bluuebunny/crossref_metadata_2025 huggingface dataset:
SV40 polyomavirus activates the Ras-MAPK signaling pathway for vacuolization, cell death, and virus release
Authors: Motamedi Nasim , Sewald Xaver , Luo Yong , Mothes Walther , DiMaio Daniel
Published: October 2018

Polyomaviruses are a family of small, non-enveloped DNA viruses that can cause severe disease in immunosuppressed individuals. Studies with SV40, a well-studied model polyomavirus, have revealed the role of host proteins in polyomavirus entry and trafficking to the nucleus, viral transcription and DNA replication, and cell transformation. In contrast, little is known about host factors or cellular signaling pathways involved in the late steps of productive infection leading to polyomavirus release. We previously showed that cytoplasmic vacuolization, a characteristic late cytopathic effect of SV40, depends on the specific interaction between the major viral capsid protein VP1 and its cell surface ganglioside receptor GM1. Here we show that late during infection, SV40 activates a signaling cascade in permissive CV-1 monkey cells involving Ras, Rac1, MKK4 and JNK to induce SV40-specific cytoplasmic vacuolization and subsequent cell lysis and virus release. Inhibition of individual components of this signaling pathway inhibits vacuolization, lysis and virus release, even though high-level intracellular virus replication occurs. The identification of this pathway for SV40-induced vacuolization and virus release provides new insights into the late steps of non-enveloped virus infection and reveals potential drug targets for the treatment of diseases caused by these viruses.

IMPORTANCE

The polyomaviruses are small DNA viruses that include important model viruses and human pathogens that can cause fatal disease, including cancer, in immunosuppressed individuals. There are no vaccines or specific antiviral agents for any polyomavirus. Here, we show that late during infection, SV40 activates a signaling cascade involving Ras, Rac, and JNK that is required for cytoplasmic vacuolization and efficient virus release. This pathway may represent a new point of intervention to control infection by these viruses.
BspA and Pmp proteins ofTrichomonas vaginalismediate adherence to host cells
Authors: Handrich Maria R. , Garg Sriram G. , Sommerville Ewen W. , Hirt Robert P. , Gould Sven B.
Published: October 2018

Trichomonas vaginalisis one of the most widespread, sexually transmitted pathogens. The infection involves a morphological switch from a free-swimming pyriform trophozoite to an amoeboid cell upon adhesion to host epithelial cells. While details on how the switch is induced and to what proteins of the host surface the parasite adheres remain poorly characterized, several surface proteins of the parasite itself have been identified as potential candidates. Among those are two expanded protein families that harbor domains that share similarity to functionally investigated surface proteins of prokaryotic oral pathogens; these are the BspA proteins of Bacteroidales and Spirochaetales, and the Pmp proteins of Chlamydiales. We sequenced the transcriptomes of five Trichomonads and screened for the presence of BspA and Pmp domain-containing proteins and tested the ability of individualT. vaginaliscandidates to mediate adhesion. Here we demonstrate that (i) BspA and Pmp domain-containing proteins are specifically expanded inT. vaginalisin comparison to other Trichomonads, and that (ii) individual proteins of both families have the ability to increase adhesion performance in a non-virulentT. vaginalisstrain andTetratrichomonas gallinarum, a parasite usually known to infect birds but not humans. Our results initiate the functional characterization of these two broadly distributed protein families, whose origin we trace back to the origin of Trichomonads themselves.
Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders
Authors: Erli Filippo , Palmos Alish B. , Raval Pooja , Mukherjee Jayanta , Sellers Katherine J. , Gatford Nicholas J.F. , Moss Stephen J. , Brandon Nicholas J. , Penzes Peter , Srivastava Deepak P.
Published: October 2018

Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic and cellular studies of SCZ and MDD using in vivo and in vitro systems have supported a key role for dysfunction of excitatory synapses in the pathophysiology of these disorders. Recent clinical studies have demonstrated that the estrogen, 17β-estradiol can ameliorate many of the symptoms experienced by patients. Yet, to date, our understanding of how 17β-estradiol exerted these beneficial effects is limited. In this study, we have tested the hypothesis that 17β-estradiol can restore dendritic spine number in a cellular model that recapitulates the loss of synapses associated with SCZ and MDD. Ectopic expression of wildtype, mutant or shRNA-mediated knockdown of Disrupted in Schizophrenia (DISC1) reduced dendritic spine density in primary cortical neurons. Acute or chronic treatment with 17β-estradiol increased spine density to control levels in neurons with altered DISC1 levels. In addition, 17β-estradiol reduced the extent to which ectopic wildtype and mutant DISC1 aggregated. Furthermore, 17β-estradiol also caused the enrichment of synaptic proteins at synapses and increased the number of dendritic spines containing PSD-95 or that overlapped with the pre-synaptic marker bassoon. Taken together, our data indicates that estrogens can restore lost excitatory synapses caused by altered DISC1 expression, potentially through the trafficking of DISC1 and its interacting partners. These data highlight the possibility that estrogens exert their beneficial effects in SCZ and MDD in part by modulating dendritic spine number.
Heteromerization of endogenous mu and delta opioid receptors tunes mu opioid receptor signaling and trafficking
Authors: Derouiche Lyes , Ugur Muzeyyen , Pierre Florian , Mann Anika , Doridot Stéphane , Ory Stéphane , Schulz Stefan , Massotte Dominique
Published: October 2018

