bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidimensional analysis of Gammaherpesvirus RNA expression reveals unexpected heterogeneity of gene expression
Authors: Oko Lauren M. , Kimball Abigail K. , Kaspar Rachael E. , Knox Ashley N. , Coleman Carrie B. , Rochford Rosemary , Chang Tim , Alderete Benjamin , Dyk Linda F. van , Clambey Eric T. 
Published: December 2018

ABSTRACTVirus-host interactions are frequently studied in bulk cell populations, obscuring cell-to-cell variation. Here we investigate endogenous herpesvirus gene expression at the single-cell level, combining a sensitive and robust fluorescent in situ hybridization platform with multiparameter flow cytometry, to study the expression of gammaherpesvirus non-coding RNAs (ncRNAs) during lytic replication, latent infection and reactivation in vitro. This method allowed robust detection of viral ncRNAs of murine gammaherpesvirus 68 (γHV68), Kaposi’s sarcoma associated herpesvirus and Epstein-Barr virus, revealing variable expression at the single-cell level. By quantifying the inter-relationship of viral ncRNA, viral mRNA, viral protein and host mRNA regulation during γHV68 infection, we find heterogeneous and asynchronous gene expression during latency and reactivation, with reactivation from latency identified by a distinct gene expression profile within rare cells. Further, during lytic replication with γHV68, we find many cells have limited viral gene expression, with only a fraction of cells showing robust gene expression, dynamic RNA localization, and progressive infection. Lytic viral gene expression was enhanced in primary fibroblasts and by conditions associated with enhanced viral replication, with multiple subpopulations of cells present in even highly permissive infection conditions. These findings, powered by single-cell analysis integrated with automated clustering algorithms, suggest inefficient or abortive γHV infection in many cells, and identify substantial heterogeneity in viral gene expression at the single-cell level.AUTHOR SUMMARYThe gammaherpesviruses are a group of DNA tumor viruses that establish lifelong infection. How these viruses infect and manipulate cells has frequently been studied in bulk populations of cells. While these studies have been incredibly insightful, there is limited understanding of how virus infection proceeds within a single cell. Here we present a new approach to quantify gammaherpesvirus gene expression at the single-cell level. This method allows us to detect cell-to-cell variation in the expression of virus non-coding RNAs, an important and understudied class of RNAs which do not encode for proteins. By examining multiple features of virus gene expression, this method further reveals significant variation in infection between cells across multiple stages of infection, even in conditions generally thought to be highly uniform. These studies emphasize that gammaherpesvirus infection can be surprisingly heterogeneous when viewed at the level of the individual cell. Because this approach can be broadly applied across diverse viruses, this study affords new opportunities to understand the complexity of virus infection within single cells.
Alternative Promoters Drive Human Cytomegalovirus Reactivation from Latency
Authors: Collins-McMillen Donna , Rak Mike , Buehler Jason , Igarashi-Hayes Suzu , Kamil Jeremy , Moorman Nat , Goodrum Felicia 
Published: December 2018

ABSTRACTReactivation from latency requires reinitiation of viral gene expression and culminates in the production of infectious progeny. The major immediate early promoter (MIEP) of human cytomegalovirus (HCMV) drives the expression of crucial lytic cycle transactivators but is silenced during latency in hematopoietic progenitor cells (HPCs). Because the MIEP is poorly active in HPCs, it is unclear how viral transactivators are expressed during reactivation. We demonstrate that transcripts originating from alternative promoters within the canonical major immediate early locus are abundantly expressed upon reactivation, whereas MIEP-derived transcripts remain undetectable. Further, we show that these promoters are necessary for efficient reactivation in primary CD34+ HPCs. Our findings change the paradigm for HCMV reactivation by demonstrating that promoter switching governs reactivation from viral latency in a context-specific manner.
Extracellular Matrix acts as pressure detector in biological tissues
Authors: Dolega Monika E. , Brunel Benjamin , Goff Magali Le , Greda Magdalena , Verdier Claude , Joanny Jean-François , Recho Pierre , Cappello Giovanni 
Published: December 2018

AbstractImposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions 1–5. To perceive mechanical perturbations of different types and magnitudes, tissues need a range of appropriate detectors 6–8, with a compliance that has to match the perturbation amplitude. As a proxy of biological tissues, we use multicellular aggregates, a composite material made of cells, extracellular matrix and permeating fluid. We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9–13, while the same amount of selective compression on cells has almost no effect 14,15. We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space. This description correctly predicts the emergent bulk modulus of the aggregate as well as the hydrodynamic diffusion coefficient of the percolating interstitial fluid under compression. We further show that, on a longer timescale, the extracellular matrix serves as a sensor that regulates cell proliferation and migration in a 3D environment through its permanent deformation and dehydration following the global compression.
CSR and sustainability reporting practices in India: an in-depth content analysis of top-listed companies
Authors: Aggarwal Priyanka , Singh Ajay Kumar 
Published: December 2018

PurposeThe purpose of this paper is to comprehensively analyze the corporate social responsibility (CSR) and sustainability reporting (SR) practices of Indian companies in terms of disclosure quantity and quality, and to investigate the differences in SR practices by SR dimension, industry, ownership structure, firm size and profitability.Design/methodology/approachData are collected from annual reports/business responsibility reports (BRR)/CSR/sustainability reports of 60 top-listed companies in India. A comprehensive sustainability reporting index is developed. Content analysis technique is used. Inter-coder reliability is established.FindingsAltogether, 18 items of the index are not disclosed by the majority of companies in India. SR quality is found significantly lower than the SR quantity. Moreover, SR practices significantly differ by dimension/category, industry-type and firm-size but are not influenced by ownership structure. However, the study fails to establish any conclusive relationship between SR and profitability.Practical implicationsThe present study has several implications for corporates, practitioners, policymakers and stakeholders. The findings underscore the need for amendments in the Global Reporting Initiative guidelines and BRR framework of the Securities and Exchange Board of India to avoid patchy disclosures and ensure complete reporting by companies.Originality/valueThis study is among the foremost studies in India evaluating SR practices of top-listed companies in the wake of the mandatory BRR requirement from a quantitative as well as qualitative perspective using a multidimensional index.
Cutaneous adult xanthogranuloma with a small portion of BRAFV600E mutated Langerhans cell histiocytosis populations: A case report and the review of published work
Authors: Ishikawa Mai , Endo Yukie , Uehara Akihito , Suto Mariko , Yasuda Masahito , Motegi Sei‐ichiro , Ishikawa Osamu 
Published: December 2018

AbstractHistiocytoses, including Langerhans cell histiocytosis (LCH), juvenile or adult xanthogranuloma (AXG) and Rosai–Dorfman disease (RDD), are rare disorders characterized by the proliferation of cells derived from monocyte/macrophage lineages. A few cases of LCH coexisting with xanthogranuloma or RDD have been reported. The etiology of these diseases remains unclear. However, oncogenic BRAFV600E mutations have been identified in LCH. Here, we report the case of a 26‐year‐old Japanese man with a 3‐month history of a solitary occipital nodule. No abnormality was detected in his other organs, and a total resection of the nodule was performed. Histopathological examination revealed the coexistence of LCH and AXG with prominent emperipolesis characteristic of RDD. Immunohistochemistry showed that most of the large histiocytes were positive for CD68, weakly positive or negative for S100, and negative for CD207 and CD1a, supporting the diagnosis of AXG. The tumor cells with emperipolesis did not show S100‐positive findings characteristic of RDD. The focally aggregated oval histiocytic cells were positive for CD1a, CD207, CD68 and S100, and were compatible with the immunophenotype of LCH cells. In addition, these cells were positive for BRAFV600E mutation. The tumor cells in our patient exhibited a cellular morphology characteristic of multiple histiocytoses in a solitary cutaneous nodule, which may imply an etiological association among LCH, AXG and RDD. To our knowledge, this is the first report of a BRAFV600E mutation‐positive case of LCH coexisting with AXG. Because patients with BRAFV600E mutation have higher risks of multisystemic LCH and recurrence, we should carefully follow up the patient.
Interactions among trees: A key element in the stabilising effect of species diversity on forest growth
Authors: Aussenac Raphaël , Bergeron Yves , Gravel Dominique , Drobyshev Igor 
Published: December 2018

