bluuebunny/crossref_metadata_2025 huggingface dataset:
Peter Dickinson: Words and Music
Authors: Dickinson Peter
Published: June 2021

Peter Dickinson has made an enduring contribution to British musical life, and his music has been regularly performed and recorded by leading musicians. His writings, brought together here for the first time, are equally noteworthy. Covering well over half a century, the subjects are fascinatingly varied. Apart from musical interests ranging from Charles Ives to John Cage, they touch on literature; and Dickinson's meetings with W.H. Auden and Philip Larkin are an intriguing insight that led to his Auden songs and the chamber work Larkin's Jazz. American themes are prominent in this collection. There are unique reviews of concert life in New York from 1959 to 1961; an account of the teaching programme at the Juilliard School of Music at that time; three studies of Ives; and featurescontaining original material on Copland, Thomson and Cage, all of whom Dickinson knew. Features on Erik Satie include the imaginary discussion marking his centenary in 1966. Dickinson also writes about his own music, providing an insight into what it was like being a British composer in the later twentieth century. Peter Dickinson was born in Lancashire in 1934 and now lives in Suffolk. His 80th birthday was marked by a whole variety of tributes, including concerts, articles, broadcasts and various interviews - some included in this book. PETER DICKINSON is a British composer andpianist as well as author and editor of Boydell/URP books on Berkeley, Copland, Cage, Barber and Berners. As a pianist, Dickinson had a twenty-five-year, international partnership with his sister, the mezzo Meriel Dickinson, for whom he wrote song cycles to poems of E. E. Cummings, Gregory Corso and Stevie Smith. He was a regular contributor to BBC Radio 3 and is widely read as a critic on the Gramophone. He is an Emeritus Professor of the Universities of Keele and London and is chair of the Bernarr Rainbow Trust, for which he has edited several books on music education.
The Index of Middle English Prose
Authors: Lucas Angela M.
Published: June 2021

This volume provides detailed descriptions of Middle English prose materials found in the important manuscript collections of seven Cambridge Colleges: Christ's, Emmanuel, Jesus, Selwyn and Sidney Sussex Colleges, Peterhouse and Trinity Hall. The texts fall roughly into two categories: religious and devotional, or scientific. The former include Wycliffite New Testaments; Emmanuel College's complete Wycliffite Bible; Richard Rolle's Commentary on the Psalms in Sidney Sussex College, and, in Trinity Hall, the Twelve Conclusions of the Lollards in a splendid manuscript designed forpresentation to Richard II. In the second category, there are several of outstanding interest: Jesus College Q.G.23 is a beautifully decorated English translation of the Chirurgie of Guy de Chauliac, while Peterhouse MS 75 is the sole manuscript of The Equatorie of the Planetis. As with all previous volumes in the series, this Handlist concludes with an alphabetical index of Incipits and Explicits intended to form part of an eventual Index of Middle English Prose. Angela M. Lucas is a Senior Member of Wolfson College, Cambridge.
The Music of Frederick Delius
Authors: Dibble Jeremy
Published: June 2021

This book examines Delius's individual approaches to genre, form, harmony, orchestration and literary texts which gave the composer's musical style such a unique voice.
The Battle of Peta (1822): when the Philhellenes fought like the Greek irregulars
Authors: Tompros Nikos , Kanellopoulos Nikos
Published: June 2021

The most direct and definite expression of Philhellenism during the Greek War of Independence (1821–9) was military action by European volunteers, generally officers, on the side of the revolutionaries. This article discusses the Philhellenes’ military action at the Battle of Peta in 1822, as recorded in the diary of one of the few survivors, the physician Johann-Daniel Elster. Elster's information is compared with other Greek and European sources about the battle and the conditions of the campaign in Epirus and the circumstances that led to the Philhellenes’ defeat re-evaluated.
Psychosocial burden of neglected tropical diseases in eastern Colombia: an explorative qualitative study in persons affected by leprosy, cutaneous leishmaniasis and Chagas disease
Authors: van Wijk Robin , van Selm Lena , Barbosa Martha C. , van Brakel Wim H. , Waltz Mitzi , Philipp Puchner Karl
Published: June 2021

Background

Leprosy, cutaneous leishmaniasis (CL) and Chagas disease (CD) are neglected tropical diseases (NTDs) with a high psychosocial burden in Norte de Santander and Arauca in Colombia. This study provides insights into affected persons' feelings, perceptions and experiences to better understand the nature of this burden.