Increasing evidence indicates that native mu and delta opioid receptors can associate to form heteromers in discrete brain neuronal circuits. However, little is known about their signaling and trafficking. Using double fluorescent knock-in mice, we investigated the impact of neuronal co-expression on the internalization profile of mu and delta opioid receptors in primary hippocampal cultures andin vivo. We established ligand selective mu-delta co-internalization upon activation by exogenous ligands and provide evidence for mu-delta co-internalization by the endogenous opioid peptide met-enkephalin, but not β-endorphin. Co-internalization was driven by the delta opioid receptor, required an active conformation of both receptors and led to sorting to the lysosomal compartment. This alteration in the mu opioid receptor intracellular fate was accompanied by sustained ERK1/2 phosphorylation. In addition, increased mu-delta neuronal co-localization in the rostral ventromedial medulla in a chronic neuropathic state suggests that mu-delta heteromers are involved in the regulation of nociceptive transmission
Nucleosome positions alone determine micro-domains in yeast chromosomes
Authors: Wiese O. , Marenduzzo D. , Brackley C. A.
Published: October 2018

We use molecular dynamics simulations based on publicly available MNase-seq data for nucleosome positions to predict the 3-D structure of chromatin in the yeast genome. Our main aim is to shed light on the mechanism underlying the formation of micro-domains, chromosome regions of around 0.5-10 kbp which show enriched self-interactions, which were experimentally observed in recent MicroC experiments. We show that the sole input of nucleosome positioning data is already sufficient to determine the patterns of chromatin interactions and domain boundaries seen experimentally to a high degree of accuracy. Since the nucleosome spacing so strongly affects the larger-scale domain structure, we next examine the genome-wide linker-length distribution in more detail, finding that it is highly irregular, and varies in different genomic regions such as gene bodies, promoters, and active and inactive genes. Finally we use our simple simulation model to characterise in more detail how irregular nucleosome spacing may affect local chromatin structure.
Deep Learning on MRI Affirms the Prominence of the Hippocampal Formation in Alzheimer's Disease Classification
Authors: Feng Xinyang , Yang Jie , Lipton Zachary C , Small Scott A , Provenzano Frank A
Published: October 2018

Deep learning techniques on MRI scans have demonstrated great potential to improve the diagnosis of neurological diseases. Here, we investigate the application of 3D deep convolutional neural networks (CNNs) for classifying Alzheimer's disease (AD) based on structural MRI data. In particular, we take on two challenges that are under-explored in the literature on deep learning for neuroimaging. First deep neural networks typically require large-scale data that is not always available in medical studies. Therefore, we explore the use of including longitudinal scans in classification studies, greatly increasing the amount of data for training and improving the generalization performance of our classifiers. Moreover, previous studies applying deep learning to classifying Alzheimer's disease from neuroimaging have typically addressed classification based on whole brain volumes but stopped short of performing in-depth regional analyses to localize the most predictive areas. Additionally, we show a deep net trained to distinguish between AD and cognitively normal subjects can be applied to classify mild cognitive impairment patients, with classification scores aligning empirically with the likelihood of progression to AD. Our initial results demonstrate both that we can classify AD with an area under the receiver operator characteristic curve (AUROC) of .990 and that we can predict conversion to AD among patients in the MCI subgroup with an AURUC of 0.787. We then localize the predictive regions, by performing both saliency-based interpretation and rigorous slice and lobar level ablation studies. Interestingly, our regional analyses identified the hippocampal formation, including the entorhinal cortex, to be the most predictive region for our models. This finding adds evidence that the hippocampal formation is an anatomical seat of AD and a prominent feature in its diagnosis. Together, the results of this study further demonstrate the potential of deep learning to impact AD classification and to identify AD's structural neuroimaging signatures. The proposed classification and regional analyses methods constitute a general framework that can easily be applied to other disorders and imaging modalities.
Robust, reproducible, and economical phosphopeptide enrichment using calcium titanate
Authors: Ahmed Adnan , Raja Vijay J. , Cavaliere Paola , Dephoure Noah
Published: October 2018

Mass spectrometry based phosphoproteomics has revolutionized phosphoprotein analysis and enhanced our understanding of diverse and fundamental cellular processes important for human health. Because of their relative scarcity, phosphopeptides must be enriched before analysis. We demonstrate an effective and robust single-step enrichment method using an off-the-shelf preparation of calcium titanate. Our method achieves a purity and depth of analysis comparable to a widely used TiO2 based method at a reduced cost and effort.
The Markov link method: a nonparametric approach to combine observations from multiple experiments
Authors: Loper Jackson , Bakken Trygve , Sumbul Uygar , Murphy Gabe , Zeng Hongkui , Blei David , Paninski Liam
Published: October 2018

