bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Early Response Genes Prevents Changes in Global Joint Metabolomic Profiles in Mouse Post-Traumatic Osteoarthritis
Authors: Haudenschild Dominik R. , Carlson Alyssa K. , Zignego Donald L. , Yik Jasper H.N. , Hilmer Jonathan K. , June Ronald K.
Published: July 2018

Osteoarthritis (OA) is the most common degenerative joint disease, and joint injury increases the risk of OA by 10-fold. Although the injury event itself damages joint tissues, a substantial amount of secondary damage is mediated by the cellular responses to the injury. Cellular responses include the production and activation of proteases (MMPs, ADAMTSs, Cathepsins), the production of inflammatory cytokines, and we hypothesize, changes to the joint metabolome. The trajectory of cellular responses is driven by the transcriptional activation of early response genes, which requires Cdk9-dependent RNA Polymerase II phosphorylation. Flavopiridol is a potent and selective inhibitor of Cdk9 kinase activity, which prevents the transcriptional activation of early response genes. To model post-traumatic osteoarthritis, we subjected mice to non-invasive ACL-rupture joint injury. Following injury, mice were treated with flavopiridol to inhibit Cdk9-dependent transcriptional activation, or vehicle control. Global joint metabolomics were analyzed 1 hour after injury. We found that injury induced metabolomic changes, including increases in Vitamin D3 metabolism and others. Importantly, we found that inhibition of primary response gene activation at the time of injury largely prevented the global changes in the metabolomics profiles. Cluster analysis of joint metabolomes identified groups of injury-induced and drug-responsive metabolites, which may offer novel targets for cell-mediated secondary joint damage. Metabolomic profiling provides an instantaneous snapshot of biochemical activity representing cellular responses, and these data demonstrate the potential for inhibition of early response genes to alter the trajectory of cell-mediated degenerative changes following joint injury.

Significance Statement

Joint injury is an excellent predictor of future osteoarthritis. It is increasingly apparent that the acute cellular responses to injury contribute to the initiation and pathogenesis of OA. Although changes to the joint transcriptome have been extensively studied in the context of joint injury, little is known about changes to small-molecule metabolites. Here we use a non-invasive ACL rupture model of joint injury in mice to identify injury-induced changes to the global metabolomic profiles. In one experimental group we prevented the activation of primary response gene transcription using the Cdk9 inhibitor flavopiridol. Through this comparison, we identified two sets of metabolites that change acutely after joint injury: those that require transcription of primary response genes, and those that do not.
Chromulinavorax destructans, a pathogenic TM6 bacterium with an unusual replication strategy targeting protist mitochondrion
Authors: Deeg Christoph M. , Zimmer Matthias M. , George Emma , Husnik Filip , Keeling Patrick J. , Suttle Curtis A.
Published: July 2018

Most of the diversity of microbial life is not available in culture, and as such we lack even a fundamental understanding of the biological diversity of several branches on the tree of life. One branch that is highly underrepresented is the candidate phylum TM6, also known as the Dependentiae. Their biology is known only from reduced genomes recovered from metagenomes around the world and two isolates infecting amoebae, all suggest that they live highly host-associated lifestyles as parasites or symbionts.Chromulinavorax destructansis an isolate from the TM6/Dependentiae that infects and lyses the abundant heterotrophic flagellate,Spumella elongata. Chromulinavorax destructansis characterized by a high degree of reduction and specialization for infection, so much so it was discovered in a screen for giant viruses. Its 1.2 Mb genome shows no metabolic potential andC. destructansinstead relies on extensive transporter system to import nutrients, and even energy in the form of ATP from the host. Accordingly, it replicates in a viral-like fashion, while extensively reorganizing and expanding the host mitochondrion. 44% of proteins contain signal sequences for secretion, which includes many proteins of unknown function as well as 98 copies of ankyrin-repeat domain proteins, known effectors of host modulation, suggesting the presence of an extensive host-manipulation apparatus.
Where do animals covered by the US Animal Welfare Act live? Analysis of USDA licensed and registered entities
Authors: Bennett Allyson J. , Schoenbeck Erin G.
Published: August 2018

