bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the multi-dimensional assessment of quality of life: introducing the WHOQOL-Combi
Authors: Skevington Suzanne M. , Rowland Christine , Panagioti Maria , Bower Peter , Krägeloh Christian
Published: December 2020

Introduction

We revisited the global concept of subjective quality of life (QoL) as assessed by the WHOQOL-BREF to investigate whether it could be elaborated into a conceptually more comprehensive instrument with good psychometric properties. Responding to a growing need for shorter QoL measures with broader social, spiritual and environmental contents, facets from WHOQOL international modules were examined for potential integration into the new WHOQOL-Combi.

Method

Adults over 65 years, diagnosed with one or more chronic diseases (n = 2833), completed 41 WHOQOL items during the CLASSIC survey; each item represented a WHOQOL facet. This pool of specific QoL facets contained 24 from the WHOQOL-BREF (excluding general items), and 17 from recent international WHOQOL short-form modules, selected for their generic properties. Rasch modelling reduced the final item pool when assessing the WHOQOL-Combi’s conceptual structure. Comparisons are made with the WHOQOL-BREF.

Results

Modelling confirmed the tenability of a 36-item solution scored as a five-domain profile, comprised of 24 WHOQOL-BREF facets and 12 new facets from modules. Social and psychological domains were strengthened by three facets, spiritual QoL by five, and physical QoL by one. The WHOQOL-Combi showed sound model fit, excellent internal consistency (α = .95), and scores discriminated between socio-demographic categories. Concurrent validity with the EQ-5D-5L was confirmed for physical and psychological domains. Performance was similar to the WHOQOL-BREF.

Conclusion

The WHOQOL-Combi offers a contemporary, comprehensive, integrated, multi-dimensional subjective QoL instrument with enhanced evaluations of social, spiritual, psychological and physical QoL. Acceptable to older people, future research should evaluate younger age groups and other cultures.
Complement Factor C5a Is Increased in Blood of Patients with Abdominal Aortic Aneurysm and Has Prognostic Potential for Aneurysm Growth
Authors: Zagrapan Branislav , Eilenberg Wolf , Scheuba Andreas , Klopf Johannes , Brandau Annika , Story Julia , Dosch Katharina , Hayden Hubert , Domenig Christoph M. , Fuchs Lukas , Schernthaner Rüdiger , Ristl Robin , Huk Ihor , Neumayer Christoph , Brostjan Christine
Published: December 2020

In this observational case-control study, circulating levels of complement factors C3a and C5a and leukotriene B4 (LTB4) were analysed in abdominal aortic aneurysm (AAA) patients regarding their association with diagnosis and prognosis. Serum C5a was significantly raised in AAA patients compared to healthy controls—median 84.5 ng/ml (IQR = 37.5 ng/ml) vs. 67.7 ng/ml (IQR = 26.2 ng/ml), p = 0.007—but was not elevated in patients with athero-occlusive disease. Serum C5a levels correlated significantly with the increase in maximum AAA diameter over the following 6 months (r = 0.319, p = 0.021). The median growth in the lowest quartile of C5a (< 70 ng/ml) was 50% less compared to the highest C5a quartile (> 101 ng/ml): 1.0 mm/6 months (IQR = 0.8 mm) vs. 2.0 mm/6 months (IQR = 1.5 mm), p = 0.014. A log-linear mixed model predicted AAA expansion based on current diameter and C5a level. To our knowledge, this is the first study linking complement activation, in particular C5a serum level, with AAA progression.

Graphical Abstract
Amerigo Vespucci's Contribution to the Modernization of Cartographic Representation
Authors: Pápay Gyula
Published: December 2020

In 2019, the Rostock University Library acquired the report by Amerigo Vespucci (1454–1512) on transatlantic discoveries, which was published in 1505 by the city secretary Hermann Barckhusen (c 1460–1528/29) in Rostock under the title “Epistola Albericij. De novo mundo” [1505] and, unlike other editions, was published with a map. The special feature of the map is that it is the oldest map with a globular projection. Vespucci reported in a letter dated July 18, 1500 to Lorenzo di Pierfrancesco de' Medici about his voyage 1499–1500, which is an important source for the fact that his longitude determinations contributed to the realization that the transatlantic discoveries were about a continent. The letter also contains evidence that Vespucci was the originator of the globular projection. This marked the beginning of a departure from ancient traditions regarding the projections for world maps. To enable the combined representation of the “old world” together with the “new world” in one map, Vespucci's projection was later modified into an oval map, which was used, for example, by Franzesco Rosselli, Sebastian Münster and Abraham Ortelius.
The mRNA Binding Proteome of Proliferating and Differentiated Muscle Cells
Authors: Hiller Monika , Geissler Miriam , Janssen George , van Veelen Peter , Aartsma-Rus Annemieke , Spitali Pietro
Published: December 2020