Methods

In 2018, 34 leprosy, CD and CL patients participated in four focus groups discussing the influence of the disease on mental well-being, social participation and stigma. Additionally, 13 leprosy patients participated in semi-structured interviews to further explore the health-related stigma related to this disease. Audio recordings were transcribed verbatim, and open coding was used to identify the most relevant categories and themes.

Results

Persons suffering from CD reported that their mental distress was mainly caused by impairments and stress related to the progressive and incurable nature of the disease. Persons affected by CL perceived the treatment for the disease as having the most impact on their psychosocial well-being. Persons affected by leprosy reported suffering most from anticipated and experienced stigma.

Conclusions

The findings indicate that these diseases are likely to impose a significant psychosocial burden on patients in the studied regions, even though these vary per condition. Consistent data collection on the psychosocial burden and the sharing of knowledge of effective interventions can contribute to the holistic approach needed to win the fight against NTDs.
Are voters' views about proportional outcomes shaped by partisan preferences? A survey experiment in the context of a real election
Authors: Blais André , Sevi Semra , Plescia Carolina
Published: June 2021

We examine citizens' evaluations of majoritarian and proportional electoral outcomes through an innovative experimental design. We ask respondents to react to six possible electoral outcomes during the 2019 Canadian federal election campaign. There are two treatments: the performance of the party and the proportionality of electoral outcomes. There are three performance conditions: the preferred party's vote share corresponds to vote intentions as reported in the polls at the time of the survey (the reference), or it gets 6 percentage points more (fewer) votes. There are two electoral outcome conditions: disproportional and proportional. We find that proportional outcomes are slightly preferred and that these preferences are partly conditional on partisan considerations. In the end, however, people focus on the ultimate outcome, that is, who is likely to form the government. People are happy when their party has a plurality of seats and is therefore likely to form the government, and relatively unhappy otherwise. We end with a discussion of the merits and limits of our research design.
How to Read This Book: Jewish Lights Publishing and the Pragmatics of Spiritual Reading
Authors: Levites Arielle
Published: June 2021

This paper considers how print culture was mobilized in the early 1990s to transmit spiritual beliefs, experiences, and emotions through an examination of the pragmatics of reading endorsed by Jewish Lights Publishing (founded in 1990). Using interviews, advertisements, internal memos, books, jacket copy, and reviews, this study reconstructs the ecology out of which Jewish Lights Publishing emerged, as well as the goals and assumptions about Judaism, Jews, and books that animated the creation of a new, and specifically spiritual, Jewish press. I argue that what makes Jewish Lights a spiritual press is not only the content and design of the books, but also the instructions the press offers for how to use the books it produces. This paper is not only about the production and circulation of spiritual Jewish books, but the production and circulation of beliefs about what spiritual Jewish books do for an imagined community of readers.
Do dietary patterns and morbidities have a relationship with primary infertility among women? A study from NFHS-4 (2015–16), India
Authors: Unisa Sayeed , Negi Kanchan , Pujari Sucharita , Chaurasia Vaishali
Published: June 2021