Nonhuman animals are housed in captivity for a range of purposes in the US and other countries. The regulation, oversight, and public transparency of decisions related to the care and use of those animals varies by species and activity. The goals of this paper are 1) to provide a concise and accessible summary of the number and types of facilities either registered or licensed by the USDA and overseen by the federal agency; and 2) to provide concise comparisons of the relative proportion of different types of use of nonhuman animals that fall under the AWA (Animal Welfare Act). Analysis of the publicly-available list of USDA certificate holders produced descriptive data for each state and the US overall. Licensed exhibitors (N=2,640; 33% of total) and breeders (N=2,701; 34% of total) comprise two-thirds of the 8,002 USDA certificate holders. Registered research facilities (N=1,110) account for 14% of the total USDA certificates. The final 19% consists of licensed dealers (N=763; 9%) and registered carriers or interim handlers (N=788; 10%). The number and distribution of types of certificates varies across states. The largest number of exhibitors and dealers are in Florida, while the largest number of breeders are in Missouri. California has the largest number of research registered facilities. Finally, a comparison of the estimated number of animals in the US that are pets, used in agriculture, exhibition, and research suggests that animals in research are between 0.07-2.3% of the total. The comparison also highlights areas in which public information about captive animals in the US is uneven or missing altogether. Together, the current report provides a concise view of basic information and data relevant to public consideration and policy decisions about animals housed in the set of captive settings to which the AWA applies.
Identifying Genes in Published Pathway Figure Images
Authors: Riutta Anders , Hanspers Kristina , Pico Alexander R.
Published: July 2018

BACKGROUND

Pathway figures are commonly found in the biomedical literature providing intuitive models of complex processes in a visually concise format. The contents of a pathway figure often reflect the key findings and relevant context of an article. Unfortunately, the vast majority of pathway figures are drawn as one-off static images despite freely available pathway tools and resources, thus rendering their contents inaccessible to search, data mining and downstream analysis.

APPROACH

Leveraging advances in optical character recognition and domain expertise in pathway modeling, we devised an approach to identify genes in published pathway figures. The approach was optimized against a set of figure images obtained from PubMed Central and tested against a set of 400 curated pathways with known content from WikiPathways (F-measure 95.2%).

RESULTS

Applied to 3982 published pathway figures spanning a four year period, our approach identified 29,189 gene symbols representing 4159 unique gene identifiers. The gene content unlocked from just this small sample of published figures includes novel and diverse pathway associations unmatched by any pathway database. Our approach over doubled the number of genes associated with the articles containing these figures as compared to combined annotations available from PubMed and PubTator. Encouraged by these initial results, we plan to scale the approach to make the molecular contents of the continuing stream of published pathway figures more accessible.
High efficiency genomic editing in Epstein-Barr virus-transformed lymphoblastoid B cells
Authors: Johnston Andrew D. , Simões-Pires Claudia A. , Suzuki Masako , Greally John M.
Published: July 2018

While lymphoblastoid cell lines (LCLs) represent a valuable resource for population genetic studies, they are usually regarded as difficult for CRISPR-mediated genomic editing. It would be valuable to be able to take the results of their functional variant studies and test them in the same LCLs. We describe a protocol using a single-stranded donor oligonucleotide (ssODN) strategy for ‘scarless’ editing in LCLs. The protocol involves optimized transfection, flow cytometric sorting of transfected cells to single cells in multi-well plates and growth in conditioned, serum-rich medium, followed by characterization of the clones. Amplicon sequencing reveals the relative proportions of alleles with different editing events, with sequencing of DNA from clones showing the frequencies of events in individual cells. We find 12/60 (20%) of clones selected in this manner to have the desired ssODN-mediated recombination event. Long-range PCR of DNA at the edited locus and of RT-PCR products for the gene traversing the edited locus reveals 3/6 characterized clones (50%) to have large structural mutations of the region that are missed by sequencing just the edited site. The protocol does not require the use of lentiviruses or stable transfection, and makes LCLs a realistic cell type for consideration for CRISPR-mediated genomic targeting.
Two Novel α-L-Arabinofuranosidases from Bifidobacterium longum subsp. longum belonging to Glycoside Hydrolase Family 43 Cooperatively Degrade Arabinan
Authors: Komeno Masahiro , Hayamizu Honoka , Fujita Kiyotaka , Ashida Hisashi
Published: July 2018

Arabinose-containing poly-or oligosaccharides are suitable carbohydrate sources for Bifidobacterium longum subsp. longum, though their degradation pathways are poorly understood. In this study, we found that the gene expression levels of bllj 1852 and bllj 1853 from B. longum subsp. longum JCM 1217 were enhanced in the presence of arabinan. Both genes encode previously uncharacterized glycoside hydrolase (GH) family 43 enzymes. Subsequently, we cloned those genes and characterized the recombinant enzymes expressed in Escherichia coli. Both enzymes exhibited α-L-arabinofuranosidase activity toward synthetic p-nitrophenyl glycoside, but the specificities for L-arabinofuranosyl linkages were different. BLLJ_1852 catalyzed the hydrolysis of α1,2- and α1,3-L-arabinofuranosyl linkages found in the side chains of arabinan and arabinoxylan. BLLJ_1852 released L-arabinose 100 times faster from arabinan than from arabinoxylan but did not act on arabinogalactan. BLLJ_1853 catalyzed the hydrolysis of α1,5-L-arabinofuranosyl linkages found on the arabinan backbone. BLLJ_1853 released L-arabinose from arabinan but not from arabinoxylan or arabinogalactan. Both enzyme activities were largely suppressed with EDTA treatment, suggesting that they require divalent metal ions. BLLJ_1852 was moderately activated in the presence of all divalent cations tested, whereas BLLJ_1853 activity was inhibited by Cu2+. The GH43 domains of BLLJ_1852 and BLLJ_1853 are classified into GH43 subfamilies 27 and 22, respectively, but hardly share similarity with other biochemically characterized members in the corresponding subfamilies.

