bluuebunny/crossref_metadata_2025 huggingface dataset:
Embedding the International Investment Regime
Authors: Jean-Michel Marcoux
Published: March 2018

Amidst numerous calls for reform of international investment law, the United Nations Conference on Trade and Development (UNCTAD) has become a multilateral forum deeply involved in seeking responses to address a growing unease regarding the governance of foreign investment. Further to a focus on sustainable development policies and paths for reform of investor–state dispute settlement, UNCTAD’s efforts have culminated in a roadmap for reform. This chapter aims to explore the potential impact of this reform on the international investment regime. It argues that the reform proposed by UNCTAD reflects an unambiguous need to embed international investment law in social concerns, in line with the second part of a double movement between economic liberalism and social protection. Such a countermovement nevertheless remains weak, as the proposed reform appears to generally constitute a norm-governed change that is unlikely to shake the fundamental principles and norms underlying the international investment regime.
Investment Treaties and the Internal Vetting of Regulatory Proposals
Authors: Gus Van Harten , Dayna Nadine Scott
Published: March 2018

This chapter discusses three findings of a study on whether investor–state dispute settlement (ISDS) has contributed to changes in government decision-making about environmental protection in Ontario, Canada. These findings are: (1) ISDS puts pressure on government decision-making due to the financial and political risks, the opportunity costs that ISDS creates for government, and as a consequence of the career risks that it creates for individual officials; (2) ISDS pressures may be overcome, especially where there is a strong political commitment to a proposed measure backed by legal capacity to scrutinize purported ISDS risks critically and throughout the policymaking process; (3) the assessment of trade or ISDS risks involves value choices and ISDS-generated changes to decision-making processes elevate the role of ‘trade values’ over competing values associated with health and environmental protection.
Expropriation in Brazil’s Cooperation and Facilitation Investment Agreements
Authors: Ely Caetano Xavier Jr , José Augusto Fontoura Costa
Published: March 2018

The recent Cooperation and Facilitation Investment agreements signed by Brazil display some innovative features, such as the exclusion of investor-state dispute settlement and the inclusion of corporate social responsibility issues. However, the expropriation provisions have not been improved to the same extent. The lack of precise definitions for expropriation, the omission of any reference to indirect expropriation, and the recurring reference to national legal systems represent some of the main problems. The strategy of revising the provision for expropriation as the agreements were negotiated and signed has resulted in a questionable decision to intentionally exclude indirect expropriation from the scope of the agreements and has created inconsistencies among the different texts. The success of the agreements is still unknown, but sidestepping expropriation is not a good beginning.
Trends in FDI, Home Country Measures and Competitive Neutrality
Authors: Karl P Sauvant , Persephone Economou , Ksenia Gal , Shawn Lim , Witold P Wilinski
Published: March 2018

This chapter begins by describing and assessing trends in foreign direct investment (FDI) in 2012. It then turns to an understudied but increasing area of concern in investment policy—home country measures (HCMs), which influence and often direct investment flows to certain destinations. These measures have an effect on “competitive neutrality” by affecting companies' decisions about where to invest and even about whether to invest; some measures effectively subsidize outward foreign direct investment so long as it is directed in particular ways. The chapter provides a detailed survey of HCMs in the top ten developed countries and the top ten emerging markets, and an analysis of the potential effects of those measures on investment decisions and the policies that home countries seek to effectuate with the establishment of measures that encourage and direct investment.
FDI trends in 2010–2011 and the challenge of investment policies for outward foreign direct investment
Authors: Persephone Economou , Sauvant Karl P
Published: March 2018

This chapter begins with a brief discussion of the latest trends in foreign direct investment (FDI). It then turns to an analysis of policies related to outward foreign direct investment and discusses issues that relate to them. It argues that FDI flows have managed to sustain their recovery in the aftermath of the 2008 financial crisis, but considerable uncertainty about prospects over the next few years remains. Emerging markets have strengthened their position in the global FDI landscape in terms of both inward and outward investment. Outward FDI policies can play a vital role in creating an environment that allows domestic firms that have the capability to become multinational enterprises (MNEs) to invest overseas and strengthen their competitiveness. The challenge is to ensure that MNE efficiency and competitiveness gains from outward FDI translate into benefits for the home economies.
Constraining hydrostatic mass bias of galaxy clusters with high-resolution X-ray spectroscopy
Authors: Ota Naomi , Nagai Daisuke , Lau Erwin T
Published: March 2018

