bluuebunny/crossref_metadata_2025 huggingface dataset:
Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis
Authors: Al-Amin Md. Mamun , Grandjean Joanes , Klohs Jan , Kim Jungsu
Published: April 2020

Although amyloid beta (Aβ) deposition is one of the major causes of white matter (WM) alterations in Alzheimer’s disease (AD), little is known about the underlying basis of WM damage and its association with global structural connectivity and network topology. We aimed to dissect the contributions of WM microstructure to structural connectivity and network properties in the ArcAβ mice model of Aβ amyloidosis.

We acquired diffusion-weighted images (DWI) of wild type (WT) and ArcAβ transgenic (TG) mice using a 9.4 T MRI scanner. Fixel-based analysis (FBA) was performed to measure fiber tract-specific properties. We also performed three complementary experiments; to identify the global differences in structural connectivity, to compute network properties and to measure cellular basis of white matter alterations.

Transgenic mice displayed disrupted structural connectivity centered to the entorhinal cortex (EC) and a lower fiber density and fiber bundle cross-section. In addition, there was a reduced network efficiency and degree centrality in weighted structural connectivity in the transgenic mice. To further examine the underlying neuronal basis of connectivity and network deficits, we performed histology experiments. We found no alteration in myelination and an increased level of neurofilament light (NFL) in the brain regions with disrupted connectivity in the TG mice. Furthermore, TG mice had a reduced number of perineuronal nets (PNN) in the EC.

The observed FDC reductions may indicate a decrease in axonal diameter or axon count which would explain the basis of connectivity deficits and reduced network efficiency in TG mice. The increase in NFL suggests a breakdown of axonal integrity, which would reduce WM fiber health. Considering the pivotal role of the EC in AD, Aβ deposition may primarily increase NFL release, damaging PNN in the entorhinal pathway, resulting in disrupted structural connectivity.
Oculomotor freezing reflects tactile temporal expectation and aids tactile perception
Authors: Badde Stephanie , Myers Caroline F. , Yuval-Greenberg Shlomit , Carrasco Marisa
Published: April 2020

The oculomotor system keeps the eyes steady in expectation of visual events. Here, recording microsaccades while people performed a tactile, frequency discrimination task enabled us to test whether the oculomotor system shows an analogous preparatory response for unrelated tactile events. We manipulated the temporal predictability of tactile targets using tactile cues, which preceded the target by either constant (high predictability) or variable (low predictability) time intervals. We find that microsaccades are inhibited prior to tactile targets and more so for constant than variable intervals, revealing a tight crossmodal link between tactile temporal expectation and oculomotor action. These findings portray oculomotor freezing as a marker of crossmodal temporal expectation. Moreover, microsaccades occurring around the tactile target presentation are associated with reduced task performance, suggesting that oculomotor freezing mitigates potential detrimental, concomitant effects of microsaccades and revealing a crossmodal coupling between tactile perception and oculomotor action.
Regular physical activity reduces the percentage of spinally projecting neurons that express mu-opioid receptors from the RVM
Authors: Sluka KA , Kolker SJ , Danielson J , Rasmussen L
Published: April 2020

Regular physical activity/exercise is an effective non-pharmacological treatment for individuals with chronic pain. Central inhibitory mechanisms, involving serotonin and opioids, are critical to analgesia produced by regular physical activity. The RVM sends projections to the spinal cord to inhibit or facilitate nociceptive neurons and plays a key role in exercise-induced analgesia. The goal of these studies was to examine if regular physical activity modifies RVM-spinal cord circuitry. Male and female mice received Fluoro-Gold placed on the spinal cord to identify spinally projecting neurons from the rostral ventromedial medulla (RVM) and the nucleus raphe obscuris/nucleus raphe pallidus (NRO/NRP), dermorphin-488 into caudal medulla to identify mu-opioid receptors, and were immunohistochemically stained for either phosphorylated-N-methyl-D-aspartate subunit NR1 (p-NR1) to identify excitatory neurons or tryptophan hydroxylase (TPH) to identify serotonin neurons. The percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH), and the percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH) and Fluoro-Gold was calculated.

Physically active animals were provided running wheels in their cages for 8 weeks and compared to sedentary animals without running wheels. Animals with chronic muscle pain, induced by two intramuscular injections of pH 4.0, were compared to sham controls (pH 7.2). Physically active animals had less mu-opioid expressing neurons projecting to the spinal cord when compared to sedentary animals in the RVM, but not the NRO/NRP. No changes were observed for TPH. These data suggest that regular exercise alters central facilitation so that there is less descending facilitation to result in a net increase in inhibition.