IMPORTANCE

We identified two novel α-L-arabinofuranosidases from B. longum subsp. longum JCM 1217 that act on different linkages in arabinan. These enzymes may be required for efficient degradation and assimilation of arabinan in the probiotic bifidobacteria. The genes encoding these enzymes are located side-by-side in a gene cluster involved in metabolic pathways for plant-derived polysaccharides, which may confer adaptability in adult intestines.
Discovery of a bacterial peptide as a modulator of GLP-1 and metabolic disease
Authors: Tomaro-Duchesneau Catherine , LeValley Stephanie L. , Röth Daniel , Sun Liang , Horrigan Frank T. , Kalkum Markus , Hyser Joseph M. , Britton Robert A.
Published: July 2018

Early work in germ-free rodents highlighted the gut microbiota’s importance in metabolic disease, including Type II Diabetes Mellitus (T2DM) and obesity. Glucagon-like peptide-1 (GLP-1) is an incretin secreted by enteroendocrine L-cells lining the gastrointestinal epithelium. GLP-1 has important functions including promoting insulin secretion, insulin sensitivity, and β-cell mass, while inhibiting gastric emptying and appetite. We set out to elucidate how the microbiota can modulate GLP-1 secretion, with the goal to identify microbial strains with GLP-1 stimulatory activity as a metabolic disease therapeutic. Over 1500 human-derived strains were isolated from fecal, breast milk, and colon and intestinal biopsy samples from healthy individuals. In vitro screening for GLP-1 modulation was performed by incubating bacterial cell-free supernatants with NCI H716 human L-cells. Approximately 45 strains capable of increasing GLP-1 levels, measured by ELISA, were discovered. Interestingly, all positive strains were identified as Staphylococcus epidermidis by 16S rRNA sequencing. Non-GLP-1 stimulatory S. epidermidis strains were also identified. Mass spectrometry analysis identified a 3 kDa peptide, termed GLP-1 stimulating peptide (GspA), present in GLP-1 positive but absent in GLP-1 neutral S. epidermidis. Studies in human L-cells and intestinal enteroids demonstrated that GspA alone is sufficient to enhance GLP-1 secretion. When administered in high-fat-fed mice, GspA-producing S. epidermidis significantly reduced markers associated with obesity and T2DM, including adiposity and hyperinsulinemia. Further characterization of GspA suggests a GLP-1 stimulatory action via calcium signaling. The presented results identify a novel host-microbe interaction which may ultimately lead to the development of a microbial peptide-based therapeutic for obesity and T2DM.

Importance

The human gastrointestinal microbiota has been shown to modulate metabolic disease, including Type II Diabetes Mellitus and obesity, through mechanisms involving gut hormone secretion. We initiated this study to identify bacterial strains that can stimulate one of these hormones, glucagon-like peptide-1. We first identified that some strains of Staphylococcus epidermidis have such stimulatory activity. We then found that these strains could be used in a mouse model of high-fat feeding to reduce markers associated with metabolic disease, including adiposity and elevated insulin levels. We also identified the peptide from S. epidermidis that stimulates glucagon-like peptide-1 and propose a mode of action through calcium signaling. This newly identified microbial-derived peptide and host-microbe interaction provide a promising therapeutic approach against Type II Diabetes Mellitus and obesity.
A Fast Likelihood Method to Reconstruct and Visualize Ancestral Scenarios
Authors: Ishikawa Sohta A. , Zhukova Anna , Iwasaki Wataru , Gascuel Olivier
Published: July 2018

The reconstruction of ancestral scenarios is widely used to study the evolution of characters along a phylogenetic tree. In the likelihood framework one commonly uses the marginal posterior probabilities of the character states, and the joint reconstruction of the most likely scenario. Both approaches are somewhat unsatisfactory. Marginal reconstructions provide users with state probabilities, but these are difficult to interpret and visualize, while joint reconstructions select a unique state for every tree node and thus do not reflect the uncertainty of inferences.