Gas motions in galaxy clusters play important roles in determining the properties of the intracluster medium (ICM) and in the constraint of cosmological parameters via X-ray and Sunyaev–Zel’dovich effect observations of galaxy clusters. The Hitomi measurements of gas motions in the core of the Perseus Cluster have provided new insights into the physics in galaxy clusters. The XARM mission, equipped with the Resolve X-ray micro-calorimeter, will continue Hitomi’s legacy by measuring ICM motions through Doppler shifting and broadening of emission lines in a larger number of galaxy clusters, and at larger radii. In this work, we investigate how well we can measure bulk and turbulent gas motions in the ICM with XARM, by analyzing mock XARM simulations of galaxy clusters extracted from cosmological hydrodynamic simulations. We assess how photon counts, spectral fitting methods, multiphase ICM structure, deprojections, and region selection affect the measurements of gas motions. We first show that XARM is capable of recovering the underlying spherically averaged turbulent and bulk velocity profiles for dynamically relaxed clusters to within ∼50% with a reasonable amount of photon counts in the X-ray emission lines. We also find that there are considerable azimuthal variations in the ICM velocities, where the velocities measured in a single azimuthal direction can significantly deviate from the true value even in dynamically relaxed systems. Such variation must be taken into account when interpreting data and developing observing strategies. We will discuss the prospect of using the upcoming XARM mission to measure non-thermal pressure and to correct for the hydrostatic mass bias of galaxy clusters. Our results are broadly applicable for future X-ray missions, such as Athena and Lynx.
Comparison of the Efficacy and Efficiency of the Use of Virtual Reality Simulation With High-Fidelity Mannequins for Simulation-Based Training of Fiberoptic Bronchoscope Manipulation
Authors: Jiang Bailin , Ju Hui , Zhao Ying , Yao Lan , Feng Yi
Published: March 2018

Introduction

This study compared the efficacy and efficiency of virtual reality simulation (VRS) with high-fidelity mannequin in the simulation-based training of fiberoptic bronchoscope manipulation in novices.

Methods

Forty-six anesthesia residents with no experience in fiberoptic intubation were divided into two groups: VRS (group VRS) and mannequin (group M). After a standard didactic teaching session, group VRS trained 25 times on VRS, whereas group M performed the same process on a mannequin. After training, participants' performance was assessed on a mannequin five consecutive times. Procedure times during training were recorded as pooled data to construct learning curves. Procedure time and global rating scale scores of manipulation ability were compared between groups, as well as changes in participants' confidence after training.

Results

Plateaus in the learning curves were achieved after 19 (95% confidence interval = 15–26) practice sessions in group VRS and 24 (95% confidence interval = 20–32) in group M. There was no significant difference in procedure time [13.7 (6.6) vs. 11.9 (4.1) seconds, t′ = 1.101, P = 0.278] or global rating scale [3.9 (0.4) vs. 3.8 (0.4), t = 0.791, P = 0.433] between groups. Participants' confidence increased after training [group VRS: 1.8 (0.7) vs. 3.9 (0.8), t = 8.321, P < 0.001; group M = 2.0 (0.7) vs. 4.0 (0.6), t = 13.948, P < 0.001] but did not differ significantly between groups.

Conclusions

Virtual reality simulation is more efficient than mannequin in simulation-based training of flexible fiberoptic manipulation in novices, but similar effects can be achieved in both modalities after adequate training.
Collective movement in ecology: from emerging technologies to conservation and management
Authors: Westley Peter A. H. , Berdahl Andrew M. , Torney Colin J. , Biro Dora
Published: March 2018

Recent advances in technology and quantitative methods have led to the emergence of a new field of study that stands to link insights of researchers from two closely related, but often disconnected disciplines: movement ecology and collective animal behaviour. To date, the field of movement ecology has focused on elucidating the internal and external drivers of animal movement and the influence of movement on broader ecological processes. Typically, tracking and/or remote sensing technology is employed to study individual animals in natural conditions. By contrast, the field of collective behaviour has quantified the significant role social interactions play in the decision-making of animals within groups and, to date, has predominantly relied on controlled laboratory-based studies and theoretical models owing to the constraints of studying interacting animals in the field. This themed issue is intended to formalize the burgeoning field of collective movement ecology which integrates research from both movement ecology and collective behaviour. In this introductory paper, we set the stage for the issue by briefly examining the approaches and current status of research in these areas. Next, we outline the structure of the theme issue and describe the obstacles collective movement researchers face, from data acquisition in the field to analysis and problems of scale, and highlight the key contributions of the assembled papers. We finish by presenting research that links individual and broad-scale ecological and evolutionary processes to collective movement, and finally relate these concepts to emerging challenges for the management and conservation of animals on the move in a world that is increasingly impacted by human activity.

This article is part of the theme issue ‘Collective movement ecology’.
The importance of individual variation in the dynamics of animal collective movements
Authors: del Mar Delgado Maria , Miranda Maria , Alvarez Silvia J. , Gurarie Eliezer , Fagan William F. , Penteriani Vincenzo , di Virgilio Agustina , Morales Juan Manuel
Published: March 2018

Animal collective movements are a key example of a system that links two clearly defined levels of organization: the individual and the group. Most models investigating collective movements have generated coherent collective behaviours without the inclusion of individual variability. However, new individual-based models, together with emerging empirical information, emphasize that within-group heterogeneity may strongly influence collective movement behaviour. Here we (i) review the empirical evidence for individual variation in animal collective movements, (ii) explore how theoretical investigations have represented individual heterogeneity when modelling collective movements and (iii) present a model to show how within-group heterogeneity influences the collective properties of a group. Our review underscores the need to consider variability at the level of the individual to improve our understanding of how individual decision rules lead to emergent movement patterns, and also to yield better quantitative predictions of collective behaviour.