This paper studiesmeasurement linkage. An example from cell biology helps explain the problem: imagine for a given cell we can either sequence the cell’s RNA or we can examine its morphology, but not both. Given a cell’s morphology, what do we expect to see in its RNA? Given a cell’s RNA, what do we expect in its morphology? More broadly, given a measurement of one type, can we predict measurements of the other type? This measurement linkage problem arises in many scientific and technological fields. To solve this problem, we develop a nonparametric approach we dub the “Markov link method” (MLM). The MLM makes a conditional independence assumption that holds in many multi-measurement contexts and provides a way to estimate thelink, the conditional probability of one type of measurement given the other. We derive conditions under which the MLM estimator is consistent and we use simulated data to show that it provides accurate measures of uncertainty. We evaluate the MLM on real data generated by a pair of single-cell RNA sequencing techniques. The MLM characterizes the link between them and helps connect the two notions of cell type derived from each technique. Further, the MLM reveals that some aspects of the link cannot be determined from the available data, and suggests new experiments that would allow for better estimates.

Significance Statement

Novel experimental techniques are developing quickly, and each technique gives new perspectives. Ideally we would build theories that account for many perspectives at once. This is not easy. One challenge is that many experiments use measurement techniques that alter or destroy the subject, making it impossible to measure the same subject with both techniques and difficult to combine data from different experiments. In this paper we develop the Markov Link Method, a new tool that overcomes this challenge.
Non-High Frequency Heart Rate Chaos: A Noninvasive Marker of REM Sleep and Obstructive Sleep Apnea Syndrome in Children
Authors: Deng Zhi-De , Arzeno Natalia M. , Katz Eliot S. , Chang Helena , Marcus Carole L. , Poon Chi-Sang
Published: October 2018

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent condition associated with considerable metabolic, cardiovascular, and neurocognitive morbidity. Childhood OSAS is underdiagnosed due to a limited number of sleep laboratories and the lack of a screening test, and the subtlety of daytime symptoms in children compared to adults. A potential marker of OSAS is apnea-induced sympathoexcitation, which is likely to be exacerbated during rapid-eyemovement (REM) sleep. However, traditional methods of assessing sympathetic activity are either too invasive or insensitive/nonspecific for clinical use, particularly as a screening test. Study population comprised pediatric patients with OSAS (16 moderate/severe, 18 mild) and 18 normal non-snoring controls. We show that the chaotic dynamics of heart rate variability (HRV) as assessed by a sensitive noise titration assay is significantly increased during REM compared to non-REM sleep in children, particularly those with OSAS. The increase in heart rate chaos prevails in the face of decreased parasympathetic-mediated high-frequency component of the HRV power spectrum, indicating that the chaos was correlated to sympathetic instead of parasympathetic activity. Receiver operating characteristic analysis shows that such non-high frequency chaos reveals changing sympathetic–parasympathetic activities that are not discernible by conventional HRV metrics such as low- to high-frequency power ratio or sample entropy, with sensitivity and specificity sufficient to detect even mild OSAS in children. Results suggest a possible role for non-high frequency heart rate chaos as a selective noninvasive marker of sympathoexcitation in REM sleep, OSAS and potentially other cardiovascular abnormalities such as congestive heart failure.
Biological adaptation under fluctuating selection
Authors: Liu Ming , Rubenstein Dustin R. , Liu Wei-Chung , Shen Sheng-Feng
Published: October 2018

Bet-hedging—an evolutionary strategy that reduces fitness variance at the expense of lower mean fitness—is the primary explanation for most forms of biological adaptation to environmental unpredictability. However, most applications of bet-hedging theory to biological problems have largely made unrealistic demographic assumptions, such as non-overlapping generations and fixed population sizes. Consequently, the generality and applicability of bet-hedging theory to real world phenomena remains unclear. Here we use continuous-time, stochastic Lotka-Volterra models to relax overly restrictive demographic assumptions and explore a suite of biological adaptations to fluctuating environments. We discover a novel “rising-tide strategy” that—unlike the bet-hedging strategy—generates both a higher mean and variance in fitness. The positive fitness effects of the rising-tide strategy’s specialization to good years can overcome any negative effects of higher fitness variance in unpredictable environments. Moreover, we show not only that the rising-tide strategy will be selected for over a much broader range of environmental conditions than the bet-hedging strategy, but also under more realistic demographic circumstances. Ultimately, our model demonstrates that there are likely to be a wide range of ways that organisms respond to environmental unpredictability.
Deep gastropod relationships resolved
Authors: Tauana Junqueira Cunha , Gonzalo Giribet
Published: October 2018

