bluuebunny/crossref_metadata_2025 huggingface dataset:
Lectin engineering: the possible and the actual
Authors: Hirabayashi Jun , Arai Ryoichi
Published: February 2019

Lectins are a widespread group of sugar-binding proteins occurring in all types of organisms including animals, plants, bacteria, fungi and even viruses. According to a recent report, there are more than 50 lectin scaffolds (∼Pfam), for which three-dimensional structures are known and sugar-binding functions have been confirmed in the literature, which far exceeds our view in the twentieth century (Fujimoto
et al.
2014
Methods Mol. Biol.
1200
, 579–606 (
doi:10.1007/978-1-4939-1292-6_46
)). This fact suggests that new lectins will be discovered either by a conventional screening approach or just by chance. It is also expected that new lectin domains including those found in enzymes as carbohydrate-binding modules will be generated in the future through evolution, although this has never been attempted on an experimental level. Based on the current state of the art, various methods of lectin engineering are available, by which lectin specificity and/or stability of a known lectin scaffold can be improved. However, the above observation implies that any protein scaffold, including those that have never been described as lectins, may be modified to acquire a sugar-binding function. In this review, possible approaches to confer sugar-binding properties on synthetic proteins and peptides are described.
Cell type and receptor identity regulate cholera toxin subunit B (CTB) internalization
Authors: Sethi Anirudh , Wands Amberlyn M. , Mettlen Marcel , Krishnamurthy Soumya , Wu Han , Kohler Jennifer J.
Published: February 2019

Cholera toxin (CT) is a secreted bacterial toxin that binds to glycoconjugate receptors on the surface of mammalian cells, enters mammalian cells through endocytic mechanisms and intoxicates mammalian cells by activating cytosolic adenylate cyclase. CT recognizes cell surface receptors through its B subunit (CTB). While the ganglioside GM1 has been historically described as the sole receptor, CTB is also capable of binding to fucosylated glycoconjugates, and fucosylated molecules have been shown to play a functional role in host cell intoxication by CT. Here, we use colonic epithelial and respiratory epithelial cell lines to examine how two types of CT receptors—gangliosides and fucosylated glycoconjugates—contribute to CTB internalization. We show that fucosylated glycoconjugates contribute to CTB binding to and internalization into host cells, even when the ganglioside GM1 is present. The contributions of the two classes of receptors to CTB internalization depend on cell type. Additionally, in a cell line that harbours both classes of receptors, gangliosides dictate the efficiency of CTB internalization. Together, the results lend support to the idea that fucosylated glycoconjugates play a functional role in CTB internalization, and suggest that CT internalization depends on both receptor identity and cell type.
Serum IgA1 shows increased levels ofα2,6-linked sialic acid in breast cancer
Authors: Lomax-Browne Hannah J. , Robertson Claire , Antonopoulos Aristotelis , Leathem Anthony J. C. , Haslam Stuart M. , Dell Anne , Dwek Miriam V.
Published: February 2019

The lectinHelix pomatiaagglutinin (HPA) recognizes altered glycosylation in solid cancers and the identification of HPA binding partners in tumour tissue and serum is an important aim. Among the many HPA binding proteins, IgA1 has been reported to be the most abundant in liver metastases. In this study, the glycosylation of IgA1 was evaluated using serum samples from patients with breast cancer (BCa) and the utility of IgA1 glycosylation as a biomarker was assessed. Detailed mass spectrometric structural analysis showed an increase in disialo-biantennaryN-linked glycans on IgA1 from BCa patients (p< 0.0001: non-core fucosylated;p= 0.0345: core fucosylated) and increased asialo-Thomsen–Friedenreich antigen (TF) and disialo-TF antigens in theO-linked glycan preparations from IgA1 of cancer patients compared with healthy control individuals. An increase inSambucus nigrabinding was observed, suggestive of increasedα2,6-linked sialic acid on IgA1 in BCa. Logistic regression analysis showed HPA binding to IgA1 and tumour size to be significant independent predictors of distant metastases (χ213.359;n= 114;p= 0.020) with positive and negative predictive values of 65.7% and 64.6%, respectively. Immunohistochemical analysis of tumour tissue samples showed IgA1 to be detectable in BCa tissue. This report provides a detailed analysis of serum IgA1 glycosylation in BCa and illustrates the potential utility of IgA1 glycosylation as a biomarker for BCa prognostication.
Leveraging genetic interaction for adverse drug-drug interaction prediction
Authors: Qian Sheng , Liang Siqi , Yu Haiyuan
Published: February 2019

In light of increased co-prescription of multiple drugs, the ability to discern and predict drug-drug interactions (DDI) has become crucial to guarantee the safety of patients undergoing treatment with multiple drugs. However, information on DDI profiles is incomplete and the experimental determination of DDIs is labor-intensive and time-consuming. Although previous studies have explored various feature spaces for in silico screening of interacting drug pairs, no method currently provides reliable predictions outside of their training sets. Here we demonstrate for the first time targets of adversely interacting drug pairs are significantly more likely to have synergistic genetic interactions than non-interacting drug pairs. Leveraging genetic interaction features and a novel training scheme, we construct a gradient boosting-based classifier that achieves robust DDI prediction even for drugs whose interaction profiles are completely unseen during training. We demonstrate that in addition to classification power—including the prediction of 432 novel DDIs—our genetic interaction approach offers interpretability by providing plausible mechanistic insights into the mode of action of DDIs.
Effects of acute lying and sleep deprivation on the behavior of lactating dairy cows
Authors: Kull Jessie A. , Proudfoot Katy L. , Pighetti Gina M. , Bewley Jeffery M. , O’Hara Bruce F. , Donohue Kevin D. , Krawczel Peter D.
Published: February 2019