Muscle formation is a coordinated process driven by extensive gene expression changes where single cells fuse together to form multinucleated muscle fibers. Newly synthesized mRNAs are then regulated by RNA binding proteins (RBPs), affecting post-transcriptional transcript metabolism. Here, we determined how large-scale gene expression changes affect the catalog of RBPs by studying proliferating and differentiated muscle cells in healthy and dystrophic conditions. Transcriptomic analysis showed that the expression of more than 7000 genes was affected during myogenesis. We identified 769 RBPs, of which 294 were muscle-specific and 49 were uniquely shared with cardiomyocytes. A subset of 32 RBPs (half of which were muscle-specific) was found to be preferentially associated with target mRNAs in either myoblasts (MBs) or myotubes (MTs). A large proportion of catalytic proteins were bound to mRNAs even though they lack classical RNA binding domains. Finally, we showed how the identification of cell-specific RBPs enabled the identification of biomarkers that can separate healthy individuals from dystrophic patients. Our data show how interactome data can shed light on new basic RNA biology as well as provide cell-specific data that can be used for diagnostic purposes.
Ruling the World
Authors: Lester Alan , Boehme Kate , Mitchell Peter
Published: December 2020

Ruling the World tells the story of how the largest and most diverse empire in history was governed, everywhere and all at once. Focusing on some of the most tumultuous years of Queen Victoria's reign, Alan Lester, Kate Boehme and Peter Mitchell adopt an entirely new perspective to explain how the men in charge of the British Empire sought to manage simultaneous events across the globe. Using case studies including Canada, South Africa, the Caribbean, Australia, India and Afghanistan, they reveal how the empire represented a complex series of trade-offs between Parliament's, colonial governors', colonists' and colonised peoples' agendas. They also highlight the compromises that these men made as they adapted their ideals of freedom, civilization and liberalism to the realities of an empire imposed through violence and governed in the interests of Britons.
Resistivity and Induced Polarization
Authors: Binley Andrew , Slater Lee
Published: December 2020

Resistivity and induced polarization methods are used for a wide range of near-surface applications, including hydrogeology, civil engineering and archaeology, as well as emerging applications in the agricultural and plant sciences. This comprehensive reference text covers both theory and practice of resistivity and induced polarization methods, demonstrating how to measure, model and interpret data in both the laboratory and the field. Marking the 100 year anniversary of the seminal work of Conrad Schlumberger (1920), the book covers historical development of electrical geophysics, electrical properties of geological materials, instrumentation, acquisition and modelling, and includes case studies that capture applications to societally relevant problems. The book is also supported by a full suite of forward and inverse modelling tools, allowing the reader to apply the techniques to a wide range of applications using digital datasets provided online. This is a valuable reference for graduate students, researchers and practitioners interested in near-surface geophysics.
Multicultural Origins of the Global Economy
Authors: Hobson John M.
Published: December 2020

Westerners on both the left and right overwhelmingly conflate globalisation with Westernisation and presume that the global economy is a pure Western-creation. Taking on the traditional Eurocentric Big Bang theory, or the 'expansion of the West' narrative, this book reveals the multicultural origins of globalisation and the global economy, not so as to marginalise the West but to show how it has long been embedded in complex interconnections and co-constitutive interactions with non-Western actors/agents and processes. The central empirical theme is the role of Indian structural power that was derived from Indian cotton textile exports. Indian structural power organised the first (historical-capitalist) global economy between 1500 and c.1850 and performed a vital, albeit indirect, role in the making of Western empire, industrialisation and the second (modern-capitalist) global economy. These textiles underpinned the complex inter-relations between Africa, West/Central/East/Southeast Asia, the Americas and Europe that collectively drove global economic development forward.
Medical transport-associated infection: Review and commentary making a case for its legitimacy
Authors: Schaps Diego , Joiner Anjni Patel , Anderson Deverick J.
Published: December 2020

The purpose of this article is to summarize existing literature about healthcare-associated infection (HAI) in the medical transport environment and to define the term medical transport–associated infection (MTAI) to unify all previous work under a single umbrella with the objective of providing a standardized definition for future research. A review of the literature yielded 34 relevant articles. These studies show that there are pathogens in the ambulance environment, that emergency medical services (EMS) personnel do not regularly comply with hygiene practices, and that patients are potentially affected by HAI as a direct result of ambulance exposure. Prospective studies must be conducted to truly understand the impact that ambulance exposure has on HAIs. MTAI is a subset of HAI and is defined as any infection acquired as a direct effect of exposure in a medical transport setting.
Regional Politics and Ethnic Identity: How Silesian Identity Has Become Politicized
Authors: Muś Anna
Published: December 2020

Ethnoregionalist movements across Western Europe are gaining scholarly attention. Central European states usually have limited places in those studies. Still, in Polish Upper Silesia, ethnoregionalist movements have been present since 1989 and have stable support from the inhabitants of the region. Since at least 2002, ethnoregionalists have attempted to secure political representation among the Upper Silesians. Recently registered parties have used the ethnic identity of this minority group as the main tool to gain support in political elections in the region. This article applies social science and political science perspectives to the politicization of ethnicity. These equip the researcher to answer the question: How has Silesian ethnic identity become politicized? In responding, the researcher explores the consequences of the emergence of the ethnoregionalist movement in Upper Silesia.
COLUMELLA 10.101: TWO EMENDATIONS
Authors: Kayachev Boris
Published: December 2020

Columella invites his readers to plant different flowers, including violets—which will be the main focus of the following discussion (10.94–102):uerum ubi iam puro discrimine pectita tellusdeposito squalore nitens sua semina poscet, 95pangite tunc uarios, terrestria sidera, flores:candida leucoia et flauentia lumina caltae,narcissique comas et hiantis saeua leonisora feri, calathisque uirentia lilia canis,necnon uel niueos uel caeruleos hyacinthos. 100tum quae pallet humi, quae frondes purpurat auro,ponatur uiola, et nimium rosa plena pudoris.

