bluuebunny/crossref_metadata_2025 huggingface dataset:
ReQTL: identifying correlations between expressed SNVs and gene expression using RNA-sequencing data
Authors: Spurr Liam F , Alomran Nawaf , Bousounis Pavlos , Reece-Stremtan Dacian , Prashant N M , Liu Hongyu , Słowiński Piotr , Li Muzi , Zhang Qianqian , Sein Justin , Asher Gabriel , Crandall Keith A , Tsaneva-Atanasova Krasimira , Horvath Anelia
Published: October 2019

Motivation

By testing for associations between DNA genotypes and gene expression levels, expression quantitative trait locus (eQTL) analyses have been instrumental in understanding how thousands of single nucleotide variants (SNVs) may affect gene expression. As compared to DNA genotypes, RNA genetic variation represents a phenotypic trait that reflects the actual allele content of the studied system. RNA genetic variation at expressed SNV loci can be estimated using the proportion of alleles bearing the variant nucleotide (variant allele fraction, VAFRNA). VAFRNA is a continuous measure which allows for precise allele quantitation in loci where the RNA alleles do not scale with the genotype count. We describe a method to correlate VAFRNA with gene expression and assess its ability to identify genetically regulated expression solely from RNA-sequencing (RNA-seq) datasets.

Results

We introduce ReQTL, an eQTL modification which substitutes the DNA allele count for the variant allele fraction at expressed SNV loci in the transcriptome (VAFRNA). We exemplify the method on sets of RNA-seq data from human tissues obtained though the Genotype-Tissue Expression (GTEx) project and demonstrate that ReQTL analyses are computationally feasible and can identify a subset of expressed eQTL loci.

Availability and implementation

A toolkit to perform ReQTL analyses is available at https://github.com/HorvathLab/ReQTL.

Supplementary information

Supplementary data are available at Bioinformatics online.
Role of Narrative and Social Networks in Thwarting Violence and Sexual Abuse in Young People’s Lives
Authors: Hydén Margareta , Gadd David , Grund Thomas
Published: October 2019

Combining narrative analysis with social network analysis, this article analyses the case of a young Swedish female who had been physically and sexually abused. We show how she became trapped in an abusive relationship at the age of fourteen years following social work intervention in her family home, and how she ultimately escaped from this abuse aged nineteen years. The analysis illustrates the significance of responses to interpersonal violence from the social networks that surround young people; responses that can both entrap them in abusive relationships by blaming them for their problems and enable them to escape abuse by recognising their strengths and facilitating their choices. The article argues that the case for social work approaches that envision young people’s social networks after protective interventions have been implemented. The article explains that such an approach has the potential to reconcile the competing challenges of being responsive to young people’s needs while anticipating the heightened risk of being exposed to sexual abuse young people face when estranged from their families or after their trust in professionals has been eroded.
Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity
Authors: Gregory Michael D , Mervis Carolyn B , Elliott Maxwell L , Kippenhan J Shane , Nash Tiffany , B. Czarapata Jasmin , Prabhakaran Ranjani , Roe Katherine , Eisenberg Daniel P , Kohn Philip D , Berman Karen F
Published: October 2019

In Williams syndrome, a condition marked by hypersociability and visuospatial impairment, Gregory et al. show that intraparietal sulcus functional connectivity is increased with social processing regions and decreased with visual processing regions. Variation in LIMK1, which is hemideleted in Williams syndrome, is also associated with functional connectivity patterns in healthy controls.
Cyclin-like proteins tip regenerative balance in the liver to favour cancer formation
Authors: Fifield Bre-Anne , Talia John , Stoyanovich Carlee , Elliott Mitchell J , Bakht Martin K , Basilious Amy , Samsoondar Joshua P , Curtis Madison , Stringer Keith F , Porter Lisa A
Published: October 2019

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. A variety of factors can contribute to the onset of this disease, including viral infection, obesity, alcohol abuse and non-alcoholic fatty liver disease (NAFLD). These stressors predominantly introduce chronic inflammation leading to liver cirrhosis and finally the onset of HCC; however, approximately 20% of HCC cases arise in the absence of cirrhosis via a poorly defined mechanism. The atypical cyclin-like protein Spy1 is capable of overriding cell cycle checkpoints, promoting proliferation and has been implicated in HCC. We hypothesize that Spy1 promotes sustained proliferation making the liver more susceptible to accumulation of deleterious mutations, leading to the development of non-cirrhotic HCC. We report for the first time that elevation of Spy1 within the liver of a transgenic mouse model leads to enhanced spontaneous liver tumourigenesis. We show that the abundance of Spy1 enhanced fat deposition within the liver and decreased the inflammatory response. Interestingly, Spy1 transgenic mice have a significant reduction in fibrosis and sustained rates of hepatocyte proliferation, and endogenous levels of Spy1 are downregulated during the normal fibrotic response. Our results provide support that abnormal regulation of Spy1 protein drives liver tumorigenesis in the absence of elevated fibrosis and, hence, may represent a potential mechanism behind non-cirrhotic HCC. This work may implicate Spy1 as a prognostic indicator and/or potential target in the treatment of diseases of the liver, such as HCC.