Summary Statement

Physically active animals has less mu-opioid expressing neurons projecting to the spinal cord in the RVM, but not the NRO/NRP, when compared to sedentary animals.
The complete mitochondrial genome sequence ofOryctes rhinoceros(Coleoptera: Scarabaeidae) based on long-read nanopore sequencing
Authors: Filipović Igor , Hereward James P. , Rašić Gordana , Devine Gregor J. , Furlong Michael J. , Etebari Kayvan
Published: April 2020

The coconut rhinoceros beetle (CRB,Oryctes rhinoceros) is a severe and invasive pest of coconut and other palms throughout Asia and the Pacific. The biocontrol agent, Oryctes rhinoceros nudivirus (OrNV), has successfully suppressedO. rhinocerospopulations for decades but new CRB invasions started appearing after 2007. A single-SNP variant within the mitochondrialcox1gene is used to distinguish the recently-invading CRB-G lineage from other haplotypes, but the lack of mitogenome sequence for this species hinders further development of a molecular toolset for biosecurity and management programmes against CRB. Here we report the complete circular sequence and annotation for CRB mitogenome, generated to support such efforts.

Sequencing data were generated using long-read Nanopore technology from genomic DNA isolated from a CRB-G female. The mitochondrial genome was assembled with Flye v.2.5, using the short-read Illumina sequences to remove homopolymers with Pilon, and annotated with MITOS. Independently-generated transcriptome data were used to assess theO. rhinocerosmitogenome annotation and transcription. The aligned sequences of 13 protein-coding genes (PCGs) (with degenerate third codon position) fromO. rhinoceros, 13 other Scarabaeidae taxa and two outgroup taxa were used for the phylogenetic reconstruction with the Maximum likelihood (ML) approach in IQ-TREE and Bayesian (BI) approach in MrBayes.

The complete circular mitochondrial genome ofO. rhinocerosis 20,898 bp-long, with a gene content canonical for insects (13 PCGs, 2 rRNA genes, and 22 tRNA genes), as well as one structural variation (rearrangement oftrnQandtrnI) and a long control region (6,204 bp). Transcription was detected across all 37 genes, and interestingly, within three domains in the control region. ML and BI phylogenies had the same topology, correctly groupingO. rhinoceroswith one other Dynastinae taxon, and recovering the previously reported relationship among lineages in the Scarabaeidae.In silicoPCR-RFLP analysis recovered the correct fragment set that is diagnostic for the CRB-G haplogroup. These results validate the high-quality of the CRB mitogenome sequence and annotation.
A rare mutation in an infant derived HIV-1 envelope glycoprotein alters interprotomer stability and susceptibility to broadly neutralizing antibodies targeting the trimer apex
Authors: Mishra Nitesh , Sharma Shaifali , Dobhal Ayushman , Kumar Sanjeev , Chawla Himanshi , Singh Ravinder , Das Bimal Kumar , Kabra Sushil Kumar , Lodha Rakesh , Luthra Kalpana
Published: April 2020

The envelope glycoprotein (Env) of human immunodeficiency virus-1 (HIV-1) is the sole target of broadly neutralizing antibodies (bnAbs). Several mechanisms, such as acquisition of mutations due to the error prone reverse transcriptase, variability of loop length and alterations in glycan pattern are employed by the virus to shield neutralizing epitopes on the env, to sustain survival and infectivity within the host. Identification of mutations that can lead to viral evasion from host immune response is essential for optimization and engineering of Env based trimeric immunogens. Herein, we report a rare leucine to phenylalanine escape mutation (L184F) at the base of hypervariable loop 2 (population frequency of 0.0045%) in a nine-month-old perinatally HIV-1 infected infant broad neutralizer. The L184F mutation disrupted the intramolecular interaction, stabilizing the trimer apex thereby leading to viral escape from autologous plasma bnAbs and known bnAbs, targeting exclusively the N160 glycan at trimer apex and not any other known epitope. The L184F amino acid change led to acquisition of a relatively open trimeric configuration, often associated with tier 1 HIV-1 isolates and an increased susceptibility to neutralization by polyclonal plasma antibodies of weak neutralizers. While there was no impact of the L184F mutation on free virus transmission, a reduction in cell-to-cell transmission was observed. In conclusion, we report a viral escape mutation that plausibly destabilized the trimer apex and favoured evasion from broadly neutralizing antibodies. Such mutations, though rare, should be taken into consideration while designing an immunogen, based on a stable correctly-folded HIV-1 Env trimer.

Importance

Design of HIV-1 envelope-based immunogens, capable of eliciting broadly neutralizing antibodies (bnAbs), are currently under active research. Some of the most potent bnAbs target the quaternary epitope at the V2 apex of HIV-1 Env trimer. By studying naturally circulating viruses from an HIV-1 perinatally infected infant, with plasma neutralizing antibodies targeted to the V2-apex, we identified a rare leucine to phenylalanine substitution in two out of six functional viral clones, that destabilized the trimer apex. This single amino acid alteration impaired the interprotomeric interactions that stabilize the trimer apex, resulting in an open trimer conformation, and escape from broadly neutralizing autologous plasma antibodies and known V2-apex directed bnAbs, thereby favouring viral evasion of the early bnAb response of the infected host. Defining the mechanisms by which viral mutations influence the sensitivity of HIV-1 to bnAbs is crucial for the development of effective vaccines against HIV-1 infection.
Copy number signature analyses in prostate cancer reveal distinct etiologies and clinical outcomes
Authors: Wang Shixiang , Li Huimin , Song Minfang , He Zaoke , Wu Tao , Wang Xuan , Tao Ziyu , Wu Kai , Liu Xue-Song
Published: April 2020

Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer, however, signatures of cancer genome copy number alteration (CNA) are still elusive in most cancer types, especially in prostate cancer (PC), which is particularly driven by complex genome alterations. Here, a user-friendly open source bioinformatics tool “sigminer” has been constructed for copy number signature extraction, analysis and visualization. Five copy number signatures are identified from human PC genome with this tool. The underlying driving forces for each signature have been illustrated. Sample clustering based on copy number signature exposure revealed considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. Copy number signature analyses provide distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.
Genetic determinism of spontaneous masculinisation in XX female rainbow trout: new insights using medium throughput genotyping and whole-genome sequencing
Authors: Fraslin Clémence , Phocas Florence , Bestin Anastasia , Charles Mathieu , Bernard Maria , Krieg Francine , Dechamp Nicolas , Ciobotaru Céline , Hozé Chris , Petitprez Florent , Milhes Marine , Lluch Jérôme , Bouchez Olivier , Poncet Charles , Hocdé Philippe , Haffray Pierrick , Guiguen Yann , Quillet Edwige
Published: April 2020

Rainbow trout has a male heterogametic (XY) sex determination system controlled by a major sex-determining gene,sdY. Unexpectedly, a few phenotypically masculinised fish are regularly observed in all-female farmed trout stocks. To better understand the genetic determinism underlying spontaneous maleness in XX-rainbow trout, we recorded the phenotypic sex of 20,210 XX-rainbow trout from a French farm at 10 and 15 months post-hatching. The masculinisation rate was 1.45%. We performed two genome-wide association studies (GWAS) using both medium-throughput genotyping (31,811 SNPs) and whole-genome sequencing (WGS, 8.7 million SNPs) on a subsample of 1,139 individuals classified as females, intersex or males. The genomic heritability of maleness ranged between 0.48 and 0.62 depending on the method and number of SNPs used for estimation. At the 31K SNPs level, we detected four QTLs on three chromosomes (Omy1, Omy12 and Omy20). Using WGS information, we narrowed down the positions of the two QTLs detected on Omy1 to 96 kb and 347 kb respectively, with the second QTL explaining up to 14% of the total genetic variance of maleness. Within this QTL, we detected three putative candidate genes,fgfa8, cyp17a1and an uncharacterised protein (LOC110527930), which might be involved in spontaneous maleness of XX-female rainbow trout.
Adversarial Deconfounding Autoencoder for Learning Robust Gene Expression Embeddings
Authors: Dincer Ayse B. , Janizek Joseph D. , Lee Su-In
Published: April 2020

Motivation

Increasing number of gene expression profiles has enabled the use of complex models, such as deep unsupervised neural networks, to extract a latent space from these profiles. However, expression profiles, especially when collected in large numbers, inherently contain variations introduced by technical artifacts (e.g., batch effects) and uninteresting biological variables (e.g., age) in addition to the true signals of interest. These sources of variations, called confounders, produce embeddings that fail to transfer to different domains, i.e., an embedding learned from one dataset with a specific confounder distribution does not generalize to different distributions. To remedy this problem, we attempt to disentangle confounders from true signals to generate biologically informative embeddings.

Results

In this paper, we introduce the AD-AE (AdversarialDeconfoundingAutoEncoder) approach to deconfounding gene expression latent spaces. The AD-AE model consists of two neural networks: (i) an autoencoder to generate an embedding that can reconstruct original measurements, and (ii) an adversary trained to predict the confounder from that embedding. We jointly train the networks to generate embeddings that can encode as much information as possible without encoding any confounding signal. By applying AD-AE to two distinct gene expression datasets, we show that our model can (1) generate embeddings that do not encode confounder information, (2) conserve the biological signals present in the original space, and (3) generalize successfully across different confounder domains. We demonstrate that AD-AE outperforms standard autoencoder and other deconfounding approaches.

Availability

Our code and data are available athttps://gitlab.cs.washington.edu/abdincer/ad-ae.

