bluuebunny/crossref_metadata_2025 huggingface dataset:
Fungarium specimens: a largely untapped source in global change biology and beyond
Authors: Andrew Carrie , Diez Jeffrey , James Timothy Y. , Kauserud Håvard
Published: November 2018

For several hundred years, millions of fungal sporocarps have been collected and deposited in worldwide collections (fungaria) to support fungal taxonomy. Owing to large-scale digitization programs, metadata associated with the records are now becoming publicly available, including information on taxonomy, sampling location, collection date and habitat/substrate information. This metadata, as well as data extracted from the physical fungarium specimens themselves, such as DNA sequences and biochemical characteristics, provide a rich source of information not only for taxonomy but also for other lines of biological inquiry. Here, we highlight and discuss how this information can be used to investigate emerging topics in fungal global change biology and beyond. Fungarium data are a prime source of knowledge on fungal distributions and richness patterns, and for assessing red-listed and invasive species. Information on collection dates has been used to investigate shifts in fungal distributions as well as phenology of sporocarp emergence in response to climate change. In addition to providing material for taxonomy and systematics, DNA sequences derived from the physical specimens provide information about fungal demography, dispersal patterns, and are emerging as a source of genomic data. As DNA analysis technologies develop further, the importance of fungarium specimens as easily accessible sources of information will likely continue to grow.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene’.
Museum specimens provide novel insights into changing plant–herbivore interactions
Authors: Meineke Emily K. , Davies T. Jonathan
Published: November 2018

Mounting evidence shows that species interactions may mediate how individual species respond to climate change. However, long-term anthropogenic effects on species interactions are poorly characterized owing to a lack of data. Insect herbivory is a major ecological process that represents the interaction between insect herbivores and their host plants, but historical data on insect damage to plants is particularly sparse. Here, we suggest that museum collections of insects and plants can fill key gaps in our knowledge on changing trophic interactions, including proximate mechanisms and the net outcomes of multiple global change drivers across diverse insect herbivore–plant associations. We outline theory on how global change may affect herbivores and their host plants and highlight the unique data that could be extracted from museum specimens to explore their shifting interactions. We aim to provide a framework for using museum specimens to explore how some of the most diverse co-evolved relationships are responding to climate and land use change.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene’.
Facets of phylodiversity: evolutionary diversification, divergence and survival as conservation targets
Authors: Kling Matthew M. , Mishler Brent D. , Thornhill Andrew H. , Baldwin Bruce G. , Ackerly David D.
Published: November 2018

Biodiversity is often described as having multiple facets, including species richness, functional diversity and phylogenetic diversity. In this paper, we argue that phylogenetic diversity itself has three distinct facets—lineage diversification, character divergence and survival time—that can be quantified using distinct branch length metrics on an evolutionary tree. Each dimension is related to different processes of macroevolution, has different spatial patterns and is tied to distinct goals for conserving biodiversity and protecting its future resilience and evolutionary potential. We compared the landscapes identified as top conservation priorities by each of these three metrics in a conservation gap analysis for California, a world biodiversity hotspot, using herbarium data on the biogeography and evolutionary relationships of more than 5000 native plant species. Our analysis incorporated a novel continuous metric of current land protection status, fine-scale data on landscape intactness and an optimization algorithm used to identify complementary priority sites containing concentrations of taxa that are evolutionarily unique, vulnerable due to small range size and/or poorly protected across their ranges. Top conservation priorities included pockets of coastal and northern California that ranked highly for all three phylodiversity dimensions and for species richness, as well as sites uniquely identified by each metric whose value may depend on whether properties such as genetic divergence, high net diversification or independent survival experience are most desirable in an Anthropocene flora.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene’.
Bookkeeping of insect herbivory trends in herbarium specimens of purple loosestrife (
Lythrum salicaria
)
Authors: Beaulieu Caroline , Lavoie Claude , Proulx Raphaël
Published: November 2018

The potential use of herbarium specimens to detect herbivory trends is enormous but largely untapped. The objective of this study was to reconstruct the long-term herbivory pressure on the Eurasian invasive plant, purple loosestrife (
Lythrum salicaria
), by evaluating leaf damage over 1323 specimens from southern Québec (Canada). The hypothesis tested is that that the prevalence of herbivory damage on purple loosestrife is low during the invasion phase and increases throughout the saturation phase. Historical trends suggest a gradual increase in hole feeding and margin feeding damage from 1883 to around 1940, followed by a period of relative stability. The percentage of specimens with window feeding damage did not begin to increase until the end of the twentieth century, from 3% (2–6%) in 1990 to 45% (14–81%) in 2015. Temporal changes in the frequency of window feeding damage support the hypothesis of an increasing herbivory pressure by recently introduced insects. This study shows that leaf damage made by insects introduced for the biocontrol of purple loosestrife, such as coleopterans of the
Neogalerucella
genus, can be assessed from voucher specimens. Herbaria are a rich source in information that can be used to answer questions related to plant-insect interactions in the context of biological invasions and biodiversity changes.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene’.
Using museum specimens to track morphological shifts through climate change
Authors: MacLean Heidi J. , Nielsen Matthew E. , Kingsolver Joel G. , Buckley Lauren B.
Published: November 2018

