bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive longitudinal microbiome analysis of the chicken cecum reveals a shift from competitive to environmental drivers and a window of opportunity for Campylobacter
Authors: Ijaz Umer Zeeshan , Sivaloganathan Lojika , Mckenna Aaron , Richmond Anne , Kelly Carmel , Linton Mark , Stratakos Alexandros , Lavery Ursula , Elmi Abdi , Wren Brendan , Dorrell Nick , Corcionivoschi Nicolae , Gundogdu Ozan 
Published: June 2018

AbstractChickens are a key food source for humans yet their microbiome contains bacteria that can be pathogenic to humans, and indeed potentially to chickens themselves. Campylobacter is present within the chicken gut and is the leading cause of bacterial foodborne gastroenteritis within humans worldwide. Infection can lead to secondary sequelae such as Guillain-Barré syndrome and stunted growth in children from low-resource areas. Despite the global health impact and economic burden of Campylobacter, how and when Campylobacter appears within chickens remains unclear. As such, there has been a motivation to decrease the number of Campylobacter within chickens and thus reduce the risk of infection to humans. The lack of day-to-day microbiome data with replicates, relevant metadata, and a lack of natural infection studies have delayed our understanding of the chicken gut microbiome and Campylobacter. Here, we performed a comprehensive day-to-day microbiome analysis of the chicken cecum from day 3 to 35 (12 replicates each day; n=396) combining metadata such as chicken weight and feed conversion rates to investigate what the driving forces are for the microbial changes within the chicken gut over time, and how this relates to Campylobacter appearance within a natural habitat setting. We found a rapidly increasing microbial diversity up to day 12 with variation observed both in terms of genera and abundance, before a stabilisation of the microbial diversity after day 20. In particular, we identified a shift from competitive to environmental drivers of microbial community from days 12 to 20 creating a window of opportunity whereby Campylobacter appears. Campylobacter was identified at day 16 which was one day after the most substantial changes in metabolic profiles observed. In addition, microbial variation over time is most likely influenced by the diet of the chickens whereby significant shifts in OTU abundances and beta dispersion of samples often corresponded with changes in feed. This study is unique in comparison to the most recent studies as neither sampling was sporadic nor Campylobacter was artificially introduced, thus the experiments were performed in a natural setting. We believe that our findings can be useful for future intervention strategies and can help elucidate the mechanism through which Campylobacter within chickens can be reduced.
Dead or Alive? Molecular life-dead distinction in human stool samples reveals significantly different composition of the microbial community
Authors: Perras Alexandra , Koskinen Kaisa , Mora Maximilian , Beck Michael , Wink Lisa , Moissl-Eichinger Christine 
Published: June 2018

AbstractThe gut microbiome is strongly interwoven with human health. Conventional gut microbiome analysis generally involves 16S rRNA gene targeting next generation sequencing (NGS) of stool microbial communities, and correlation of results with clinical parameters. However, some microorganisms may not be alive at the time of sampling, and thus their impact on the human health is potentially less significant. As conventional NGS methods do not differentiate between viable and dead microbial components, retrieved results provide only limited information.Propidium monoazide (PMA) is frequently used in food safety monitoring and other disciplines to discriminate living from dead cells. PMA binds to free DNA and masks it for subsequent procedures. In this article we show the impact of PMA on the results of 16S rRNA gene-targeting NGS from human stool samples and validate the optimal applicable concentration to achieve a reliable detection of the living microbial communities.Fresh stool samples were treated with a concentration series of zero to 300 μM PMA, and were subsequently subjected to amplicon-based NGS. The results indicate that a substantial proportion of the human microbial community is not intact at the time of sampling. PMA treatment significantly reduced the diversity and richness of the sample depending on the concentration and impacted the relative abundance of certain important microorganisms (e.g. Akkermansia, Bacteroides). Overall, we found that a concentration of 100 μM PMA was sufficient to quench signals from disrupted microbial cells.The optimized protocol proposed here can be easily implemented in classical microbiome analyses, and helps to retrieve an improved and less blurry picture of the microbial community composition by excluding signals from background DNA.
Application of mechanistic methods to clinical trials in multiple sclerosis: the simvastatin case
Authors: Eshaghi Arman , Kievit Rogier A , Prados Ferran , Sudre Carole , Nicholas Jennifer , Cardoso M Jorge , Chan Dennis , Nicholas Richard , Ourselin Sebastien , Greenwood John , Thompson Alan J , Alexander Daniel C , Barkhof Frederik , Chataway Jeremy , Ciccarelli Olga 
Published: June 2018