Contact

abdincer@cs.washington.edu;suinlee@cs.washington.edu
LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade
Authors: Yanatori Izumi , Dhekne Herschel S. , Vides Edmundo G. , Sobu Yuriko , Diez Federico , Pfeffer Suzanne R.
Published: April 2020

Activating mutations in LRRK2 kinase cause Parkinson’s disease. Pathogenic LRRK2 phosphorylates a subset of Rab GTPases and blocks ciliogenesis. Thus, defining novel phospho-Rab interacting partners is critical to our understanding of the molecular basis of LRRK2 pathogenesis. RILPL2 binds with strong preference to LRRK2-phosphorylated Rab8A and Rab10. RILPL2 is a binding partner of the motor protein and Rab effector, Myosin Va. We show here that the globular tail domain of Myosin Va also contains a high affinity binding site for LRRK2-phosphorylated Rab10, and certain tissue-specific Myosin Va isoforms strongly prefer to bind phosphorylated Rab10. In the presence of pathogenic LRRK2, RILPL2 relocalizes to the peri-centriolar region in a phosphoRab10- and Myosin Va-dependent manner. In the absence of phosphoRab10, expression of RILPL2 or depletion of Myosin Va increase centriolar RILPL2 levels, and either condition is sufficient to block ciliogenesis in RPE cells. These experiments show that LRRK2 generated phosphoRab10 dramatically redistributes Myosin Va-RILPL2 complexes to the mother centriole, which may sequester Myosin Va and RILPL2 in a manner that blocks their normal roles in ciliogenesis.
LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion
Authors: Camillo Chiara , Facchinello Nicola , Villari Giulia , Mana Giulia , Gioelli Noemi , Sandri Chiara , Astone Matteo , Tortarolo Dora , Clapero Fabiana , Gays Dafne , Oberkersch Roxana E. , Arese Marco , Tamagnone Luca , Valdembri Donatella , Santoro Massimo , Serini Guido
Published: April 2020

Dynamic modulation of endothelial cell-to-cell and cell-to-extracellular matrix (ECM) adhesion is essential for blood vessel patterning and functioning. Yet, the molecular mechanisms involved in this process have not been completely deciphered. We identify the adhesion G protein-coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of endothelial cell (EC) adhesion and barrier function. In cultured ECs, endogenous LPHN2 localizes at ECM contacts, signals through cAMP/Rap1, and inhibits focal adhesion (FA) formation and nuclear localization of YAP/TAZ transcriptional regulators, while promoting tight junction (TJ) assembly. ECs also express an endogenous LPHN2 ligand, fibronectin-leucine-rich transmembrane 2 (FLRT2), that prevents ECM-elicited EC behaviors in a LPHN2-dependent manner. Vascular ECs oflphn2aknock-out zebrafish embryos become abnormally stretched, display a hyperactive YAP/TAZ pathway, and lack proper intercellular TJs. Consistently, blood vessels are hyperpermeable and intravascularly injected cancer cells extravasate more easily inlphn2anull animals. Thus, LPHN2 ligands, such as FLRT2, may be therapeutically exploited to interfere with cancer metastatic dissemination.

Camillo et al. show that the LPHN2 receptor, upon activation by FLRT2 ligand, inhibits focal adhesion formation and promotes tight junction assembly in endothelial cells. Blood vessels oflphn2anull animals are hyperpermeable and injected cancer cells extravasate more easily.
Dopaminergic Gene Dosage in Autism versus Developmental Delay: From Complex Networks to Machine Learning approaches
Authors: Santos André , Caramelo Francisco , de Melo Joana Barbosa , Castelo-Branco Miguel
Published: April 2020

The neural basis of behavioural changes in Autism Spectrum Disorders (ASD) remains a controversial issue. One factor contributing to this challenge is the phenotypic heterogeneity observed in ASD, which suggests that several different system disruptions may contribute to diverse patterns of impairment between and within study samples. Here, we took a retrospective approach, using SFARI data to study ASD by focusing on participants with genetic imbalances targeting the dopaminergic system. Using complex network analysis, we investigated the relations between participants, Gene Ontology (GO) and gene dosage related to dopaminergic neurotransmission from a polygenic point of view. We converted network analysis into a machine learning binary classification problem to differentiate ASD diagnosed participants from DD (developmental delay) diagnosed participants. Using 1846 participants to train a Random Forest algorithm, our best classifier achieved on average a diagnosis predicting accuracy of 85.18% (sd 1.11%) on a test sample of 790 participants using gene dosage features. In addition, we observed that if the classifier uses GO features it was also able to infer a correct response based on the previous examples because it is tied to a set of biological process, molecular functions and cellular components relevant to the problem. This yields a less variable and more compact set of features when comparing with gene dosage classifiers. Other facets of knowledge-based systems approaches addressing ASD through network analysis and machine learning, providing an interesting avenue of research for the future, are presented through the study.