The cyclin-like protein Spy1 enhances lipid deposition and reduces fibrosis in the liver. Spy1 also promotes increased hepatocyte proliferation and onset of non-cirrhotic hepatocellular carcinoma (HCC). Thus, Spy1 may be used as a potential target in the treatment of HCC.
Virtual Infrastructure Orchestration For Cloud Service Deployment
Authors: Qadeer Arslan , Waqar Malik Asad , Ur Rahman Anis , Mian Muhammad Hamayun , Ahmad Arsalan
Published: October 2019

Cloud adoption has significantly increased using the infrastructure-as-a-service (IaaS) paradigm, in order to meet the growing demands of computing, storage and networking, in small as well as large enterprises. Different vendors provide their customized solutions for OpenStack deployment on bare metal or virtual infrastructure. Among these many available IaaS solutions, OpenStack stands out as being an agile and open-source platform. However, its deployment procedure is a time-taking and complex process with a learning curve. This paper addresses the lack of basic infrastructure automation in almost all of the OpenStack deployment projects. We propose a flexible framework to automate the process of infrastructure bring up for deployment of several OpenStack distributions, as well as resolving dependencies for a successful deployment. Our experimental results demonstrate the effectiveness of the proposed framework in terms of automation status and deployment time, that is, reducing the time spent in preparing a basic virtual infrastructure by four times, on average.
High sensitivity of a keystone forage fish to elevated CO2 and temperature
Authors: Murray Christopher S , Wiley David , Baumann Hannes
Published: October 2019

Sand lances of the genus Ammodytes are keystone forage fish in coastal ecosystems across the northern hemisphere. Because they directly support populations of higher trophic organisms such as whales, seabirds or tuna, the current lack of empirical data and, therefore, understanding about the climate sensitivity of sand lances represent a serious knowledge gap. Sand lances could be particularly susceptible to ocean warming and acidification because, in contrast to other tested fish species, they reproduce during boreal winter months, and their offspring develop slowly under relatively low and stable pCO2 conditions. Over the course of 2 years, we conducted factorial pCO2 × temperature exposure experiments on offspring of the northern sand lance Ammodytes dubius, a key forage species on the northwest Atlantic shelf. Wild, spawning-ripe adults were collected from Stellwagen Bank National Marine Sanctuary (Cape Cod, USA), and fertilized embryos were reared at three pCO2 conditions (400, 1000 and 2100 μatm) crossed with three temperatures (5, 7 and 10 ˚C). Exposure to future pCO2 conditions consistently resulted in severely reduced embryo survival. Sensitivity to elevated pCO2 was highest at 10 ˚C, resulting in up to an 89% reduction in hatching success between control and predicted end-of-century pCO2 conditions. Moreover, elevated pCO2 conditions delayed hatching, reduced remaining endogenous energy reserves at hatch and reduced embryonic growth. Our results suggest that the northern sand lance is exceptionally CO2-sensitive compared to other fish species. Whether other sand lance species with similar life history characteristics are equally CO2-sensitive is currently unknown. But the possibility is a conservation concern, because many boreal shelf ecosystems rely on sand lances and might therefore be more vulnerable to climate change than currently recognized. Our findings indicate that life history, spawning habitat, phenology and developmental rates mediate the divergent early life CO2 sensitivities among fish species.
Does physiological tolerance to acute hypoxia and salinity change explain ecological niche in two intertidal crab species?
Authors: Falconer Thomas R L , Marsden Islay D , Hill Jonathan V , Glover Chris N
Published: October 2019

Lay summary

In response to acute salinity change or hypoxia, Hemigrapsus crenulatus exhibited better maintenance of osmoregulatory and cardiovascular function than Hemigrapsus sexdentatus. The greater physiological resilience of H. crenulatus is consistent with its habitation of an ecological niche that promotes greater exposure to environmental stressors than that of H. sexdentatus.
Plato’s queer time: dialogic moments in the life and death of Socrates
Authors: Atack Carol
Published: October 2019

Critics, from Athenaeus in the second century CE and Eduard Zeller in the nineteenth, to the present day, have been concerned with problems of authenticity and the dating of Plato’s work, including the inconsistent internal dramatic dates of the dialogues and other anachronisms within them. This article examines the relationship between the imaginary time of the dialogues and Plato’s own context, between the blurring of time and temporal relationships in the dialogues and the arguments that they contain, the construction of anachronistic communities and genealogies within them, through which Plato negotiates his own relationship with Socrates, and the deconstruction and re-negotiation of familial relationships, particularly those between fathers and sons. It uses insights from recent explorations of temporality in queer theory to generate a historicist reading that emphasizes the affective role of time within Plato’s writing. It argues that Plato uses the temporal setting of dialogues to underscore themes of their arguments, and that these anachronic settings can be read as an artefact of Plato’s own reception of Socrates’ life and death, and its context in the turmoil of the Peloponnesian War and the loss and restoration of democracy.
Machine learning approach to literature mining for the genetics of complex diseases
Authors: Schuster Jessica , Superdock Michael , Agudelo Anthony , Stey Paul , Padbury James , Sarkar Indra Neil , Uzun Alper
Published: October 2019