The objective was to determine the effects of sleep or lying deprivation on the behavior of dairy cows. Data were collected from 8 multi- and 4 primiparous cows (DIM = 199 ± 44 (mean ± SD); days pregnant = 77 ± 30). Using a crossover design, each cow experienced: 1) sleep deprivation implemented by noise or physical contact when their posture suggested sleep, and 2) lying deprivation imposed by a grid placed on the pen floor. One day before treatment (baseline), and treatment day (treatment) were followed by a 12-d washout period. Study days were organized from 2100 to 2059. During habituation (d −3 and −2 before treatment), baseline (d −1), and trt (d 0), housing was individual boxstalls (mattress with no bedding). After treatment, cows returned to sand-bedded freestalls for a 7-d recovery period (d 1 to 7) where data on lying behaviors were collected. Daily lying time, number lying bouts, bout duration, and number of steps were recorded by dataloggers attached to the hind leg of cows throughout the study period. Data were analyzed using a mixed model in SAS including fixed effects of treatment (sleep deprivation vs. sleep and lying deprivation), day, and their interaction with significant main effects separated using a PDIFF statement (P ≤ 0.05). Interactions between treatment and day were detected for daily lying time and the number of bouts. Lying time was lower for both treatments during the treatment period compared to baseline. Lying time increased during the recovery period for both lying and sleep deprived cows. However, it took 4 d for the lying deprived cows to fully recover their lying time after treatment, whereas it took the sleep deprived cows 2 d for their lying time to return to baseline levels. Results suggest that both sleep and lying deprivation can have impact cow behavior. Management factors that limit freestall access likely reduce lying time and sleep, causing negative welfare implications for dairy cows.
SCFAs-induced GLP-1 Secretion Links the Regulation of Gut Microbiome on Hepatic Lipogenesis in Chickens
Authors: Zhang Jianmei , Sun Yin shuang , Zhao Liqin , Chen Tiantian , Fan Meina , Jiao Hongchao , Zhao Jingpeng , Wang Xiaojuan , Li Fuchang , Li Haifang , Lin Hai
Published: February 2019

Chickens represent a specific case in lipid metabolism that liver is the main site of lipid synthesis. As ovipara, their gut microbiota could be strongly influenced by environment and diets after hatching. The aim of this study is to elucidate the linkage of gut microbiota and fat synthesis in broilers. The broilers were subjected to dietary treatments of combined probiotics (Clostridium butyrate4×108cfu/kg,Bifidobacterium2×108cfu/kg,Lactobacillus plantarum2×108cfu/kg andLactococcus faecalis2×108cfu/kg, PB) and guar gum (1 g/kg, GG). The result showed that dietary supplementation of PB and GG changed the cecal microbiota diversity, altered short chain fatty acids (SCFAs) contents, and suppressed lipogenesis in liver and abdominal fat tissues. In intestinal epithelial cells (IECs), acetate, propionate, and butyrate upregulated the expression of glucagon-like peptide-1 (GLP-1) via MAPK pathways, especially via the ERK and p38 MAPK pathways. GLP-1 suppressed lipid accumulation in primary hepatocytes with the involvement of AMPK/ACC signaling. In conclusion, the result suggests that SCFAs-induced GLP-1 secretion links the regulation of gut microbiome on hepatic lipogenesis in chickens.

IMPORTANCE

Intestinal microbes metabolize SCFAs and stimulate intestinal epithelium L cells to produce GLP-1. Recent evidence showed that GLP-1 reduced fat deposition by reducing appetite and increasing satiety. However, how SCFAs stimulate the secretion of GLP-1 and whether GLP-1 directly affects fat metabolism is not clear. Poultry adipocytes have limited ability to produce fat, and 90% of carcass fat is synthesized in the liver. In addition, large intake of feeds easily leads to fatty liver diseases in chickens. The aim of this study is to investigate how SCFAs mediate secretion of GLP-1 and whether GLP-1 could directly affect hepatic deposition in broiler chickens. The hepatic lipogenesis regulated by the intestinal microbiota of chickens is of great significance to the study of intestinal microbiota and fat deposition in poultry, and this work could provide reference for intestinal microorganism and fat metabolism in mammals and humans.
Resilience trinity: safeguarding ecosystem services across three different time horizons and decision contexts
Authors: Weise H , Auge H , Baessler C , Bärlund I , Bennett E.M. , Berger U , Bohn F , Bonn A , Borchardt D , Brand F , Chatzinotas A , Corstanje R , De Laender F , Dietrich P , Dunker S , Durka W , Fazey I , Groeneveld J , Guilbaud CSE , Harms H , Harpole S , Harris J , Jax K , Jeltsch F , Johst K , Joshi J , Klotz S , Kühn I , Kuhlicke C , Müller B , Radchuk V , Reuter H , Rinke K , Schmitt-Jansen M , Seppelt R , Singer A , Standish RJ , Thulke HH , Tietjen B , Weitere M , Wirth C , Wolf C , Grimm V
Published: February 2019