Lay Summary

There are important issues in the differential diagnosis of Autism Spectrum Disorders. Gene dosage effects may be important in this context. In this work, we studied genetic alterations related to dopamine processes that could impact brain development and function of 2636 participants. On average, from a genetic sample we were able to correctly separate autism from developmental delay with an accuracy of 85%.
Tetramerisation of the CRISPR ring nuclease Csx3 facilitates cyclic oligoadenylate cleavage
Authors: Athukoralage Januka S. , McQuarrie Stuart , Grüschow Sabine , Graham Shirley , Gloster Tracey M. , White Malcolm F.
Published: April 2020

Type III CRISPR systems detect foreign RNA and activate the cyclase domain of the Cas10 subunit, generating cyclic oligoadenylate (cOA) molecules that act as a second messenger to signal infection, activating nucleases that degrade the nucleic acid of both invader and host. This can lead to dormancy or cell death; to avoid this, cells need a way to remove cOA from the cell once a viral infection has been defeated. Enzymes specialised for this task are known as ring nucleases, but are limited in their distribution. Here, we demonstrate that the widespread CRISPR associated protein Csx3, previously described as an RNA deadenylase, is a ring nuclease that rapidly degrades cyclic tetra-adenylate (cA4). The enzyme has an unusual cooperative reaction mechanism involving an active site that spans the interface between two dimers, sandwiching the cA4substrate. We propose the name Crn3 (CRISPR associated ring nuclease 3) for the Csx3 family.
Contrasting response of twoLotus corniculatusL. accessions to combined waterlogging-saline stress
Authors: Antonelli C.J. , Calzadilla P.I. , Campestre M.P. , Escaray F.J. , Ruiz O.A.
Published: April 2020

Waterlogging and salinity impair crops growth and productivity worldwide, being their combined effects larger than the additive effects of both stresses separately. Recently, a newLotus corniculatusaccession has been collected from a coastal area with a high frequency of waterlogging-saline stress events. This population is diploid and has potential to increase nutritional values ofLotuscultivars used as forages. Due to its environmental niche, we hypothesize that this accession would show a better adaptation to combined waterlogging-saline stress compared to another commonly used tetraploidL. corniculatus(cv. San Gabriel). Shoot and root growth under waterlogging, salinity and combined waterlogging-saline treatments were addressed, together with chlorophyll fluorescence and gas exchange measurements. Results showed that salinity and waterlogging effects were more severe for the tetraploid accession, being the differences larger under the combined stress condition. In addition, Na+, Cl−and K+concentrations were measured in young and old leaves, and in roots. A larger accumulation of Na+and Cl−was observed under both saline and combined stress treatments for the tetraploidL. corniculatus, for which ion toxicity effects were evident. The expression of theNHX1andCLCgenes, coding for Na+and Cl−transporters respectively, was only increased in response to combined stress in the diploidL. corniculatusplants, suggesting that ion compartmentalization mechanisms were induced in this accession. As a conclusion, the recent characterizedL. corniculatusmight be used for the introduction of new tolerant traits to combined stresses, in otherLotusspecies used as forage.
LDpred2: better, faster, stronger
Authors: Privé Florian , Arbel Julyan , Vilhjálmsson Bjarni J.
Published: April 2020

Polygenic scores have become a central tool in human genetics research. LDpred is a popular method for deriving polygenic scores based on summary statistics and a matrix of correlation between genetic variants. However, LDpred has limitations that may reduce its predictive performance. Here we present LDpred2, a new version of LDpred that addresses these issues. We also provide two new options in LDpred2: a “sparse” option that can learn effects that are exactly 0, and an “auto” option that directly learns the two LDpred parameters from data. We benchmark predictive performance of LDpred2 against the previous version on simulated and real data, demonstrating substantial improvements in robustness and predictive accuracy compared to LDpred1. We then show that LDpred2 also outperforms other polygenic score methods recently developed, with a mean AUC over the 8 real traits analyzed here of 65.1%, compared to 63.8% for lassosum, 62.9% for PRS-CS and 61.5% for SBayesR. Note that, in contrast to what was recommended in the first version of this paper, we now recommend to run LDpred2 genome-wide instead of per chromosome. LDpred2 is implemented in R package bigsnpr.
Tumor invasion as non-equilibrium phase separation
Authors: Kang Wenying , Ferruzzi Jacopo , Spatarelu Catalina-Paula , Han Yu Long , Sharma Yasha , Koehler Stephan A. , Mitchel Jennifer A. , Butler James P. , Roblyer Darren , Zaman Muhammad H. , Park Jin-Ah , Guo Ming , Chen Zi , Pegoraro Adrian F. , Fredberg Jeffrey J.
Published: April 2020

Tumor invasion depends upon properties of both cells and of the extracellular matrix (ECM). Despite ample evidence that cancer cells can modulate their material state during invasion, underlying biophysical mechanisms remain unclear. Here, we show the potential for coexistence of – and transition between – solid-like, fluid-like, and gas-like phases in invading breast cancer spheroids. Epithelial spheroids are nearly jammed and solid-like in the core but unjam at the periphery to invade as a fluid-like collective. Conversely, post-metastatic spheroids are unjammed and fluid-like in the core and – depending on ECM density – can further unjam and invade as gas-like single cells, or re-jam to invade as a fluid-like collective. A novel jamming phase diagram predicts material phases that are superficially similar to inanimate systems at thermodynamic equilibrium, but here arising in living systems, which exist far from equilibrium. We suggest that non-equilibrium phase separation may provide a unifying physical picture of tumor invasion.