To generate a parsimonious gene set for understanding the mechanisms underlying complex diseases, we reasoned it was necessary to combine the curation of public literature, review of experimental databases and interpolation of pathway-associated genes. Using this strategy, we previously built the following two databases for reproductive disorders: The Database for Preterm Birth (dbPTB) and The Database for Preeclampsia (dbPEC). The completeness and accuracy of these databases is essential for supporting our understanding of these complex conditions. Given the exponential increase in biomedical literature, it is becoming increasingly difficult to manually maintain these databases. Using our curated databases as reference data sets, we implemented a machine learning-based approach to optimize article selection for manual curation. We used logistic regression, random forests and neural networks as our machine learning algorithms to classify articles. We examined features derived from abstract text, annotations and metadata that we hypothesized would best classify articles with genetically relevant content associated to the disorder of interest. Combinations of these features were used build the classifiers and the performance of these feature sets were compared to a standard ‘Bag-of-Words’. Several combinations of these genetic based feature sets outperformed ‘Bag-of-Words’ at a threshold such that 95% of the curated gene set obtained from the original manual curation of all articles were extracted from the articles classified by machine learning as ‘considered’. The performance was superior in terms of the reduction of required manual curation and two measures of the harmonic mean of precision and recall. The reduction in workload ranged from 0.814 to 0.846 for the dbPTB and 0.301 to 0.371 for the dbPEC. Additionally, a database of metadata and annotations is generated which allows for rapid query of individual features. Our results demonstrate that machine learning algorithms can identify articles with relevant data for databases of genes associated with complex diseases.
Host-Plant Specific Feeding Relationships and Insect Developmental Stage Modulate the Impact of Rainfall on Diamondback Moth Larvae
Authors: Rahman M D Mahbubur , Zalucki Myron P , Furlong Michael J
Published: October 2019

The impact of simulated rainfall on diamondback moth (DBM), Plutella xylostella (L.) (Lepidoptera: Plutellidae), larvae depends on their stage-specific feeding behavior, physical characteristics, and host plants. Neonates released at typical oviposition sites on Chinese cabbage (Brassica rapa var. pekinensis L. [Brassicales: Brassicaceae]) plants moved less (3–72 cm) and spend shorter periods (>1 h) than it has been previously reported for common cabbage (Brassica oleracea var. capitata L. [Brassicales: Brassicaceae]) (>80 cm and >3 h, respectively) before establishing feeding sites. On both host plants, larvae spent longer on the abaxial surfaces of leaves and were more likely to establish mines there than on the adaxial surfaces. On Chinese cabbage plants, ≈40% of neonates were removed when exposed to rainfall (5.6 cm/h for 3 min) within 5 min of release. Larval losses decreased rapidly as the interval between release and rainfall exposure increased and exposure to rainfall 2 h after release did not affect survival. On common cabbage plants, ≈65% of neonates were removed when exposed to rainfall within 30 min of release, losses decreased as the interval between release and rainfall exposure increased, but they decreased more slowly than on Chinese cabbage, and rainfall caused significant larval mortality up to 4 h after release. Rainfall also affected later instar larvae (susceptibility: 2nd> 3rd = 4th) but neither the susceptibility of these larvae nor that of pupae was affected by the host plant. Wet leaf surfaces disrupted movement and feeding site establishment by neonates. When dislodged from plants on to the surface of wet soil, most later stage larvae could relocate host plants, but most neonates could not.
Solidarity between Generations in Extended Families: Old-Age Income as a Way Out of Child Poverty?
Authors: Verbist Gerlinde , Diris Ron , Vandenbroucke Frank
Published: October 2019

We analyse intergenerational solidarity within multigenerational households (MGHs) and assess how the formation of these households is related to poverty across European countries. Our aim is to assess how this type of household is a coping strategy with respect to financial distress for families with children. Using data from EU Statistics on Income and Living Conditions (EU-SILC), we examine three specific empirical questions with regards to this complex form of intergenerational solidarity, notably (i) we identify to what extent co-residence within MGHs is financially beneficial to the young and/or the old generation; (ii) we analyse how the income brought into these households by the old generation impacts on child poverty, and (iii) we test how sensitive this impact is to hypotheses about the way resources are shared in the household. We define MGHs as those households where three generations cohabit. The results indicate that the formation of MGH operates mainly as solidarity from older to younger generations. Although not designed for this purpose, pensions alleviate child poverty in countries where MGH is most prevalent.
The pan-genome of Saccharomyces cerevisiae
Authors: Li Gang , Ji Boyang , Nielsen Jens
Published: October 2019