Ensuring ecosystem resilience is an intuitive approach to safeguard future provisioning of ecosystem services (ES). However, resilience is an ambiguous concept and difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough because the usefulness of a mechanism is context-dependent. We suggest a conceptual framework, resilience trinity, to facilitate management of resilience mechanisms in three distinctive decision contexts and time-horizons. i) reactive, when there is an imminent threat to ES resilience and a high pressure to act, ii) adjustive, when the threat is known in general but there is still time to adapt management, and iii) provident when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. This emphasizes that resilience has different interpretations and implications at different time horizons which however need to be reconciled. The inclusion of time into resilience thinking ensures that longer-term management actions are not missed while urgent threats to ES are given priority.
Paternal age affects offspring’s behavior possibly via an epigenetic mechanism recruiting a transcriptional repressor REST
Authors: Yoshizaki Kaichi , Koike Tasuku , Kimura Ryuichi , Kikkawa Takako , Oki Shinya , Koike Kohei , Mochizuki Kentaro , Inada Hitoshi , Kobayashi Hisato , Matsui Yasuhisa , Kono Tomohiro , Osumi Noriko
Published: February 2019

Advanced paternal age has deleterious effects on mental health of next generation. Using a mouse model, we have confirmed that offspring derived from aged fathers showed impairments in behavior and abnormalities in the brain structure and activity. Comprehensive target DNA methylome analyses revealed in aged sperm more hypo-methylated genomic regions, in which REST/NRSF binding motif was enriched. Gene set enrichment analyses also identified enrichment of “REST/NRSF target genes”, in addition to “Late-fetal genes” and autism spectrum disorder-related “SFARI genes”, in up-regulated genes of developing brains from aged father. Indeed, gene sets near hypo-methylated genomic regions with REST/NRSF binding motif were also enriched in up-regulated genes of developing brains. Taken altogether, DNA hypo-methylation due to paternal aging in sperm will induce leaky expression of REST/NRSF target genes in the developing brain, thereby causing neuronal abnormalities and subsequent behavioral alteration in offspring.
Using time causal quantifiers to characterize sleep stages
Authors: Mateos Diego M. , Gómez-Ramírez Jaime , Rosso Osvaldo A.
Published: February 2019

Sleep plays substantial role in daily cognitive performance, mood and memory. The study of sleep has attracted the interest of neuroscientists, clinicans and the overall population, with increasing number of adults suffering from insufficient amounts of sleep. Sleep is an activity composed of different stages whose temporal dynamics, cycles and inter dependencies are not fully understood. Healthy body function and personal well being, however, depends on proper unfolding and continuance of the sleep cycles. The characterization of the different sleep stages can be undertaken with the development of biomarkers derived from sleep recording. For this purpose, in this work we analyzed single-channel EEG signals from 106 healthy subjects. The signals were quantified using the permutation vector approach using five different information theoretic measures: i) Shannon’s entropy, ii) MPR statistical complexity, iii) Fisher information, iv) Renyí Min-entropy and v) Lempel-Ziv complexity. The results show that all five information theory-based measures make possible to quantify and classify the underlying dynamics of the different sleep stages. In addition to this, we combine these measures to show that planes containing pairs of measures, such as the plane composed of Lempel-Ziv and Shannon, have a better performance for differentiating sleep states than measures used individually for the same purpose.
Noisy Perturbation Models Distinguish Network Specific from Embedding Variability
Authors: Piehler A.
Published: February 2019

Recently, measurement technologies allowing to determine the abundance of tens signaling proteins in thousands of single cells became available. The interpretation of this high dimensional end-point time course data is often difficult, because sources of cell-to-cell abundance variation in measured species are hard to determine. Here I present an analytic tool to tackle this problem. By using a recently developed chemical signal generator to manipulate input noise of biochemical networks, measurement of state variables and modeling of input noise propagation, pathway-specific variability can be distinguished from environmental variability caused by network embedding. By employing different sources of natural input noise, changes in the output variability were quantified, indicating that also synthetic noisy perturbations are biologically feasible. The presented analytic tool shows how signal generators can improve our understanding of the origin of cellular variability and help to interpret multiplexed single cell information.
A Differentially Methylated CpG Site in theIL4Gene Associated with Anti-FVIII Inhibitor Antibody Development in Hemophilia A
Authors: de Souza Thiago Barbosa , de Souza Thais Louvain , Santos Ferreira Cristina dos , da Silva Cleiton Figueiredo Osório , Rossetti Liliana Carmen , Marchione Vanina Daniela , De Brasi Carlos Daniel , Medina-Acosta Enrique
Published: February 2019