SummaryThe analysis of clinical trials is limited to pre-specified outcomes, thereby precluding a mechanistic understanding of the treatment response. Multivariate mechanistic models can elucidate thecausalchain of events by simultaneous analysis of multimodal data that link intermediate variables to outcomes of interest. A double-blind, randomised, controlled, phase 2 clinical trial in secondary progressive multiple sclerosis (MS-STAT,NCT00647348) demonstrated that simvastatin (80mg/day) over two years reduced the brain atrophy rate and was associated with beneficial effects on cognitive and disability outcomes. Therefore, this trial offers an opportunity to apply mechanistic models to investigate the hypothesised pathways that link simvastatin to clinical outcome measures, either directly or indirectly via changes in serum total cholesterol levels and to determine which is the more likely.
Mitotic chromosome alignment is required for proper nuclear envelope reassembly
Authors: Fonseca Cindy L. , Malaby Heidi L.H. , Sepaniac Leslie A. , Martin Whitney , Byers Candice , Czechanski Anne , Messinger Dana , Tang Mary , Ohi Ryoma , Reinholdt Laura G. , Stumpff Jason 
Published: June 2018

SUMMARYChromosome alignment at the equator of the mitotic spindle is a highly conserved step during cell division, however, its importance to genomic stability and cellular fitness are not understood. Normal mammalian somatic cells lacking Kif18A function complete cell division without aligning chromosomes. These alignment-deficient cells display normal chromosome copy numbers in vitro and in vivo, suggesting that chromosome alignment is largely dispensable for maintenance of euploidy. However, we find that loss of chromosome alignment leads to interchromosomal compaction defects during anaphase, abnormal organization of chromosomes into a single nucleus at mitotic exit, and the formation of micronuclei in vitro and in vivo. These defects slow cell proliferation and reduce postnatal growth and survival with variable penetrance in mice. Our studies support a model in which the alignment of mitotic chromosomes promotes proper nuclear envelope reassembly and continued proliferation by ensuring that chromosomes segregate as a compact mass during anaphase.
The systemic activin response to pancreatic cancer: Implications for effective cancer cachexia therapy
Authors: Zhong Xiaoling , Pons Marianne , Poirier Christophe , Jiang Yanlin , Liu Jianguo , Sandusky George E. , Liu Yunlong , Jiang Guanglong , Couch Marion , Koniaris Leonidas G. , Zimmers Teresa A. 
Published: June 2018

AbstractPancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy with high rates of cachexia. Serum activin correlates with PDAC cachexia and mortality, while activin administration causes cachexia in mice. We studied activin in human tumors and in mice with orthotopic or genetic PDAC. Cachexia severity correlated with activin expression in tumor lines. Activins were expressed in both cancer and tumor stromal cells, but also in organs in murine PDAC cachexia. Tumor cells expressed activin-βA, orInhba, while organs expressed both activin-βA and activin-βB, orInhbb. PDAC elicits activin expression; PDAC conditioned medium induced activin and atrophy of myotubes. Treatment with the activin trap, ACVR2B/Fc, reduced cachexia and prolonged survival in mice with activin-low tumors, and reduced cachexia in activin-high tumors, without affecting activin expression in organs. Mice expressing dominant negative ACVR2B in muscle were protected for weight loss but not survival. Overall our results indicate that PDAC induces a systemic activin response, leading to cachexia, and that activin targets might include organs beyond muscle. Targeting of both tumor-derived and host-derived activins could improve cachexia therapy.
Liberating links between datasets using lightweight data publishing: an example using plant names and the taxonomic literature
Authors: Page Roderic D. M. 
Published: June 2018