This article is part of the theme issue ‘Collective movement ecology’.
Friendship across species borders: factors that facilitate and constrain heterospecific sociality
Authors: Sridhar Hari , Guttal Vishwesha
Published: March 2018

Our understanding of animal sociality is based almost entirely on single-species sociality. Heterospecific sociality, although documented in numerous taxa and contexts, remains at the margins of sociality research and is rarely investigated in conjunction with single-species sociality. This could be because heterospecific and single-species sociality are thought to be based on fundamentally different mechanisms. However, our literature survey shows that heterospecific sociality based on mechanisms similar to single-species sociality is reported from many taxa, contexts and for various benefits. Therefore, we propose a conceptual framework to understand conspecific versus heterospecific social partner choice. Previous attempts, which are all in the context of social information, model partner choice as a trade-off between information benefit and competition cost, along a single phenotypic distance axis. Our framework of partner choice considers both direct grouping benefits and information benefits, allows heterospecific and conspecific partners to differ in degree and qualitatively, and uses a multi-dimensional trait space analysis of costs (competition and activity matching) and benefits (relevance of partner and quality of partner). We conclude that social partner choice is best-viewed as a continuum: some social benefits are obtainable only from conspecifics, some only from dissimilar heterospecifics, while many are potentially obtainable from conspecifics and heterospecifics.

This article is part of the theme issue ‘Collective movement ecology'.
Identification of a newly described OsHV-1 µvar from the North Adriatic Sea (Italy)
Authors: Abbadi Miriam , Zamperin Gianpiero , Gastaldelli Michele , Pascoli Francesco , Rosani Umberto , Milani Adelaide , Schivo Alessia , Rossetti Emanuele , Turolla Edoardo , Gennari Lorenzo , Toffan Anna , Arcangeli Giuseppe , Venier Paola
Published: March 2018

The surveillance activities for abnormal bivalve mortality events in Italy include the diagnosis of ostreid herpesvirus type 1 (OsHV-1) in symptomatic oysters. OsHV-1-positive oysters (Crassostrea gigas) were used as a source for in vivo virus propagation and a virus-rich sample was selected to perform shotgun sequencing based on Illumina technology. Starting from this unpurified supernatant sample from gills and mantle, we generated 3.5 million reads (2×300 bp) and de novo assembled the whole genome of an Italian OsHV-1 microvariant (OsHV-1-PT). The OsHV-1-PT genome encodes 125 putative ORFs, 7 of which had not previously been predicted in other sequenced Malacoherpesviridae. Overall, OsHV-1-PT displays typical microvariant OsHV-1 genome features, while few polymorphisms (0.08 %) determine its uniqueness. As little is known about the genetic determinants of OsHV-1 virulence, comparing complete OsHV-1 genomes supports a better understanding of the virus pathogenicity and provides new insights into virus–host interactions.
The genetic basis of the human-cannabis relationship
Authors: Henry Philippe
Published: March 2018

Cannabis can elicit various reactions in different consumers. In order to shed light on the mechanisms underlying the human-cannabis relationship, we begin to investigate the genetic basis of this differential response. The web-based platform OpenSNP was used to collect selfreported genetic and phenotypic data. Participants either reported a positively or negative affinity to cannabis. A total of 26 individuals were retained, 10 of which indicated several negative responses and the remaining 16 indicating strong affinity for Cannabis. A total of 325’895 single nucleotide polymorphisms (SNPs) were retained. The software TASSEL 5 was used to run a genome-wide association study (GWAS), with a generalized liner model (GLM) and1000 permutations. The analysis yielded a set of 45 SNPs that were significantly associated with the reported affinity to cannabis, including one strong outlier found in the MYO16 gene. A diagnostic process is proposed by which individuals can be assessed for their affinity to cannabis. We believe this type of tool may be helpful in alleviating some of the stigma associated with cannabis use in individuals sensitive to THC and other cannabis constituents such as myrcene, which may potentiate negative responses.
Tendency towards being a “Morning person” increases risk of Parkinson’s disease: evidence from Mendelian randomisation
Authors: Noyce AJ , Kia DA , Heilbron K , Jepson JEC , Hemani G ,   The International Parkinson’s Disease Genomics Consortium,   The 23andMe Research Team, Hinds DA , Lawlor DA , Davey Smith G , Hardy J , Singleton A , Nalls MA , Wood NW
Published: March 2018

Background

Circadian rhythm may play a role in neurodegenerative diseases such as Parkinson’s disease (PD). Chronotype is the behavioural manifestation of circadian rhythm and Mendelian randomisation (MR) involves the use of genetic variants to explore causal effects of exposures on outcomes. This study aimed to explore a causal relationship between chronotype and coffee consumption on risk of PD.