This study assessed the rate of primary infertility and its associated factors among 402,807 currently married women aged 20–49 years in India using National Family Health Survey-4 data collected in 2015–2016. Dietary patterns and selected morbidities were included as independent variables, and socioeconomic variables were considered as covariates. Bivariate and multivariate analyses were done to estimate the prevalence of primary infertility and assess its association with the selected variables, respectively. The rate of primary infertility among currently married women in India in 2015–16 was 1.9% and this was significantly associated with younger age (<35 years), higher age at marriage (≥18 years), urban residence, higher secondary or above education and poverty. The consumption of dairy products (OR = 0.79, CI = 0.73–0.86), dark green leafy vegetables (OR = 0.57, CI = 0.39–0.81) and fruit (OR = 0.88, CI = 0.77–1.01) significantly reduced the odds of primary infertility. Daily consumption of fish and aerated drinks was related to 1.06–1.21 times higher odds of primary infertility. Overweight/obesity, high blood pressure and high blood glucose levels were associated with 1.08–1.21 times elevated odds of primary infertility. Thyroid disorder (OR = 1.38, CI = 1.21–1.60), heart disease (OR = 1.17, CI = 1.16–1.19) and severe anaemia (OR = 1.24, CI = 1.00–1.53) were associated with an increased likelihood of primary infertility among women (OR 1.17–1.39, CI 1.00–1.60). The findings provide compelling evidence that primary infertility among women is related to dietary patterns and morbidities. Interventions and programmes targeting the promotion of healthy diets and lifestyles could be beneficial in addressing the issue of primary infertility among women.
External auditory canal exostoses: long-term surgical satisfaction and its relationship with surgical complications
Authors: Costa J R , Castro A , Lino J , Soares T , Almeida e Sousa C
Published: June 2021

Objective

The main purpose of the present study was to evaluate whether complications related to surgery for exostoses are associated with a decrease in patients’ quality of life.

Methods

This was a retrospective study for which the following information was collected: sex, age, pre- and post-operative symptoms, pre- and post-operative audiological evaluation results, surgical approach, instruments used, complications, and Glasgow Benefit Inventory score.

Results

The study included 67 patients (94 ears). The three main complaints reported were wax retention, otitis externa and hearing loss. Surgical complications occurred in 14.9 per cent of patients. Patients experienced a significant benefit from surgery, especially in relation to somatic state, with a global Glasgow Benefit Inventory score of + 44.3. No significant difference was found between the global Glasgow Benefit Inventory changes and surgery-related complications (p = 0.093).

Conclusion

After surgery for exostoses, the vast majority of patients showed improvement. Complications related to surgery in general do not seem to influence patients’ satisfaction with surgery.
Congenital toxoplasmosis in humans: an update of worldwide rate of congenital infections
Authors: Dubey J. P. , Murata F. H. A. , Cerqueira-Cézar C. K. , Kwok O. C. H. , Villena I.
Published: June 2021

The morbidity due to congenital toxoplasmosis in humans is very high. Most of these infected children are likely to develop symptoms of clinical toxoplasmosis. Sequelae in fetus resulting from Toxoplasma gondii infections in women who become infected with this parasite during pregnancy can be devastating and enormous efforts are directed in some countries to prevent these consequences. Here, an update on congenital toxoplasmosis in humans, especially the rate of congenital infections in humans worldwide, is provided. Although several countries have surveillance programmes, most information on the rate of congenital transmission is from France and Brazil. Because of compulsory national screening programme in France to detect and treat women with recently acquired T. gondii infection with anti-toxoplasma therapy, the rate of congenital transmission and the severity of disease in children are declining. Infections by this parasite are widely prevalent in Brazil. The severity of clinical toxoplasmosis in Brazilian children is very high and may be associated with the genetic characteristics of T. gondii isolates prevailing in animals and humans in Brazil. Virtually little or no information is available on this topic from China, India and other countries in Asia.
Attention-deficit/hyperactivity disorder and other neurodevelopmental disorders in offspring of parents with depression and bipolar disorder
Authors: Propper L. , Sandstrom A. , Rempel S. , Howes Vallis E. , Abidi S. , Bagnell A. , Lovas D. , Alda M. , Pavlova B. , Uher R.
Published: June 2021

Background

Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls.

Method

We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder.

Results

Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23–4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03–3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring.

Conclusions

Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.
Lack of fit with the neighbourhood social environment as a risk factor for psychosis – a national cohort study
Authors: Schofield Peter , Das-Munshi Jayati , Webb Roger T. , Horsdal Henriette Thisted , Pedersen Carsten B. , Agerbo Esben
Published: June 2021

Background

Many studies report an ethnic density effect whereby psychosis incidence among ethnic minority groups is higher in low co-ethnic density areas. It is unclear whether an equivalent density effect applies with other types of socioeconomic disadvantages.

