iñaki , Alzate-Morales Jans
Published: April 2019

Cyclin-dependent kinase 2 (CDK2) is an important member of the CDK family exerting its most important function in the regulation of the cell cycle. It catalyzes the transfer of the gamma phosphate group from an ATP (adenosine triphosphate) molecule to a Serine/Threonine residue of a peptide substrate. Due to the importance of this enzyme, and protein kinases in general, a detailed understanding of the reaction mechanism is desired. Thus, in this work the phosphoryl transfer reaction catalyzed by CDK2 was revisited and studied by means of hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. Our results show that the base-assisted mechanism is preferred over the substrate-assisted pathway, in agreement with a previous theoretical study. The base-assisted mechanism resulted to be dissociative, with a potential energy barrier of 14.3 kcal/mol, very close to the experimental derived value. An interesting feature of the mechanism is the proton transfer from Lys129 to the phosphoryl group at the second transition state, event that could be helping in neutralizing the charge on the phosphoryl group upon the absence of a second Mg2+ ion. Furthermore, important insights into the mechanisms in terms of bond order and charge analysis were provided. These descriptors helped to characterize the synchronicity of bond forming and breaking events, and to characterize charge transfer effects. Local interactions at the active site are key to modulate the charge distribution on the phosphoryl group and therefore alter its reactivity.
Research applications of primary biodiversity databases in the digital age
Authors: Ball-Damerow Joan E. , Brenskelle Laura , Barve Narayani , Soltis Pamela S. , Sierwald Petra , Bieler Rüdiger , LaFrance Raphael , Ariño Arturo H. , Guralnick Robert
Published: April 2019

We are in the midst of unprecedented change—climate shifts and sustained, widespread habitat degradation have led to dramatic declines in biodiversity rivaling historical extinction events. At the same time, new approaches to publishing and integrating previously disconnected data resources promise to help provide the evidence needed for more efficient and effective conservation and management. Stakeholders have invested considerable resources to contribute to online databases of species occurrences and genetic barcodes. However, estimates suggest that only 10% of biocollections are available in digital form. The biocollections community must therefore continue to promote digitization efforts, which in part requires demonstrating compelling applications of the data. Our overarching goal is therefore to determine trends in use of mobilized species occurrence data since 2010, as online systems have grown and now provide over one billion records. To do this, we characterized 501 papers that use openly accessible biodiversity databases. Our standardized tagging protocol was based on key topics of interest, including: database(s) used, taxa addressed, general uses of data, other data types linked to species occurrence data, and data quality issues addressed. We found that the most common uses of online biodiversity databases have been to estimate species distribution and richness, to outline data compilation and publication, and to assist in developing species checklists or describing new species. Only 69% of papers in our dataset addressed one or more aspects of data quality, which is low considering common errors and biases known to exist in opportunistic datasets. Globally, we find that biodiversity databases are still in the initial stages of data compilation. Novel and integrative applications are restricted to certain taxonomic groups and regions with higher numbers of quality records. Continued data digitization, publication, enhancement, and quality control efforts are necessary to make biodiversity science more efficient and relevant in our fast-changing world.
The characteristic radiation of copper Kα1,2,3,4
Authors: Melia Hamish A. , Chantler Christopher T. , Smale Lucas F. , Illig Alexis J.
Published: April 2019

A characterization of the Cu Kα1,2 spectrum is presented, including the 2p satellite line, Kα3,4, the details of which are robust enough to be transferable to other experiments. This is a step in the renewed attempts to resolve inconsistencies in characteristic X-ray spectra between theory, experiment and alternative experimental geometries. The spectrum was measured using a rotating anode, monolithic Si channel-cut double-crystal monochromator and backgammon detector. Three alternative approaches fitted five Voigt profiles to the data: a residual analysis approach; a peak-by-peak fit; and a simultaneous constrained method. The robustness of the fit is displayed across three spectra obtained with different instrumental broadening. Spectra were not well fitted by transfer of any of three prior characterizations from the literature. Integrated intensities, line widths and centroids are compared with previous empirical fits. The novel experimental setup provides insight into the portability of spectral characterizations of X-ray spectra. From the parameterization, an estimated 3d shake probability of 18% and a 2p shake probability of 0.5% are reported.
The influence of hierarchical organizational culture, supportive environment and sexual harassment on Korean women’s work-to-family enrichment
Authors: Park Sunyoung , Jo Sung Jun , Park Chan Kyun
Published: April 2019

Purpose

The purpose of this study is to examine the relationships among hierarchical organizational culture, organizational support for women, sexual harassment and work-to-family enrichment of working women in South Korea.

Design/methodology/approach

A total of 196 responses from married female employees who had a child (or children) in for-profit organizations in South Korea were analyzed by using structural equation modeling and bootstrapping analysis.