96 pangite Heinsius: pingite SAR || 99 nitentia Gesner || 101 frondes SA: frondens R | purpurat auro ϛ: purpura tabo SAR: purpura et auro Ursinus: purpurat albo Heinsius

This is the text of Rodgers's recent OCT, but with a somewhat modified apparatus criticus. For the purposes of my argument, it will be useful also to quote from the outset a related catalogue of melliferous flowers from another book of Columella's treatise (9.4.4):

mille praeterea semina uel crudo caespite uirentia uel subacto sulco flores amicissimos apibus creant, ut sunt in uirgineo solo […] gladiolus narcissi. at in hortensi lira consita nitent candida lilia nec his sordidiora leucoia, tum Punicae rosae luteolaeque et Sarranae uiolae, nec minus caelestis luminis hyacinthus.

There are a number of more general similarities, but the relevant point is that the two catalogues list many of the same flowers and describe them in similar ways, which means that one catalogue can serve as an interpretative guide to the other. The first two items in the prose list of garden flowers (nitent candida lilia nec his sordidiora leucoia) correspond to candida leucoia and calathisque uirentia lilia canis, similarly listed in the first half of the verse catalogue; nitent (lilia) can thus support Gesner's emendation nitentia for uirentia (lilia), unduly neglected by recent editors. The metaphoric periphrasis gladiolus narcissi can be compared with narcissique comas. Both texts describe the hyacinth as sky-blue, which seems to be otherwise unparalleled (nec minus caelestis luminis hyacinthus and necnon […] caeruleos hyacinthos: note also that in both cases the reference is introduced by a litotes). Finally, just like the prose list (tum Punicae rosae luteolaeque et Sarranae uiolae), Columella's poem groups roses with two varieties of violet (note also that both passages are introduced with tum):tum quae pallet humi, quae frondes purpurat auro,ponatur uiola, et nimium rosa plena pudoris.The prose version makes it all but certain that the poem should likewise refer to a yellow and a purple varieties of violet. While Columella's verse description of the former variety is fairly unambiguous (if not very informative), that of the latter raises questions.
BEYOND THE HORIZON: THE DEPICTION OF TIME IN KARLHEINZ STOCKHAUSEN'S KLANG
Authors: Parsons Ian
Published: December 2020

Karlheinz Stockhausen's cycle of chamber and electronic music, KLANG – die 24 Stunden des Tages (SOUND – The 24 Hours of the Day) was one of several music cycles, both realised and planned, in which the composer sought to capture the passage and meaning of time. Stockhausen's death in 2007 left KLANG with only 21 of its proposed 24 pieces composed. This article draws on Martin Heidegger's concept of time as ‘the horizon for the understanding of being’ as a lens through which to examine the musical content and imagery of KLANG and as a means of understanding the notion of being that Stockhausen conveyed in these compositions written at the end of his life. It will suggest a significant difference in Stockhausen's thinking about the nature of life and being, moving from the cyclic concepts conveyed in the earlier time-focused works such as SIRIUS and LICHT to a more linear notion of being in KLANG. Finally, the article will use this analysis to suggest that, despite Stockhausen's stated intentions to compose two more time-focused cycles after KLANG, he had begun to confront his own mortality, while continuing to believe in the possibility, if not the knowability, of hope beyond death.
Recent advances in processing negation
Authors: Morante Roser , Blanco Eduardo
Published: December 2020

Negation is a complex linguistic phenomenon present in all human languages. It can be seen as an operator that transforms an expression into another expression whose meaning is in some way opposed to the original expression. In this article, we survey previous work on negation with an emphasis on computational approaches. We start defining negation and two important concepts: scope and focus of negation. Then, we survey work in natural language processing that considers negation primarily as a means to improve the results in some task. We also provide information about corpora containing negation annotations in English and other languages, which usually include a combination of annotations of negation cues, scopes, foci, and negated events. We continue the survey with a description of automated approaches to process negation, ranging from early rule-based systems to systems built with traditional machine learning and neural networks. Finally, we conclude with some reflections on current progress and future directions.
Aerobic and anaerobic iron oxidizers together drive denitrification and carbon cycling at marine iron-rich hydrothermal vents
Authors: McAllister Sean M , Vandzura Rebecca , Keffer Jessica L , Polson Shawn W , Chan Clara S
Published: December 2020