AbstractConstructing a biodiversity knowledge graph will require making millions of cross links between diversity entities in different datasets. Researchers trying to bootstrap the growth of the biodiversity knowledge graph by constructing databases of links between these entities lack obvious ways to publish these sets of links. One appealing and lightweight approach is to create a “datasette”, a database that is wrapped together with a simple web server that enables users to query the data. Datasettes can be packaged into Docker containers and hosted online with minimal effort. This approach is illustrated using a dataset of links between globally unique identifiers for plant taxonomic names, and identifiers for the taxonomic articles that published those names.
Wolbachiaboth aids and hampers the performance of spider mites on different host plants
Authors: Zélé Flore , Santos Joaquim L. , Godinho Diogo Prino , Magalhães Sara 
Published: June 2018

AbstractIn the last decades, many studies had revealed the potential role of arthropod bacterial endosymbionts in shaping the host range of generalist herbivores and their performance on different host plants, which, in turn, might affect endosymbiont distribution in herbivores populations. We tested this by measuring the prevalence of endosymbionts in natural populations of the generalist spider miteTetranychus urticaeon different host plants. Focusing onWolbachia, we then analysed how symbionts affected mite life-history traits on the same host-plants in the laboratory. Overall, the prevalences ofCardiniumandRickettsiawere low, whereas that ofWolbachiawas high, with the highest values on bean and eggplant and the lowest on purple, tomato and zuchini. Although most mite life-history traits were affected by the plant species only,Wolbachiainfection was detrimental for egg hatching rate on purple and zucchini, and led to a more female-biased sex ratio on purple and eggplant. These results suggest that endosymbionts may affect the host range of polyphagous herbivores, both by aiding and hampering their performance, depending on the host plant and on the life-history trait that affects performance the most. Conversely, endosymbiont spread may be facilitated or hindered by the plants on which infected herbivores occur.
Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network
Authors: Ung Peter Man-Un , Sonoshita Masahiro , Scopton Alex P. , Dar Arvin C. , Cagan Ross L. , Schlessinger Avner 
Published: June 2018

AbstractDrosophila provides an inexpensive and quantitative platform for measuring whole animal drug response. A complementary approach is virtual screening, where chemical libraries can be efficiently screened against protein target(s). Here, we present a unique discovery platform integrating structure-based modeling with Drosophila biology and organic synthesis. We demonstrate this platform by developing chemicals targeting a Drosophila model of Medullary Thyroid Cancer (MTC) with disease-promoting kinase network activated by mutant dRetM955T. Structural models for kinases relevant to MTC were generated for virtually screening to identify initial hits that were dissimilar to known kinase inhibitors yet suppressed dRetM955T-induced oncogenicity. We then combined features from the hits and known inhibitors to create a ‘hybrid’ molecule with improved dRetM955T phenotypic outcome. Our platform provides a framework to efficiently explore novel chemical spaces, develop compounds outside of the current inhibitor chemical space, and ‘correct’ cancer-causing signaling networks to improve disease prognosis while minimizing whole body toxicity.AUTHOR SUMMARYEffective and safe treatment of multigenic diseases often involves drugs that modulate whole systems by interacting with multiple nodes in pathways and networks, i.e., polypharmacology. Polypharmacology is increasingly appreciated as a potential desirable property of kinase drugs; however, most known drugs that interact with multiple targets have been identified as such by chance, and most polypharmacological compounds are not chemically unique resembling to structures of known kinase inhibitors. The fruit fly Drosophila has been established as a robust screening platform that provides an inexpensive, rapid, and quantitative measure of whole animal drug response, complementing computational approaches. We present a chemical genetics approach that efficiently combines Drosophila with structural prediction and virtual screening, creating a unique discovery platform. We demonstrate the utility of our approach by developing useful small molecules targeting a kinase network in a Drosophila model of Medullary Thyroid Cancer (MTC) driven by the active mutant dRetM955T.
Tryptophan recovers sensitivity to cell membrane stress inSaccharomyces cerevisiae
Authors: Schroeder Lea , Lazarevskiy Pauletta , Ikui Amy E. 
Published: June 2018