TWO-SENTENCE SUMMARY

Using tumor spheroids invading into an engineered three-dimensional matrix, we show here that the cellular collective exhibits coexistent solid-like, fluid-like, and gas-like phases. The spheroid interior develops spatial and temporal heterogeneities in material phase which, depending upon cell type and matrix density, ultimately result in a variety of phase separation patterns at the invasive front, as captured by a jamming phase diagram.
Efficient gene-environment interaction tests for large biobank-scale sequencing studies
Authors: Wang Xinyu , Lim Elise , Liu Ching-Ti , Sung Yun Ju , Rao Dabeeru C. , Morrison Alanna C. , Boerwinkle Eric , Manning Alisa K. , Chen Han
Published: April 2020

Complex human diseases are affected by genetic and environmental risk factors and their interactions. Gene-environment interaction (GEI) tests for aggregate genetic variant sets have been developed in recent years. However, existing statistical methods become rate limiting for large biobank-scale sequencing studies with correlated samples. We propose efficient Mixed-model Association tests for GEne-Environment interactions (MAGEE), for testing GEI between an aggregate variant set and environmental exposures on quantitative and binary traits in large-scale sequencing studies with related individuals. Joint tests for the aggregate genetic main effects and GEI effects are also developed. A null generalized linear mixed model adjusting for covariates but without any genetic effects is fit only once in a whole genome GEI analysis, thereby vastly reducing the overall computational burden. Score tests for variant sets are performed as a combination of genetic burden and variance component tests by accounting for the genetic main effects using matrix projections. The computational complexity is dramatically reduced in a whole genome GEI analysis, which makes MAGEE scalable to hundreds of thousands of individuals. We applied MAGEE to the exome sequencing data of 41,144 related individuals from the UK Biobank, and the analysis of 18,970 protein coding genes finished within 10.4 CPU hours.
Cyber security and the disaster resilience framework
Authors: Panda Abhilash , Bower Andrew
Published: April 2020

Purpose

The purpose of this paper is to concentrate on the place of cyber security risk in the framework of global commitments adopted in 2015 to reduce disaster risks in an all-hazards approach. It explores the correlations between traditional risks associated with critical infrastructures – as understood by the Sendai framework – cyber security risks and the cascading effects characteristic of today’s complex and interrelated shocks and stresses. It takes a step further, expanding the focus of traditionally understood technological risks to explore cyber security risks, at the heart of our societies’ digital transformations,and showcase opportunities from the European context.

Design/methodology/approach

By reviewing existing literature on cyber security, disaster resilience and cascading disasters, this paper highlights current challenges and good practices undertaken by various governments.

Findings

Understanding disaster risks is a precondition to improving the mitigation of impacts of existing risks and preventing new risks. Effective risk reduction relies on a solid understanding of losses resulting from events to inform future actions, and on the assessment of risks relying on a robust evidence base and state-of-the-art scientific capacity to model and simulate potential hazards. In this context, embedding cyber security risks, and the complexity of cascading impacts in improving the understanding of disaster risks, calls for appropriate methods and tools allowing for a multi-risk and holistic focus to the assessment of risks and the planning of risk management capacities that follow.

Research limitations/implications

Globally and in Europe, focus on interconnected risk and their impacts is steadily increasing. Risk assessments are still conservative; incorporation of cyber resilience into national and local level DRR plans is yet not visible.

Originality/value

Existing research is restricted to cyber security and disaster resilience, as separated subjects. This paper, for the first time, brings together the interconnection between the two topic options to address them.
Criteria for flood warning levels in Vietnam
Authors: Huong Huynh Thi Lan , Dzung Luong Huu
Published: April 2020

Purpose

Determining alarm levels of river floods is considered an effective non-structural measure to prevent and mitigate the damages of flood and inundation. This study aims to propose a holistic approach, a comprehensive review of the factors affecting flooding and flood risk, based on which the water level (WL) is proposed for the flood alarm levels. The corresponding proposed WL to the necessary flood alarm levels is based on observed data, as well as simulated data from statistical methods and hydrological and hydraulic models.

Design/methodology/approach

In this paper, the proposed criteria to delineate WLs corresponding to flood alarm levels include flood magnitude; flood derivation and flood duration; flood risks and damage; correlation with neighboring stations; flood characteristics and local characteristics; and other criteria (flood prevention strategy and flood experience).

Findings

The paper proposed a synthesis approach to determine flood warning levels in Vietnam. The retrieved levels are the basics to revise the Decision 632/2010 of the Vietnam Government on determining water alarm levels for flood prevention. The study proposes a new flood alarm system including revised flood levels at 115 existing stations and new flood levels at 30 additional stations. The proposed flood warning level can help manage the flooding problem in major river systems that supports flood protection and prevention services in Vietnam.

Originality/value

The paper proposed a novel synthesis approach to flood prevention in Vietnam.
Exploring the effects of economic growth, population density and international trade on energy consumption and environmental quality in India
Authors: Rahman Mohammad Mafizur
Published: April 2020

Purpose

This paper aims to investigate the effects of economic growth, population density and international trade on energy consumption and environmental quality in India.