Methods

We followed a population cohort of 2 million native Danes comprising all those born on 1st January 1965, or later, living in Denmark on their 15th birthday. Socioeconomic disadvantage, based on parents' circumstances at age 15 (low income, manual occupation, single parent and unemployed), was measured alongside neighbourhood prevalence of these indices.

Results

Each indicator was associated with a higher incidence of non-affective psychosis which remained the same, or was slightly reduced, if neighbourhood levels of disadvantage were lower. For example, for individuals from a low-income background there was no difference in incidence for those living in areas where a low-income was least common [incidence rate ratio (IRR) 1.01; 95% confidence interval (CI) 0.93–1.10 v. those in the quintile where a low income was most common. Typically, differences associated with area-level disadvantage were the same whether or not cohort members had a disadvantaged background; for instance, for those from a manual occupation background, incidence was lower in the quintile where this was least v. most common (IRR 0.83; 95% CI 0.71–0.97), as it was for those from a non-manual background (IRR 0.77; 95% CI 0.67–0.87).

Conclusion

We found little evidence for group density effects in contrast to previous ethnic density studies. Further research is needed with equivalent investigations in other countries to see if similar patterns are observed.
Review of the direct derivation method: quantitative phase analysis with observed intensities and chemical composition data
Authors: Toraya Hideo
Published: June 2021

The direct derivation (DD) method is a technique for quantitative phase analysis (QPA). It can be characterized by the use of the total sums of scattered/diffracted intensities from individual components as the observed data. The crystal structure parameters are required when we calculate the intensities of reflections or diffraction patterns. Intensity can, however, be calculated only with the chemical composition data if it is not of individual reflections but of a total sum of diffracted/scattered intensities for that material. Furthermore, it can be given in a form of the scattered intensity per unit weight. Therefore, we can calculate the weight proportion of a component material by dividing the total sum of observed scattered/diffracted intensities by the scattered intensity per unit weight. The chemical composition data of samples under investigation are known in almost all cases at the stage of QPA. Thus, a technical problem is how to separate the observed diffraction pattern of a mixture into individual component patterns. Various pattern decomposition techniques currently available can be used for separating the pattern of a mixture. In this report, the theoretical background of the DD method and various techniques for pattern decompositions are reviewed along with the examples of applications.
Three plays and a shared socio-spiritual horizon in the modern Buddhist revivals in India and China
Authors: Zu Jessica
Published: June 2021

The current study reveals that the Buddhist egalitarian spiritual message found global resonance in an era of globalized inequality. By comparing three modern retellings of an ancient romance between an outcaste (untouchable/Dalit) maiden and the Buddha's attendant Ānanda, this study showcases a shared socio-spiritual horizon that emerged in the Indian and Chinese Buddhist revivals and that thwarted colonial epistemic domination and offered powerful social critiques. More specifically, this study shows that the Indian and Chinese afterlives of the romance display innovative formations of Buddhist social consciousness. The authors reinterpreted equality and freedom on Buddhist terms, creating a new standard of civilization. Employing this “already democratic” Buddhist civilization, they launched critiques of the Indian caste system and Chinese patriarchy. This socio-spiritual horizon subverts the typecast images of “spiritual India” and “rational China.” Whereas these images reflect the limits of the comparative lens based on political regimes – namely, Indian democracy and Chinese socialism – the current study goes beyond regime types by examining diverse formations of universal religion in the cultural sphere. More broadly, a critical strategy for provincializing Europe is to block the colonial gaze and instead showcase the vibrant cultural productions and meaning-making that circulated at the margins of empire.
Towards Wind Vector and Wave Height Retrievals Over Inland Waters Using CYGNSS
Authors: Loria Eric , O'Brien Andrew , Zavorotny Valery , Zuffada Cinzia
Published: June 2021