We propose a simple and fast approach, which is in between these two extremes. We use decision-theory concepts and the Brier criterion to associate each node in the tree to a set of likely states. A unique state is predicted in the tree regions with low uncertainty, while several states are predicted in the uncertain regions, typically around the tree root. To visualize the results, we cluster the neighboring nodes associated to the same states and use graph visualization tools. The method is implemented in the PastML program and web server.

The results on simulated data consistently show the accuracy and robustness of the approach. The method is applied to large tree comprising 3,619 sequences from HIV-1M subtype C sampled worldwide, which is processed in a few minutes. Results are very convincing: we retrieve and visualize the main transmission routes of HIV-1C; we demonstrate that drug resistance mutations mostly emerge independently under treatment pressure, but some resistance clusters are found, corresponding to transmissions among untreated patients.
microRNA regulation of persistent stress-enhanced memory
Authors: Sillivan Stephanie E. , Jamieson Sarah , de Nijs Laurence , Jones Meghan , Snijders Clara , Klengel Torsten , Joseph Nadine F. , Krauskopf Julian , Kleinjans Jos , Vinkers Christiaan H. , Boks Marco P.M. , Geuze Elbert , Vermetten Eric , Ressler Kerry J. , Rutten Bart P.F. , Rumbaugh Gavin , Miller Courtney A.
Published: July 2018

Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. Using a stress-enhanced fear learning protocol that results in differential susceptibility in inbred mice, we integrated small-RNA sequencing with quantitative proteomics on basolateral amygdala tissue collected one month after training. We identified persistently changed microRNAs, including mir-135b-5p, and predicted target proteins associated with PTSD-like heightened fear expression. Functional manipulations of mir-135b-5p bidirectionally modulated stress-associated memory. mir-135b-5p is expressed in human amygdala and its passenger strand was elevated in serum from a well-characterized military PTSD cohort. miR-135b-5p is a therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.

One Sentence Summary

mir-135 can be manipulated to weaken persistent, stress-associated memory and serve as a biomarker of PTSD.
MYCN Amplification and ATRX Mutations are Incompatible in Neuroblastoma
Authors: Zeineldin Maged , Federico Sara , Chen Xiang , Fan Yiping , Xu Beisi , Stewart Elizabeth , Zhou Xin , Jeon Jongrye , Griffiths Lyra , Easton John , Mulder Heather , Yergeau Donald , Liu Yanling , Wu Jianrong , Ryn Collin Van , Naranjo Arlene , Hogarty Michael D. , Kamiński Marcin M. , Valentine Marc , Pruett-Miller Shondra M. , Pappo Alberto , Zhang Jinghui , Clay Michael R. , Bahrami Armita , Lee Seungjae , Shelat Anang , George Rani E. , Mardis Elaine R. , Wilson Richard K. , Downing James R. , Dyer Michael A. ,   for the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project
Published: July 2018

Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate with high-risk disease and poor prognosis. Here we show that ATRX mutations and MYCN amplification are mutually exclusive across all ages and stages in neuroblastoma. Using human cell lines and mouse models, we found that elevated MYCN expression and ATRX mutations are incompatible. Elevated MYCN levels promote metabolic reprogramming, mitochondrial dysfunction, reactive-oxygen species generation, and DNA-replicative stress. The combination of replicative stress caused by defects in the ATRX–histone chaperone complex and that induced by MYCN-mediated metabolic reprogramming leads to synthetic lethality. Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.
A unifying model to predict multiple object orienting behaviors in tethered flies
Authors: Poehlmann Andreas , Soselisa Sayan J. , Fenk Lisa M. , Straw Andrew D.
Published: July 2018

Individual visual processing circuits forDrosophilalocomotor control have been studied in detail, but contributions of specific pathways to multiple behaviors remain unclear. To address how both flexible and stereotyped visual object response behaviors potentially share neural circuit components, we investigated models of asymmetric motion responses. Such models have predicted that object fixation without explicit neural encoding of position is possible. Here we investigated what neural circuits and behaviors are consistent with such models. In behavioral experiments on tethered flying flies, we found close correspondence between T4/T5-neuron dependent turning responses to objects and model output for high frequency perturbations. Furthermore, we found that the model predicts key results from several published accounts of stereotyped object tracking. The concurrence of experiment and theory suggests a neural substrate and algorithmic basis for stereotyped object tracking and informs future studies of flexible visual behaviors and their neural bases.
Urinary protein changes in the early phase of smoking-induced Chronic Obstructive Pulmonary Disease in a rat model
Authors: Huang He , Wang Ting , Gao Youhe
Published: July 2018