Design/methodology/approach

Taking annual data of 1971-2011, autoregressive distributed lag bounds testing technique is applied to explore the long run link between the series. The Granger causality test is used to determine the direction of causality between the variables.

Findings

The obtained results confirm the cointegration of variables, and economic growth and population density are found to have significant positive effects on energy consumption in both the short and long runs. CO2emissions are also positively and significantly affected by population density and energy consumption, and negatively affected by economic growth.

Originality/value

The paper is original and valuable in the sense that it has considered two relevant additional explanatory variables, namely, population density and trade openness, which got little attention in the past. This research is an improvement over the previous studies because it has looked at the separate effects of explanatory variables on energy consumption, in addition to the effects on carbon emissions. Therefore, the findings of this research are more reliable because this adopted methodology is better and extensive, and the authors have properly addressed the issue of omitted variable bias.
The sustainable development of university student loans based on the evolutionary game
Authors: Zhang Yan , You Xiaoqiong , Wang Wenke , Lin Ting
Published: April 2020

Purpose

National student loans help solve the problem of tuition fees for students from poor families to a great extent. This paper aims to study the behavior of three main players involved in university student loans, namely, universities, banks and students and explores necessary conditions for promoting the steady development of student loans, as well as the sustainability of cooperation and coordination among players, thus promoting the further development of student loans.

Design/methodology/approach

First, from the perspectives of the three related players of banks, students and universities and their behavior, this paper establishes a three-player behavioral evolutionary game model, conducts a sustainable game analysis among the different players, and by replicating the dynamic equations with the Jacobian matrix solve the evolutionarily stable strategy. Finally, applying MATLAB tools, a sensitivity analysis of relevant impacting factors is carried out to explore the influencing mechanism of the sustainable development of student loans.

Findings

To achieve the mechanism of mutual coordination and cooperation between participants, banks need to be guided to actively issue student loans and conduct strict loan review. College students should be encouraged to establish good credit and strengthen penalties should be implemented for violations of regulations. Universities should be encouraged to help banks reduce information asymmetry, promote financial knowledge and student integrity education and promote the sustainable development of national student loans.

Originality/value

This research will help scholars better understand the interaction mechanism among universities, banks and students, and promote the sustainable development of national student loans.
Long-term care in Spain: a reform failure or the regulation of a development path?
Authors: Aguilar-Hendrickson Manuel
Published: April 2020

Purpose

Spain departed from the Southern European tradition of residual long-term care services with the 2006 reform. The paper aims to present the main traits of the reform and its implementation, explores the reasons that may explain why the reform happened and to which extent and why it fell short of expectations.

Design/methodology/approach

The article draws on available literature on the reform and on administrative data to present a complex and nuanced view of the reform process and its limits.

Findings

The reform was actually a measure to enhance and rationalize a preexisting process of social care services development, rather than the creation of a completely new care system. A rapid increase in female labor market participation since the 1990s and the looming demands of a late baby-boom and the subsequent fertility crash appear to be two key factors that explain both the previous development and its bolstering by the reform. The budgetary constraints of the Great Recession and governance problems, linked to a complex and sometimes dysfunctional multilevel governance arrangement, help to understand why the reform bogged down. Nevertheless, the overall balance is more nuanced, and significantly more services are provided 12 years after the reform.

Originality/value

While many assessments of the reform have been negative, putting it into a larger context of social care development, the 2006 Dependency Act has contributed to a significant increase in expenditure and coverage. The impact of budgetary restrictions has been important, but other factors, such as governance arrangements, may explain more of the problems of the implementation.
On being posthuman in human spaces: critical posthumanist social work with interspecies families
Authors: Laing Melissa
Published: April 2020

Purpose

The purpose of this paper is twofold. First, it proposes a critical posthumanist orientation to social work as an approach to address the impediments to care experienced by interspecies families. Secondly, it challenges the anthropocentric assumptions that underpin this exclusion of nonhuman family members in human services disciplines such as social work.

Design/methodology/approach

This article presents primary data from a qualitative study into social work and other human services practice in the family violence and homelessness sectors in the state of Victoria, Australia.

Findings

Social workers undertook companion animal-inclusive practice to counter vulnerability to interspecies families caused by gender- and species-based violence, and by homelessness. Gender- and species-based violence was exacerbated by a lack of refuge options, and contributed to women considering their companion animals to be their children. The vulnerability that homelessness brought upon interspecies families was amplified by stigma within and external to social work and related professions, and the impediment that experiences of homelessness had on being able to provide care for their nonhuman family members. These factors shaped practice with interspecies families. Scope for future practice was also identified.

Research limitations/implications

The research findings can be used to inform policy change that includes consideration of nonhuman family members, as well as critical posthuman program design in social work education.