Methods

Two-sample MR was undertaken using publicly available GWAS data. Associations between genetic instrumental variables (IV) and “morning person” (one extreme of chronotype) were obtained from the personal genetics company 23andMe, Inc., and UK Biobank, and consisted of the per-allele odds ratio of being a “morning person” for 15 independent variants. The per-allele difference in log-odds of PD for each variant was estimated from a recent meta-analysis. The inverse variance weight method was used to estimate an odds ratio (OR) for the effect of being a “morning person” on PD. Additional MR methods were used to check for bias in the IVW estimate, arising through violation of MR assumptions. The results were compared to analyses employing a genetic instrument of coffee consumption, because coffee consumption has been previously inversely linked to PD.

Findings

Being a “morning person” was causally linked with risk of PD (OR 1⋅27; 95% confidence interval 1⋅06-1⋅51; p=0⋅012). Sensitivity analyses did not suggest that invalid instruments were biasing the effect estimate and there was no evidence for a reverse causal relationship between liability for PD and chronotype. There was no robust evidence for a causal effect of high coffee consumption using IV analysis, but the effect was imprecisely estimated (OR 1⋅12; 95% CI 0⋅89-1⋅42; p=0⋅22).

Interpretation

We observed causal evidence to support the notion that being a “morning person”, a phenotype driven by the circadian clock, is associated with a higher risk of PD. Further work on the mechanisms is warranted and may lead to novel therapeutic targets.

Funding

No specific funding source.
Competing endogenous RNA network: Potential entrants to gene editing in Hepatocellular Carcinoma Gene editing of ceRNA in Hepatocellular Carcinoma
Authors: Shafei Ayman El-Sayed , Matboli Marwa , Ali Mahmoud A. , Nagy Ziad , Reda Maged , Salah Mohamed , Hamdy Ahmed , Abdelgawad Mahmoud , Ashry Ahmed , Tarek Mohammad , Saber Osama , Azazy Ahmed , Mohamed Badr , Hassan Mohmed K. , El-Khazragy Nashwa , El-Khamisy Sherif
Published: March 2018

Background

Hepatocellular Carcinoma (HCC) is the leading cause of cancer deaths worldwide as well as in Egypt. We aimed to use Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) gene editing technique to induce forced down-regulation of the circRNA which consequently modified miRNA expression in HepG2 cell line to prove the regulatory relationship between the RNA parts of an in silico-detected competing endogenous RNA network in HCC

Method

We first retrieved hsa_circ_0000064-miR-1285-TRIM2 mRNA from public microarray databases followed by in silico modelling to mimic the regulation kinetics of cirRNA associated ceRNA network. Secondly, we performed polymerase chain reaction (PCR)-based amplification of synthetic fragments, Gibson assembly of both CRISPR and non CRISPR based circuits, E-coli transformation, plasmid purification, HePG2 cell line transfection. Finally Expression levels of the chosen RNAs in hepatocellular carcinoma (HCC) cell line, HepG2, were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the cytotoxic effect was validated by viability assay.TRIM2 protein expression was proved by immunohistochemistry and flowcytometry.

Results

Induction of hsa_circ_0000064 into HepG2 cell line via CRISPR-and non-CRISPR mediated synthetic circuit resulted in statistically significant decrease in cell number and, then, cellular viability with marked increase in hsa_circ_0000064 and TRIM2 mRNA levels and concomitant decrease in miR-1285 expression in HepG2 cell line compared with control (p<0.0). Moreover exogenous expression of hsa_circ_0000064 in HepG2 cell line showed increased expression of the tumor suppressor protein, TRIM2.

Conclusions

Our integrative approach, including in silico data analysis and experimental validation proved that CRISPR-mediated synthetic circuit-based overexpression of hsa_circ_0000064 was more efficient than conventional transient transfection, representing a promising therapeutic strategy for HCC.

Data Availability

Our Data was made available online on the IGEM wiki of team AFCM-EGYPT:http://2017.igem.org/Team:AFCM-Egypt. Synthetic parts have been submitted to IGEM Parts Registry.

Financial Disclosure

The project was funded by Armed Forces College of Medicine AFCM, Zewail City of Science and Technology, National Research Center NRC, VitaBiotics, PHARCO Pharmaceuticals, Sim Era and DANUB Paintings. IDT provided 20 kb of DNA synthesis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Deciphering signaling specificity with interpretable deep neural networks
Authors: Luo Yunan , Ma Jianzhu , Liu Yang , Ye Qing , Ideker Trey , Peng Jian
Published: March 2018

Protein kinase phosphorylation is a prevalent post-translational modification (PTM) regulating protein function and transmitting signals throughout the cell. Defective signal transductions, which are associated with protein phosphorylation, have been revealed to link to many human diseases, such as cancer. Defining the organization of the phosphorylation-based signaling network and, in particular, identifying kinase-specific substrates can help reveal the molecular mechanism of the signaling network. Here, we present DeepSignal, a deep learning framework for predicting the substrate specificity for kinase/SH2 sequences with or without mutations. Empowered by the memory and selection mechanism of recurrent neural network, DeepSignal can identify important specificity-defining residues to predict kinase specificity and changes upon mutations. Evaluated on several public benchmark datasets, DeepSignal significantly outperforms current methods on predicting substrate specificity on both kinase and SH2 domains. Further analysis in The Cancer Genome Atlas (TCGA) demonstrated that DeepSignal is able to aggregate mutations on both kinase/SH2 domains and substrates to quantify binding specificity changes, predict cancer genes related to signaling transduction, and identify novel perturbed pathways.