Gastropod mollusks are arguably the most diverse and abundant animals in the oceans, and are successful colonizers of terrestrial and freshwater environments. Here we resolve deep relationships between the five major gastropod lineages - Caenogastropoda, Heterobranchia, Neritimorpha, Patellogastropoda and Vetigastropoda - with highly congruent and supported phylogenomic analyses. We expand taxon sampling for underrepresented lineages with new transcriptomes, and conduct analyses accounting for the most pervasive sources of systematic errors in large datasets, namely compositional heterogeneity, site heterogeneity, heterotachy, variation in evolutionary rates among genes, matrix completeness and gene tree conflict. We find that vetigastropods and patellogastropods are sister taxa, and that neritimorphs are the sister group to caenogastropods and heterobranchs. With this topology, we reject the traditional Archaeogastropoda, which united neritimorphs, vetigastropods and patellogastropods, and is still used in the organization of collections of many natural history museums. Several traits related to development and life history support our molecular results. Importantly, the time of differentiation of the embryonic 4d cell (mesentoblast, responsible for mesoderm formation), differs between the two major clades, highlighting the degree of conservation and significance of development in the evolution of gastropods, as it is also known for spiralian animals more broadly.
Antibacterial activity of total flavonoids from Ilex rotunda Thunb. and different antibacterials on different multidrug-resistant bacteria alone or in combination
Authors: Wu Yongji , Chai Beibei , Wang Lizhen , Jiang Weijia , Hu Mei , Zhao Yuchuan , Si Hongbin
Published: October 2018

The problem of bacterial resistance is becoming more and more serious, which has become an urgent problem to be solved in human and veterinary. One approach to control and delay bacterial resistance is combination therapy in which antibiotics are given together with other antimicrobial or non-antimicrobial agents. Studies have shown that flavonoids from Traditional Chinese medicine (TCM) possess a high level of antibacterial activity against antibiotic resistant strains. The aim of this study was to evaluate the antibacterial effects of a combined therapy of total flavonoids from Ilex rotunda Thunb. and antibiotics against seven kinds of veterinary bacteria which were multidrug resistance bacteria. A microdilution checkerboard method was used to determine the minimal inhibitory concentrations of both types of antimicrobials, alone and in combination. The fractional inhibitory concentration index was calculated and used to classify observed collective antibacterial activity as synergistic, additive, indifferent or antagonistic.

From the performed tests, the total flavonoids and antimicrobial agents were combined to inhibit different multidrug-resistant bacteria, such as Escherichia coli, Streptococcus, Pseudomonas aeruginosa, Enterococcus faecalis, Proteus vulgaris, Staphylococcus aureus, Acinetobacter baumannii. For these bacteria, total flavonoids from Ilex Rotunda Thunb. presented synergistic or additive with different antibiotics and had a certain antibacterial effect on the separated multidrug-resistant bacteria. The study shows total flavonoids from Ilex rotunda Thunb. have potential as adjuvants for the treatment of animal bacterial diseases.
External evaluation of population pharmacokinetic models for vancomycin in neonates
Authors: Tasa Tõnis , Kalamees Riste , Vilo Jaak , Lutsar Irja , Metsvaht Tuuli
Published: October 2018

Introduction

Numerous vancomycin population pharmacokinetic (PK) models of neonates have been published. We aimed to comparatively evaluate a set of these models by quantifying their model-based and Bayesian concentration prediction performances using an external retrospective dataset, and estimate their attainment rates in predefined therapeutic target ranges.

Methods

Implementations of 12 published PK models were added in the Bayesian dose optimisation tool, DosOpt. Model based concentration predictions informed by variable number of individual concentrations were evaluated using multiple error metrics. A simulation study assessed the probabilities of target attainment (PTA) in trough concentration target ranges 10–15 mg/L and 10–20 mg/L.

Results

Normalized prediction distribution error analysis revealed external validation dataset discordances (global P < 0.05) with all population PK models. Inclusion of a single concentration improved both precision and accuracy. The model by Marques-Minana et al. (2010) attained 68% of predictions within 30% of true concentrations. Absolute percentage errors of most models were within 20-30%. Mean PTA with Zhao et al. (2013) was 40.4% [coefficient-of-variation (CV) 0.5%] and 62.9% (CV 0.4%) within 10–15 mg/L and 10–20 mg/L, respectively.

Conclusion

Predictive performances varied widely between models. Population based predictions were discordant with external validation dataset but Bayesian modelling with individual concentrations improved both precision and accuracy. Current vancomycin PK models achieve relatively low attainment of commonly recommended therapeutic target ranges.
Indirect genetic effects clarify how traits can evolve even when fitness does not
Authors: Fisher David N. , McAdam Andrew G.
Published: October 2018