In principle, iron oxidation can fuel significant primary productivity and nutrient cycling in dark environments such as the deep sea. However, we have an extremely limited understanding of the ecology of iron-based ecosystems, and thus the linkages between iron oxidation, carbon cycling, and nitrate reduction. Here we investigate iron microbial mats from hydrothermal vents at Lōʻihi Seamount, Hawaiʻi, using genome-resolved metagenomics and metatranscriptomics to reconstruct potential microbial roles and interactions. Our results show that the aerobic iron-oxidizing Zetaproteobacteria are the primary producers, concentrated at the oxic mat surface. Their fixed carbon supports heterotrophs deeper in the mat, notably the second most abundant organism, Candidatus Ferristratum sp. (uncultivated gen. nov.) from the uncharacterized DTB120 phylum. Candidatus Ferristratum sp., described using nine high-quality metagenome-assembled genomes with similar distributions of genes, expressed nitrate reduction genes narGH and the iron oxidation gene cyc2 in situ and in response to Fe(II) in a shipboard incubation, suggesting it is an anaerobic nitrate-reducing iron oxidizer. Candidatus Ferristratum sp. lacks a full denitrification pathway, relying on Zetaproteobacteria to remove intermediates like nitrite. Thus, at Lōʻihi, anaerobic iron oxidizers coexist with and are dependent on aerobic iron oxidizers. In total, our work shows how key community members work together to connect iron oxidation with carbon and nitrogen cycling, thus driving the biogeochemistry of exported fluids.
Deubiquitylases in developmental ubiquitin signaling and congenital diseases
Authors: Basar Mohammed A. , Beck David B. , Werner Achim
Published: December 2020

Metazoan development from a one-cell zygote to a fully formed organism requires complex cellular differentiation and communication pathways. To coordinate these processes, embryos frequently encode signaling information with the small protein modifier ubiquitin, which is typically attached to lysine residues within substrates. During ubiquitin signaling, a three-step enzymatic cascade modifies specific substrates with topologically unique ubiquitin modifications, which mediate changes in the substrate’s stability, activity, localization, or interacting proteins. Ubiquitin signaling is critically regulated by deubiquitylases (DUBs), a class of ~100 human enzymes that oppose the conjugation of ubiquitin. DUBs control many essential cellular functions and various aspects of human physiology and development. Recent genetic studies have identified mutations in several DUBs that cause developmental disorders. Here we review principles controlling DUB activity and substrate recruitment that allow these enzymes to regulate ubiquitin signaling during development. We summarize key mechanisms of how DUBs control embryonic and postnatal differentiation processes, highlight developmental disorders that are caused by mutations in particular DUB members, and describe our current understanding of how these mutations disrupt development. Finally, we discuss how emerging tools from human disease genetics will enable the identification and study of novel congenital disease-causing DUBs.
Zero-bias mid-infrared graphene photodetectors with bulk photoresponse and calibration-free polarization detection
Authors: Wei Jingxuan , Li Ying , Wang Lin , Liao Wugang , Dong Bowei , Xu Cheng , Zhu Chunxiang , Ang Kah-Wee , Qiu Cheng-Wei , Lee Chengkuo
Published: December 2020

Bulk photovoltaic effect (BPVE), featuring polarization-dependent uniform photoresponse at zero external bias, holds potential for exceeding the Shockley-Queisser limit in the efficiency of existing opto-electronic devices. However, the implementation of BPVE has been limited to the naturally existing materials with broken inversion symmetry, such as ferroelectrics, which suffer low efficiencies. Here, we propose metasurface-mediated graphene photodetectors with cascaded polarization-sensitive photoresponse under uniform illumination, mimicking an artificial BPVE. With the assistance of non-centrosymmetric metallic nanoantennas, the hot photocarriers in graphene gain a momentum upon their excitation and form a shift current which is nonlocal and directional. Thereafter, we demonstrate zero-bias uncooled mid-infrared photodetectors with three orders higher responsivity than conventional BPVE and a noise equivalent power of 0.12 nW Hz−1/2. Besides, we observe a vectorial photoresponse which allows us to detect the polarization angle of incident light with a single device. Our strategy opens up alternative possibilities for scalable, low-cost, multifunctional infrared photodetectors.
Organism body size structures the soil microbial and nematode community assembly at a continental and global scale
Authors: Luan Lu , Jiang Yuji , Cheng Menghua , Dini-Andreote Francisco , Sui Yueyu , Xu Qinsong , Geisen Stefan , Sun Bo
Published: December 2020

Body size is a key life-history trait that influences community assembly by affecting how ecological processes operate at the organism level. However, the extent to which the relative influences of ecological processes mediate the assembly of differentially sized soil organisms is still unknown. Here, we investigate the community assembly of differentially sized soil microorganisms and microfauna using a continental-scale sampling effort combined with a global-scale meta-analysis. Our results reveal a general relationship between organism body size and the stochastic-deterministic balance operating on community assembly. The smallest microorganisms (bacteria) are relatively more influenced by dispersal-based stochastic processes, while larger ones (fungi, protists and nematodes) are more structured by selection-based deterministic processes. This study elucidates a significant and consistent relationship between an organism life-history trait and how distinct ecological processes operate in mediating their respective community assemblages, thus providing a better understanding of the mechanisms supporting soil biodiversity.
Giant thermoelectric power factor in charged ferroelectric domain walls of GeTe with Van Hove singularities
Authors: Dangić Ðorđe , Fahy Stephen , Savić Ivana
Published: December 2020