AbstractThere is mounting evidence that species diversity increases the temporal stability of forest growth. This stabilising effect of diversity has mainly been attributed to species differences in their response to fluctuating environmental conditions. Interactions among individuals could also contribute to the stabilising effect of diversity by increasing the mean and reducing the variance of tree growth, however, this has never been directly demonstrated.We used tree‐ring width chronologies from temperate and boreal mixed stands of Eastern Canada to identify the role of interactions among individuals in the stabilising effect of diversity on forest growth. Using neighbourhood competition index and a mixed model, we compared the effect of interspecific and intraspecific interactions on the mean and the variance of tree growth.We found that interspecific interactions are less detrimental to tree growth than intraspecific interactions. We also found that interspecific interactions buffer tree response to drought and thereby reduce the variance of tree growth.Our results indicate diversity may increase the mean and reduce the variance of tree growth through interactions among individuals. Thus, we demonstrate interactions among individuals play a role in the stabilising effect of diversity on forest growth, and in doing so, we bring to light other mechanisms of the insurance hypothesis.Aplain language summaryis available for this article.
Maternal diet and age alter direct and indirect relationships between life‐history traits across multiple generations
Authors: Goos Jared M. , Swain Cameron J. , Munch Stephan B. , Walsh Matthew R. 
Published: December 2018

Abstract

Maternal age has important consequences for offspring fitness, with influences on size, development and reproductive schedules. Such maternal age effects may be driven by differential provisioning of resources; yet, little is known about the role of environmental supply of nutritional resources in mediating such effects.

We tested the influence of limiting nutritional resource, dietary phosphorus (P), on maternal age effects across multiple generations by examining the potential interactive effects of maternal nutrition and age on daughter and granddaughter life‐history traits in the freshwater crustacean Daphnia pulicaria.

Maternal age and diet had significant but contrasting effects on offspring life history. We did not observe any evidence that age effects on offspring life history are mediated by maternal diet. However, granddaughter growth and size at maturation were influenced by the interaction between grandmaternal age and diet, suggesting that the appearance of transgenerational effects of age and diet were delayed by one generation.

Because offspring life history is often linked directly and/or indirectly to life history variation in previous generations, we utilized structural equation modelling (SEM) to assess such direct or indirect relationships.

SEM revealed striking differences in the relationship between growth, development time and fecundity both within and among generations, depending on the age and diet in the F0 generation. Interestingly, direct and persistent relationships between the F0 generation and the F2 generation are most prevalent when grandmothers are old and fed low P diets, and such relationships are largely driven by fecundity in the F0 generation. Additionally, indirect causal relationships between the F0 generation and F2 generation are most pronounced when grandmothers are young and fed low P diets or when grandmothers are old and fed high P diets.

Our results indicate that transgenerational effects of maternal age and environment persist across multiple generations, and vary between successive generations. Further, our examination of the interaction network between life‐history traits of each generation suggest that the mechanisms for such persistent transgenerational effects are highly dependent on maternal condition.

A plain language summary is available for this article.
Catch diversification provides multiple benefits in inland fisheries
Authors: Matsuzaki Shin‐Ichiro S. , Shinohara Ryuichiro , Uchida Kei , Sasaki Takehiro 
Published: December 2018

Abstract

Diversification of fisheries and agroecosystems can increase and stabilize production and revenue, despite unpredictable changes in ecosystems and markets. Recent work suggests that diversification can provide multiple benefits simultaneously, but empirical evidence of relationships between catch or crop diversification and the provision of multiple benefits is scarce. The effect of diversification on multiple benefits may vary temporally and among systems.