Chronic obstructive pulmonary disease (COPD) is a group of severe respiratory diseases. Identifying COPD through early urinary biomarkers by proteomics technology may help to reduce the mortality rate of the disease, improve the quality of life of patients and reduce the burden on society. Urine samples from a COPD rat model induced by smoking were taken at week 2, week 4 and week 8. By LC-MS/MS, 15 differential proteins with human orthologs were identified. After smoking for 2 weeks when there were no significant pathological changes, 8 differential proteins were identified: 2 proteins had been reported to be markers of COPD, while 4 proteins were associated with COPD. After smoking for 4 weeks, which is when slight pathological changes were observed, 7 differential proteins were identified: 3 of them were reported to be associated with COPD, while 1 protein had been reported to be a marker of COPD. After smoking for 8 weeks, there were significant pathological changes: 5 differential proteins were identified, 3 of which were reported to be associated with COPD. The results of this study suggest that differential urinary proteins may provide important clues for the early diagnosis of COPD.
Differential effects of conspecific and heterospecific density on the development of Aedes aegypti and Aedes albopictus larvae
Authors: Paton Robert S , Heath Katherine , Wilson Anthony J , Bonsall Michael B
Published: August 2018

Between-species competition shapes the distribution and abundance of populations. Aedes aegypti and Ae. albopictus are vectors of pathogens such as dengue and are known to compete at the larval stage.

The outcome of this inter-species competition has been found to be context dependent, with the strength and direction changing with resource availability and type. We were motivated by this uncertainty, and aimed to elucidate the magnitude and mechanism of competition.

We manipulated the larval density of mixed and single species cohorts of larvae, measuring the effects on survivorship and development time. Unlike other related studies, we adjusted the feeding regime so that the per-capita resource availability was kept constant across all density treatments, at a level sufficient for successful development. This ensured that each larvae at least had the opportunity to gain the requisite resources for pupation.

Our analysis found that Ae. aegypti suffered notably less mortality due to intra- and interspecific competition. For both species, intra- and interspecific competition led to the survival of faster developing individuals, with the exception that slower developing Ae. albopictus larvae survived when exposed a combination of both high con- and heterospecific densities.

These results show that the competition between Ae. aegypti and Ae. albopictus can still occur even when resources are theoretically adequate for development. This suggests that larvae can alter resource seeking and consumption parameters when exposed to high densities of conspecifics and heterospecifics, leading to contest competition. Evidence for resource-independent mechanisms of competition such as crowding are also found, as is evidence for the importance of demographic stochasticity in population processes.
TreeN93: a non-parametric distance-based method for inferring viral transmission clusters
Authors: Moshiri Niema
Published: August 2018

Highly-used methods for identifying transmission clusters of rapidly-evolving pathogens from molecular data require a user-determined distance threshold. The choice of threshold is often motivated by epidemiological information known a priori, which may be unfeasible for epidemics without rich epidemiological information. TreeN93 is a fully non-parametric distance-based method for transmission cluster identification that scales polynomially.

Availability and implementation

TreeN93 is implemented in Python 3 and is freely available at https://github.com/niemasd/TreeN93/.

Contact

niemamoshiri@gmail.com
Neural competitive queuing of ordinal structure underlies skilled sequential action
Authors: Kornysheva Katja , Bush Dan , S Meyer Sophie , Sadnicka Anna , Barnes Gareth , Burgess Neil
Published: August 2018

The fluent retrieval and production of movement sequences is essential for a variety of daily activities such as speech, tool-use, musical and athletic performance, but the neural mechanisms underlying sequence planning remain elusive. Here, participants learned sequences of finger presses with different timings and different finger orders, and reproduced them in a magneto-encephalography (MEG) scanner. We classified the MEG patterns immediately preceding each press in the sequence, and examined their dynamics over the production of the whole sequence. Our results confirm a role for the ‘competitive queuing’ of upcoming action representations in the production of learned motor sequences, extending previous computational and non-human primate recording studies to non-invasive measures in humans. In addition, we show that competitive queuing does not simply reflect specific motor actions, but representations of higher-level sequential order that generalise across different motor sequences. Finally, we show that the quality of competitive queuing predicts participants’ production accuracy, and originates from parahippocampal and cerebellar sources. These results suggest that the brain learns and produces multiple behavioural sequences by flexibly combining representations of specific actions with more abstract, parallel representations of sequential structure.
Encircling the regions of the pharmacogenomic landscape that determine drug response
Authors: Fernández-Torras Adrià , Duran-Frigola Miquel , Aloy Patrick
Published: August 2018

Background

The integration of large-scale drug sensitivity screens and genome-wide experiments is changing the field of pharmacogenomics, revealing molecular determinants of drug response without the need for previous knowledge about drug action. In particular, transcriptional signatures of drug sensitivity may guide drug repositioning, prioritize drug combinations and point to new therapeutic biomarkers. However, the inherent complexity of transcriptional signatures, with thousands of differentially expressed genes, makes them hard to interpret, thus giving poor mechanistic insights and hampering translation to clinics.