There are many situations in nature where we expect traits to evolve but not necessarily for mean fitness to increase. However, these scenarios are hard to reconcile simultaneously with Fisher’s Fundamental Theorem of Natural Selection and the Price identity. The consideration of indirect genetic effects on fitness reconciles these fundamental theorems with the observation that traits sometimes evolve without any adaptation, by explicitly considering the correlated evolution of the social environment, which is a form of transmission bias. While transmission bias in the Price identity is often assumed to be absent, here we show that explicitly considering indirect genetic effects as a form of transmission bias for fitness has several benefits: 1) it makes clear how traits can evolve while mean fitness remains stationary, 2) it reconciles the fundamental theorem of natural selection with the evolution of maladaptation, 3) it explicitly includes density-dependent fitness through negative social effects that depend on the number of interacting conspecifics, and 4) its allows mean fitness to evolve even when direct genetic variance in fitness is zero, if related individuals interact and/or if there is multilevel selection. In summary, considering fitness in the context of indirect genetic effects aligns important theorems of natural selection with many situations observed in nature and provides a useful lens through which we might better understand evolution and adaptation.
A practical guide to methods controlling false discoveries in computational biology
Authors: Korthauer Keegan , Kimes Patrick K , Duvallet Claire , Reyes Alejandro , Subramanian Ayshwarya , Teng Mingxiang , Shukla Chinmay , Alm Eric J , Hicks Stephanie C
Published: October 2018

Background

In high-throughput studies, hundreds to millions of hypotheses are typically tested. Statistical methods that control the false discovery rate (FDR) have emerged as popular and powerful tools for error rate control. While classic FDR methods use only p-values as input, more modern FDR methods have been shown to increase power by incorporating complementary information as “informative covariates” to prioritize, weight, and group hypotheses. However, there is currently no consensus on how the modern methods compare to one another. We investigated the accuracy, applicability, and ease of use of two classic and six modern FDR-controlling methods by performing a systematic benchmark comparison using simulation studies as well as six case studies in computational biology

Results

Methods that incorporate informative covariates were modestly more powerful than classic approaches, and did not underperform classic approaches, even when the covariate was completely uninformative. The majority of methods were successful at controlling the FDR, with the exception of two modern methods under certain settings. Furthermore, we found the improvement of the modern FDR methods over the classic methods increased with the informativeness of the covariate, total number of hypothesis tests, and proportion of truly non-null hypotheses.

Conclusions

Modern FDR methods that use an informative covariate provide advantages over classic FDR-controlling procedures, with the relative gain dependent on the application and informativeness of available covariates. We present our findings as a practical guide and provide recommendations to aid researchers in their choice of methods to correct for false discoveries.
The interaction between genotype and maternal nutritional environments affects tomato seed and seedling quality
Authors: Geshnizjani Nafiseh , Khorami Saadat Sarikhani , Willems Leo A.J. , Snoek Basten L. , Hilhorst Henk W.M. , Ligterink Wilco
Published: October 2018

Seed and seedling traits are affected by the conditions of the maternal environment, such as light, temperature and nutrient availability. In this study, we have investigated whether different maternally applied nitrate and phosphate concentrations affect the seed and seedling performance of two tomato genotypes:Solanum lycopersicumcv. Money maker andSolanum pimpinellifoliumaccession CGN14498. We observed large differences for seed and seedling traits between the two genotypes. Additionally, we have shown that for nitrate most of the seed and seedling traits were significantly affected by genotype by environment interactions (G×E). The effect of the maternal environment was clearly visible in the primary metabolites of the dry seeds. For example, we could show that the amount of γ-aminobutyric acid (GABA) in Money maker seeds was affected by the differences in the maternal environments and was positively correlated with seed germination under high temperature. Overall, compared to phosphate, nitrate had a larger effect on seed and seedling performance in tomato. In general, the different responses to the maternal environments of the two tomato genotypes show a major role of genotype by environment interactions in shaping seed and seedling traits.

Highlight

The presented data specifically provides knowledge towards understanding a multi-level effect of the maternal nutritional environment on seed and seedling characteristics in tomato. We show a clear genotype by environment interactions (G×E) especially for maternal growth on different nitrate concentrations. Additionally we identified metabolites with either positive or negative correlations with maternal environment affected phenotypical traits.
Structure-based mechanism of action of a viral poly(ADP-ribose) polymerase 1-interacting protein facilitating virus replication
Authors: Chung Woo-Chang , Kim Junsoo , Kim Byung Chul , Kang Hye-Ri , Son JongHyeon , Ki Hosam , Hwang Kwang Yeon , Song Moon Jung
Published: October 2018

Poly(ADP-ribose) polymerase 1 (PARP-1), an enzyme that modifies nuclear proteins by poly(ADP-ribosyl)ation, regulates various cellular activities and restricts the lytic replication of oncogenic gammaherpesviruses by inhibiting the function of replication and transcription activator (RTA), a key switch molecule of the viral life cycle. A viral PARP-1-interacting protein (vPIP) encoded by murine gammaherpesvirus 68 (MHV-68) orf49 facilitates lytic replication by disrupting interactions between PARP-1 and RTA. Here, the structure of MHV-68 vPIP was determined at 2.2 Å resolution. The structure consists of 12 α-helices with characteristic N-terminal β-strands (Nβ) and forms a V-shaped-twist dimer in the asymmetric unit. Structure-based mutagenesis revealed that Nβ and the α1 helix (residues 2–26) are essential for the nuclear localization and function of vPIP; three residues were then identified (Phe5, Ser12 and Thr16) that were critical for the function of vPIP and its interaction with PARP-1. A recombinant MHV-68 harboring mutations of these three residues showed severely attenuated viral replication both in vitro and in vivo. Moreover, ORF49 of Kaposi's sarcoma-associated herpesvirus also directly interacted with PARP-1, indicating a conserved mechanism of action of vPIPs. The results elucidate the novel molecular mechanisms by which oncogenic gammaherpesviruses overcome repression by PARP-1 using vPIPs.
Crystal structure of glycosyltrehalose synthase fromSulfolobus shibataeDSM5389
Authors: Okazaki Nobuo , Blaber Michael , Kuroki Ryota , Tamada Taro
Published: October 2018