Museum specimens offer a largely untapped resource for detecting morphological shifts in response to climate change. However, morphological shifts can be obscured by shifts in phenology or distribution or sampling biases. Additionally, interpreting phenotypic shifts requires distinguishing whether they result from plastic or genetic changes. Previous studies using collections have documented consistent historical size changes, but the limited studies of other morphological traits have often failed to support, or even test, hypotheses. We explore the potential of collections by investigating shifts in the functionally significant coloration of a montane butterfly,Colias meadii,over the past 60 years within three North American geographical regions. We find declines in ventral wing melanism, which correspond to reduced absorption of solar radiation and thus reduced risk of overheating, in two regions. However, contrary to expected responses to climate warming, we find melanism increases in the most thoroughly sampled region. Relationships among temperature, phenology and morphology vary across years and complicate the distinction between plastic and genetic responses. Differences in these relationships may account for the differing morphological shifts among regions. Our findings highlight the promise of using museum specimens to test mechanistic hypotheses for shifts in functional traits, which is essential for deciphering interacting responses to climate change.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene’.
Continuous Evaluation of Ligand Protein Predictions: A Weekly Community Challenge for Drug Docking
Authors: Wagner Jeffrey R. , Churas Christopher P. , Liu Shuai , Swift Robert V. , Chiu Michael , Shao Chenghua , Feher Victoria A. , Burley Stephen K. , Gilson Michael K. , Amaro Rommie E.
Published: November 2018

1

Docking calculations can be used to accelerate drug discovery by providing predictions of the poses of candidate ligands bound to a targeted protein. However, studies in the literature use varied docking methods, and it is not clear which work best, either in general or for specific protein targets. In addition, a complete docking calculation requires components beyond the docking algorithm itself, such as preparation of the protein and ligand for calculations, and it is difficult to isolate which aspects of a method are most in need of improvement. To address such issues, we have developed the Continuous Evaluation of Ligand Protein Predictions (CELPP), a weekly blinded challenge for automated docking workflows. Participants in CELPP create a workflow to predict protein-ligand binding poses, which is then tasked with predicting 10-100 new (never before released) protein-ligand crystal structures each week. CELPP evaluates the accuracy of each workflow’s predictions and posts the scores online. CELPP is a new cyberinfrastructure resource to identify the strengths and weaknesses of current approaches, help map docking problems to the algorithms most likely to overcome them, and illuminate areas of unmet need in structure-guided drug design.
Chronic corticosterone enhancement aggravates alpha-synuclein brain spreading pathology and substantia nigra neurodegeneration in mice
Authors: Burtscher Johannes , Copin Jean-Christophe , Rodrigues João , Thangaraj Senthil K. , Chiki Anass , de Suduiraut Marie-Isabelle Guillot , Sandi Carmen , Lashuel Hilal A.
Published: November 2018

Chronic stress and associated heightened glucocorticoid levels are risk factors for depression, a common non-motor symptom in Parkinson’s disease (PD). However, how heightened glucocorticoids influence PD neuropathology [alpha-synuclein (α-Syn) containing Lewy pathology and neurodegeneration] and disease progression is unclear. To address this knowledge gap, we investigated the impact of chronic corticosterone administration on α-Syn pathology, neurodegeneration, behavior and mitochondrial function in a mouse model of α-Syn pathology spreading after intracerebral injection of α-Syn preformed fibrils (PFFs). Our results demonstrate that heightened corticosterone aggravates neurodegeneration and α-Syn pathology spreading, intriguingly to specific brain regions, such as the entorhinal cortex. Corticosterone-treatment abolished distinct physiological adaptations after PFF-injection and induced differential physiological and behavioral consequences. Taken together, our work points to elevated glucocorticoids as a risk factor for the development of the neuropathological hallmarks of PD. Strategies aimed at reducing glucocorticoid levels might slow down pathology spreading and disease progression in synucleinopathy.
A Combined Behavioral and Neuroimaging Battery to Test Positive Appraisal Style Theory of Resilience in Longitudinal Studies
Authors: Kampa Miriam , Schick Anita , Yuen Kenneth , Sebastian Alexandra , Chmitorz Andrea , Saase Victor , Wessa Michèle , Tüscher Oliver , Kalisch Raffael
Published: November 2018