Methods

To simplify drug signatures, we have developed a network-based methodology to identify functionally coherent gene modules. Our strategy starts with the calculation of drug-gene correlations and is followed by a pathway-oriented filtering and a network-diffusion analysis across the interactome.

Results

We apply our approach to 189 drugs tested in 671 cancer cell lines and observe a connection between gene expression levels of the modules and mechanisms of action of the drugs. Further, we characterize multiple aspects of the modules, including their functional categories, tissue-specificity and prevalence in clinics. Finally, we prove the predictive capability of the modules and demonstrate how they can be used as gene sets in conventional enrichment analyses.

Conclusions

Network biology strategies like module detection are able to digest the outcome of large-scale pharmacogenomic initiatives, thereby contributing to their interpretability and improving the characterization of the drugs screened.
Dissection of complex, fitness-related traits in multiple Drosophila mapping populations offers insight into the genetic control of stress resistance
Authors: Everman Elizabeth , McNeil Casey , Hackett Jennifer , Bain Clint , Macdonald Stuart J
Published: August 2018

We leverage two complementary Drosophila melanogaster mapping panels to genetically dissect starvation resistance, an important fitness trait. Using >1600 genotypes from the multiparental Drosophila Synthetic Population Resource (DSPR) we map numerous starvation stress QTL that collectively explain a substantial fraction of trait heritability. Mapped QTL effects allowed us to estimate DSPR founder phenotypes, predictions that were correlated with the actual phenotypes of these lines. We observe a modest phenotypic correlation between starvation resistance and triglyceride level, traits that have been linked in previous studies. However, overlap among QTL identified for each trait is low. Since we also show that DSPR strains with extreme starvation phenotypes differ in desiccation resistance and activity level, our data imply multiple physiological mechanisms contribute to starvation variability. We additionally exploited the Drosophila Genetic Reference Panel (DGRP) to identify sequence variants associated with starvation resistance. Consistent with prior work these sites rarely fall within QTL intervals mapped in the DSPR. We were offered a unique opportunity to directly compare association mapping results across labs since two other groups previously measured starvation resistance in the DGRP. We found strong phenotypic correlations among studies, but extremely low overlap in the sets of genomewide significant sites. Despite this, our analyses revealed that the most highly-associated variants from each study typically showed the same additive effect sign in independent studies, in contrast to otherwise equivalent sets of random variants. This consistency provides evidence for reproducible trait-associated sites in a widely-used mapping panel, and highlights the polygenic nature of starvation resistance.
A macrophage-based screen identifies antibacterial compounds selective for intracellularSalmonellaTyphimurium
Authors: Ellis Michael J. , Tsai Caressa N. , Johnson Jarrod W. , French Shawn , Elhenawy Wael , Porwollik Steffen , Andrews-Polymenis Helene , McClelland Michael , Magolan Jakob , Coombes Brian K. , Brown Eric D.
Published: August 2018

SalmonellaTyphimurium (S. Tm) evades the innate immune response by residing within host phagocytes. To identify inhibitors of intracellularS. Tm growth, we performed parallel chemical screens againstS. Tm growing in macrophage-mimicking media and within macrophages. These screens identified novel antibacterials, and revealed that antibiotics with limited Gram-negative coverage are active against intracellularS. Tm. Screening of aS. Tm deletion library in the presence of one compound, metergoline, revealed that outer membrane perturbation enhanced activityin vitro. Combined with our observation of atypical cell surface characteristics of intracellularS. Tm, our work indicates that the bacterial outer membrane is permeabilized within macrophages. We show that metergoline targets the bacterial cytoplasmic membrane, and prolongs animal survival during a systemicS. Tm infection. This work highlights the predictive nature of intracellular screens forin vivoefficacy, and uncovers new aspects of bacterial physiology of intracellularS. Tm.
The effect of transitioning to renewable energy consumption on the Nigerian oil and gas exports
Authors: Waziri Bukar Zanna , Hassan Aminu , Kouhy Reza
Published: July 2018

Purpose

Net energy importing countries (NEICs) pursue strategic policies to reduce the consumption of energy from conventional sources and increase that of renewable energy to attain energy security and sustainable development. However, net energy exporting countries (NEECs) rely substantially on the proceeds realised from oil and gas exports to mainly NEICs to finance government activities. This paper aims to investigate the effect of increased consumption of renewable energy in developed NEICs on the Nigeria’s oil and gas exports.

Design/methodology/approach

The study was undertaken by analysing macro-economic annual time-series data set (1980-2014) using autoregressive distributed lag (ARDL) bounds testing approach.

Findings

Both the short-run and the long-run results of the ARDL modelling reveal that renewable energy consumption in developed NEICs is affecting Nigeria’s oil and gas exports negatively, thereby causing significant decrease in the amounts of revenue being generated therefrom.