Availability

Implementation of DeepSignal is athttps://github.com/luoyunan/DeepSignal
Characterisation of gut microbiota of farmed Chinook salmon using metabarcoding
Authors: Ciric Milica , Waite David , Draper Jenny , Jones John Brian
Published: March 2018

With the growing importance of aquaculture worldwide, characterisation of the microbial flora of high-value aquaculture species and identification of gut flora shifts induced by changes in fish physiology or nutrition is of special interest.

Here we report the first metabarcoding survey of the intestinal bacteria of Chinook salmon (Oncorhynchus tshawytscha), an economically important aquacultured species. The microbiota of 30 farmed Chinook salmon from a single cohort was surveyed using metabarcode profiling of the V3-V4 hypervariable region of the bacterial 16S rRNA gene. Seawater, feed and intestinal samples, and controls were sequenced in quadruplicate to assess both biological and technical variation in the microbial profiles.

Over 1,000 operational taxonomic units (OTUs) were identified within the cohort, providing a first glimpse into the gut microbiota of farmed Chinook salmon. The taxonomic distribution of the salmon microbiota was reasonably stable, with around two thirds of individuals dominated by members of the familyVibrionaceae.

This survey was performed amid a summer heat wave, during which the fish exhibited reduced feeding. Although the sampled fish appeared healthy, they had minimal intestinal content, and the observed intestinal flora may represent the microbiota of fasting and stressed fish. Limited comparison betweenMycoplasmaandVibriosequences from the Chinook salmon gut and published microbial sequences from the intestines of a variety of fish species (including Atlantic salmon) indicated that despite the starvation and temperature variations, the replacement ofVibriowithMycoplasmais occurring within expected ecological parameters and does not necessarily reflect colonisation by atypical microbes.

DATA SUMMARY

Raw sequences from Chinook salmon intestinal microbiome 16S survey generated on the Illumina platform are publically available through NCBI Sequence Read Archive (SRA) database:

Bioproject PRJNA421844

SRA study SRP134829

https://www.ncbi.nlm.nih.gov/bioproject/PRJNA421844

IMPACT STATEMENT

Although 16S metabarcoding surveys are becoming routine, little is still known about the microbiota of fish. This is the first survey of the intestinal microbiota of Chinook salmon, a species native to the Pacific Northwest which is farmed in New Zealand and Chile. While most intestinal microbiota studies are performed on faecal material, we directly sampled the intestine epithelium and content.

During the time of sampling, the farmed fish population was experiencing stress from a summer heat wave and had little intestinal content. Over 1,000 operational taxonomic units (OTUs) were identified within the intestines of the cohort, providing a first glimpse into the gut microbiota of farmed Chinook salmon.

We believe this survey will be of interest not only to those interested in fish biology and aquaculture, but also as an addition to the ongoing debate in the literature on sampling and DNA extraction methods for challenging samples.
Cyclophilins A and B Oppositely Regulate Renal Tubular Epithelial Phenotype
Authors: Sarró Eduard , Durán Mónica , Rico Ana , Croatt Anthony J. , Nath Karl A. , Teresa Salcedo Maria , Gundelach Justin H. , Batlle Daniel , Bram Richard J. , Meseguer Anna
Published: March 2018

Cyclophilins (Cyp) are peptidil-prolyl-isomerases and the intracellular receptors for the immunosuppressant Cyclosporine-A (CsA), which produces epithelial-mesenchymal-transition (EMT) and renal tubule-interstitial fibrosis. Since CsA inhibits Cyp enzymatic activity, we hypothesized that Cyp could be involved in EMT and fibrosis. Here, we demonstrate that CypB is a critical regulator of tubule epithelial cell plasticity on the basis that: i) CypB silencing caused epithelial differentiation in proximal tubule-derived HK-2 cells, ii) CypB silencing prevented TGFβ-induced EMT in HK-2, and iii) CypB knockdown mice exhibited reduced UUO-induced inflammation and kidney fibrosis. By contrast, silencing of CypA induces a more undifferentiated phenotype and favors TGFβ effects. EMT mediators Slug and Snail were up-regulated in CypA-silenced cells, while in CypB silencing, Slug, but not Snail, was down-regulated; thus, reinforcing the role of Slug in kidney fibrosis. CypA regulates Slug through its PPIase activity whereas CypB depends on its ER location, where interacts with calreticulin, a calcium modulator which is involved in TGFβ signaling. In conclusion, this work uncovers new roles for CypA and CypB in modulating proximal tubular cell plasticity.
Discovery and Characterization of Novel Lignocellulose-Degrading Enzymes from the Porcupine Microbiome
Authors: Thornbury Mackenzie , Sicheri Jacob , Guinard Caroline , Mahoney David , Routledge Francis , Curry Matthew , Elaghil Mariam , Boudreau Nicholas , Tsai Angela , Slaine Patrick , Finlayson-Trick Emma , Getz Landon , Cook Jamie , Rohde John , McCormick Craig
Published: March 2018