Resilience is the maintenance or rapid recovery of mental health during and after stressor exposure. It is becoming increasingly clear that resilience results from a complex and dynamic process of adaptation to stressors involving the biological, psychological and social levels. Positive appraisal style theory of resilience (PASTOR) claims that the common final pathway to maintained mental health lies in the non-negative (non-catastrophizing, non-pessimistic) appraisal of potential stressors, permitting the organism to fine-tune stress responses to optimal levels, thus avoiding unnecessary stress, inefficient deployment of resources and concomitant deleterious allostatic load effects. Successful adaptation consists in developing or strengthening a positive appraisal style. Another key element of PASTOR is that a positive appraisal style is strongly determined by the efficacy and efficiency of the neural and cognitive processes that underlie positive stressor appraisal. We here present a combined behavioral and functional magnetic resonance imaging (fMRI) battery designed to assess such processes repeatedly in longitudinal settings. The battery includes tests of stress reactivity and recovery, reward sensitivity, safety learning and memory in the context of fear conditioning and extinction, volitional situation-focused reappraisal, volitional self-focused reappraisal, and emotional interference inhibition, along with structural MRI and resting-state MRI scans. A detailed description of the battery methods is provided. The feasibility of the battery was successfully tested in N=55 healthy subjects; group results of the individual tasks largely replicate existing literature.
Acquired interbacterial defense systems protect against interspecies antagonism in the human gut microbiome
Authors: Ross Benjamin D. , Verster Adrian J. , Radey Matthew C. , Schmidtke Danica T. , Pope Christopher E. , Hoffman Lucas R. , Hajjar Adeline M. , Peterson S. Brook , Borenstein Elhanan , Mougous Joseph D.
Published: November 2018

The impact of direct interactions between co-resident microbes on microbiome composition is not well understood. Here we report the occurrence of acquired interbacterial defense (AID) gene clusters in bacterial residents of the human gut microbiome. These clusters encode arrays of immunity genes that protect against type VI secretion toxin-mediated intra- and inter-species bacterial antagonism. Moreover, the clusters reside on mobile elements and we demonstrate that their transfer is sufficient to confer toxin resistance in vitro and in gnotobiotic mice. Finally, we identify and validate the protective capacity of a recombinase-associated AID subtype (rAID-1) present broadly in Bacteroidales genomes. These rAID-1 gene clusters have a structure suggestive of active gene acquisition and include predicted immunity factors of toxins deriving from diverse organisms. Our data suggest that neutralization of contact-dependent interbacterial antagonism via AID systems shapes human gut microbiome ecology.
DNA methylation modules associate with incident cardiovascular disease and cumulative risk factor exposure
Authors: Westerman Kenneth , Sebastiani Paola , Jacques Paul , Liu Simin , DeMeo Dawn , Ordovás José M.
Published: November 2018

1

Background

Epigenome-wide association studies using DNA methylation have the potential to uncover novel biomarkers and mechanisms of cardiovascular disease (CVD) risk. However, the direction of causation for these associations is not always clear, and investigations to-date have generally failed to replicate at the level of individual loci. Here, we undertook module- and region-based DNA methylation analyses of incident CVD in the Women’s Health Initiative (WHI) and Framingham Heart Study Offspring Cohort (FHS) in order to find more robust epigenetic biomarkers for cardiovascular risk.

Methods and Findings

We applied weighted gene correlation network analysis (WGCNA) and the Comb-p algorithm to find methylation modules and regions associated with incident CVD in the WHI dataset. We discovered two modules whose activation correlated with CVD risk and replicated across cohorts. One of these modules was enriched for development-related processes and overlaps strongly with epigenetic aging sites. For the other, we showed preliminary evidence for monocyte-specific effects and statistical links to cumulative exposure to traditional cardiovascular risk factors. Additionally, we found three regions (associated with the genes SLC9A1, SLC1A5, and TNRC6C) whose methylation associates with CVD risk.

Conclusions

In sum, we present several epigenetic associations with incident CVD that reveal disease mechanisms related to development and monocyte biology. Furthermore, we show that epigenetic modules may act as a molecular readout of cumulative cardiovascular risk factor exposure, with implications for the improvement of clinical risk prediction.
Imputed gene associations identify replicable trans-acting genes enriched in transcription pathways and complex traits
Authors: Wheeler Heather E. , Ploch Sally , Barbeira Alvaro N. , Bonazzola Rodrigo , Andaleon Angela , Sishpirani Alireza Fotuhi , Saha Ashis , Battle Alexis , Roy Sushmita , Im Hae Kyung
Published: November 2018

Regulation of gene expression is an important mechanism through which genetic variation can affect complex traits. A substantial portion of gene expression variation can be explained by both local (cis) and distal (trans) genetic variation. Much progress has been made in uncovering cis-acting expression quantitative trait loci (cis-eQTL), but trans-eQTL have been more difficult to identify and replicate. Here we take advantage of our ability to predict the cis component of gene expression coupled with gene mapping methods such as PrediXcan to identify high confidence candidate trans-acting genes and their targets. That is, we correlate the cis component of gene expression with observed expression of genes in different chromosomes. Leveraging the shared cis-acting regulation across tissues, we combine the evidence of association across all available GTEx tissues and find 2356 trans-acting/target gene pairs with high mappability scores. Reassuringly, trans-acting genes are enriched in transcription and nucleic acid binding pathways and target genes are enriched in known transcription factor binding sites. Interestingly, trans-acting genes are more significantly associated with selected complex traits and diseases than target or background genes, consistent with percolating trans effects. Our scripts and summary statistics are publicly available for future studies of trans-acting gene regulation.
NDV-3A vaccination protects mice fromCandida albicansbiofilm infection
Authors: Alqarihi Abdullah , Singh Shakti , Edwards John E. , Ibrahim Ashraf S. , Uppuluri Priya
Published: November 2018