Understanding genotype–phenotype relationship is fundamental in biology. With the benefit from next-generation sequencing and high-throughput phenotyping methodologies, there have been generated much genome and phenome data for Saccharomyces cerevisiae. This makes it an excellent model system to understand the genotype–phenotype relationship. In this paper, we presented the reconstruction and application of the yeast pan-genome in resolving genotype–phenotype relationship by a machine learning-assisted approach.
Complete Genome Sequence of the Biocontrol Agent Bacillus velezensis UFLA258 and Its Comparison with Related Species: Diversity within the Commons
Authors: Silva Fabíola de Jesus , Ferreira Larissa Carvalho , Campos Vicente Paulo , Cruz-Magalhães Valter , Barros Aline Ferreira , Andrade Jackeline Pereira , Roberts Daniel P , de Souza Jorge Teodoro
Published: October 2019

In this study, the full genome sequence of Bacillus velezensis strain UFLA258, a biological control agent of plant pathogens was obtained, assembled, and annotated. With a comparative genomics approach, in silico analyses of all complete genomes of B. velezensis and closely related species available in the database were performed. The genome of B. velezensis UFLA258 consisted of a single circular chromosome of 3.95 Mb in length, with a mean GC content of 46.69%. It contained 3,949 genes encoding proteins and 27 RNA genes. Analyses based on Average Nucleotide Identity and Digital DNA–DNA Hybridization and a phylogeny with complete sequences of the rpoB gene confirmed that 19 strains deposited in the database as Bacillus amyloliquefaciens were in fact B. velezensis. In total, 115 genomes were analyzed and taxonomically classified as follows: 105 were B. velezensis, 9 were B. amyloliquefaciens, and 1 was Bacillus siamensis. Although these species are phylogenetically close, the combined analyses of several genomic characteristics, such as the presence of biosynthetic genes encoding secondary metabolites, CRISPr/Cas arrays, Average Nucleotide Identity and Digital DNA–DNA Hybridization, and other information on the strains, including isolation source, allowed their unequivocal classification. This genomic analysis expands our knowledge about the closely related species, B. velezensis, B. amyloliquefaciens, and B. siamensis, with emphasis on their taxonomical status.
Resolving Phylogenetic Relationships within Passeriformes Based on Mitochondrial Genes and Inferring the Evolution of Their Mitogenomes in Terms of Duplications
Authors: Mackiewicz Paweł , Urantówka Adam Dawid , Kroczak Aleksandra , Mackiewicz Dorota
Published: October 2019

Mitochondrial genes are placed on one molecule, which implies that they should carry consistent phylogenetic information. Following this advantage, we present a well-supported phylogeny based on mitochondrial genomes from almost 300 representatives of Passeriformes, the most numerous and differentiated Aves order. The analyses resolved the phylogenetic position of paraphyletic Basal and Transitional Oscines. Passerida occurred divided into two groups, one containing Paroidea and Sylvioidea, whereas the other, Passeroidea and Muscicapoidea. Analyses of mitogenomes showed four types of rearrangements including a duplicated control region (CR) with adjacent genes. Mapping the presence and absence of duplications onto the phylogenetic tree revealed that the duplication was the ancestral state for passerines and was maintained in early diverged lineages. Next, the duplication could be lost and occurred independently at least four times according to the most parsimonious scenario. In some lineages, two CR copies have been inherited from an ancient duplication and highly diverged, whereas in others, the second copy became similar to the first one due to concerted evolution. The second CR copies accumulated over twice as many substitutions as the first ones. However, the second CRs were not completely eliminated and were retained for a long time, which suggests that both regions can fulfill an important role in mitogenomes. Phylogenetic analyses based on CR sequences subjected to the complex evolution can produce tree topologies inconsistent with real evolutionary relationships between species. Passerines with two CRs showed a higher metabolic rate in relation to their body mass.
Quantitative and Qualitative Role of Antagonistic Heterogeneity in Genetics of Blood Lipids
Authors: Kulminski Alexander M , Loika Yury , Nazarian Alireza , Culminskaya Irina
Published: October 2019