Glycosyltrehalose synthase (GTSase) converts the glucosidic bond between the last two glucose residues of amylose from an α-1,4 bond to an α-1,1 bond, generating a nonreducing glycosyl trehaloside, in the first step of the biosynthesis of trehalose. To better understand the structural basis of the catalytic mechanism, the crystal structure of GTSase from the hyperthermophilic archaeonSulfolobus shibataeDSM5389 (5389-GTSase) has been determined to 2.4 Å resolution by X-ray crystallography. The structure of 5389-GTSase can be divided into five domains. The central domain contains the (β/α)8-barrel fold that is conserved as the catalytic domain in the α-amylase family. Three invariant catalytic carboxylic amino acids in the α-amylase family are also found in GTSase at positions Asp241, Glu269 and Asp460 in the catalytic domain. The shape of the catalytic cavity and the pocket size at the bottom of the cavity correspond to the intramolecular transglycosylation mechanism proposed from previous enzymatic studies.
Combining crystallogenesis methods to produce diffraction-quality crystals of a psychrophilic tRNA-maturation enzyme
Authors: de Wijn Raphaël , Hennig Oliver , Ernst Felix G. M. , Lorber Bernard , Betat Heike , Mörl Mario , Sauter Claude
Published: October 2018

The determination of conditions for the reproducible growth of well diffracting crystals is a critical step in every biocrystallographic study. On the occasion of a new structural biology project, several advanced crystallogenesis approaches were tested in order to increase the success rate of crystallization. These methods included screening by microseed matrix screening, optimization by counter-diffusion and crystal detection by trace fluorescent labeling, and are easily accessible to any laboratory. Their combination proved to be particularly efficient in the case of the target, a 48 kDa CCA-adding enzyme from the psychrophilic bacterium Planococcus halocryophilus. A workflow summarizes the overall strategy, which led to the production of crystals that diffracted to better than 2 Å resolution and may be of general interest for a variety of applications.
Crystal structure at 100 K of bis[1,2-bis(diphenylphosphanyl)ethane]nickel(II) bis(trifluoromethanesulfonate): a possible negative thermal expansion molecular material
Authors: Cano-Benítez Cristian A. , Metta-Magaña Alejandro J. , Duarte-Ruiz Álvaro
Published: October 2018

In the title salt, [Ni(C26H24P2)2](CF3SO3)2 or [Ni(dppe)2]2+·(OTf−)2 [dppe = 1,2-bis(diphenylphosphanyl)ethane and OTf− = trifluoromethanesulfonate], the Ni atom (site symmetry \overline{1}) has a square-planar geometry with the bidentate ligands chelating the metal. As a result of the steric hindrance of the phenyl rings, the counter-ions are blocked from the metal coordination sphere. The dynamic disorder of the anion existing at 296 K is reduced at 100 K and based on these two temperatures, negative thermal expansion behaviour is observed.
Crystal structure and Hirshfeld surface analysis of (E)-1-[(4,7-dimethylquinolin-2-yl)methylidene]semicarbazide dihydrate
Authors: Aydemir Ercan , Kansiz Sevgi , Dege Necmi , Genc Hasan , Gaidai Snizhana V.
Published: October 2018

In the title compound, C13H14N4O·2H2O, the organic molecule is almost planar. In the crystal, the molecules are linked by O—H...O, N—H...O and O—H...N hydrogen bonds, forming a two-dimensional network parallel to (10\overline{1}). Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (55.4%), H...O/O...H (14.8%), H...C/C...H (11.7%) and H...N/N...H (8.3%) interactions.
How arbitrary are the weights assigned to books in performance-based research funding? An empirical assessment of the weight and size of monographs in Flanders
Authors: Verleysen Frederik T. , Engels Tim C.E.
Published: October 2018

Purpose

The purpose of this paper is to present an empirical assessment of the weight assigned to monographs in the publication indicator of the performance-based research funding system (PRFS) in Flanders, Belgium. By relating publication weight to publication size the authors offer an alternative perspective on the production of scholars who publish monographs. This perspective on weights is linked to the aggregation level at which PRFS indicators are used: the national/regional one as opposed to the local one. In Flanders as elsewhere the publication indicator designed for funding distribution between universities has sometimes trickled down to institutions, their faculties and departments.