Increasing the Seebeck coefficient S in thermoelectric materials usually drastically decreases the electrical conductivity σ, making significant enhancement of the thermoelectric power factor σS2 extremelly challenging. Here we predict, using first-principles calculations, that the extraordinary properties of charged ferroelectric domain walls (DWs) in GeTe enable a five-fold increase of σS2 in the DW plane compared to bulk. The key reasons for this enhancement are the confinement of free charge carriers at the DWs and Van Hove singularities in the DW electronic band structure near the Fermi level. These effects lead to an increased energy dependence of the DW electronic transport properties, resulting in more than a two-fold increase of S with respect to bulk, without considerably degrading the in-plane σ. We propose a design of a nano-thermoelectric device that utilizes the exceptional thermoelectric properties of charged ferroelectric DWs. Our findings should inspire further investigation of ferroelectric DWs as efficient thermoelectric materials.
Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate
Authors: Roozendaal Ramon , Hendriks Jenny , van Effelterre Thierry , Spiessens Bart , Dekking Liesbeth , Solforosi Laura , Czapska-Casey Dominika , Bockstal Viki , Stoop Jeroen , Splinter Daniel , Janssen Sarah , Baelen Ben van , Verbruggen Nadia , Serroyen Jan , Dekeyster Eline , Volkmann Ariane , Wollmann Yvonne , Carrion Ricardo , Giavedoni Luis D. , Robinson Cynthia , Leyssen Maarten , Douoguih Macaya , Luhn Kerstin , Pau Maria Grazia , Sadoff Jerry , Vandebosch An , Schuitemaker Hanneke , Zahn Roland , Callendret Benoit
Published: December 2020

It has been proven challenging to conduct traditional efficacy trials for Ebola virus (EBOV) vaccines. In the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model. We here propose to infer the protective effect of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen with an 8-week interval in humans by immunobridging. Immunogenicity and protective efficacy data were obtained for Ad26.ZEBOV and MVA-BN-Filo vaccine regimens using a fully lethal EBOV Kikwit challenge model in cynomolgus monkeys (nonhuman primates [NHP]). The association between EBOV neutralizing antibodies, glycoprotein (GP)-binding antibodies, and GP-reactive T cells and survival in NHP was assessed by logistic regression analysis. Binding antibodies against the EBOV surface GP were identified as the immune parameter with the strongest correlation to survival post EBOV challenge, and used to infer the predicted protective effect of the vaccine in humans using published data from phase I studies. The human vaccine-elicited EBOV GP-binding antibody levels are in a range associated with significant protection against mortality in NHP. Based on this immunobridging analysis, the EBOV GP-specific-binding antibody levels elicited by the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in humans will likely provide protection against EBOV disease.
Plasma-MDS, a metadata schema for plasma science with examples from plasma technology
Authors: Franke Steffen , Paulet Lucian , Schäfer Jan , O’Connell Deborah , Becker Markus M.
Published: December 2020

A metadata schema, named Plasma-MDS, is introduced to support research data management in plasma science. Plasma-MDS is suitable to facilitate the publication of research data following the FAIR principles in domain-specific repositories and with this the reuse of research data for data driven plasma science. In accordance with common features in plasma science and technology, the metadata schema bases on the concept to separately describe the source generating the plasma, the medium in which the plasma is operated in, the target the plasma is acting on, and the diagnostics used for investigation of the process under consideration. These four basic schema elements are supplemented by a schema element with various attributes for description of the resources, i.e. the digital data obtained by the applied diagnostic procedures. The metadata schema is first applied for the annotation of datasets published in INPTDAT—the interdisciplinary data platform for plasma technology.
Herpes simplex virus 1 targets IRF7 via ICP0 to limit type I IFN induction
Authors: Shahnazaryan David , Khalil Rana , Wynne Claire , Jefferies Caroline A. , Ní Gabhann-Dromgoole Joan , Murphy Conor C.
Published: December 2020

Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV-1) infection, is the commonest cause of infectious blindness in the developed world. Following infection the virus is initially suspended in the tear film, where it encounters a multi-pronged immune response comprising enzymes, complement, immunoglobulins and crucially, a range of anti-viral and pro-inflammatory cytokines. However, given that HSV-1 can overcome innate immune responses to establish lifelong latency throughout a susceptible individual’s lifetime, there is significant interest in understanding the mechanisms employed by HSV-1 to downregulate the anti-viral type I interferon (IFN) mediated immune responses. This study aimed to investigate the interactions between infected cell protein (ICP)0 and key elements of the IFN pathway to identify possible novel targets that contribute to viral immune evasion. Reporter gene assays demonstrated the ability of ICP0 to inhibit type I IFN activity downstream of pathogen recognition receptors (PRRs) which are known to be involved in host antiviral defences. Further experiments identified interferon regulatory factor (IRF)7, a driver of type I IFN, as a potential target for ICP0. These findings increase our understanding of the pathogenesis of HSK and suggest IRF7 as a potential therapeutic target.
Noise representations of open system dynamics
Authors: Szańkowski Piotr , Cywiński Łukasz
Published: December 2020