Research limitations/implications

Like most empirical studies, the conduct of this research has encountered some challenges. Thus, the use of rather small sample in terms of period covered (1980-2014), annual frequency of data and focus on one NEEC (Nigeria) are the key limitations of this paper. While the first two challenges were dealt with by using ARDL, future research can focus on other NEECs to extend the study.

Practical implications

The findings have several policy implications, including the need for Nigeria to focus on developing internal market trajectories to increase domestic utilisation of its conventional energy rather than depending on external markets. The results also suggest the need for public policymakers to develop a strategic plan that will effectively address the external economic threat arising from the influence of global energy transition.

Originality/value

To the best of the authors’ knowledge, this paper represents the first effort to empirically examine the effect of renewable energy consumption by developed NEICs on the Nigeria’s oil and gas exports. The paper contributes to the literature by providing insight into and documenting evidence that the world is taking transitioning to cleaner energy sources very seriously.
Immigration detention and liberal democracies
Authors: Ikegwuruka Cosmas
Published: July 2018

Purpose

Liberal democratic states have involved the use of private companies for purposes of detention and the debate is whether such involvement is only for immigration control or whether they are primarily for macro-economic benefits. This paper aims to present the argument that a State wishing to detain migrants must do so within the purview of immigration control and in conformity to international human rights standards rather than other latent reasons such as macro-economic benefits. The exponential growths of immigration detention over the years, this paper argues, smack of latent reasons with unarguably macro-economic benefits accruing to these States.

Design/methodology/approach

The methodology is doctrinal research focusing on immigration detention and privatization. Doctrinal research is library-based and reliance will be placed on primary and secondary materials such as legislations, case laws, soft laws on the one hand and textbooks, journals, articles, legal encyclopedia, databases and many valuable websites on the other hand.

Findings

Findings have been made of similarities in State practice between the UK, the USA and Australia and conclude that the trend is worrying given that privatization of the detention estate lends credence to the fact that growing international prison industry influences prison and detention policies.

Research limitations/implications

These have portent implications for the violations of the rights of detainees and weaken the protection of rights under international human rights law.

Originality/value

The originality of this paper lies in its ability to unravel the legitimacy of immigration detention in the face of privatization and macro-economic benefits accruing to States, thereby querying the availability of the rights of migrants within the remit of State practice.
Trends in learning analytics practices: a review of higher education institutions
Authors: Wong Billy Tak-Ming , Li Kam Cheong , Choi Samuel Ping-Man
Published: July 2018

Purpose

This paper aims to review and identify the major patterns and trends in learning analytics practices in higher education institutions. The review covers the characteristics of the institutions, as well as the characteristics and outcomes of the learning analytics practices.

Design/methodology/approach

This research collected literature published in 2011-2016 which reported learning analytics practices from Scopus and Google Scholar, covering a total of 47 institutions, and categorised the information about the relevant institutions and practices.

Findings

The results show that most of the institutions were public ones in the USA and the UK of various sizes and offering different levels of study. The learning analytics practices were mainly institution-wide, apart from a small number focusing on selected courses. The purposes of the practices were mainly to enhance the effectiveness of learning support and administration, followed by facilitating students’ learning progress. The most common types of data collected for the practices were students’ academic behaviours and their background information. Positive outcomes were reported for a majority of the practices, and the most frequent ones being an increase in cost-effectiveness and understanding of students’ learning behaviours. Other outcomes included the improvement of student retention, timely feedback and intervention, support for informed decision-making and the provision of personalised assistance to students.

Originality/value

The results provide an overview of the use of learning analytics in the higher education sector. They also reveal the trends in learning analytics practices, as well as future research directions.
Corporate diversification
Authors: Smith Garrett C.C. , Coy Jeffrey M.
Published: August 2018

Purpose

The purpose of this study is to compare two theories that relate the proportion of diversified firms in the economy and the implied discount for diversified firms: the first is a real-options model predicting a positive relationship between the discount and management’s choice to operate a diversified firm; the second is based on catering theory, in which a negative relationship is predicted, as management is attentive to investor preference concerning diversified firms.

Design/methodology/approach

This study proposes a new aggregate measure of the diversification discount. The authors’ measure allows for decomposition of the discount into firm-level mispricing, industry-level mispricing and long-run fundamental value components.

Findings

Results support a catering theory of diversification. The discount appears to be the result of firm-level mispricing. Thus, providing an explanation for why, in light of the observed discount, a large number of diversified firms persist.