Design/methodology/approach

As an alternative indicator of scholarly production the authors propose the median number of pages of a publication type. Measuring the size of publications allows to compare the weight ratio between monographs and journal articles in the publication indicator to their size ratio in the VABB-SHW database. The authors compare two levels, one of four universities and one of 16 disciplines.

Findings

Median publication size differences between disciplines are much larger than those between universities. This indicates that an increase of monographs’ weight in the publication indicator would hardly affect funding distribution at the regional level. Disciplines with a relatively large share of monographs, however, would contribute more to the publication indicator. Hence an increase of monographs’ weight might provide a better balance between fields and between publication types.

Originality/value

This paper presents a thought experiment regarding the weight assigned to different publication types in the publication indicator of the Flemish PRFS: what would happen if this weight were replaced by the median number of pages of a publication type? In doing so, we highlight that such weighting schemes play an important role in finding a balance between fields of research. The sizeable differences between weight and size ratios offer a new and critical perspective on the weighting schemes currently used in PRFS, also in other countries.
Are book publications disappearing from scholarly communication in the social sciences and humanities?
Authors: Engels Tim C.E. , Istenič Starčič Andreja , Kulczycki Emanuel , Pölönen Janne , Sivertsen Gunnar
Published: October 2018

Purpose

The purpose of this paper is to analyze the evolution in terms of shares of scholarly book publications in the social sciences and humanities (SSH) in five European countries, i.e. Flanders (Belgium), Finland, Norway, Poland and Slovenia. In addition to aggregate results for the whole of the social sciences and the humanities, the authors focus on two well-established fields, namely, economics & business and history.

Design/methodology/approach

Comprehensive coverage databases of SSH scholarly output have been set up in Flanders (VABB-SHW), Finland (VIRTA), Norway (NSI), Poland (PBN) and Slovenia (COBISS). These systems allow to trace the shares of monographs and book chapters among the total volume of scholarly publications in each of these countries.

Findings

As expected, the shares of scholarly monographs and book chapters in the humanities and in the social sciences differ considerably between fields of science and between the five countries studied. In economics & business and in history, the results show similar field-based variations as well as country variations. Most year-to-year and overall variation is rather limited. The data presented illustrate that book publishing is not disappearing from an SSH.

Research limitations/implications

The results presented in this paper illustrate that the polish scholarly evaluation system has influenced scholarly publication patterns considerably, while in the other countries the variations are manifested only slightly. The authors conclude that generalizations like “performance-based research funding systems (PRFS) are bad for book publishing” are flawed. Research evaluation systems need to take book publishing fully into account because of the crucial epistemic and social roles it serves in an SSH.

Originality/value

The authors present data on monographs and book chapters from five comprehensive coverage databases in Europe and analyze the data in view of the debates regarding the perceived detrimental effects of research evaluation systems on scholarly book publishing. The authors show that there is little reason to suspect a dramatic decline of scholarly book publishing in an SSH.
Achieving leanness with BIM-based integrated data management in a built environment project
Authors: Ma Xiaozhi , Chan Albert P.C. , Wu Hengqin , Xiong Feng , Dong Na
Published: October 2018

Purpose

Although various concepts and techniques are introduced to the built environment to achieve a substantially efficient building production, the effective application of these methods in projects is of immense significance to the field of building construction. Among these initiatives, lean construction and building information modelling (BIM) are mainstream endeavours that share many common principles to improve the productivity of the built environment. This study aims to explore and explain how BIM-based integrated data management (IDM) facilitates the achievement of leanness in a built environment project.

Design/methodology/approach

This research is conducted through an ethnographic-action research that relies on the design-science approach and case study through a collaborative research project. As participants of the project, the researchers of this study cooperate with the practitioners to design the project approach and production workflows. Research data and evidence are obtained via participative observation, including direct observation, results of activities, unstructured meetings and self-analysis.

Findings

In this study, the project and production perspectives clarify the building design and production process, as well as analyse how BIM facilitates the achievement of leanness in building design and construction. BIM-based frameworks for IDM have been developed to handle miscellaneous information and data, as well as enhance multidisciplinary collaboration throughout the project life cycle. The role of the integrated BIM model as an information hub between the building design and building construction has been identified.

Research/limitations implications

The project and production views of building and construction are used in this study because the research purpose is to link the BIM-based IDM to lean construction. Although this mixed approach can slightly undermine the theoretical foundation of this study, a substantially comprehensive understanding can be gained as well.

Practical implications

This study provides a new perspective to understand how BIM-based IDM contributes to lean construction.

Originality/value

This study provides new insights into IDM in a built environment project with project and production views and presents BIM-based frameworks for IDM to achieve lean construction through the BIM process.
Managers’ perceptions of trust in the workplace in times of strategic change
Authors: Komodromos Marcos , Halkias Daphne , Harkiolakis Nicholas
Published: October 2018

Purpose

The purpose of this paper is to explore and present current trends and developments in the field of managers’ perceptions of trust and the management of change in Cyprus, Greece and Romania, in a period of strategic organizational change. A total of 126 managerial employees (communication managers, operation managers, quality control managers, safety & environmental managers, and office managers) working in different departments of organizations in Cyprus, Greece, and Romania respond and complete the online questionnaire.