We analyze the conditions under which the dynamics of a quantum system open to a given environment can be simulated with an external noisy field that is a surrogate for the environmental degrees of freedom. We show that such a field is either a subjective or an objective surrogate; the former is capable of simulating the dynamics only for the specific system–environment arrangement, while the latter is an universal simulator for any system interacting with the given environment. Consequently, whether the objective surrogate field exists and what are its properties is determined exclusively by the environment. Thus, we are able to formulate the sufficient criterion for the environment to facilitate its surrogate, and we identify a number of environment types that satisfy it. Finally, we discuss in what sense the objective surrogate field representation can be considered classical and we explain its relation to the formation of system–environment entanglement, and the back-action exerted by the system onto environment.
Cross-testing of major molecular markers indicates distinct pathways of tumorigenesis in gastric adenocarcinomas and synchronous gastrointestinal stromal tumors
Authors: Kocsmár Éva , Kocsmár Ildikó , Szalai Luca , Lendvai Gábor , Szijártó Attila , Schaff Zsuzsa , Kiss András , Kovalszky Ilona , Papp Gergő , Lotz Gábor
Published: December 2020

Small subtype of the gastrointestinal stromal tumor (micro-GIST, MG) is usually asymptomatic and is frequently found incidentally in association with gastric adenocarcinoma (GAC). The background of this coincidence is still an open question. This study comprehensively characterized nine MGs and GACs present in the same surgical specimen by cross-testing the markers of the major pathogenetic pathways of both tumor types. All of the MGs were immunohistochemically positive for CD117/KIT, CD34, and DOG1. DOG1 was also detected in four GACs. Four MGs carried mutations in c-KIT (exons 9, 11, and 13) and two cases in PDGFRα (exon 18). None of the GACs carried activating mutations in c-KIT or PDGFRα. MMR immunopanel identified one GAC as microsatellite unstable tumor. No EBV-positive tumor was found. According to the TCGA molecular classification, one GAC was categorized in the MSI subgroup, three GACs in the genomically stable subgroup, and the rest into the chromosomal instability subgroup. Although a common carcinogenic effect cannot be ruled out, our data suggest a distinct molecular background in the evolvement of the synchronous MGs and GACs. The presence of a MG in gastric resection specimens may be indicative of the development of synchronous malignant tumors in or outside the stomach.
Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway
Authors: Peterson Jackson , Li Siqi , Kaltenbrun Erin , Erdogan Ozgun , Counter Christopher M.
Published: December 2020

The ability to translate three nucleotide sequences, or codons, into amino acids to form proteins is conserved across all organisms. All but two amino acids have multiple codons, and the frequency that such synonymous codons occur in genomes ranges from rare to common. Transcripts enriched in rare codons are typically associated with poor translation, but in certain settings can be robustly expressed, suggestive of codon-dependent regulation. Given this, we screened a gain-of-function library for human genes that increase the expression of a GFPrare reporter encoded by rare codons. This screen identified multiple components of the mitogen activated protein kinase (MAPK) pathway enhancing GFPrare expression. This effect was reversed with inhibitors of this pathway and confirmed to be both codon-dependent and occur with ectopic transcripts naturally coded with rare codons. Finally, this effect was associated, at least in part, with enhanced translation. We thus identify a potential regulatory module that takes advantage of the redundancy in the genetic code to modulate protein expression.
Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
Authors: Fodale Valentina , Pintauro Roberta , Daldin Manuel , Altobelli Roberta , Spiezia Maria Carolina , Bisbocci Monica , Macdonald Douglas , Bresciani Alberto
Published: December 2020

Huntington’s disease (HD) is a monogenetic neurodegenerative disorder that is caused by the expansion of a polyglutamine region within the huntingtin (HTT) protein, but there is still an incomplete understanding of the molecular mechanisms that drive pathology. Expression of the mutant form of HTT is a key aspect of diseased tissues, and the most promising therapeutic approaches aim to lower expanded HTT levels. Consequently, the investigation of HTT expression in time and in multiple tissues, with assays that accurately quantify expanded and non-expanded HTT, are required to delineate HTT homeostasis and to best design and interpret pharmacodynamic readouts for HTT lowering therapeutics. Here we evaluate mutant polyglutamine-expanded (mHTT) and polyglutamine-independent HTT specific immunoassays for validation in human HD and control fibroblasts and use to elucidate the CSF/brain and peripheral tissue expression of HTT in preclinical HD models.
Identification of hnRNP-A1 as a pharmacodynamic biomarker of type I PRMT inhibition in blood and tumor tissues
Authors: Noto Paul B. , Sikorski Timothy W. , Zappacosta Francesca , Wagner Craig D. , Montes de Oca Rocio , Szapacs Matthew E. , Annan Roland S. , Liu Yan , McHugh Charles F. , Mohammad Helai P. , Piccoli Steven P. , Creasy Caretha L.
Published: December 2020

Arginine methylation has been recognized as a post-translational modification with pleiotropic effects that span from regulation of transcription to metabolic processes that contribute to aberrant cell proliferation and tumorigenesis. This has brought significant attention to the development of therapeutic strategies aimed at blocking the activity of protein arginine methyltransferases (PRMTs), which catalyze the formation of various methylated arginine products on a wide variety of cellular substrates. GSK3368715 is a small molecule inhibitor of type I PRMTs currently in clinical development. Here, we evaluate the effect of type I PRMT inhibition on arginine methylation in normal human peripheral blood mononuclear cells and utilize a broad proteomic approach to identify type I PRMT substrates. This work identified heterogenous nuclear ribonucleoprotein A1 (hnRNP-A1) as a pharmacodynamic biomarker of type I PRMT inhibition. Utilizing targeted mass spectrometry (MS), methods were developed to detect and quantitate changes in methylation of specific arginine residues on hnRNP-A1. This resulted in the development and validation of novel MS and immune assays useful for the assessment of GSK3368715 induced pharmacodynamic effects in blood and tumors that can be applied to GSK3368715 clinical trials.
Piezoelectric and dielectric properties of Bi3TiNbO9 prepared by hot pressing from powders activated using the serial dilution method
Authors: Spitsin A. I. , Bush A. A. , Kamentsev K. E.
Published: December 2020