Hemophilia A is the most common clotting disorder in humans. It affects one in five thousand live-born children. Mutations in the X-chromosome linkedF8gene lead to the deficiency of circulating factor VIII (FVIII). The defect is characterized by severe bleeding. The standard therapy is to replace the deficient factor intravenously. The main adverse event of the therapy is the development of anti-FVIII inhibitor antibodies that impair coagulation and result in increased complications and risk of death. Several risk factors have been described for the development of inhibitor antibodies, among them age, type of FVIII administered, ethnicity, and variant alleles in immune response genes. Epigenetic risks factors have not yet been explored. This work aimed to evaluate the methylation statuses at thirteen CpG sites (5meCpG) in regulatory regions of theIL1B, IL2, IL4, IL6, IL10, TNF, IFNG, CTLA4, CD28, andCST7immune regulation genes in hemophilia A affected males on replacement therapy who develop or do not develop inhibitor antibodies. At each of the thirteen specific CpG sites, we observed one of three possible statuses: hypermethylated, hypomethylated or intermediate methylated. We found a statistically significant (p= 0.04) decrease in the methylation level at one CpG site in theIL4intron 1 (CpG-3) in the affected group of patients presenting with anti-FVIII inhibitors as compared with the group of patients without inhibitors. The differential 5meCpG-3 maps within a predicted enhancer region inIL4intron 1 that overlaps DNase I hypersensitive chromatin region of the Th2IL5, IL13, andIL4cytokine gene cluster and, therefore, permissive for gene expression. Six-bp upstream of the differentially 5meCpG-3 is the rs2227282cisexpression quantitative trait locus that influences the transcript levels of thePDLIM4, SLC22A4, SLC22A5, RAD50, IL4, KIF3A, SEPT8genes. We consider theIL4(CpG-3) site a promising lead epigenetic mark, the potential value of which must be appraised in a larger group of patients. The methodology employed also allowed to evaluate the distribution of theIL6rs35081782 insertion/deletion variant, associated with white blood cell count traits in genome-wide association studies, and which showed no difference in distribution between the groups of patients.
Loss of TET proteins in regulatory T cells unleashes effector function
Authors: Yue Xiaojing , Lio Chan-Wang J. , Samaniego-Castruita Daniela , Li Xiang , Rao Anjana
Published: February 2019

TET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and other oxidized methylcytosines, mediating DNA demethylation and serving as new epigenetic marks. Here we examine the role of TET proteins in Foxp3+ regulatory T (Treg) cells, a distinct lineage of CD4+ T cells that prevent autoimmunity and maintain immune homeostasis. We report that Tet2/3fl/flFoxp3Cre mice that lack Tet2 and Tet3 specifically in Treg cells develop splenomegaly, leukocyte infiltration into tissues and inflammatory disease. Treg cells from these mice showed altered expression of Treg signature genes, with upregulation of genes involved in cell cycle regulation, DNA damage repair and cancer. In littermate mice with more severe inflammation, both CD4+ Foxp3+ and CD4+ Foxp3- cells showed strong skewing towards Tfh and/or Th17 phenotypes. Notably, the presence of wild type Treg cells in mixed bone marrow chimeras and Tet2/3fl/flFoxp3WT/Cre heterozygous female mice did not suppress the aberrant phenotype and function of Tet2/3fl/flFoxp3Cre Treg cells. Fate-mapping experiments indicated that Treg cells from Tet2/3fl/flFoxp3Cre mice were more prone to lose Foxp3 expression; moreover, transfer of total CD4+ T cells isolated from Tet2/3fl/flFoxp3Cre mice could elicit inflammatory disease in fully immunocompetent mice. Together, these data indicate that Tet2 and Tet3 are guardians of Treg cell stability and immune homeostasis in mice.
Alpaca: a kmer-based approach for investigating mosaic structures in microbial genomes
Authors: Salazar Alex N. , Abeel Thomas
Published: February 2019

Microbial genomes are often mosaic: different regions can possess different evolutionary origins due to genetic recombination. The recent feasibility to assemble microbial genomes completely and the availability of sequencing data for complete microbial populations, means that researchers can now investigate the potentially rich evolutionary history of a microbe at a much higher resolution. Here, we present Alpaca: a method to investigate mosaicism in microbial genomes based on kmer similarity of large sequencing datasets. Alpaca partitions a given assembly into various sub-regions and compares their similarity across a population of genomes. The result is a high-resolution map of an entire genome and the most similar scoring clades across the given population.

Availability

https://github.com/AbeelLab/Alpaca

Contact

t.abeel@tudelft.nl
AligNet: Alignment of Protein-Protein Interaction Networks
Authors: Alberich R. , Alcalá A. , Llabrés M. , Rosselló F. , Valiente G.
Published: February 2019

One of the most difficult problems difficult problem in systems biology is to discover protein-protein interactions as well as their associated functions. The analysis and alignment of protein-protein interaction networks (PPIN), which are the standard model to describe protein-protein interactions, has become a key ingredient to obtain functional orthologs as well as evolutionary conserved pathways and protein complexes. Several methods have been proposed to solve the PPIN alignment problem, aimed to match conserved subnetworks or functionally related proteins. However, the right balance between considering network topology and biological information is one of the most difficult and key points in any PPIN alignment algorithm which, unfortunately, remains unsolved. Therefore, in this work, we propose AligNet, a new method and software tool for the pairwise global alignment of PPIN that produces biologically meaningful alignments and more efficient computations than state-of-the-art methods and tools, by achieving a good balance between structural matching and protein function conservation as well as reasonable running times.
Extracellular matrix mineralization in the mouse osteoblast-like cell line MC3T3-E1 is regulated by actin cytoskeleton reorganization and non-protein molecules secreted from the cells themselves
Authors: Suzuki Hiraku , Tatei Kazuaki , Ohshima Noriyasu , Sato Seiichi , Izumi Takashi
Published: February 2019