Originality/value

To the authors’ knowledge, this is the first study to provide evidence that firm-level mispricing may drive the observed diversification discount.
Water retention effects on elastic properties of Opalinus shale
Authors: Yurikov Alexey , Lebedev Maxim , Pervukhina Marina , Gurevich Boris
Published: July 2018

Shales play an important role in many engineering applications such as nuclear waste, CO2 storage and oil or gas production. Shales are often utilized as an impermeable seal or an unconventional reservoir. For both situations, shales are often studied using seismic waves. Elastic properties of shales strongly depend on their hydration, which can lead to substantial structural changes. Thus, in order to explore shaly formations with seismic methods, it is necessary to understand the dependency of shale elastic properties on variations in hydration. In this work, we investigate structural changes in Opalinus shale at different hydration states using laboratory measurements and X‐ray micro‐computed tomography. We show that the shale swells with hydration and shrinks with drying with no visible damage. The pore space of the shale deforms, exhibiting a reduction in the total porosity with drying and an increase in the total porosity with hydration. We study the elastic properties of the shale at different hydration states using ultrasonic velocities measurements. The elastic moduli of the shale show substantial changes with variations in hydration, which cannot be explained with a single driving mechanism. We suggest that changes of the elastic moduli with variations in hydration are driven by multiple competing factors: (1) variations in total porosity, (2) substitution of pore‐filling fluid, (3) change in stiffness of contacts between clay particles and (4) chemical hardening/softening of clay particles. We qualitatively and quantitatively analyse and discuss the influence of each of these factors on the elastic moduli. We conclude that depending on the microstructure and composition of a particular shale, some of the factors dominate over the others, resulting in different dependencies of the elastic moduli on hydration.
Why are demographic Allee effects so rarely seen in social animals?
Authors: Lerch Brian A. , Nolting Ben C. , Abbott Karen C.
Published: July 2018

Allee effects in group‐living species are common, but little is known about the way in which Allee effects at the group‐level scale up to influence population dynamics. Most notably, it remains unclear whether component Allee effects within groups (where some component of fitness in small groups decreases with decreasing group size) will translate into a population‐level demographic Allee effect (where per capita fitness in small populations decreases with decreasing overall population size).

The African wild dog (Lycaon pictus) is an obligate cooperative breeder that lives in packs and has a multitude of group‐level component Allee effects. With the African wild dog as a case study, we use models to determine the effect that group structure has on the population dynamics of social animals and, specifically, whether Allee effects operating at the group level lead to a demographic Allee effect at the population level.

We developed a suite of models to analyse the population dynamics of group‐living species, as well as comparable “packless” models lacking group structure. By comparing these models, we can identify how Allee effects within groups influence population‐level dynamics.

Our results show that group structure buffers populations against a demographic Allee effect, because mechanisms affecting birth and mortality are more strongly influenced by group size than population size. We find that interactions between groups are vital in determining the relationship between density dependence within groups and density dependence at the population level.

As sufficiently large groups provide protection against positive density dependence, even at low overall population sizes, our results have conservation implications for group‐living species, as they suggest group size is a necessary population feature to consider in efforts to manage population size. Furthermore, we provide novel insight regarding the role that dispersal and pack size variation play in the buffering nature of social structure in groups subject to Allee effects.
No role for xylem embolism or carbohydrate shortage in temperate trees during the severe 2015 drought
Authors: Dietrich Lars , Delzon Sylvain , Hoch Guenter , Kahmen Ansgar
Published: July 2018

Temperate forests are predicted to experience an increased frequency and intensity of climate change‐induced summer droughts and heat waves in the near future. Yet, while previous studies clearly showed a high drought sensitivity of different temperate tree species, the vulnerability of the physiological integrity of these trees remains unclear.

Here, we assessed the sensitivity of six temperate tree species to severe water limitation during three consecutive growing seasons, including the exceptional 2015 central European summer drought and heat wave. Specifically, we assessed stem increment growth, sap flow, water potentials, hydraulic vulnerability, and nonstructural carbohydrate contents in leaves and branches to determine how mature temperate trees responded to this exceptional weather event and how the observed responses relate to variation in xylem embolism and carbohydrate economy.

We found that the trees' predawn water potentials reached their minimum values during the 2015 summer drought and most species reduced their sap flow by up to 80%. Also, increment growth was strongly impaired with the onset of the drought in all species. Despite the strong responses in the trees' growth and water relations, all species exhibited minimum midday shoot water potentials well away from values associated with severe embolism (P50). In addition, we detected no distinct decrease in nonstructural carbohydrate contents in leaves, bark, and stems throughout the drought event.

Synthesis. This study shows that mature individuals of six common central European forest tree species strongly reacted to a severe summer drought by reducing their water consumption and stopping growth. We found, however, no indications for xylem embolism or carbohydrate depletion in these trees. This suggests, that xylem embolism formation and carbohydrate reserve depletion are not routine in temperate trees during seasonal strong drought and reveals a low vulnerability of the physiological integrity of temperate trees during drought events as we describe here.