Plant cell walls are comprised of cellulose, hemicellulose, and lignin, collectively known as lignocellulose. Microorganisms degrade these components to liberate sugars to meet metabolic demands. Using a metagenomic sequencing approach, we previously demonstrated that the microbiome of the North American porcupine (Erethizon dorsatum) is replete with novel lignocellulose-degrading enzymes. Here, we report the identification, synthesis and partial characterization of four genes from the porcupine microbiome encoding putative novel lignocellulose-degrading enzymes, including a β-xylanase, endoxylanase, β-glucosidase, and an ⍺-L-arabinofuranosidase. These genes were identified via conserved catalytic domains associated with cellulose and hemicellulose degradation. We cloned the putative β-xylanase into the pET26b(+) plasmid, enabling inducible gene expression inEscherichia coli(E. coli) and periplasmic localization. We demonstrated IPTG-inducible accumulation of β-xylanase protein but failed to detect xylobiose degrading activity in a reporter assay. Alternative assays may be required to measure activity of this putative β-xylanase. In this report, we describe how a synthetic metagenomic pipeline can be used to identify novel microbial lignocellulose-degrading enzymes and take initial steps to introduce a hemicellulose-degradation pathway intoE. colito enable biofuel production from wood pulp feedstock.
Strong replicators associated with open chromatin are sufficient to establish an early replicating domain
Authors: Brossas Caroline , Chilaka Sabarinadh , Counillon Antonin , Laurent Marc , Goncalves Coralie , Duriez Bénédicte , Prioleau Marie-Noëlle
Published: March 2018

Vertebrate genomes replicate according to a precise temporal program strongly correlated with their organization into topologically associating domains. However, the molecular mechanisms underlying the establishment of early-replicating domains remain largely unknown. We defined two minimal cis-element modules containing a strong replication origin and chromatin modifier binding sites capable of shifting a targeted mid-late replicating region for earlier replication. When inserted side-by-side, these modules acted in cooperation, with similar effects on two late-replicating regions. Targeted insertions of these two modules at two chromosomal sites separated by 30 kb brought these two modules into close physical proximity and induced the formation of an early-replicating domain. Thus, combinations of strong origins and cis-elements capable of opening the chromatin structure are the basic units of early-replicating domains, and are absent from late-replicated regions. These findings are consistent with those of genome-wide studies mapping strong initiation sites and open chromatin marks in vertebrate genomes.
Porter 5: state-of-the-art ab initio prediction of protein secondary structure in 3 and 8 classes
Authors: Torrisi Mirko , Kaleel Manaz , Pollastri Gianluca
Published: March 2018

Motivation

Although Secondary Structure Predictors have been developed for more than 60 years, current ab initio methods have still some way to go to reach their theoretical limits. Moreover, the continuous effort towards harnessing ever increasing data sets and more sophisticated, deeper Machine Learning techniques, has not come to an end.

Results

Here we present Porter 5, the last release of one of the best performing ab initio secondary structure predictor. Version 5 achieves 84% accuracy (84% SOV) when tested on 3 classes, and 73% accuracy (82% SOV) on 8 classes, on a large independent set, significantly outperforming all the most recent ab initio predictors we have tested.

Availability

The web and standalone versions of Porter5 are available at http://distilldeep.ucd.ie/porter.

Contact

name@bio.com

Supplementary information

Supplementary data are available at Bioinformatics online.
Soil salinity inhibits plant shade avoidance
Authors: Hayes Scott , Tween Adrian Louis , van Gelderen Kasper , de Vries Michel , Prat Salomé , Schuurink Robert. C. , Testerink Christa , Pierik Ronald
Published: March 2018

Global food production is set to keep increasing despite a predicted decrease in total arable land [1]. To achieve higher production, denser planting will be required on increasingly degraded soils. When grown in dense stands, crops elongate and raise their leaves in an effort to reach sunlight, a process termed shade-avoidance [2]. Shade is perceived by a reduction in the ratio of red (R) to (FR) light and results in the stabilisation of a class of transcription factors known as PHYTOCHROME INTERACTING FACTORs (PIFs) [3,4]. PIFs activate the expression of auxin biosynthesis genes [4,5] and enhance auxin sensitivity [6], which promotes cell wall loosening and drives elongation growth. Despite our molecular understanding of shade-induced growth, little is known about how this developmental programme is integrated with other environmental factors.