NDV-3A, a novel fungal vaccine undergoing clinical trials, contains a recombinant version of theCandida albicansrAls3 N-terminus protein (rAls3p-N) in aluminum hydroxide. In a Phase 1b/2a clinical trial, NDV-3A protected women from recurrent vulvovaginal candidiasis. Here, we reveal that active immunization in mice with NDV-3A induces high titers of anti-rAls3p-N antibodies that interfere withC. albicansability to adhere to and invade endothelial cells, and form biofilmin vitro. The anti-rAls3p-N antibodies also protect againstC. albicansbiofilm formation in a central venous catheter mouse model. Finally, anti-rAls3p-N antibodies significantly inhibit yeast dispersal from the hyphal layers of biofilms. Overall these preclinical studies suggest that NDV-3A may serve as an immunotherapeutic strategy for prevention of infections on indwelling medical devices.
Truncated, uncapped mRNA 5’ ends targeted by cytoplasmic recapping cluster at CAGE tags and some transcripts are alternatively spliced
Authors: Berger Mikaela R. , Alvarado Rolando , Kiss Daniel L.
Published: November 2018

Until cytoplasmic recapping was discovered, decapping was thought to irreversibly destine an mRNA to degradation. Contradicting this idea, we readily observe mRNAs targeted by cytoplasmic capping in uncapped, yet stable forms. 5’ RACE shows that nearly all uncapped ends correspond to CAGE tags and that the recapping of ZNF207 mRNA may be restricted to a single splice isoform. A modified RACE approach detected uncapped 5’ RNA ends mapping to 46 mRNAs in dominant negative cytoplasmic capping enzyme expressing and normal cells. 11 of 46 cloned mRNAs also contained splice isoform-limiting sequences. Collectively, these data reinforce earlier work and suggest that alternative splicing may play a role in targeting transcripts for– and/or determining the position of– cytoplasmic capping.
Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis
Authors: Gumucio Jonathan P , Qasawa Austin H , Ferrara Patrick J , Malik Afshan N , Funai Katsuhiko , McDonagh Brian , Mendias Christopher L
Published: November 2018

Myosteatosis is the pathological accumulation of lipid that can occur in conjunction with atrophy and fibrosis following skeletal muscle injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many clinical studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our objective was to determine the pathological changes that result in lipid accumulation in injured muscle fibers. We used a rat model of rotator cuff injury in this study, as the rotator cuff muscle group is particularly prone to the development of myosteatosis after injury. Muscles were collected from uninjured controls, or 10, 30, or 60 days after injury, and analyzed using a combination of muscle fiber contractility assessments, RNA sequencing, and undirected metabolomics, lipidomics and proteomics, along with bioinformatics techniques, to identify potential pathways and cellular processes that are dysregulated after rotator cuff tear. Bioinformatics analyses indicated that mitochondrial function was likely disrupted after injury. Based on these findings, and given the role that mitochondria play in lipid metabolism, we then performed targeted biochemical and imaging studies and determined that mitochondrial dysfunction and reduced fatty acid oxidation likely leads to the accumulation of lipid in myosteatosis.
The effects of the angiotensin II receptor antagonist losartan on appetitive versus aversive learning
Authors: Pulcu Erdem , Shkreli Lorika , Holst Carolina Guzman , Woud Marcella L. , Craske Michelle G. , Browning Michael , Reinecke Andrea
Published: November 2018

Exposure therapy is a first-line treatment for anxiety disorders but remains ineffective in a large proportion of patients. A proposed mechanism of exposure involves a form of inhibitory learning where the association between a stimulus and an aversive outcome is suppressed by a new association with an appetitive or neutral outcome. The blood pressure medication losartan augments fear extinction in rodents and might have similar synergistic effects on human exposure therapy, but the exact cognitive mechanisms underlying these effects remain unknown. In this study, we used a reinforcement learning paradigm with compound rewards and punishments to test the prediction that losartan augments learning from appetitive relative to aversive outcomes. Healthy volunteers (N=53) were randomly assigned to single-dose losartan (50mg) versus placebo. Participants then performed a reinforcement learning task which simultaneously probes appetitive and aversive learning. Participant choice behaviour was analysed using both a standard reinforcement learning model and by analysis of choice switching behaviour. Losartan significantly reduced learning rates from aversive events (losses) when participants were first exposed to the novel task environment, while preserving learning from positive outcomes. The same effect was seen in choice switching behaviour. Losartan enhances learning from positive relative to negative events. This effect may represent a computationally defined neurocognitive mechanism by which the drug could enhance the effect of exposure in clinical populations.
MolMeDB: Molecules on Membranes Database
Authors: Juračka Jakub , Šrejber Martin , Melíková Michaela , Bazgier Václav , Berka Karel
Published: November 2018