Prevailing strategies in genome-wide association studies (GWAS) mostly rely on principles of medical genetics emphasizing one gene, one function, one phenotype concept. Here, we performed GWAS of blood lipids leveraging a new systemic concept emphasizing complexity of genetic predisposition to such phenotypes. We focused on total cholesterol, low- and high-density lipoprotein cholesterols, and triglycerides available for 29,902 individuals of European ancestry from seven independent studies, men and women combined. To implement the new concept, we leveraged the inherent heterogeneity in genetic predisposition to such complex phenotypes and emphasized a new counter intuitive phenomenon of antagonistic genetic heterogeneity, which is characterized by misalignment of the directions of genetic effects and the phenotype correlation. This analysis identified 37 loci associated with blood lipids but only one locus, FBXO33, was not reported in previous top GWAS. We, however, found strong effect of antagonistic heterogeneity that leaded to profound (quantitative and qualitative) changes in the associations with blood lipids in most, 25 of 37 or 68%, loci. These changes suggested new roles for some genes, which functions were considered as well established such as GCKR, SIK3 (APOA1 locus), LIPC, LIPG, among the others. The antagonistic heterogeneity highlighted a new class of genetic associations emphasizing beneficial and adverse trade-offs in predisposition to lipids. Our results argue that rigorous analyses dissecting heterogeneity in genetic predisposition to complex traits such as lipids beyond those implemented in current GWAS are required to facilitate translation of genetic discoveries into health care.
5. Conducting a Literature Search
Authors: Clark Tom , Foster Liam , Bryman Alan
Published: October 2019

Today, the world of research is quite literally available through the touch of a few buttons via online resaerch. But this increase in access and availability is not without its challenges. With ‘hits’ that can run into millions, unless the student knows how to search effectively and efficiently, the information that he or she finds can quickly become overwhelming. This chapter guides students through the process of literature searching for their dissertation. It outlines how to develop a successful search strategy and what to do with the literature once it is discovered. Topics covered include what counts as literature; different ‘types’ of literature searching; how to develop a literature search strategy; and common problems associated with literature searching.
7. Building Your Project
Authors: Clark Tom , Foster Liam , Bryman Alan
Published: October 2019

Once students have developed an idea, outlined a rationale for their research, and found the relevant literature, they then need to start mapping out what their project will look like. To do this, they will need to make some decisions about how they will answer their research questions. Research can be approached and conducted in many different ways. Broadly speaking, there are four interrelated stages of building a social science dissertation: research strategy: the type of data under investigation (qualitative, quantitative, or mixed methods); research design: the framework through which that data will be collected; research methods: the methods associated with collecting the type of data selected; and type of analysis: the techniques through which the data will be analysed. This chapter focuses on the decisions that students can make in relation to the first two stages: research strategy and research design.
ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome
Authors: Holdener Bernadette C , Percival Christopher J , Grady Richard C , Cameron Daniel C , Berardinelli Steven J , Zhang Ao , Neupane Sanjiv , Takeuchi Megumi , Jimenez-Vega Javier C , Uddin Sardar M Z , Komatsu David E , Honkanen Robert , Dubail Johanne , Apte Suneel S , Sato Takashi , Narimatsu Hisashi , McClain Steve A , Haltiwanger Robert S
Published: October 2019

Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene. Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs). Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily. Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets. To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles. Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development. The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS. In addition, we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly. We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function. Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways
Authors: Kleinstern Geffen , Yan Huihuang , Hildebrandt Michelle A T , Vijai Joseph , Berndt Sonja I , Ghesquières Hervé , McKay James , Wang Sophia S , Nieters Alexandra , Ye Yuanqing , Monnereau Alain , Brooks-Wilson Angela R , Lan Qing , Melbye Mads , Jackson Rebecca D , Teras Lauren R , Purdue Mark P , Vajdic Claire M , Vermeulen Roel C H , Giles Graham G , Cocco Pier Luigi , Birmann Brenda M , Kraft Peter , Albanes Demetrius , Zeleniuch-Jacquotte Anne , Crouch Simon , Zhang Yawei , Sarangi Vivekananda , Asmann Yan , Offit Kenneth , Salles Gilles , Wu Xifeng , Smedby Karin E , Skibola Christine F , Slager Susan L , Rothman Nathaniel , Chanock Stephen J , Cerhan James R
Published: October 2019

We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10−13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10−12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.
PAICS deficiency, a new defect of de novo purine synthesis resulting in multiple congenital anomalies and fatal outcome
Authors: Pelet Anna , Skopova Vaclava , Steuerwald Ulrike , Baresova Veronika , Zarhrate Mohammed , Plaza Jean-Marc , Hnizda Ales , Krijt Matyas , Souckova Olga , Wibrand Flemming , Andorsdóttir Guðrið , Joensen Fróði , Sedlak David , Bleyer Anthony J , Kmoch Stanislav , Lyonnet Stanislas , Zikanova Marie
Published: October 2019