Findings

The findings indicated that hierarchical organizational culture was negatively associated with organizational support and was positively associated with sexual harassment. In addition, an organizational atmosphere that is friendly and supportive to women had a positive effect on work-to-family enrichment. However, the more sexual harassment female workers experienced, the less positive the relationship between their work and family lives. Hierarchical organizational culture negatively affected work-to-family enrichment, but the effect was indirect through organizational support and sexual harassment.

Originality/value

These findings emphasize the importance of transforming the traditional culture in Korean organizations to reduce power distance to create a more female-friendly and supportive environment. With the dramatic recent increase in the number of female workers, building such an environment can enhance organizations’ competitiveness by creating a positive spillover effect between women’s work and family lives.
Determinants of small accommodation business size
Authors: Ye Shun , Xiao Honggen , Ying Tianyu , Zhou Lingqiang
Published: April 2019

Purpose

This paper aims to model and empirically test the determinants of small accommodation business (SAB) size.

Design/methodology/approach

This study distinguishes among three aspects of SAB size (accommodation scale, investment and employment) and between two modes of growth (managerial and entrepreneurial growth). A conceptual framework was developed based on business growth theory, whereby three econometric models were constructed and estimated to predict size variations. Data were collected through a survey on 200 SABs in North Zhejiang Province of China. Effects of the determinants were contrasted between different size indicators.

Findings

The SAB size can be affected by personal factors (employed working experience, education level, industry-specific know-how), interpersonal factor (relative ties to other SABs) and environmental factor (association support). The interpersonal and environmental factors tend to contribute to managerial growth, while the personal factors are usually conducive to entrepreneurial growth.

Research limitations/implications

This study addresses the questions of “why some SABs grow larger in size than others” and “why different SABs grow in different ways”. But more contexts and business types should be examined so as to ensure generalizability through future studies.

Practical implications

The research findings can provide guidelines for local tourism administration to encourage or regulate SAB development.

Originality/value

This study is among the first endeavors to examine the multidimensionality and determinants of business size in tourism and hospitality; it contributes to literature by expanding tourism entrepreneurship research into a/the “growth paradigm”.
Understanding the antecedents and consequences of the perceived usefulness of travel review websites
Authors: Wang Ping , Li Hongxiu
Published: April 2019

Purpose

The purpose of this study is to understand the antecedents and consequences of the perceived usefulness (PU) of travel review websites.

Design/methodology/approach

An integrated model was proposed and 199 valid data were collected via a questionnaire survey from an online travel service company. The partial least squares structural equation modeling (PLS-SEM) was applied in data analysis.

Findings

The antecedents of the PU of travel review websites are utilitarian and hedonic perceptions, specifically the information quality of eWOM (utilitarian perceptions), curiosity fulfilment and enjoyment in travel review websites usage (hedonic perceptions). The PU of travel review websites positively impacts travelers’ eWOM generation, eWOM use and purchase decision.

Practical implications

This paper provides implications for travel review websites, social media managers and website designers on how to make a useful travel review website which will lead to eWOM use and generation, as well as purchase decision.

Originality/value

Prior literature has highlighted the importance of the PU of eWOM in determining travelers’ use of eWOM and purchase decision, the PU of eWOM websites has not attracted the attention of researchers. This paper is a new attempt to investigate the antecedents and consequences of the PU of travel review websites.
A review and synthesis of environmentalism within the Olympic Movement
Authors: Del Fiacco Anthony Gino , Orr Madeleine
Published: April 2019

Purpose

The purpose of this paper is to delineate shifts in environmental sustainability leadership in the Olympic Movement through a historical narrative.

Design/methodology/approach

A systematic literature review was conducted and data were analyzed chronologically.

Findings

Four eras are identified, distinguished by different leadership and levels of commitment toward the natural environment: public-driven environmental sustainability, host city-driven environmental sustainability, International Olympic Committee-mandated environmental sustainability and environmental regression.

Research limitations/implications

This paper is limited to secondary data collected through a systematic literature review.

Practical implications

The findings inform a list of best practices for Olympic environmental sustainability, grounded in evidence of past successes and lessons learned from environmentally insensitive events.

Originality/value

This is the first historical narrative and synthesis of environmental leadership in the Olympic Movement, a topic previously covered in studies focused solely on the institutions responsible for hosting the event, ignoring external parties and the deep history of environmentalism dating back to the 1930s, or focusing just on actions, ignoring the actors who drove the environmental movement.
Rediscovering relevance
Authors: Lambert Douglas M.
Published: April 2019

Purpose

The purpose of this paper is to document the growing concerns about the lack of relevance of business school research, and offer suggestions for journal editors and faculty members in logistics and supply chain management.

Design/methodology/approach

This paper is a review of literature related to the relevance of business school research and an analysis of trends related to the editorial review boards of the three main logistics journals.