Originality/value

Companion animal-inclusive practice with interspecies families in social work is an under researched area, and there is little empirical data available on the nature of this work in Australia. This paper addresses this gap by centring social workers' own accounts of practice. This paper has scope to contribute to education in social work and other welfare fields, with the potential to empower students to challenge assumptions about social work being solely focused on human-centred concerns.
Analysis of cassava value chain in Ghana: implications for upgrading smallholder supply systems
Authors: Darko-Koomson Samuel , Aidoo Robert , Abdoulaye Tahirou
Published: April 2020

Purpose

Commercialization of cassava is increasing because of increased urban demand for processed products and increased recognition of the industrial potential of the crop. This study aims to examine the cassava value chain in Ghana and its implications for upgrading.

Design/methodology/approach

A combination of purposive, simple random and snowball sampling methods was adopted to select key actors in the cassava value chain. A semi-structured questionnaire was used to collect primary data. Analysis of the data was largely descriptive, except for profitability of cassava production in selected regions, which was examined by employing gross and net marketing margin analysis. A comprehensive value chain map was generated to show the different product pathways for cassava from the farm gate to the final consumer, and roles of key value chain actors and their relationships were summarized through simple narrations.

Findings

Evidence has shown chains of more than four different channels through which fresh cassava roots move from the farm gate to final consumers. Production of cassava in Ghana is profitable, generating positive net marketing margins across major producing centres. Processing of cassava has both dry and wet/fresh value chains depending on the derived products for the final consumer. There is weak governance system in the cassava value chain in Ghana as majority of actors use spot market transactions in dealing with trading partners. The use of standardized grading and weighing system is very limited in the chain, and limited access to credit is a critical constraint to value chain upgrading.

Research limitations/implications

With the exception of results from the profitability analysis of producers, the findings on marketing margins of other value chain actors may not be generalizable. Future studies could determine the profitability associated with cassava value-adding activities like processing into various forms and explore the possibility of converting waste from processing into energy.

Practical implications

The study includes implications that focus on product and process upgrading efforts by smallholders in the cassava value chain. This paper recommends innovative financing models for smallholders to improve access to microcredit via internal and external funding sources.

Originality/value

This paper reveals specific intervention areas in which smallholders can direct efforts in an attempt to improve the cassava value chain through product, process and functional upgrading.
Macroeconomic responses to fiscal shocks in Portugal
Authors: Bova Elva , Klyviene Violeta
Published: April 2020

Purpose

This study analyses the impact of fiscal shocks on GDP, inflation and interest rates in Portugal over 1995–2017.

Design/methodology/approach

Multipliers are estimated using a structural VAR (SVAR) a' la Blanchard and Perotti (2002) using OECD elasticities. Changes in direct and indirect taxes are considered for fiscal shocks on the revenue side and changes in public consumption, investment and transfers for fiscal shocks on the expenditure side.

Findings

The analysis finds small tax multipliers and larger government consumption multipliers for growth, while short-term responses to shocks in transfer and investment spending are found to be negligible. Fiscal shocks have an ambiguous impact on inflation, and fiscal shocks of an expansionary nature are found to trigger declines in interest rates. The results are robust to different orderings of variables, to the selection of an alternative time period which excludes the financial crisis and to an alternative estimation technique.

Research limitations/implications

A major limitation of the study relates to the relatively short time period which does not allow capturing the impact of possible structural breaks.

Practical implications

This analysis is relevant for countries, like Portugal, that display high debt levels and volatile market sentiment and lack an independent monetary policy.

Originality/value

Overall, the analysis of output multipliers compares well with some other studies conducted on the Portuguese economy and confirms the importance of the disposable income channel in the transmission of fiscal shocks to the rest of the economy. The study is one of the first to focus also on the implications of fiscal shocks on inflation and long-term interest rates. It is the first to apply the local projection method to estimate multipliers in Portugal.
The convergence of carbon dioxide emissions: a survey of the empirical literature
Authors: Payne James E.
Published: April 2020

Purpose

This survey of the literature on the convergence of carbon dioxide (CO2) emissions informs researchers on areas for future research by summarizing the countries examined, the types of convergence tested and the methodological approaches undertaken.

Design/methodology/approach

This survey examines peer-reviewed empirical studies of CO2emissions convergence with respect to country coverage and alternative approaches to test for various types of convergence.

Findings

For large multicountry studies, the support for convergence is quite limited. However, studies focused exclusively on a subset of countries defined by income classification, geographic region or institutional structure reveal the finding of convergence is more prevalent. Studies at the subnational level have primarily been in the cases of the US and China with the exception of two studies across industry sectors in Portugal and Sweden.

Research limitations/implications

This study focuses exclusively on peer-reviewed published studies.

Practical implications

This study is relevant to the design of mitigation strategies to reduce CO2emissions and the assumption of convergence underlying climate change models.

Social implications

As a major component of greenhouse gas emissions, CO2emissions is of global importance in its impact on the environment and climate change.

Originality/value

This study provides the most recent and comprehensive survey of the empirical literature on the convergence of CO2emissions.