GNSS Reflectometry (GNSS‐R) measurements over inland water bodies, such as lakes, rivers, and wetlands exhibit strong coherent signals. The strength of the coherent reflections is highly sensitive to small‐scale surface roughness. For inland waters, this roughness is primarily due to wind‐driven surface waves. The sensitivity of the coherent reflections to surface roughness can be leveraged to estimate wave height profiles across inland waters. Coupled with a wind wave model, an approach to retrieve a wind vector is described using a forward model, which is potentially able to predict scattered power profiles for different wind speeds and directions and choosing the minimum‐squared error solution. The ability for spaceborne or airborne GNSS‐R to measure an inland water wind vector and wave heights could contribute to scientific applications focused on understanding nearshore ecosystems, monitoring climate change effects on inland waters, sediment resuspension, biomass production, fish habitat, and others. This paper presents a novel approach to potentially retrieve wind vector and wave heights over inland waters using GNSS‐R and discusses the issues with performing such retrievals using simulation and very few available raw signals recorded from CYGNSS satellites.
Contrasting Response of West and East Antarctic Ice Sheets to Glacial Isostatic Adjustment
Authors: Coulon Violaine , Bulthuis Kevin , Whitehouse Pippa L. , Sun Sainan , Haubner Konstanze , Zipf Lars , Pattyn Frank
Published: June 2021

The Antarctic ice sheet (AIS) lies on a solid Earth that displays large spatial variations in rheological properties, with a thin lithosphere and low‐viscosity upper mantle (weak Earth structure) beneath West Antarctica and an opposing structure beneath East Antarctica. This contrast is known to have a significant impact on the ice‐sheet grounding‐line stability. Here, we embed within an ice‐sheet model a modified glacial‐isostatic Elastic Lithosphere‐Relaxing Asthenosphere model that considers a dual pattern for the Earth structure beneath West and East Antarctica supplemented with an approximation of gravitationally consistent geoid changes, allowing to approximate near‐field relative sea‐level changes. We show that this elementary GIA model captures the essence of global Self‐Gravitating Viscoelastic solid‐Earth Models (SGVEMs) and compares well with both SGVEM outputs and geodetic observations, allowing to capture the essential features and processes influencing Antarctic grounding‐line stability in a computationally efficient way. In this framework, we perform a probabilistic assessment of the impact of uncertainties in solid‐Earth rheological properties on the response of the AIS to future warming. Results show that on multicentennial‐to‐millennial timescales, spatial variability in solid‐Earth deformation plays a significant role in promoting the stability of the West Antarctic ice sheet (WAIS). However, WAIS collapse cannot be prevented under high‐emissions climate scenarios. On longer timescales and for unmitigated climate scenarios, continent‐wide mass loss projections may be underestimated because spatially uniform Earth models, as typically considered in numerical ice sheet models, will overestimate the stabilizing effect of GIA across East Antarctica, which is characterized by thick lithosphere and high upper‐mantle viscosity.
A Large Magma Reservoir Beneath the Tengchong Volcano Revealed by Ambient Noise Adjoint Tomography
Authors: Zhao Y. , Guo Z. , Wang K. , Yang Y. J.
Published: June 2021

The Tengchong volcano (TCV) is a large active volcano system in the southeastern Tibetan Plateau. It is characterized by large‐volume magmatic gas emission, active hydrothermal circulation, and intense volcanic and earthquake activities, posing a threat of near future eruptions. However, there is still no available model of the magmatic plumbing system beneath the volcano system, limiting the quantitative assessments of the eruption hazards. Here, we present a high‐resolution 3D model of the TCV constructed using ambient noise adjoint tomography. Our 3D model reveals a large basaltic magma reservoir with a volume of ∼7,000 km3 at depths of 20–35 km, which has a melt fraction of ∼2%–4.5%. Our results suggest that the deep crustal magma reservoir is fed by partial melting in the uppermost mantle and is recharging the shallow magma chambers beneath the TCV. Our results are key to understanding the volcanic activities and assessing future eruption hazards.
LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit
Authors: Zhao Senlin , Guan Bingjie , Mi Yushuai , Shi Debing , Wei Ping , Gu Yanzi , Cai Sanjun , Xu Ye , Li Xinxiang , Yan Dongwang , Huang Mingzhu , Li Dawei
Published: June 2021