Using long‐term (11–54 years) capture fishery statistics from five Japanese lakes, we examined whether catch diversity increased multiple benefits, including revenue, nitrogen and phosphorus removal, and seasonal commercial species diversity. We also assessed whether catch species diversity increased the stability of each benefit via a portfolio effect (PE).

Our study revealed positive relationships between catch diversity and the bundle of benefits (the mean of all normalized benefits; i.e., the provisioning of multiple benefits) in all five lakes, even after controlling for the total catch. The effects of catch diversity on individual benefits were positive or insignificant and differed among the study lakes. These differences were likely caused by the range and variation of functional characteristics among catch species. The influence of the annual mean price on revenue suggested that market forces did have an effect.

We also found that aggregated revenue as well as N and P removal were 1.6–2.1 times (four lakes), 1.5–2.2 times (four lakes), and 1.4–2.2 times (all five lakes) more stable, respectively, than would be expected if only a single species were harvested. This greater stability suggests that maintaining catch species diversity may increase the stability of multiple benefits through PEs.

Synthesis and applications. Our analysis suggests that catch diversification has great potential to increase the magnitude and stability of multiple benefits. Although total catch alone was sufficient to provide multiple benefits, a goal of maximization with specialization may decrease stability and deplete resources. Under fluctuating environmental and economic conditions, diversification strategies promise to be a potential management option for achieving resilient and sustainable inland fisheries.
Diet and diet‐associated bacteria shape early microbiome development in Yellowtail Kingfish (Seriola lalandi)
Authors: Wilkes Walburn Jackson , Wemheuer Bernd , Thomas Torsten , Copeland Elizabeth , O'Connor Wayne , Booth Mark , Fielder Stewart , Egan Suhelen 
Published: December 2018

SummaryThe supply of quality juveniles via land‐based larviculture represents a major bottleneck to the growing finfish aquaculture industry. As the microbiome plays a key role in animal health, this study aimed to assess the microbial community associated with early larval development of commercially raised Yellowtail Kingfish (Seriola lalandi). We used qPCR and 16S rRNA gene amplicon sequencing to monitor changes in the microbiome associated with the development of S. lalandi from larvae to juveniles. We observed an increase in the bacterial load during larval development, which consisted of a small but abundant core microbiota including taxa belonging to the families Rhodobacteraceae, Lactobacillaceae and Vibrionaceae. The greatest change in the microbiome occurred as larvae moved from a diet of live feeds to formulated pellets, characterized by a transition from Proteobacteria to Firmicutes as the dominant phylum. A prediction of bacterial gene functions found lipid metabolism and secondary metabolite production were abundant in the early larval stages, with carbohydrate and thiamine metabolism functions increasing in abundance as the larvae age and are fed formulated diets. Together, these results suggest that diet is a major contributor to the early microbiome development of commercially raised S. lalandi.
In‐depth comparative analysis of Illumina® MiSeq run metrics: Development of a wet‐lab quality assessment tool
Authors: Kastanis George John , Santana‐Quintero Luis V. , Sanchez‐Leon Maria , Lomonaco Sara , Brown Eric W. , Allard Marc W. 
Published: December 2018

AbstractWhole genome sequencing of bacterial isolates has become a daily task in many laboratories, generating incredible amounts of data. However, data acquisition is not an end in itself; the goal is to acquire high‐quality data useful for understanding genetic relationships. Having a method that could rapidly determine which of the many available run metrics are the most important indicators of overall run quality and having a way to monitor these during a given sequencing run would be extremely helpful to this effect. Therefore, we compared various run metrics across 486 MiSeq runs, from five different machines. By performing a statistical analysis using principal components analysis and a K‐means clustering algorithm of the metrics, we were able to validate metric comparisons among instruments, allowing for the development of a predictive algorithm, which permits one to observe whether a given MiSeq run has performed adequately. This algorithm is available in an Excel spreadsheet: that is, MiSeq Instrument & Run (In‐Run) Forecast. Our tool can help verify that the quantity/quality of the generated sequencing data consistently meets or exceeds recommended manufacturer expectations. Patterns of deviation from those expectations can be used to assess potential run problems and plan preventative maintenance, which can save valuable time and funding resources.
A Campus Fractured: Neoliberalization and the Clash of Academic Democracies in France
Authors: Thorkelson Eli 
Published: December 2018