Bone tissue constantly undergoes turnover via bone formation by osteoblasts and bone resorption by osteoclasts. This process enables bone to maintain its overall shape while altering its local structure. However, the detailed mechanism of how osteoblast cell-signaling systems induce various structural changes in bone tissue have not yet been completely elucidated. In this study, we focused on the actin cytoskeleton as a regulatory system for bone formation and constructed anin vitroexperimental system using the mouse osteoblast-like cell line MC3T3-E1. We found that, in MC3T3-E1 cells, the actin cytoskeleton had an important role in matrix mineralization via activation of specific developmental pathways and it was regulated by non-protein molecules secreted from MC3T3-E1 cells themselves. In MC3T3-E1 cells, we observed changes of actin cytoskeleton reorganization and accumulation of PIP2related to actin filament convergences during cell differentiation, in the undifferentiated, early, middle and late stage. Actin cytoskeleton disruption with Cyto D, polymerization inhibitor of actin filament, in early and middle stage cells induced significant increase of osteocalcin mRNA expression normally expressed only in late stage, decrease of Alkaline phosphatase mRNA expression after 24h and abnormal matrix mineralization in MC3T3-E1 cells. Inhibition of Giα with PTX known to regulate actin cytoskeleton in middle stage induced changes in the actin cytoskeleton and PIP2accumulation and suppression of matrix mineralization after 5 days. Furthermore, addition of non-protein molecules from culture medium of cells at various differentiation stage induced difference of PIP2accumulation after 5 min, actin cytoskeleton in 20 min, and matrix mineralization after 5 days. These results not only provide new knowledge about the actin cytoskeleton function in bone-forming cells, but also suggest that cell signaling via non-protein molecules such as lipids plays important roles in bone formation.
Network-wide abnormalities explain memory variability in hippocampal amnesia
Authors: Argyropoulos Georgios P. D. , Loane Clare , Roca-Fernandez Adriana , Lage-Martinez Carmen , Gurau Oana , Irani Sarosh R , Butler Christopher R
Published: February 2019

Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n=38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Such network abnormalities may explain the variability across studies of amnesia and speak to theoretical debates in memory neuroscience.
Evaluations of short telomere risk-associated single nucleotide polymorphisms in telomerase reverse transcriptase gene on telomere length maintenance
Authors: Xu Jialin , Trudeau Matthew A. , Sandford Andrew J. , Wong Judy M.Y.
Published: February 2019

Telomere biology disorders (TBDs) refer to a spectrum of tissue degenerative disorders caused by genetic mutations in telomere biology genes. Most patients with TBDs suffer from telomere maintenance defects secondary to telomerase deficiency. While the highly penetrant mutations in the telomerase reverse transcriptase (TERT) gene that drive disease onset and progression of TBDs are relatively rare, there exist several single nucleotide polymorphisms (SNPs) in TERT that have been linked to various diseases in the TBD spectrum. In this study, we investigated the biochemical properties of five TERT variants. In an ex vivo cell model, we found that primary human fibroblasts expressing nonsynonymous TERT SNPs had comparable cell growth kinetics to primary cells expressing WT-TERT, while a parallel vector control expressing-cell line entered replicative senescence. At the molecular level, primary cells expressing the minor alleles of two of the five TERT variants (A279T, ΔE441) had replication-dependent loss of telomere length. In an in vitro primer extension assay, these two variants showed reduced telomerase nucleotide addition processivity. Together, our data suggested that selective, common TERT variants could be revealed to harbour telomere maintenance defects, leading to a plausible explanation for their observed associations to telomere biology disorders.
How to improve the stated helpfulness of hotel reviews? A multilevel approach
Authors: Liang Sai , Schuckert Markus , Law Rob
Published: February 2019

Purpose

The prevalence of online review websites and the ever-growing difficulty of judging review quality result in the increasing need for consumers to reduce cognitive costs. Thus, the purpose of this study is to find out the determinants of review helpfulness based on a comprehensive theoretical framework and empirical model.

Design/methodology/approach

This study applied a comprehensive framework, including both review content quality and reviewer background, to investigate the determinants of review helpfulness. It also presents empirical models to further control factors around product features.

Findings

Consumers are more likely to give helpful votes to those informative and readable reviews accompanied by extreme ratings. Reviewers who disclose information, have a high reputation and report a poor experience are always identified as helpful. Consumers also tend to signal suggestions from users with a local cultural background as subjective and useless.

Research limitations

This study focuses on upscale hotels in China. Information registered on TripAdvisor was used presenting a residential address not nationality. Only few controlling factors available because of the limited information are shown on online review websites.