Here we demonstrate that low levels of NaCl in soil strongly impair the ability of plants to respond to shade. This block is dependent upon abscisic acid (ABA) signalling and the canonical ABA signalling pathway. Low R:FR light enhances the expression of a positive regulator of the brassinosteroid (BR) signalling pathway, BRASSINOSTEROID SIGNALLING KINASE 5 (BSK5). We found that ABA inhibits BSK5 up-regulation and interferes with GSK3-like kinase inactivation by the BR pathway, thus leading to a suppression of PIF function. By demonstrating a link between the ABA and BR-signalling pathways this study provides an important step forward in our understanding of how environmental cues are integrated into plant development.
Mesenchymal stromal cell remodeling of a gelatin hydrogel microenvironment defines an artificial hematopoietic stem cell niche
Authors: Gilchrist Aidan E. , Lee Sunho , Hu Yuhang , Harley Brendan A.C.
Published: March 2018

Hematopoietic stem cells (HSCs) reside in the bone marrow within discrete niches defined by a complex milieu of external signals including biophysical cues, bound and diffusible biomolecules, and heterotypic cell-cell interactions. Recent studies have shown the importance of autocrine-mediated feedback of cell-secreted signals and the interplay between matrix architecture and biochemical diffusion on hematopoietic stem cell activity. Autocrine and paracrine signaling from HSCs and niche-associated mesenchymal stromal cells (MSCs) have both been suggested to support HSC maintenance in vivo and in vitro. Here we report the development of a library of methacrylamide-functionalized gelatin (GelMA) hydrogels to explore the balance between autocrine feedback and paracrine signals from co-encapsulated murine bone marrow MSCs on murine HSCs. The use of a degradable GelMA hydrogel enables the possibility for significant MSC-mediated remodeling, yielding dynamic shifts in the matrix environment surrounding HSCs. We identify a combination of an initially low-diffusivity hydrogel and a 1:1 HSPC:MSC seeding ratio as conducive to enhanced HSC population maintenance and quiescence. Further, gene expression and serial mechanical testing data suggests that MSC-mediated matrix remodeling is significant for the long-term HSC culture, reducing HSC autocrine feedback and potentially enhancing MSC-mediated signaling over 7-day culture in vitro. This work demonstrates the design of an HSC culture system that couples initial hydrogel properties, MSC co-culture, and concepts of dynamic reciprocity mediated by MSC remodeling to achieve enhanced HSC maintenance.

One Sentence Summary

Coupling effects of hydrogel biotransport, heterotypic cell culture, and matrix remodeling enhances hematopoietic stem cell culture and quiescence.
A comprehensive toolkit to enable MinION sequencing in any laboratory
Authors: Schalamun Miriam , Kainer David , Beavan Eleanor , Nagar Ramawatar , Eccles David , Rathjen John P. , Lanfear Robert , Schwessinger Benjamin
Published: March 2018

Long-read sequencing technologies are transforming our ability to assemble highly complex genomes. Realising their full potential relies crucially on extracting high quality, high molecular weight (HMW) DNA from the organisms of interest. This is especially the case for the portable MinION sequencer which potentiates all laboratories to undertake their own genome sequencing projects, due to its low entry cost and minimal spatial footprint. One challenge of the MinION is that each group has to independently establish effective protocols for using the instrument, which can be time consuming and costly. Here we present a workflow and protocols that enabled us to establish MinION sequencing in our own laboratories, based on optimising DNA extractions from a challenging plant tissue as a case study. Following the workflow illustrated we were able to reliably and repeatedly obtain > 8.5 Gb of long read sequencing data with a mean read length of 13 kb and an N50 of 26 kb. Our protocols are open-source and can be performed in any laboratory without special equipment. We also illustrate some more elaborate workflows which can increase mean and average read lengths if this is desired. We envision that our workflow for establishing MinION sequencing, including the illustration of potential pitfalls, will be useful to others who plan to establish long-read sequencing in their own laboratories.
Cullin1 represses systematic inflammasome activation by binding and catalyzing NLRP3 ubiquitination
Authors: Wan Pin , Zhang Qi , Liu Weiyong , Jia Yaling , Wang Tianci , Wang Wenbiao , Pan Pan , Yang Ge , Xiang Qi , Huang Siyu , Yang Qingyu , Zhang Wei , Liu Fang , Wu Kailang , Liu Yingle , Wu Jianguo
Published: March 2018

Activation of the NLRP3 inflammasome is a key process of host immune response, the first line of defense against cellular stresses and pathogen infections. However, excessive inflammasome activation damages the hosts, and thus it must be precisely controlled. The mechanism underlying the repression of systematic inflammasome activation remains largely unknown. This study reveals that CUL1, a key component of the SCF E3 ligase, plays a critical role in regulation of the inflammasome. CUL1 suppresses the inflammasome activation in HEK293T cells, inhibits endogenous NLRP3 in macrophages, and represses inflammatory responses in C57BL/6 mice. Under normal physiological conditions, CUL1 interacts with NLRP3 to disrupt the inflammasome assembly, and catalyzes NLRP3 ubiquitination to repress the inflammasome activation. In response to inflammatory stimuli, CUL1 disassociates from NLRP3 to release the repression of NLRP3 inflammasome activation. This work reveals a distinct mechanism underlying the repression of inflammasome activation under physiological conditions and the induction of inflammasome activation in response to inflammatory stimuli, and thus provides insights into the prevention and treatment of infectious and inflammatory diseases.
All-optical electrophysiology for high-throughput functional characterization of human iPSC-derived motor neuron model of ALS
Authors: Kiskinis Evangelos , Kralj Joel M. , Zou Peng , Weinstein Eli N. , Zhang Hongkang , Tsioras Konstantinos , Wiskow Ole , Ortega J. Alberto , Eggan Kevin , Cohen Adam E.
Published: March 2018