Design/methodology/approach

A qualitative study using an online questionnaire with interview questions was developed to arrive at the study’s findings. To acknowledge relevant perceptions of trust and the management of change during organizational change in different organizations in Cyprus, Greece and Romania, unique questions helped to support the research results and highlight themes that emerged from interview sessions with the study participants.

Findings

The findings highlight the need for organizational leadership to establish mutual trust and effective communication with managerial employees for successful cooperation during times of strategic change and enhanced overall employee performance. This study is relevant for researchers and academics in the areas of change management and communication, presenting current trends and developments in perceptions of trust and change management in Cyprus, Greece and Romania. It may also help them achieve recognition among their peers and colleagues from other disciplines.

Research limitations/implications

An important implication of the study derives from the finding on the uniqueness of the knowledge and information work carried out by the respondents and the impact that this can have in their working environment and their productivity. As a result of the above, this study provides indications to recruiters and managers regarding a number of desirable and necessary skills, and motivational factors that future employees may need to have or develop in order to carry out their job efficiently and effectively.

Practical implications

Researching managerial employees’ perceptions of trust and the management of change in organizations can have significant implications for human resources management during a time of strategic change.

Social implications

This research study may contribute to the management and communication area in European countries in stimulating new approaches to management and social issues and in the corporate management practice.

Originality/value

This study produces new knowledge instead of summarizing what is already known in a new form in the area of management and corporate communication. The researcher reports the results in analysis and interprets the results by discussing possible implications and solutions.
Business intelligence and big data in hospitality and tourism: a systematic literature review
Authors: Mariani Marcello , Baggio Rodolfo , Fuchs Matthias , Höepken Wolfram
Published: October 2018

Purpose

This paper aims to examine the extent to which Business Intelligence and Big Data feature within academic research in hospitality and tourism published until 2016, by identifying research gaps and future developments and designing an agenda for future research.

Design/methodology/approach

The study consists of a systematic quantitative literature review of academic articles indexed on the Scopus and Web of Science databases. The articles were reviewed based on the following features: research topic; conceptual and theoretical characterization; sources of data; type of data and size; data collection methods; data analysis techniques; and data reporting and visualization.

Findings

Findings indicate an increase in hospitality and tourism management literature applying analytical techniques to large quantities of data. However, this research field is fairly fragmented in scope and limited in methodologies and displays several gaps. A conceptual framework that helps to identify critical business problems and links the domains of business intelligence and big data to tourism and hospitality management and development is missing. Moreover, epistemological dilemmas and consequences for theory development of big data-driven knowledge are still a terra incognita. Last, despite calls for more integration of management and data science, cross-disciplinary collaborations with computer and data scientists are rather episodic and related to specific types of work and research.

Research limitations/implications

This work is based on academic articles published before 2017; hence, scientific outputs published after the moment of writing have not been included. A rich research agenda is designed.

Originality/value

This study contributes to explore in depth and systematically to what extent hospitality and tourism scholars are aware of and working intendedly on business intelligence and big data. To the best of the authors’ knowledge, it is the first systematic literature review within hospitality and tourism research dealing with business intelligence and big data.
I think someone is walking with me: the use of mobile phone for social capital development among women in four refugee communities
Authors: Koh Lee Cheng , Walker Rae , Wollersheim Dennis , Liamputtong Pranee
Published: October 2018

Purpose

The purpose of this paper is to present a mixed method study of social capital development and use, based on an intervention which provided women from refugee backgrounds with social capital development skills and tools.

Design/methodology/approach

In total, 111 Afghan, Burmese and Sudanese women living in Melbourne, Australia, received peer-support training and a free unlimited fixed-dial mobile phone for one year.

Findings

Interview and call log data suggest that the training sessions and mobile phones played important roles in bonding social capital development, resulting in a complex support network among participants. To a lesser extent, there was also evidence of bridging social capital creation. By providing linkages to government institutions through an interpreter service, the mobile phones gave participants easy access to linking social capital, in their heritage language.

Originality/value

The program supplements existing community resources with mobile phone technology to create social capital rich networks within these disadvantaged communities, and the authors describe the community characteristics that make participants amenable to such an intervention.
Executing large-scale processes in a blockchain
Authors: Ramkumar Mahalingam
Published: October 2018

Purpose

The purpose of this paper is to examine the blockchain as a trusted computing platform. Understanding the strengths and limitations of this platform is essential to execute large-scale real-world applications in blockchains.

Design/methodology/approach

This paper proposes several modiﬁcations to conventional blockchain networks to improve the scale and scope of applications.

Findings

Simple modifications to cryptographic protocols for constructing blockchain ledgers, and digital signatures for authentication of transactions, are sufficient to realize a scalable blockchain platform.

Originality/value

The original contributions of this paper are concrete steps to overcome limitations of current blockchain networks.