Biological membranes act as barriers or reservoirs for many compounds within the human body. As such, they play an important role in pharmacokinetics and pharmacodynamics of drugs and other molecular species. Until now, most membrane/drug interactions have been inferred from simple partitioning between octanol and water phases. However, the observed variability in membrane composition and among compounds themselves stretches beyond such simplification as there are multiple drug-membrane interactions. Numerous experimental and theoretical approaches are used to determine the molecule-membrane interactions with variable accuracy, but there is no open resource for their critical comparison. For this reason, we have built Molecules on Membranes Database (MolMeDB), which gathers data about over 3600 compound-membrane interactions including partitioning, penetration, and positioning. The data have been collected from scientific articles published in peer-reviewed journals and complemented by inhouse calculations from high-throughput COSMOmic approach to set up a baseline for further comparison. The data in MolMeDB are fully searchable and browsable by means of name, SMILES, membrane, method, or dataset and we offer the collected data openly for further reuse and we are open to further additions. MolMeDB can be a powerful tool that could help researchers better understand the role of membranes and to compare individual approaches used for the study of molecule/membrane interactions.

Database URL:http://molmedb.upol.cz.
Prefix-Free Parsing for Building Big BWTs
Authors: Boucher Christina , Gagie Travis , Kuhnle Alan , Langmead Ben , Manzini Giovanni , Mun Taher
Published: November 2018

High-throughput sequencing technologies have led to explosive growth of genomic databases; one of which will soon reach hundreds of terabytes. For many applications we want to build and store indexes of these databases but constructing such indexes is a challenge. Fortunately, many of these genomic databases are highly-repetitive—a characteristic that can be exploited to ease the computation of the Burrows-Wheeler Transform (BWT), which underlies many popular indexes. In this paper, we introduce a preprocessing algorithm, referred to as prefix-free parsing, that takes a text T as input, and in one-pass generates a dictionary D and a parse P of T with the property that the BWT of T can be constructed from D and P using workspace proportional to their total size and O(|T|)-time. Our experiments show that D and P are significantly smaller than T in practice, and thus, can fit in a reasonable internal memory even when T is very large. In particular, we show that with prefix-free parsing we can build an 131-megabyte run-length compressed FM-index (restricted to support only counting and not locating) for 1000 copies of human chromosome 19 in 2 hours using 21 gigabytes of memory suggesting that we can build a 6.73 gigabyte index for 1000 complete human-genome haplotypes in approximately 102 hours using about 1 terabyte of memory
The Barcode, UMI, Set format and BUStools
Authors: Melsted Páll , Ntranos Vasilis , Pachter Lior
Published: November 2018

We introduce the Barcode-UMI-Set format (BUS) for representing pseudoalignments of reads from single-cell RNA-seq experiments. The format can be used with all single-cell RNA-seq technologies, and we show that BUS files can be efficiently generated. BUStools is a suite of tools for working with BUS files and facilitates rapid quantification and analysis of single-cell RNA-seq data. The BUS format therefore makes possible the development of modular, technology-specific, and robust workflows for single-cell RNA-seq analysis.
The impact of interspecies recombination on human herpes simplex virus evolution and host immune recognition
Authors: Casto Amanda M. , Roychoudhury Pavitra , Xie Hong , Selke Stacy , Perchetti Garrett A. , Wofford Haley , Huang Meei-Li , Verjans Georges M. G. M. , Gottlieb Geoffrey S. , Wald Anna , Jerome Keith R. , Koelle David M. , Johnston Christine , Greninger Alexander L.
Published: November 2018

Among the most ubiquitous of human pathogens, HSV-1 and HSV-2 are distinct viral species that diverged about six million years ago. At least four ancient HSV-1 x HSV-2 interspecies recombination events have affected the HSV-2 genome, with recombinants and non-recombinants at each locus circulating today. Though interspecies recombination has occurred in the past, its importance in HSV evolution remains incompletely defined. Using 255 newly-sequenced and 219 existing HSV genome sequences, we comprehensively assessed interspecies recombination in HSV. The novel recombinants we identify demonstrate that the sizes and locations of interspecies recombination events in HSV-2 are more variable than previously appreciated. One novel recombinant arose in its current host, showing for the first time that interspecies recombination occurs in contemporary HSV populations. We also demonstrate that interspecies recombination affects T-cell recognition of HSV. Our findings indicate that interspecies recombination can significantly influence genetic variation in and host immunologic response to HSV-2.
The Medical Genome Reference Bank: Whole genomes and phenotype of 2,570 healthy elderly
Authors: Pinese Mark , Lacaze Paul , Rath Emma M. , Stone Andrew , Brion Marie-Jo , Ameur Adam , Nagpal Sini , Puttick Clare , Husson Shane , Degrave Dmitry , Cristina Tina Navin , Kahl Vivian F. Silva , Statham Aaron L. , Woods Robyn L. , McNeil John J. , Riaz Moeen , Barr Margo , Nelson Mark R. , Reid Christopher M. , Murray Anne M. , Shah Raj C. , Wolfe Rory , Atkins Joshua R. , Fitzsimmons Chantel , Cairns Heath M. , Green Melissa J. , Carr Vaughan J. , Cowley Mark J. , Pickett Hilda A. , James Paul A. , Powell Joseph E. , Kaplan Warren , Gibson Greg , Gyllensten Ulf , Cairns Murray J. , McNamara Martin , Dinger Marcel E. , Thomas David M.
Published: November 2018

Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2,570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analysed the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. Individuals in the MGRB had fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK BioBank cohorts, consistent with risk depletion. Pervasive age-related somatic changes were correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing. This research has been conducted using the UK Biobank Resource under Application Number 17984.
Widespread roles of enhancer-like transposable elements in cell identity and long-range genomic interactions
Authors: Cao Yaqiang , Chen Guoyu , Wu Gang , Zhang Xiaoli , McDermott Joseph , Chen Xingwei , Xu Chi , Jiang Quanlong , Chen Zhaoxiong , Zeng Yingying , Ai Daosheng , Huang Yi , Han Jing-Dong J.
Published: November 2018

A few families of transposable elements (TEs) have been shown to evolve into cis-regulatory elements (CREs). Here, to extend these studies to all classes of TEs in the human genome, we identified widespread enhancer-like repeats (ELRs) and find that ELRs reliably mark cell identities, are enriched for lineage-specific master transcription factor binding sites, and are mostly primate-specific. In particular, elements of MIR and L2 TE families whose abundance co-evolved across chordate genomes, are found as ELRs in most human cell types examined. MIR and L2 elements frequently share long-range intra-chromosomal interactions and binding of physically interacting transcription factors. We validated that eight L2 and nine MIR elements function as enhancers in reporter assays, and among 20 MIR-L2 pairings, one MIR repressed and one boosted the enhancer activity of L2 elements. Our results reveal a previously unappreciated co-evolution and interaction between two TE families in shaping regulatory networks.
Effect of scrubbing efficiency on fuel scrubbing inerting for aircraft fuel tanks
Authors: Shao Lei , Feng Shiyu , Li Chaoyue , Liu Weihua , Huang Xuying
Published: November 2018

Purpose

This paper aims to improve the previous fuel scrubbing model and find out the relationship between bubble diameter and scrubbing efficiency (ƞ).

Design/methodology/approach

A fuel tank scrubbing test bench was established to verify the accuracy of this model. Ullage and dissolved oxygen concentration were measured, and images of bubble size and distribution were collected and analyzed using image analysis software.

Findings

The bubble diameter has a great influence on ullage and dissolved oxygen concentration during the fuel scrubbing process. The scrubbing efficiency (ƞ) has an exponential relationship with bubble diameter and decreases rapidly as the bubble diameter increases.

Practical implications

The variation of the ullage and dissolved oxygen concentration predicted by this model is more accurate than that of the previous model. In addition, the study of bubble size can provide a guidance for the design of fuel scrubber.

Originality/value

This study not only improves the previous fuel scrubbing model but also develops a method to calculate scrubbing efficiency (ƞ) based on bubble diameter. In addition, a series of tests and analyses were conducted, including numerical calculation, experiment and image analysis.
A practical guide for understanding online business models
Authors: Kim Won
Published: November 2018

Purpose

There is a lack of clarity about what online business models are. The top 20 Google search results on online business models are articles that explain online business models. However, each of them deals with just one or two elements of business strategies. The list of business models is also a mixture of business strategies. This paper aims to provide practical guide that puts these business models into proper perspective.

Design/methodology/approach

A business model includes all key elements of the business, marketing and operational strategies. There are many such elements. The author has reviewed the popular use of the term online business models and found that just five of the key elements can put almost all of them into proper perspective.

Findings

Five elements of the business and marketing strategies constitute a practical guide for understanding, discussing and even designing the first working draft of a business plan.

Practical implications

The practical guide will serve as a robust vehicle for understanding, discussing and even designing the first working draft of a business plan. The current haphazard use of the term online business models does not shed light on online business models.