AbstractThrough an ethnographic case study of campus politics at a Parisian university, this paper shows that neoliberal university reforms in France failed to create neoliberal subjectivities. Instead, the reforms provoked conflicts between direct and representative democracy, traditions which had organized post‐1960s French university culture. These conflicts suggest that we can decenter neoliberalism and instead examine the confluence of multiple modes of academic production, along with the antagonistic emergence of non‐neoliberal subjectivities.
Comprehensive characterization of horse genome variation by whole‐genome sequencing of 88 horses
Authors: Jagannathan V. , Gerber V. , Rieder S. , Tetens J. , Thaller G. , Drögemüller C. , Leeb T. 
Published: December 2018

SummaryWhole‐genome sequencing studies are vital to gain a thorough understanding of genomic variation. Here, we summarize the results of a whole‐genome sequencing study comprising 88 horses and ponies from diverse breeds at 19.1× average coverage. The paired‐end reads were mapped to the current EquCab3.0 horse reference genome assembly, and we identified approximately 23.5 million single nucleotide variants and 2.3 million short indel variants. Our dataset included at least 7 million variants that were not previously reported. On average, each individual horse genome carried ∼5.7 million single nucleotides and 0.8 million small indel variants with respect to the reference genome assembly. The variants were functionally annotated. We provide two examples for potentially deleterious recessive alleles that were identified in a heterozygous state in individual genome sequences. Appropriate management of such deleterious recessive alleles in horse breeding programs should help to improve fertility and reduce the prevalence of heritable diseases. This comprehensive dataset has been made publicly available, will represent a valuable resource for future horse genetic studies and supports the goal of accelerating the rates of genetic gain in domestic horse.
Chemically modified peanut extract shows increased safety while maintaining immunogenicity
Authors: van der Kleij Hanneke P. M. , Warmenhoven Hans J. M. , van Ree Ronald , Versteeg Serge A. , Pieters Raymond H. H. , Dreskin Stephen C. , Knulst André C. , van Hoffen Els , Opstelten Dirk Jan E. , Koppelman Stef J. , Smit Joost J. 
Published: December 2018

AbstractBackgroundPeanuts are most responsible for food‐induced anaphylaxis in adults in developed countries. An effective and safe immunotherapy is urgently needed. The aim of this study was to investigate the immunogenicity, allergenicity, and immunotherapeutic efficacy of a well‐characterized chemically modified peanut extract (MPE) adsorbed to Al(OH)3.MethodsPeanut extract (PE) was modified by reduction and alkylation. Using sera of peanut‐allergic patients, competitive IgE‐binding assays and mediator release assays were performed. The immunogenicity of MPE was evaluated by measuring activation of human PE‐specific T‐cell lines and the induction of PE‐specific IgG in mice. The safety and efficacy of MPE adsorbed to Al(OH)3 was tested in two mouse models by measuring allergic manifestations upon peanut challenge in peanut‐allergic mice.ResultsCompared to PE, the IgE‐binding and capacity to induce allergic symptoms of MPE were lower in all patients. PE and MPE displayed similar immunogenicity in vivo and in vitro. In mice sensitized to PE, the threshold for anaphylaxis (drop in BT) upon subcutaneous challenge with PE was 0.01 mg, while at 0.3 mg MPE no allergic reaction occurred. Anaphylaxis was not observed when PE and MPE were fully adsorbed to Al(OH)3. Both PE and MPE + Al(OH)3 showed to be efficacious in a model for immunotherapy.ConclusionIn our studies, an Al(OH)3 adsorbed MPE showed reduced allergenicity compared to unmodified PE, while the efficacy of immunotherapy is maintained. The preclinical data presented in this study supports further development of modified peanut allergens for IT.