We report for the first time an autosomal recessive inborn error of de novo purine synthesis (DNPS)—PAICS deficiency. We investigated two siblings from the Faroe Islands born with multiple malformations resulting in early neonatal death. Genetic analysis of affected individuals revealed a homozygous missense mutation in PAICS (c.158A>G; p.Lys53Arg) that affects the structure of the catalytic site of the bifunctional enzyme phosphoribosylaminoimidazole carboxylase (AIRC, EC 4.1.1.21)/phosphoribosylaminoimidazole succinocarboxamide synthetase (SAICARS, EC 6.3.2.6) (PAICS). The mutation reduced the catalytic activity of PAICS in heterozygous carrier and patient skin fibroblasts to approximately 50 and 10% of control levels, respectively. The catalytic activity of the corresponding recombinant enzyme protein carrying the mutation p.Lys53Arg expressed and purified from E. coli was reduced to approximately 25% of the wild-type enzyme. Similar to other two known DNPS defects—adenylosuccinate lyase deficiency and AICA-ribosiduria—the PAICS mutation prevented purinosome formation in the patient’s skin fibroblasts, and this phenotype was corrected by transfection with the wild-type but not the mutated PAICS. Although aminoimidazole ribotide (AIR) and aminoimidazole riboside (AIr), the enzyme substrates that are predicted to accumulate in PAICS deficiency, were not detected in patient’s fibroblasts, the cytotoxic effect of AIr on various cell lines was demonstrated. PAICS deficiency is a newly described disease that enhances our understanding of the DNPS pathway and should be considered in the diagnosis of families with recurrent spontaneous abortion or early neonatal death.
Bone morphogenetic protein 1 cleaves the linker region between ligand-binding repeats 4 and 5 of the LDL receptor and makes the LDL receptor non-functional
Authors: Strøm Thea Bismo , Bjune Katrine , Leren Trond P
Published: October 2019

The cell-surface low-density lipoprotein receptor (LDLR) internalizes low-density lipoprotein (LDL) by receptor-mediated endocytosis and plays a key role in the regulation of plasma cholesterol levels. The ligand-binding domain of the LDLR contains seven ligand-binding repeats of approximately 40 residues each. Between ligand-binding repeats 4 and 5, there is a 10-residue linker region that is subject to enzymatic cleavage. The cleaved LDLR is unable to bind LDL. In this study, we have screened a series of enzyme inhibitors in order to identify the enzyme that cleaves the linker region. These studies have identified bone morphogenetic protein 1 (BMP1) as being the cleavage enzyme. This conclusion is based upon the use of the specific BMP1 inhibitor UK 383367, silencing of the BMP1 gene by the use of siRNA or CRISPR/Cas9 technology and overexpression of wild-type BMP1 or the loss-of-function mutant E214A-BMP1. We have also shown that the propeptide of BMP1 has to be cleaved at RSRR120↓ by furin-like proprotein convertases for BMP1 to have an activity towards the LDLR. Targeting BMP1 could represent a novel strategy to increase the number of functioning LDLRs in order to lower plasma LDL cholesterol levels. However, a concern by using BMP1 inhibitors as cholesterol-lowering drugs could be the risk of side effects based on the important role of BMP1 in collagen assembly.
Disentangling the influence of fishing, demography, and environment on population dynamics of Iberian Peninsula waters fish stocks
Authors: Quinzán M , Castro J , Massutí E , Rueda L , Hidalgo M
Published: October 2019

Overexploitation and climate change are increasingly causing unanticipated changes in marine ecosystems such as higher variability in fish recruitment or shifts in species dominance and distribution that alter the productivity of fish stocks. This study analyses how external and internal drivers influence population dynamics of hake (Merluccius merluccius), white anglerfish (Lophius piscatorius), four-spot megrim (Lepidorhombus boscii), and horse mackerel (Trachurus trachurus) of Iberian Peninsula waters of the Northeast Atlantic across different spatiotemporal scales. Available spawning stock biomass and recruitment have been used as biological data, whereas fishing mortality, demographic data as well as climatic and oceanographic data have been used as drivers. The obtained results indicate that population dynamics of these species are mainly driven by oceanographic variability at regional scale along with fishing pressure and demographic factors, while the impact of large-scale climate indices was minimal. The identified variables represent relevant oceanographic regional processes candidate to be potentially integrated into the stock assessment models and management procedures of these important fishery resources.
Review of Heat and Mass Transfer Enhancement Techniques and Current Advancement for Adsorption Heating/Cooling Systems
Authors: Mat Wajid Norhayati , Mompuouo Blaise , Omer Siddig , Riffat Saffa B
Published: October 2019

Adsorption heating/cooling became an alternative to vapour compression system due to low ozone depletion potential (ODP) and global warming potential (GWP). However, more investigation is required due their low efficiency when compared to conventional heating/cooling systems. This review emphasizes on the mathematical modelling simplification and heat transfer enhancement method that applied by many researchers to improve the performance of adsorption heating and cooling technologies. Various techniques investigated by many researchers on solving low thermal conductivity and the different methods for enhancing heat and mass transfer in the adsorbed bed/pipe also discussed. Common techniques used to enhance heat and mass transfer in the adsorbed bed/pipe include the fin type adsorbent tube/ heat exchanger, amalgamated adsorbent bed with a metal foam, consolidated adsorbent, adsorbent coating and adsorbent with multi cooling tubes. Other than that, recent advancements in adsorption cooling/heating systems also discussed in this review.
The Non-selfadjoint Approach to the Hao–Ng Isomorphism
Authors: Katsoulis Elias G , Ramsey Christopher
Published: October 2019