Bi-based layer structure ferroelectrics are the most promising compounds for the fabrication of high-temperature piezoelectric materials. Studies aiming to develop and optimize the techniques to produce efficient high-density piezoelectric ceramics, and to investigate the effects of ceramics production conditions on their structure and functional properties, have become high-priority objectives of modern piezo-engineering. We applied ultra high dilution (UHD) technology to pre-treat Bi3TiNbO9 powders and used hot pressing to prepare perovskite-layer structured ceramic specimens. Main characteristics of the synthesized piezoelectric ceramic specimens (the dimensions of the Bi3TiNbO9 orthorhombic unit cell, dielectric permittivity, dielectric loss, piezoelectric coefficient d33 and pyroelectric coefficient pσ) and their temperature-dependent variations were studied using piezoelectric, dielectric, and pyroelectric measurements. X-ray diffraction studies demonstrated that the prepared ceramics were single phased, and highly textured, as their plate-like crystallites were preferentially aligned perpendicularly to the pressure axis on hot pressing. For d33, an increase in values of more than 20% was found for samples obtained using a combined modification of the UHD technology and hot pressing (12 pC/N) relative to intact samples, and more than two times relative to unmodified Bi3TiNbO9 ceramics (6 pC/N). Due to their characteristics, the obtained ceramics are promising materials for high-temperature applications; of particular interest is potential use, as electroacoustic transducers and sensors for operation at high temperatures. Thus, the UHD technology can modify the properties of ceramics and is relatively easy to implement. This makes it attractive for use in various fields of science and technology.
An altered microbiome in urban coyotes mediates relationships between anthropogenic diet and poor health
Authors: Sugden Scott , Sanderson Dana , Ford Kyra , Stein Lisa Y. , St. Clair Colleen Cassady
Published: December 2020

Generalist species able to exploit anthropogenic food sources are becoming increasingly common in urban environments. Coyotes (Canis latrans) are one such urban generalist that now resides in cities across North America, where diseased or unhealthy coyotes are frequently reported in cases of human-wildlife conflict. Coyote health and fitness may be related to habitat use and diet via the gut microbiome, which has far-reaching effects on animal nutrition and physiology. In this study, we used stomach contents, stable isotope analysis, 16S rRNA gene amplicon sequencing, and measures of body condition to identify relationships among habitat use, diet, fecal microbiome composition, and health in urban and rural coyotes. Three distinct relationships emerged: (1) Urban coyotes consumed more anthropogenic food, which was associated with increased microbiome diversity, higher abundances ofStreptococcusandEnterococcus, and poorer average body condition. (2) Conversely, rural coyotes harbored microbiomes rich in Fusobacteria,Sutterella,andAnaerobiospirillum, which were associated with protein-rich diets and improved body condition. (3) Diets rich in anthropogenic food were associated with increased abundances ofErysipelotrichiaceae,Lachnospiraceae, andCoriobacteriaceae, which correlated with larger spleens in urban coyotes. Urban coyotes also had an increased prevalence of the zoonotic parasiteEchinococcus multilocularis, but there were no detectable connections between parasite infection and microbiome composition. Our results demonstrate how the consumption of carbohydrate-rich anthropogenic food by urban coyotes alters the microbiome to negatively affect body condition, with potential relationships to parasite susceptibility and conflict-prone behavior.
Curcumin protects rat hippocampal neurons against pseudorabies virus by regulating the BDNF/TrkB pathway
Authors: Yang Bingjie , Luo Guodong , Zhang Chen , Feng Luqiu , Luo Xianmei , Gan Ling
Published: December 2020

Pseudorabies virus (PRV) infection can elicit nervous system disorders. Curcumin has been reported to have neuroprotective effects. However, whether curcumin can protect neurons against PRV infection and the underlying mechanisms remain unclear. In the present study, for the first time, the protective effects of curcumin against PRV-induced oxidative stress, apoptosis, and mitochondrial dysfunction in rat hippocampal neurons and the brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway were investigated. Results indicated that PRV with a titer of 3.06 × 106 TCID50 (50% tissue culture infective dose) induced oxidative damage of hippocampal neurons 2 h post-infection and that 10 μM curcumin improved the viability of PRV-infected hippocampal neurons. Blocking the BDNF/TrkB pathway reversed the neuroprotective effects of curcumin, which were imparted by decreasing the PRV-induced upregulation of nitric oxide synthase expression, repressing the PRV-activated mitochondrial apoptotic pathway, and mitochondrial dysfunction. To conclude, curcumin exhibited a neuroprotective role against PRV infection by upregulating the BDNF/TrkB pathway. This study provides insight into the anti-PRV neuroprotective application of curcumin and the underlying mechanism in the prophylaxis and treatment of neurological disorders caused by PRV infection.
Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion
Authors: Rivera Kevin O. , Russo Fabrizio , Boileau Ryan M. , Tomlinson Ryan E. , Miclau Theodore , Marcucio Ralph S. , Desai Tejal A. , Bahney Chelsea S.
Published: December 2020