Practical implications

Managers of both hotels and online review websites need to focus on reviews and/or reviewers as KOLs who attract consumers’ attention and affect their subsequent decisions. A dialogue with those KOLs can be by focusing on responding to reviews with certain characteristics. A reward system for reviews and KOLs may benefit review quality on online review websites and reduce cognition costs.

Originality/value

This positivistic research design, with multilevel approach, presenting a comprehensive conceptual framework and empirical model not only considering review- and reviewer-related factors but also controlled factors in product or service level (hotel-related characteristics).
Territory, firms and value co-creation synergies
Authors: Baccarani Claudio , Cassia Fabio , Rossato Chiara , Cavallo Daniela
Published: February 2019

Purpose

Recent literature on the implications of applying service-dominant (S-D) logic to conceptualise value-creation processes views territory only as an operand resource (a resource upon which an act is performed). This study aims to show that territory is both an operand and operant resource (a resource that acts on other resources) and to examine how this conceptualisation may extend knowledge about co-creation processes between a firm and its territory.

Design/methodology/approach

The study develops a conceptual contribution, drawing on previous research and combining managerial thinking with architectural–urban planning thinking, using illustrative examples.

Findings

This study shows that the territory actively participates in value co-creation through interactions with other actors (e.g. firms, inhabitants and tourists). The territory is not only an output of human actions but also a process through which its essence and traits emerge over time. It can infinitely inspire firms with ideas, provided they are able to listen to it and recognise its value co-creator nature.

Research limitations/implications

Contrary to the traditional firm location theory, this study highlights that a territory’s attractiveness is related to its potential, active contribution to value co-creation. The study’s arguments provide a contribution to the current debate about territorial servitisation but should be refined through empirical analyses.

Practical implications

The paper provides suggestions on platform-designing methods – supported by technologies – to enable the territory to engage in value co-creation.

Originality/value

While some studies have applied the S-D logic to territories, this study is the first to recognise that the territory has an active role in value co-creation.
The consequences of land sparing for birds in the United Kingdom
Authors: Lamb Anthony , Finch Tom , Pearce‐Higgins James W. , Ausden Malcolm , Balmford Andrew , Feniuk Claire , Hirons Graham , Massimino Dario , Green Rhys E.
Published: February 2019

Land sparing has been proposed as a strategy to reconcile biodiversity conservation with agricultural production, with empirical studies on five continents indicating that most species would benefit if food demand was met through high‐yield farming combined with the protection or restoration of natural habitat.

Most such studies come from landscapes covered by large areas of natural habitat and without a long history of intense human modification. However, much of Europe consists of human‐dominated landscapes, where biodiversity responses to land sparing may differ. To test this, we use estimates of bird population density in different (semi‐)natural habitats, and forecasts of population density in farmland habitat, to assess the future consequences for birds of land‐sparing scenarios in the United Kingdom.

Our scenarios predict that whilst up to 18 of the 156 species assessed (predominantly farmland associated species) might decline in UK conservation status under land sparing, up to 35 UK bird species (mainly woodland and wetland species) might improve in status. This contrasts with a maximum of eight species likely to improve in conservation status without land sparing, with up to seven species deteriorating.

Combining land sparing with demand management measures (reducing food waste and the consumption of animal products) led to more positive population changes under all scenarios.

Synthesis and applications. Land sparing has the potential to benefit UK bird populations in aggregate but would likely have negative impacts on farmland bird species. These findings are likely to be applicable across human‐dominated landscapes beyond the UK, though effects on other taxa, implementation mechanisms and the sustainability of higher yields all require careful consideration.
Social network engagement and subjective well‐being: a life‐course perspective
Authors: Wheatley Daniel , Buglass Sarah L.
Published: February 2019

Social networking is a digital phenomenon embraced by billions worldwide. Use of online social platforms has the potential to generate a number of benefits including to well‐being from enhanced social connectedness and social capital accumulation, but is also associated with several negative behaviours and impacts. Employing a life‐course perspective, this paper explores social networking use and its relationship with measures of subjective well‐being. Large‐scale UK panel data from wave 3 (2011–12) and 6 (2014–15) ofUnderstanding Societyreveals that social network users are on average younger, aged under 25, but that rising use is reported across the life‐course including into old age. Probit, multinomial logistic, and ANCOVA and change‐score estimations reveal that membership, and greater use, of social networks is associated with higher levels of overall life satisfaction. However, heavy use of social networking sites has negative impacts, reflected in reductions in subjective well‐being. Socio‐economic disadvantage may drive these impacts among young (in education), unemployed and economically inactive heavy SNS users.
Attitude towards and factors affecting uptake of population‐basedBRCAtesting in the Ashkenazi Jewish population: a cohort study
Authors: Manchanda R , Burnell M , Gaba F , Sanderson S , Loggenberg K , Gessler S , Wardle J , Side L , Desai R , Brady AF , Dorkins H , Wallis Y , Chapman C , Jacobs C , Tomlinson I , Beller U , Menon U , Jacobs I
Published: February 2019

Objective

To evaluate factors affecting unselected population‐basedBRCAtesting in Ashkenazi Jews (AJ).

Design

Cohort‐study set within recruitment to the GCaPPS trial (ISRCTN73338115).