Originality/value

The author has examined 20 top Google search results for “online business models” and “business models”. These are articles that talk about 3-17 “business models”. The author examined all of them and confirmed that the five key elements of the business and marketing strategies can put all of them into proper perspective.
Why do farm accidents persist? Normalising danger on the farm within the farm family
Authors: Shortall Sally , McKee Annie , Sutherland Lee‐Ann
Published: November 2018

In the western world, farming is the most dangerous occupation with the highest rates of accidents and fatalities. Farming remains largely a family business and most accidents happen to family members. Why do safety campaigns have such limited success and why do farm families bring this terrible grief on themselves? This article argues that farm accidents are a persistent social pattern requiring analysis of how families are socialised to interact with the farming space. Based on qualitative data gathered for a Scottish study, it is argued that within farm families there is a socialisation and normalisation of danger. Accidents are to be expected. Two key arguments are advanced. First, danger is normalised and children are socialised to undertake risky behaviour. Second, it is suggested that when women do take up farming, they consciously undertake dangerous farming activities to prove that they are ‘authentic’ farmers. No previous research has considered women's approach to danger, and the existing literature suggests women are more safety conscious. This is not supported by our findings. We argue that farm accidents and fatalities are a persistent social problem because family members socialise each other to accept danger as the norm.
“He looks gorgeous” – iuMR images and the transforming of foetal and parental identities
Authors: Lie Mabel , Graham Ruth , Robson Stephen C , Griffiths Paul D
Published: November 2018

The MERIDIAN study examined whether in‐utero MRI (iuMRI) improves the accuracy of diagnosis of foetal brain abnormalities, when used as an adjunct to ultrasound anomaly scanning. A diagnostic iuMRI differs from routine ultrasound screening because of its infrequent use and scanning procedure. Nested within this trial, this sociological study explored the acceptability of iuMRI as a technology and its contribution to parental decision‐making. Our sociological interpretation of the role of iuMR images in prenatal diagnosis draws on narrative interviews with women (and some partners) who underwent MRI imaging at three different centres. Overall, participants found iuMRI helpful in decision‐making because it either confirmed or disconfirmed previous results, or provided additional information. Expectant couples experienced the iuMR imaging process as informative, but also as having emotive and practical value. Our paper extends the existing sociological literature on antenatal testing and visualising the foetus, by using iuMR diagnostic imaging to further explore the concept of the unborn entity. Our data suggest that alongside the iuMR images, the ‘parental gaze’ and accompanying commentary are used by parents to construct and transform foetal and parental identities despite ongoing uncertainties about, and shifting social contexts to their pregnancy.
Pleading Guilty: Why Vulnerability Matters
Authors: Peay Jill , Player Elaine
Published: November 2018

This article examines the Sentencing Council's recent definitive guideline on what reductions in sentence can be offered for a guilty plea. We argue that its emphasis on facilitating early guilty pleas represents more than just an incentive to those intending to plead guilty and poses significant risks for defendants with vulnerabilities. The article questions whether the guideline can amount to an inducement to plead guilty which places uneven burdens on defendants and fails to pay due regard to the duties owed by public authorities under the Equality Act 2010. In so doing it asks questions about the integrity of the criminal justice process and argues that issues of cost‐efficiency and the constructed interests of victims may have outweighed both the rights of those with vulnerabilities and the objectives of the legislative framework designed to protect them. The issues raised are universally relevant to any system that favours defendants who offer guilty pleas.
Contract Interpretation Regimes
Authors: Wielsch Dan
Published: November 2018

Freedom of contract requires the integrity of social institutions that ensure the preconditions for private autonomy. This has been largely ignored by a private law doctrine that works on the assumption of the state being the supplier of background justice. The article argues for an institutional turn in contract interpretation. Depending on whether contracts can link up to existing conventions or have to create their institutional context in the first place, courts may apply either an ‘institution‐preserving interpretation’ or an ‘institution‐creating interpretation’. This implies the need to refrain from following universal rules of contractual interpretation. Rather, legal doctrine should focus on the development of sector‐specific standards of interpretation and on support for private legal regimes that ensure socially reflexive constructions of contracts.
An evaluation of the Virtual Monitoring Clinic, a novel nurse‐led service for monitoring patients with stable rheumatoid arthritis
Authors: Chew Li‐Ching , Xin Xiaohui , Yang Hui , Thumboo Julian
Published: November 2018

Objectives

To study clinical and patient reported outcomes for the Virtual Monitoring Clinic (VMC), a remote nurse‐led telemonitoring service for monitoring Rheumatoid Arthritis (RA) patients treated with disease‐modifying antirheumatic drugs (DMARDs).

Methods

Patients with stable RA enrolled in the VMC were followed up prospectively. The primary outcomes evaluated at 1‐year follow‐up were: Disease Activity Score‐28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), and patient satisfaction assessed using an 11‐point Likert scale.

Results

Of the 251 patients enrolled, 186 completed 1‐year of follow‐up. There was a 2.3% (n = 450) reduction in the annual workload from the rheumatology specialist outpatient clinic as a result of the VMC. Statistically significant improvement was seen in the mean patient satisfaction score (7.70‐8.16, P ≤ 0.001), with 61.5% of patients opting for the VMC alternating with rheumatology outpatient clinic visits as their preferred mode of follow‐up vis‐à‐vis standard care. There was a marginal increase in mean DAS28 and RAPID3 scores from 2.56 to 2.78 (P < 0.05) and 5.28 to 6.03 (P < 0.05), respectively. However, given that at 1‐year follow‐up more than half (72.0% and 63.4% based on DAS28 and RAPID3) of the patients’ disease activity had improved or remained stable, and was in remission or low activity (73.1% and 53.2% based on DAS28 and RAPID3), the VMC seemed to maintain a stable RA disease activity for the majority of patients.