Glycolysis plays a crucial role in reprogramming the metastatic tumor microenvironment. A series of lncRNAs have been identified to function as oncogenic molecules by regulating glycolysis. However, the roles of glycolysis-related lncRNAs in regulating colorectal cancer liver metastasis (CRLM) remain poorly understood. In the present study, the expression of the glycolysis-related lncRNA MIR17HG gradually increased from adjacent normal to CRC to the paired liver metastatic tissues, and high MIR17HG expression predicted poor survival, especially in patients with liver metastasis. Functionally, MIR17HG promoted glycolysis in CRC cells and enhanced their invasion and liver metastasis in vitro and in vivo. Mechanistically, MIR17HG functioned as a ceRNA to regulate HK1 expression by sponging miR-138-5p, resulting in glycolysis in CRC cells and leading to their invasion and liver metastasis. More interestingly, lactate accumulated via glycolysis activated the p38/Elk-1 signaling pathway to promote the transcriptional expression of MIR17HG in CRC cells, forming a positive feedback loop, which eventually resulted in persistent glycolysis and the invasion and liver metastasis of CRC cells. In conclusion, the present study indicates that the lactate-responsive lncRNA MIR17HG, acting as a ceRNA, promotes CRLM through a glycolysis-mediated positive feedback circuit and might be a novel biomarker and therapeutic target for CRLM.
The FLI portion of EWS/FLI contributes a transcriptional regulatory function that is distinct and separable from its DNA-binding function in Ewing sarcoma
Authors: Boone Megann A. , Taslim Cenny , Crow Jesse C. , Selich-Anderson Julia , Byrum Andrea K. , Showpnil Iftekhar A. , Sunkel Benjamin D. , Wang Meng , Stanton Benjamin Z. , Theisen Emily R. , Lessnick Stephen L.
Published: June 2021

Ewing sarcoma is an aggressive bone cancer of children and young adults defined by the presence of a chromosomal translocation: t(11;22)(q24;q12). The encoded protein, EWS/FLI, fuses the amino-terminal domain of EWS to the carboxyl-terminus of FLI. The EWS portion is an intrinsically disordered transcriptional regulatory domain, while the FLI portion contains an ETS DNA-binding domain and two flanking regions of unknown function. Early studies using non-Ewing sarcoma models provided conflicting information on the roles of each domain of FLI in EWS/FLI oncogenic function. We therefore sought to define the specific contributions of each FLI domain to EWS/FLI activity in a well-validated Ewing sarcoma model and, in doing so, to better understand Ewing sarcoma development mediated by the fusion protein. We analyzed a series of engineered EWS/FLI mutants with alterations in the FLI portion using a variety of assays. Fluorescence anisotropy, CUT&RUN, and ATAC-sequencing experiments revealed that the isolated ETS domain is sufficient to maintain the normal DNA-binding and chromatin accessibility function of EWS/FLI. In contrast, RNA-sequencing and soft agar colony formation assays revealed that the ETS domain alone was insufficient for transcriptional regulatory and oncogenic transformation functions of the fusion protein. We found that an additional alpha-helix immediately downstream of the ETS domain is required for full transcriptional regulation and EWS/FLI-mediated oncogenesis. These data demonstrate a previously unknown role for FLI in transcriptional regulation that is distinct from its DNA-binding activity. This activity is critical for the cancer-causing function of EWS/FLI and may lead to novel therapeutic approaches.
A comparison of genotyping arrays
Authors: Verlouw Joost A. M. , Clemens Eva , de Vries Jard H. , Zolk Oliver , Verkerk Annemieke J. M. H. , am Zehnhoff-Dinnesen Antoinette , Medina-Gomez Carolina , Lanvers-Kaminsky Claudia , Rivadeneira Fernando , Langer Thorsten , van Meurs Joyce B. J. , van den Heuvel-Eibrink Marry M. , Uitterlinden André G. , Broer Linda
Published: June 2021