Setting

North London AJ population.

Population or sample

Ashkenazi Jews women/men >18 years, recruited through self‐referral.

Methods

Ashkenazi Jews women/men underwent pre‐test counselling forBRCAtesting through recruitment clinics (clusters). Consenting individuals provided blood samples forBRCAtesting. Data were collected on socio‐demographic/family history/knowledge/psychological well‐being along with benefits/risks/cultural influences (18‐item questionnaire measuring ‘attitude’). Four‐item Likert‐scales analysed initial ‘interest’ and ‘intention‐to‐test’ pre‐counselling. Uni‐ and multivariable logistic regression models evaluated factors affecting uptake/interest/intention to undergoBRCAtesting. Statistical inference was based on cluster robust standard errors and joint Wald tests for significance. Item‐Response Theory and graded‐response models modelled responses to 18‐item questionnaire.

Main outcome measures

Interest, intention, uptake, attitude towardsBRCAtesting.

Results

A total of 935 individuals (women = 67%/men = 33%; mean age = 53.8 (SD = 15.02) years) underwent pre‐test genetic‐counselling. During the pre‐counselling, 96% expressed interest in and 60% indicated a clear intention to undergoBRCAtesting. Subsequently, 88% opted forBRCAtesting.BRCA‐related knowledge (P = 0.013) and degree‐level education (P = 0.01) were positively and negatively (respectively) associated with intention‐to‐test. Being married/cohabiting had four‐fold higher odds forBRCAtesting uptake (P = 0.009). Perceived benefits were associated with higher pre‐counselling odds for interest in and intention to undergoBRCAtesting. Reduced uncertainty/reassurance were the most important factors contributing to decision‐making. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotional impact/inability to prevent cancer/marriage ability/ethnic focus/stigmatisation) were significantly associated with lower odds of uptake ofBRCAtesting, and discriminated between acceptors and decliners. Male gender/degree‐level education (P = 0.001) had weaker correlations, whereas having children showed stronger (P = 0.005) associations with attitudes towardsBRCAtesting.

Conclusions

BRCAtesting in theAJpopulation has high acceptability. Pre‐test counselling increases awareness of disadvantages/limitations ofBRCAtesting, influencing final cost‐benefit perception and decision‐making on undergoing testing.

Tweetable abstract

BRCAtesting in Ashkenazi Jews has high acceptability and uptake. Pre‐test counselling facilitates informed decision‐making.
Toxic potential of some indigenous plant oils against the rice weevil, Sitophilus oryzae (Linnaeus)
Authors: Khan Hafiz Azhar Ali , Akram Waseem , Lee Sumi , Ahmad Taskeen , Maqsood Kamran , Khan Hassan Ali , Nazir Muhammad Waqas , Javaid Muhammad Faisal
Published: February 2019

The present study was conducted to evaluate the toxic potential of five indigenous plant oils: black pepper (Piper nigrum), Chinese cinnamon (Cinnamomum cassia), garlic (Allium sativum), river red gum (Eucalyptus camaldulensis), and yellow oleander (Thevetia peruviana), against laboratory reared Sitophilus oryzae adults. The bioassays were done by the diet incorporation method with concentrations ranging from 50 ppm to 500 ppm. Based on lethal concentrations to kill 50% (LC50) of the subjected weevils, T. peruviana proved to be the most toxic having the lowest LC50 values, 414.58, 201.94, and 129.52 ppm, after 7, 14, and 21 days of exposure, respectively, followed by E. camaldulensis (475.51, 366.65, and 251.28 ppm, respectively). The rest of the plant oils also showed toxic potential, but these were less toxic compared with T. peruviana and E. camaldulensis. With respect to the time taken to cause 50% mortality (LT50) of the exposed weevils, T. peruviana had LT50 at 14.54 days followed by P. nigrum (22.09 days), E. camaldulensis (24.29 days), and C. cassia (28.71 days). Whereas, A. sativum took the longest time (44.47 days) to cause 50% mortality of the exposed weevils. In conclusion, the result revealed toxic potential of tested plant oils, and suggests further studies under simulated‐field conditions should be included in the management plan for S. oryzae.
Efficacious transition from reference infliximab to biosimilar infliximab in clinical practice
Authors: Layegh Zohra , Ruwaard Jill , Hebing Renske C. F. , l’ Ami Merel J. , van der Weele Wilfred , Nurmohamed Mike T. , Krieckaert Charlotte , Wolbink Gertjan
Published: February 2019

Objectives

To evaluate the transition from reference infliximab Remicade to biosimilar Remsima in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA).

Methods

Patients were informed through a letter about the transition to a biosimilar and were subsequently contacted for possible additional questions and whether they agreed upon the transition. Once agreed, Remsima was administered at the same dosage and interval as previous treatment with Remicade. Data on the transition were analyzed in January 2018. The primary outcome was the percentage of patients continuing treatment with Remsima and secondary outcome was the change in disease activity measured with the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28‐ESR). In addition, the reasons for discontinuation with infliximab or restarting Remicade were recorded.