Human induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch clamp electrophysiology. Here we describe an optimized all-optical electrophysiology, “Optopatch”, pipeline for high-throughput functional characterization of human iPSC-derived neuronal cultures. We demonstrate the method in a human iPSC-derived motor neuron model of ALS. In a comparison of neurons with an ALS-causing mutation (SOD1 A4V) with their genome-corrected controls, the mutants showed elevated spike rates under weak or no stimulus, and greater likelihood of entering depolarization block under strong optogenetic stimulus. We compared these results to numerical simulations of simple conductance-based neuronal models and to literature results in this and other iPSC-based models of ALS. Our data and simulations suggest that deficits in slowly activating potassium channels may underlie the changes in electrophysiology in the SOD1 A4V mutation.
Crystal structures of alkali metal (Group 1) citrate salts
Authors: Rammohan Alagappa , Kaduk James A.
Published: March 2018

The crystal structures of 16 new alkali metal citrates were determined using powder and/or single crystal techniques. These structures and 12 previously determined citrate structures were optimized using density functional techniques. The central portion of a citrate ion is fairly rigid, while the conformations of the terminal carboxylate groups exhibit no preferences. The citrate–metal bonding is ionic. Trends in metal–citrate coordination are noted. The energy of an O—H...O hydrogen bond is proportional to the square root of the H...acceptor Mulliken overlap population, and a correlation between the hydrogen bond energy and the H...acceptor distance was developed:E(kJ mol−1) = 137.5 (5) − 45.7 (8) (H...A, Å). The hydrogen bond contribution to the crystal energy ranges from 62.815 to 627.6 kJ mol−1 citrate−1and comprises ∼5 to 30% of the crystal energy. The general order of ionization of the three carboxylic acid groups of citric acid is: central, terminal, terminal, although there are a few exceptions. Comparisons of the refined and DFT-optimized structures indicate that crystal structures determined using powder diffraction data may not be as accurate as single-crystal structures.
Involving young people in drug and alcohol research
Authors: Brady Louca-Mai , Templeton Lorna , Toner Paul , Watson Judith , Evans David , Percy-Smith Barry , Copello Alex
Published: March 2018

Purpose

Young people’s involvement should lead to research, and ultimately services, that better reflect young people’s priorities and concerns. Young people with a history of treatment for alcohol and/or drug problems were actively involved in the youth social behaviour and network therapy study. The purpose of this paper is to explore the impact of that involvement on the study and what was learnt about involving young people in drug and alcohol research.

Design/methodology/approach

The initial plan was to form a young people’s advisory group (YPAG), but when this proved problematic the study explored alternative approaches in collaboration with researchers and young people. Input from 17 young people informed all key elements of the study.

Findings

Involvement of young people needs to be dynamic and flexible, with sensitivity to their personal experiences. Engagement with services was crucial both in recruiting young people and supporting their ongoing engagement. This research identified a need to critically reflect on the extent to which rhetorics of participation and involvement give rise to effective and meaningful involvement for young service users. It also highlights the need for researchers to be more flexible in response to young people’s personal circumstances, particularly when those young people are “less frequently heard”.

Research limitations/implications

This research highlights the need for researchers to be more flexible in response to young people’s personal circumstances, particularly when those young people are “less frequently heard”. It highlights the danger of young people in drug and alcohol research being unintentionally disaffected from involvement through conventional approaches and instead suggests ways in which young people could be involved in influencing if and how they participate in research.

Practical implications

There is an apparent contradiction between dominant discourses and cultures of health services research (including patient and public involvement) that often do not sit easily with ideas of co-production and young people-centred involvement. This paper provides an alternative approach to involvement of young people that can help to enable more meaningful and effective involvement.

Originality/value

The flexible and young people-centred model for involvement which emerged from this work provides a template for a different approach. This may be particularly useful for those who find current practice, such as YPAG, inaccessible.
Doctorateness and the DBA: what next?
Authors: Poole Brian
Published: March 2018

Purpose

The purpose of this paper is to examine the extent to which Doctor of Business Administration (DBA) programmes currently offered by UK universities are appropriate to the needs of all stakeholders, including those of the experienced business and management professionals who enrol on them.

Design/methodology/approach

The paper proceeds to its conclusions by scrutinising DBA programme descriptors on UK university websites, by critically reviewing the content of recent academic papers on doctorates in the fields of business and management, and by considering current provision in the light of ongoing debates about the nature of “doctorateness” taking place in the field of doctoral education as a whole.

Findings

On the basis of a detailed review of relevant scholarly literature and of UK university website material, the paper concludes by suggesting, among other things, three possible futures for the DBA: one in which essentially the status quo prevails; a second in which all doctorates carry the award title PhD (though with two variants); and a third in which, in response to views expressed elsewhere in Europe, the current “professional doctorate” in business administration is no longer referred to as a “doctorate” but takes on a new title.

Originality/value

This paper is an original contribution to the debate about the value and purpose of professional doctorates (and, in particular of the DBA) to the professional development of experienced managers and to their skills in research and workplace problem solving and decision making.