In an earlier work, the authors proposed a non-selfadjoint approach to the Hao–Ng isomorphism problem for the full crossed product, depending on the validity of two conjectures stated in the broader context of crossed products for operator algebras. By work of Harris and Kim, we now know that these conjectures in the generality stated may not always be valid. In this paper we show that in the context of hyperrigid tensor algebras of $\mathrm{C}^*$-correspondences, each one of these conjectures is equivalent to the Hao–Ng problem. This is accomplished by studying the representation theory of non-selfadjoint crossed products of C$^*$-correspondence dynamical systems; in particular we show that there is an appropriate dilation theory. A large class of tensor algebras of $\mathrm{C}^*$-correspondences, including all regular ones, are shown to be hyperrigid. Using Hamana’s injective envelope theory, we extend earlier results from the discrete group case to arbitrary locally compact groups; this includes a resolution of the Hao–Ng isomorphism for the reduced crossed product and all hyperrigid $\mathrm{C}^*$-correspondences. A culmination of these results is the resolution of the Hao–Ng isomorphism problem for the full crossed product and all row-finite graph correspondences; this extends a recent result of Bedos, Kaliszewski, Quigg, and Spielberg.
Measure Rigidity for Horospherical Subgroups of Groups Acting on Trees
Authors: Ciobotaru Corina , Finkelshtein Vladimir , Sert Cagri
Published: October 2019

We prove analogues of some of the classical results in homogeneous dynamics in nonlinear setting. Let $G$ be a closed subgroup of the group of automorphisms of a biregular tree and $\Gamma \leq G$ a discrete subgroup. For a large class of groups $G$, we give a classification of the probability measures on $G/\Gamma $ invariant under horospherical subgroups. When $\Gamma $ is a cocompact lattice, we show the unique ergodicity of the horospherical action. We prove Hedlund’s theorem for geometrically finite quotients. Finally, we show equidistribution of large compact orbits.
Antibiotic use in pregnancy: knowledge, attitudes and practices among pregnant women in Cape Town, South Africa
Authors: Bulabula Andre N H , Dramowski Angela , Mehtar Shaheen
Published: October 2019

Objectives

To establish the knowledge, attitudes and practices (KAP) regarding antibiotic use and self-medication among pregnant women.

Methods

We conducted a KAP survey of 301 pregnant women hospitalized at a tertiary hospital obstetric service in Cape Town, South Africa in November and December 2017, using an interviewer-administered 12 item questionnaire. We stratified analysis of attitudes and practices by participants’ mean knowledge score (K-score) group (<6 versus ≥6 out of 7 questions). Multivariate models were built to identify independent predictors of antibiotic self-medication and K-score.

Results

The mean age of pregnant women was 29 (SD 6.1) years, 44/247 (17.8%) were nulliparous, 69/247 (27.9%) were HIV-infected, 228/247 (92.3%) had completed secondary school and 78/247 (31.6%) reported a monthly household income in the lowest category of ≤50–100 US dollars (USD). The mean K-score was 6.1 (SD 1.02) out of 7 questions. Sixteen percent of the cohort reported antibiotic self-medication, with higher rates among pregnant women with K-score <6 [18/48 (37.5%) versus 32/253 (12.6%); P < 0.001]. The monthly household income category of >500 USD (the highest category) was the only predictor of antibiotic self-medication behaviour [adjusted OR = 6.4 (95% CI 1.2–35.2), P = 0.03].

Conclusions

Higher antibiotic knowledge scores are associated with lower rates of antibiotic self-medication, whereas higher household income is correlated with increasing self-medication behaviours. Education of pregnant women regarding the potential dangers of antibiotic self-medication and stricter enforcement of existing South African antibiotic prescribing and dispensing regulations are needed.
Risk of Cold-Hardy Apple Cultivars for Injury From the Brown Marmorated Stink Bug (Hemiptera: Pentatomidae)
Authors: Shanovich Hailey N , Burkness Eric C , Koch Robert L
Published: October 2019