Results

In total 47 patients were approached, 45 patients switched from Remicade to Remsima, two patients disagreed upon transition and continued Remicade. At the end of the follow‐up period of 2 years, 39 patients (87%) continued with Remsima, three patients (7%) restarted Remicade due to inefficacy according to the patient (this was not objectified by the rheumatologist) 2 (4%) patients switched to another biological due to lack of effect and in one patient (2%) infliximab was stopped because of lung malignancy. Furthermore, the DAS28‐ESR remained comparable before and after the switch, with a mean (SD) of 2.34 (±1.02) and 2.31 (±1.11) respectively.

Conclusion

In our population, 87% of patients continued Remsima during the follow‐up period of approximately 2 years. Three patients restarted Remicade, while retaining stable DAS28‐ESR.
Business models and the managerial sensemaking process
Authors: Islam Syrus
Published: February 2019

This study examines the managerial sensemaking process around business models. Drawing on fieldwork, this study introduces a model to describe how managerial sensemaking occurs around business model development and use. This study shows that managerial sensemaking around business models occurs through a mutually co‐constituted process, a separate yet shared process, or a combination of them resulting from an interplay between sensemaking and sensegiving activities. To facilitate their sensemaking around business models, managers draw on several schemas. Over time, some schemas underlying business models remain unchanged, while others change in varying degrees.
Exemplary Lives and the Normative Theory of Culture
Authors: Church Jeffrey
Published: February 2019

This article defends an essentialist account of culture against the recent turn toward nonessentialism in contemporary liberal multiculturalism. It does so by drawing on Friedrich Nietzsche's early period and argues that Nietzsche provides an alternative to the dominant tradition of Volk conceptions of culture that derive from J. G. Herder. Nietzsche's alternative—what I call the “Exemplar Account” of culture—defines culture in terms of the patterns of human excellence that constitute it. This alternative overcomes standard concerns about essentialism by embracing the nonessentialist insight into the fluidity and variability of any culture's beliefs, values, and practices, yet holds that exemplary lives transcend the flux of culture and individuate one culture from another. I suggest in conclusion a practical benefit of this conception of culture for contemporary multiculturalism—namely, it fares better than other conceptions in fostering integration among diverse cultures, a pressing worry facing the current project of multiculturalism.
Influence of calving difficulty on dry matter intake immediately after calving of dairy cows
Authors: Reshalaitihan Maimaiti , Hanada Masaaki
Published: February 2019

We investigated the influence of calving difficulty on dry matter intake (DMI) in Holstein cows immediately after calving using 15 pregnant heifers and 15 multiparous cows. DMI was measured for 6 days after calving. Calving difficulty was evaluated with a calving score, and urinary cortisol was measured. The calving score was higher in the first lactation heifers than in the multiparous cows. The average DMI 6 days after calving was lower in the first lactation heifers than in the multiparous cows. The urinary cortisol concentration at 4 days after calving was higher in the first lactation heifers than in the multiparous cows and was positively associated with the calving score. The DMI was negatively associated with the calving score and the urinary cortisol concentration at 4 days after calving and was positively associated with the average milk yield 6 days after calving and the serum calcium concentration at 3 days after calving. We conclude that DMI immediately after calving is influenced not only by nutrient requirements of cows but also stress derived from calving, and the low DMI in the first lactation heifers is due to the lower energy requirement and high susceptibility to the stress compared with multiparous cows.
Predicting the dose of vancomycin in ICU patients receiving different types of RRT therapy: a model‐based meta‐analytic approach
Authors: Claisse Guillaume , Zufferey Paul J. , Trone Jane C. , Maillard Nicolas , Delavenne Xavier , Laporte Silvy , Ollier Edouard
Published: February 2019

Aim

Previous pharmacokinetic (PK) studies have proposed various dosing regimens for vancomycin in intensive care unit (ICU) patients undergoing renal replacement therapy (RRT), but all are restricted to specific RRT modalities. To be useful in practice, a population PK model would need to predict vancomycin clearance during any RRT modality. Development of such a model is feasible using meta‐analysis of published summarized estimates of vancomycin PK parameters. Our aims were: (i) to develop and validate a population PK model for vancomycin that takes into account any RRT modalities, and (ii) to predict vancomycin dosing for RRT patients in ICU.

Methods

Vancomycin pharmacokinetics were assumed to be two‐compartmental, total body clearance being the sum of non‐RRT clearance and RRT‐induced clearance. Drug disposition and non‐RRT clearance parameters were estimated by systematic review and meta‐analysis of previously published parameter estimates. The relationship between RRT‐induced clearance and RRT flowrate settings was assessed using a model‐based meta‐analysis. Prediction performances of the PK model were assessed using external data.

Results

The meta‐analyses of disposition parameters, non‐RRT clearance and RRT‐induced clearance included 11, 6 and 38 studies (84 RRT clearance measurements) respectively. The model performed well in predicting external individual PK data. Individual vancomycin concentrations during RRT were accurately predicted using Bayesian estimation based solely on pre‐RRT measurements.

Conclusions

The PK model allowed accurate prediction of the vancomycin pharmacokinetics during RRT in ICU patients. Based on the model of RRT‐induced clearance, an appropriate adjustment of the vancomycin dosing regimen could be proposed for any kind of flowrate settings.