Conclusions

The VMC is an effective and well‐accepted novel approach for the management of patients with stable RA.
Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease‐modifying antirheumatic drug prescribing
Authors: Pontifex Eliza K. , Dissanayake Kokum , Bursill David , Gill Tiffany
Published: November 2018

Aim

Discrepancies exist between international treatment guidelines and current Australian Pharmaceutical Benefits Scheme (PBS) criteria for funding biologic disease‐modifying antirheumatic drug (bDMARD) prescribing in psoriatic arthritis (PsA). We aimed to determine the prevalence of minimal disease activity (MDA) achievement and differences in inflammatory marker levels between PsA patients who have and have not met the Australian PBS criteria for bDMARDs.

Method

Consecutive participants diagnosed with PsA were assessed for MDA components and serum inflammatory markers. For those on bDMARDs, joint counts and inflammatory markers at the time of bDMARD qualification were compared with matched rheumatoid arthritis (RA) controls.

Results

Minimal disease activity was achieved by 56/105 participants overall. There were no differences in inflammatory marker levels or involved joint count patterns between the PsA and RA groups at the time of bDMARD qualification. Seventy‐three percent of the 53 PsA patients on bDMARD achieved MDA, vs 33% in the non‐bDMARD group (P < 0.001). More bDMARD than non‐bDMARD patients achieved four out of seven MDA components. Of those with any enthesitis, its prevalence was higher in the non‐bDMARD group (22 vs 10, P = 0.009). Regardless of treatment, there was no difference in inflammatory marker levels between those who did and did not achieve MDA.

Conclusion

The Australian PBS criteria, funding bDMARD prescribing for PsA, select well for MDA achievers. A high prevalence of MDA non‐achievement remains in patients ineligible for bDMARD funding, and enthesitis in this population is more common. Inflammatory markers were not discriminators between treatment or MDA achievement groups.
A response regulator of the OmpR family is part of the regulatory network controlling the oxidative stress response of Rhodobacter sphaeroides
Authors: Zhao Zhiping , Peng Tao , Oh Jeong‐Il , Glaeser Jens , Weber Lennart , Li Qingfeng , Klug Gabriele
Published: November 2018

As a free‐living bacterium Rhodobacter sphaeroides needs to respond to many environmental stresses. Oxidative stress, membrane stress or heat stress induce the ompR‐1 gene encoding a protein of the OmpR family. Overexpression of OmpR‐1 results in increased resistance to organic peroxides and diamide. Our data demonstrate that OmpR‐1 positively affects expression of several sRNAs with an established role in R. sphaeroides stress defences and negatively affects the promoter of the rpoHI gene. The RpoHI sigma factor has a main role in the activation of many stress responses. Thus OmpR‐1 has a balancing effect on the activation of the RpoHI regulon. We present a model with OmpR‐1 as part of a regulatory network controlling stress defences in R. sphaeroides.
Networking Cities after Paris: Weighing the Ambition of Urban Climate Change Experimentation
Authors: Smeds Emilia , Acuto Michele
Published: November 2018

Over the past few decades, cities have repeatedly demonstrated high levels of ambition with regard to climate action. Global environmental governance has been marked by a proliferation of policy actions taken by local governments around the world to demonstrate their potential to advance climate change mitigation and adaptation. Leading ‘by example’ and demonstrating the extent of action that it is possible to deliver, cities have aspired to raise the ambition of national and international climate governance and put action into practice via a growing number of ‘climate change experiments’ delivered on the ground. Yet accounts of the potential of cities in global environmental governance have often stopped short of a systematic valuation of the nature and impact of the networked dimension of this action. This article addresses this by assessing the nature, and challenges faced by, urban climate governance in the post‐Paris era, focusing on the ‘experimentation’ undertaken in cities and the city networks shaping this type of governance. First, we unpack the concept of ‘urban climate change experimentation’, the ways in which it is networked, and the forces driving it. In the second and third parts of the article, we discuss two main pitfalls of networked urban experimentation in its current form, focusing on issues of scaling experiments and the nature of experimentation. We call for increased attention to ‘scaling up’ experiments beyond urban levels of governance, and to transformative experimentation with governance and politics by and in cities. Finally, we consider how these pitfalls allow us to weigh the potential of urban climate ambition, and consider the pathways available for supporting urban climate change experimentation.
Introduction: Climate Governance After Paris
Authors: Held David , Roger Charles
Published: November 2018

The articles in this special section together begin to chart a pathway, and offer sound reasons for hoping that the containment of climate change may still be possible.