An invasive species, the brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), has emerged as a serious pest of orchard crops in the United States with the highest economic losses to date in Mid-Atlantic apple, Malus domestica Borkh. (Rosales: Rosaceae). If populations continue to grow and spread in the Midwest, H. halys has the potential to become a significant apple pest in the region. The purpose of this study was to assess the risk for injury from H. halys to several popular cold-hardy apple cultivars (Haralson, Honeycrisp, and Zestar!) grown in the Midwestern United States utilizing both field no-choice tests and laboratory choice tests at multiple timings. Results from the field no-choice tests revealed a greater risk for Honeycrisp from H. halys injury compared with Zestar! in mid-August. Results from the laboratory choice tests revealed a greater risk for injury by H. halys for Honeycrisp compared with Zestar! at all timings tested and a greater risk for Haralson compared with Honeycrisp at a later timing. These results echo previous findings in that relative maturity of the fruit seems to play a role in determining the risk of an apple cultivar to H. halys injury. These results also serve as the first assessment of the potential impact of H. halys on different cold-hardy apple cultivars, which will help guide growers in cultivar selection and identifying which apple cultivars should be prioritized for scouting and management efforts.
Repeatability of Adaptive Radiation Depends on Spatial Scale: Regional Versus Global Replicates of Stickleback in Lake Versus Stream Habitats
Authors: Paccard Antoine , Hanson Dieta , Stuart Yoel E , von Hippel Frank A , Kalbe Martin , Klepaker Tom , Skúlason Skúli , Kristjánsson Bjarni K , Bolnick Daniel I , Hendry Andrew P , Barrett Rowan D H
Published: October 2019

The repeatability of adaptive radiation is expected to be scale-dependent, with determinism decreasing as greater spatial separation among “replicates” leads to their increased genetic and ecological independence. Threespine stickleback (Gasterosteus aculeatus) provide an opportunity to test whether this expectation holds for the early stages of adaptive radiation—their diversification in freshwater ecosystems has been replicated many times. To better understand the repeatability of that adaptive radiation, we examined the influence of geographic scale on levels of parallel evolution by quantifying phenotypic and genetic divergence between lake and stream stickleback pairs sampled at regional (Vancouver Island) and global (North America and Europe) scales. We measured phenotypes known to show lake-stream divergence and used reduced representation genome-wide sequencing to estimate genetic divergence. We assessed the scale dependence of parallel evolution by comparing effect sizes from multivariate models and also the direction and magnitude of lake-stream divergence vectors. At the phenotypic level, parallelism was greater at the regional than the global scale. At the genetic level, putative selected loci showed greater lake-stream parallelism at the regional than the global scale. Generally, the level of parallel evolution was low at both scales, except for some key univariate traits. Divergence vectors were often orthogonal, highlighting possible ecological and genetic constraints on parallel evolution at both scales. Overall, our results confirm that the repeatability of adaptive radiation decreases at increasing spatial scales. We suggest that greater environmental heterogeneity at larger scales imposes different selection regimes, thus generating lower repeatability of adaptive radiation at larger spatial scales.
Knowledge in action: logico-philosophical approach to linguistic evidentiality
Authors: Barés-Gómez C , Fontaine M , Nepomuceno A
Published: October 2019

The present study focuses on a grammatical category called evidentiality. The primary meaning of evidentiality is concerned with information source. That is, it expresses whether something has been seen, heard or inferred. The aim here is to conduct a conceptual study of evidentiality in which use is made of formal tools. The fundamental intuition is that the distinction between ‘evidence’as ‘proof’and ‘evidentiality’as ‘to do with proof’is a crucial one. Evidentiality is a dynamic notion to be analysed through the use of knowledge by the agents, a knowledge in action, which involves an in-coming state and an out-coming state that is typical of the transmission of information. We propose our own approach in which the dynamics of knowledge in action is grasped in the context of a dynamic epistemic logic.
Limit Theory for Forecasts of Extreme Distortion Risk Measures and Expectiles
Authors: Hoga Yannick
Published: October 2019

We develop central limit theory for tail risk forecasts in general location–scale models. We do so for a wide range of risk measures, viz. distortion risk measures (DRMs) and expectiles. Two popular members of the class of DRMs are the Value-at-Risk and the Expected Shortfall. The forecasts we consider are motivated by a Pareto-type tail assumption for the innovations and allow for extrapolation beyond the range of available observations. Simulations reveal adequate coverage of the forecast intervals derived from the limit theory. An empirical application demonstrates that our estimators outperform nonparametric alternatives when forecasting extreme risk in sufficiently large samples.
Social Trust and Public Opinion about Territorial Disputes: Evidence from a Survey in India
Authors: Justwan Florian , Fisher Sarah
Published: October 2019

This article explores the sources of public opinion about territorial disputes. Specifically, it investigates the impact of one particular character trait—social trust—on the policy preferences of Indian citizens in the context of the Sino-Indian dispute over Arunachal Pradesh/South Tibet. We argue that social trust shapes how a citizen thinks about a given territorial dispute and influences which policy options this individual favors in response to another country's claim. Our empirical analysis is based on original survey data collected in the National Capital Territory of Delhi (NCT) in January/February 2017. In line with our theoretical expectations, we find that high-trust individuals are: (1) more likely to regard China's claim to Arunachal Pradesh/South Tibet as legitimate; (2) more willing to favor the onset of conflict management; and (3) more supportive of concessions. This article therefore adds to a growing literature examining the individual-level determinants of public opinion in territorial disputes.