AbstractSodium dodecyl sulfate is a detergent that disrupts cell membranes, activates cell wall integrity signaling and restricts cell growth inSaccharomyces cerevisiae. However, the underlying mechanism of how sodium dodecyl sulfate inhibits cell growth is not fully understood. Because deletion of theMCK1gene leads to sensitivity to sodium dodecyl sulfate, we implemented a suppressor gene screening revealing that theTAT2tryptophan permease rescues cell growth to sodium dodecyl sulfate-treatedΔmck1cells. Therefore, we questioned the involvement of tryptophan in the response to sodium dodecyl sulfate treatment. In this work, we show thatΔtrp1cells have a disadvantage in the response to sodium dodecyl sulfate compared to auxotrophy for adenine, histidine, leucine or uracil. While also critical in the response to tea tree oil,TRP1does not avert growth inhibition due to other cell wall/membrane perturbations that activate cell wall integrity signaling such as calcofluor white, Congo Red or heat stress. This implicates a distinction from the cell wall integrity pathway and suggests specificity to membrane stress as opposed to cell wall stress. We discover that tyrosine biosynthesis is also essential upon sodium dodecyl sulfate perturbation whereas phenylalanine biosynthesis appears dispensable. Finally, we observe enhanced tryptophan import within minutes upon exposure to sodium dodecyl sulfate indicating that these cells are not starved for tryptophan. In summary, our results expose a functional link between internal tryptophan levels and tryptophan biosynthesis in the response to plasma membrane damage.
Functions of farmers’ preferred tree species and their potential carbon stocks in southern Burkina Faso: implications for biocarbon initiatives
Authors: Dimobe Kangbéni , Tondoh Jérôme E. , Weber John C. , Bayala Jules , Greenough Karen , Kalinganire Antoine 
Published: June 2018

AbstractThe success of terrestrial carbon sequestration projects for rural development in sub-Saharan Africa lies in the (i) involvement of local populations in the selection of woody species, which represent the biological assets they use to meet their daily needs, and (ii) information about the potential of these species to store carbon. Although the latter is a key prerequisite, there is very little information available. To help fill this gap, the present study was undertaken in four pilot villages (Kou, Dao, Vrassan and Cassou) in Ziro Province, south-central Burkina Faso. The objective was to determine carbon storage potential for top-priority woody species preferred by local smallholders. We used (i) participatory rural appraisal consisting of group discussions and key informant interviews to identify priority species and functions, and (ii) landscape assessment of carbon stocks in the preferred woody species. Results revealed over 79 priority tree and shrub species grouped into six functions, of which medicine, food and income emerge as the most important ones for the communities. For these functions, smallholders overwhelmingly listed Vitellaria paradoxa, Parkia biglobosa, Afzelia africana, Adansonia digitata, Detarium microcarpum, and Lannea microcarpa among the most important tree species. Among the preferred woody species in Cassou and Kou, the highest quantity of carbon was stored by V. paradoxa (1,460.6 ±271.0 kg C ha−1 to 2,798.1±521.0 kg C ha−1) and the lowest by Grewia bicolor (1.6±1.3 kg C ha−1). The potential carbon stored by the preferred tree communities was estimated at 5,766.2 Mg C ha−1 (95% CI: 5,258.2; 6,274.2 Mg C ha−1) in Kou and 6,664.0 Mg C ha−1 (95% CI: 5,810.2; 7,517.8 Mg C ha−1) in Cassou. The findings of this study will help design data-based development of biocarbon projects, which are rare in the West African Sahel despite being considered as one of the most impactful climate change resilient strategies.
Analysis of seven putative Na+/H+antiporters ofArthrospira platensisNIES-39 using transcription profiling andIn-silicostudies: an indication towards alkaline pH acclimation
Authors: Jangir Monika M. , Vani B. , Chowdhury Shibasish 
Published: June 2018