Findings

The current business school research model is unsustainable. The metrics used are driving the wrong behavior. Logistics journals, traditionally known for an emphasis on practical relevance, appear to be emulating the journals of other business functions at a time when there is a growing consensus that these journals are publishing, more often than not, research of little or no value to practicing managers or society.

Practical implications

The cost of faculty research at AACSB schools, which increasingly benefits no one but the authors, has been estimated at roughly US$3.8bn annually. Imagine the potential benefits if business school deans realigned the incentives to encourage faculty to produce credible research that is useful to business and society.

Originality/value

The hope is to influence senior logistics faculty with tenure to work with business executives or policymakers to identify long-term big idea projects that will impact business and society, and publish their research in the logistics journals. Traditionally, the editors of logistics journals included business executives on the editorial review boards and encouraged research of practical relevance. Journal editors should look back and realize what was good about the journals and not discard the good for current fads.
After all these years, what has happened to the international prevalence of NPM-inspired managerial practices?
Authors: Aoki Naomi
Published: April 2019

Purpose

According to a widely accepted narrative, managerial reforms associated with new public management (NPM) originated in wealthy market economies and liberal democracies and were then promoted globally. However, scientific and systematic cross-national evidence of NPM practices has remained limited in scope, and debates over their survival and prevalence remain unsettled. The purpose of this paper is to narrow this empirical gap.

Design/methodology/approach

Using international data from public education in approximately 65 economies in 2012, this study systematically investigated the prevalence of managerial practices, namely, the managerial responsibilities of school principals, goal orientation in school management, and performance-based human resource management (HRM). It also tested correlations between the status of these practices and political and economic conditions across economies.

Findings

As of 2012, the top users of NPM practices were geographically spread across the world in regions that included Southeast Asia, Eastern Europe, the Middle East, and North Africa. Economies exhibited dissimilarities in their deployment of managerial practices. Performance-based HRM tended to be used more extensively in less accountable and less wealthy economies.

Originality/value

By focusing on actual practices, this study offers an empirically valid, critical analysis of the global prevalence of NPM. The findings clarify some observers’ current understandings of NPM. They deliver a powerful message that debates on global reform waves can benefit greatly from empirical evidence drawn from world regions beyond one’s parochial focus.
Historical policies affecting women’s military and family roles
Authors: King Erika Lee , DiNitto Diana M.
Published: April 2019

Purpose

The US military depends on women to meet recruiting goals, but women participate at lower rates than men. Theorists suggest that military and family policies affect women’s lower participation. Research has confirmed the impact of policy changes on women’s military service during specific time periods. The purpose of this paper is to examine how and when military policies affecting women developed over the course of history, exploring two related hypotheses: first, when women’s military participation is vital, policies affecting their military and family roles punctuate in tandem, and second, cultural values impact policy solutions to reconcile women’s roles.

Design/methodology/approach

Punctuated equilibrium and a women’s military participation theory informed the hypotheses. US Census and Defense Department data were used to identify periods of service when women’s military participation was vital. Historical policies were mapped and analyzed to identify policy patterns and themes affecting women’s military participation 1895–2015.

Findings

Evidence supports both hypotheses. When women are needed during wartimes, policies simultaneously encourage their service and regulate their family roles. However, policies evolved from separating servicewomen’s roles prior to the 1970s (e.g. prohibiting motherhood), to supporting their families (e.g. maternity leave) – a shift precipitated by sweeping changes in broader society and the military’s change from the draft to an All-Volunteer Force.

Originality/value

Findings elucidate the link between military and family policies affecting US women’s military participation and retention. Results may inform policy advocacy aimed at optimizing the US Department of Defense’s diversity efforts.
Modelling wholesale distribution operations: an artificial intelligence framework
Authors: Bottani Eleonora , Centobelli Piera , Gallo Mosé , Kaviani Mohamad Amin , Jain Vipul , Murino Teresa
Published: April 2019

Purpose

The purpose of this paper is to propose an artificial intelligence-based framework to support decision making in wholesale distribution, with the aim to limit wholesaler out-of-stocks (OOSs) by jointly formulating price policies and forecasting retailer’s demand.

Design/methodology/approach

The framework is based on the cascade implementation of two artificial neural networks (ANNs) connected in series. The first ANN is used to derive the selling price of the products offered by the wholesaler. This represents one of the inputs of the second ANN that is used to anticipate the retailer’s demand. Both the ANNs make use of several other input parameters and are trained and tested on a real wholesale supply chain.

Findings

The application of the ANN framework to a real wholesale supply chain shows that the proposed methodology has the potential to decrease economic loss due to OOS occurrence by more than 56 percent.

Originality/value

The combined use of ANNs is a novelty in supply chain operation management. Moreover, this approach provides wholesalers with an effective tool to issue purchase orders according to more dependable demand forecasts.