There are currently no pharmacological approaches in fracture healing designed to therapeutically stimulate endochondral ossification. In this study, we test nerve growth factor (NGF) as an understudied therapeutic for fracture repair. We first characterized endogenous expression of Ngf and its receptor tropomyosin receptor kinase A (TrkA) during tibial fracture repair, finding that they peak during the cartilaginous phase. We then tested two injection regimens and found that local β-NGF injections during the endochondral/cartilaginous phase promoted osteogenic marker expression. Gene expression data from β-NGF stimulated cartilage callus explants show a promotion in markers associated with endochondral ossification such as Ihh, Alpl, and Sdf-1. Gene ontology enrichment analysis revealed the promotion of genes associated with Wnt activation, PDGF- and integrin-binding. Subsequent histological analysis confirmed Wnt activation following local β-NGF injections. Finally, we demonstrate functional improvements to bone healing following local β-NGF injections which resulted in a decrease in cartilage and increase of bone volume. Moreover, the newly formed bone contained higher trabecular number, connective density, and bone mineral density. Collectively, we demonstrate β-NGF’s ability to promote endochondral repair in a murine model and uncover mechanisms that will serve to further understand the molecular switches that occur during cartilage to bone transformation.
Exploring the effectiveness of a COVID-19 contact tracing app using an agent-based model
Authors: Almagor Jonatan , Picascia Stefano
Published: December 2020

A contact-tracing strategy has been deemed necessary to contain the spread of COVID-19 following the relaxation of lockdown measures. Using an agent-based model, we explore one of the technology-based strategies proposed, a contact-tracing smartphone app. The model simulates the spread of COVID-19 in a population of agents on an urban scale. Agents are heterogeneous in their characteristics and are linked in a multi-layered network representing the social structure—including households, friendships, employment and schools. We explore the interplay of various adoption rates of the contact-tracing app, different levels of testing capacity, and behavioural factors to assess the impact on the epidemic. Results suggest that a contact tracing app can contribute substantially to reducing infection rates in the population when accompanied by a sufficient testing capacity or when the testing policy prioritises symptomatic cases. As user rate increases, prevalence of infection decreases. With that, when symptomatic cases are not prioritised for testing, a high rate of app users can generate an extensive increase in the demand for testing, which, if not met with adequate supply, may render the app counterproductive. This points to the crucial role of an efficient testing policy and the necessity to upscale testing capacity.
Tracing selection signatures in the pig genome gives evidence for selective pressures on a unique curly hair phenotype in Mangalitza
Authors: Schachler Kathrin , Distl Ottmar , Metzger Julia
Published: December 2020

Selection for desirable traits and breed-specific phenotypes has left distinctive footprints in the genome of pigs. As representative of a breed with strong selective traces aiming for robustness, health and performance, the Mangalitza pig, a native curly-haired pig breed from Hungary, was investigated in this study. Whole genome sequencing and SNP chip genotyping was performed to detect runs of homozygosity (ROH) in Mangalitza and Mangalitza-crossbreeds. We identified breed specific ROH regions harboring genes associated with the development of the curly hair type and further characteristics of this breed. Further analysis of two matings of Mangalitza with straight-coated pig breeds confirmed an autosomal dominant inheritance of curly hair. Subsequent scanning of the genome for variant effects on this trait revealed two variants potentially affecting hair follicle development and differentiation. Validation in a large sample set as well as in imputed SNP data confirmed these variants to be Mangalitza-specific. Herein, we demonstrated how strong artificial selection has shaped the genome in Mangalitza pigs and left traces in the form of selection signatures. This knowledge on genomic variation promoting unique phenotypes like curly hair provides an important resource for futures studies unraveling genetic effects for special characteristics in livestock.
The role of semantics in the perceptual organization of shape
Authors: Schmidt Filipp , Kleis Jasmin , Morgenstern Yaniv , Fleming Roland W.
Published: December 2020

Establishing correspondence between objects is fundamental for object constancy, similarity perception and identifying transformations. Previous studies measured point-to-point correspondence between objects before and after rigid and non-rigid shape transformations. However, we can also identify ‘similar parts’ on extremely different objects, such as butterflies and owls or lizards and whales. We measured point-to-point correspondence between such object pairs. In each trial, a dot was placed on the contour of one object, and participants had to place a dot on ‘the corresponding location’ of the other object. Responses show correspondence is established based on similarities between semantic parts (such as head, wings, or legs). We then measured correspondence between ambiguous objects with different labels (e.g., between ‘duck’ and ‘rabbit’ interpretations of the classic ambiguous figure). Despite identical geometries, correspondences were different across the interpretations, based on semantics (e.g., matching ‘Head’ to ‘Head’, ‘Tail’ to ‘Tail’). We present a zero-parameter model based on labeled semantic part data (obtained from a different group of participants) that well explains our data and outperforms an alternative model based on contour curvature. This demonstrates how we establish correspondence between very different objects by evaluating similarity between semantic parts, combining perceptual organization and cognitive processes.