AbstractNa+/H+antiporters mediated pH regulation is one of the known mechanism(s), which advocates a possible role of the antiporters in the alkaline pH tolerance ofArthrospira platensisNIES-39 too. Seven putative Na+/H+antiporters have been reported inA. platensis. We have characterized these seven antiporters, where A1, Q2, L2 and L6 belong to the CPA1 family whereas C5, D5 and O6 belong to CPA2 family through variousIn-silicoanalysis. Conserved domain analysis of these seven putative antiporters indicate the presence of nine different kinds of domains. Out of these nine domains, six domains function as monovalent cation-proton antiporters and two as the universal stress protein (Usp) category. Transcription profile of these seven antiporters was also generated at three different pH and time frames which showed a significant difference in the m-RNA levels at pH 7, 9 and at 11 along with a temporal pattern of the expression profile. TheInsilicoand the real time PCR analysis, put together, suggest the active participation of these seven putative Na+/H+antiporters in alkaline pH homeostasis of this cyanobacterial strain where CPA1 subfamily antiporters play a major role.
Isolating the value-relevant part of advertising spending
Authors: Guenther Peter , Guenther Miriam 
Published: June 2018

Purpose
This paper aims to examine how much importance the financial market attaches to advertising spending’s short-term productivity vis-à-vis its investment component and the impact of important contextual factors (investor mix and analyst coverage) on this trade-off.

Design/methodology/approach
A stochastic frontier estimation (SFE) approach is used to help disentangle advertising spending. Using a panel internal instruments model and 10,017 firm-year observations from publicly listed US companies over a 13-year period, this study relates aggregated advertising spending and disentangled advertising spending, together with important contextual factors, to Tobin’s q.

Findings
The results do not indicate an effect of aggregated advertising spending on Tobin’s q. However, after advertising spending is disentangled, results show the component with an efficient immediate revenue response to have a positive effect on Tobin’s q, whereas the effect of the remaining investment component is negative. Contextual factors moderate investors’ valuation of the components.

Research limitations/implications
Findings are limited to US publicly listed firms, and are based on secondary, non-experimental data. The results imply that investors reward firms only for short-term advertising productivity, casting doubt on investors’ understanding of the long-term value of marketing.

Practical implications
The results confirm managers’ belief that not all money spent on advertising creates shareholder value. Managers should use the outlined SFE to benchmark their firms’ short-term advertising productivity against that of industry peer firms.

Originality/value
This study advances a new perspective, suggesting that advertising spending can be decomposed into two distinct parts by considering how financial market investors evaluate advertising spending. Important contextual effects on this evaluation from firms’ investor mix and analyst coverage are also shown for the first time. The findings help in reconciling conflicting prior results, and shed new light on how the financial market evaluates marketing expenditures.
Creative tourism: catalysing artisan entrepreneur networks in rural Portugal
Authors: Bakas Fiona Eva , Duxbury Nancy , Vinagre de Castro Tiago 
Published: June 2018

Purpose
Given limited research about how artisans become integrated into tourism, the purpose of this paper is to investigate the emergence of artisan entrepreneur–mediators who link artisans to tourism in rural areas and small cities in Portugal. Using social embeddedness as a conceptual framework, this paper views artisan entrepreneur–mediators as existing within an entrepreneurial ecosystem. The paper investigates their role within this ecosystem and how social networks influence the artisan entrepreneur–mediators’ roles in connecting artisans to creative tourism.

Design/methodology/approach
The paper is based on new (2017 and 2018) empirical evidence developed through two rounds of semi-structured interviews of five artisan entrepreneur–mediators.

Findings
This paper finds that artisan entrepreneur–mediators in rural areas or small cities take on multiple roles as networking agents who organize and offer creative tourism experiences, providing the missing link between artisans and tourists. An analysis of the nuances of the operations of these artisan entrepreneur–mediators suggests that high levels of social embeddedness within local rural communities are important in order for these neo-rural entrepreneurs to attain their goals.

Originality/value
Originality lies in the identification of a gap in artisan entrepreneurship literature in a rural context. It is the first time that a critical analysis of artisan entrepreneur–mediators who facilitate the link between artisans and tourism is carried out in terms of social embeddedness, their roles and connections to creative tourism, and types of community engagement.