Array technology to genotype single-nucleotide variants (SNVs) is widely used in genome-wide association studies (GWAS), clinical diagnostics, and linkage studies. Arrays have undergone a tremendous growth in both number and content over recent years making a comprehensive comparison all the more important. We have compared 28 genotyping arrays on their overall content, genome-wide coverage, imputation quality, presence of known GWAS loci, mtDNA variants and clinically relevant genes (i.e., American College of Medical Genetics (ACMG) actionable genes, pharmacogenetic genes, human leukocyte antigen (HLA) genes and SNV density). Our comparison shows that genome-wide coverage is highly correlated with the number of SNVs on the array but does not correlate with imputation quality, which is the main determinant of GWAS usability. Average imputation quality for all tested arrays was similar for European and African populations, indicating that this is not a good criterion for choosing a genotyping array. Rather, the additional content on the array, such as pharmacogenetics or HLA variants, should be the deciding factor. As the research question of a study will in large part determine which class of genes are of interest, there is not just one perfect array for all different research questions. This study can thus help as a guideline to determine which array best suits a study’s requirements.
Improved prediction of solvation free energies by machine-learning polarizable continuum solvation model
Authors: Alibakhshi Amin , Hartke Bernd
Published: June 2021

Theoretical estimation of solvation free energy by continuum solvation models, as a standard approach in computational chemistry, is extensively applied by a broad range of scientific disciplines. Nevertheless, the current widely accepted solvation models are either inaccurate in reproducing experimentally determined solvation free energies or require a number of macroscopic observables which are not always readily available. In the present study, we develop and introduce the Machine-Learning Polarizable Continuum solvation Model (ML-PCM) for a substantial improvement of the predictability of solvation free energy. The performance and reliability of the developed models are validated through a rigorous and demanding validation procedure. The ML-PCM models developed in the present study improve the accuracy of widely accepted continuum solvation models by almost one order of magnitude with almost no additional computational costs. A freely available software is developed and provided for a straightforward implementation of the new approach.
The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins
Authors: Geller Alexander Martin , Pollin Inbal , Zlotkin David , Danov Aleks , Nachmias Nimrod , Andreopoulos William B. , Shemesh Keren , Levy Asaf
Published: June 2021

The extracellular Contractile Injection System (eCIS) is a toxin-delivery particle that evolved from a bacteriophage tail. Four eCISs have previously been shown to mediate interactions between bacteria and their invertebrate hosts. Here, we identify eCIS loci in 1,249 bacterial and archaeal genomes and reveal an enrichment of these loci in environmental microbes and their apparent absence from mammalian pathogens. We show that 13 eCIS-associated toxin genes from diverse microbes can inhibit the growth of bacteria and/or yeast. We identify immunity genes that protect bacteria from self-intoxication, further supporting an antibacterial role for some eCISs. We also identify previously undescribed eCIS core genes, including a conserved eCIS transcriptional regulator. Finally, we present our data through an extensive eCIS repository, termed eCIStem. Our findings support eCIS as a toxin-delivery system that is widespread among environmental prokaryotes and likely mediates antagonistic interactions with eukaryotes and other prokaryotes.
Emission impacts of China’s solid waste import ban and COVID-19 in the copper supply chain
Authors: Ryter John , Fu Xinkai , Bhuwalka Karan , Roth Richard , Olivetti Elsa A.
Published: June 2021

Climate change will increase the frequency and severity of supply chain disruptions and large-scale economic crises, also prompting environmentally protective local policies. Here we use econometric time series analysis, inventory-driven price formation, dynamic material flow analysis, and life cycle assessment to model each copper supply chain actor’s response to China’s solid waste import ban and the COVID-19 pandemic. We demonstrate that the economic changes associated with China’s solid waste import ban increase primary refining within China, offsetting the environmental benefits of decreased copper scrap refining and generating a cumulative increase in CO2-equivalent emissions of up to 13 Mt by 2040. Increasing China’s refined copper imports reverses this trend, decreasing CO2e emissions in China (up to 180 Mt by 2040) and globally (up to 20 Mt). We test sensitivity to supply chain disruptions using GDP, mining, and refining shocks associated with the COVID-19 pandemic, showing the results translate onto disruption effects.
Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection
Authors: Chen Peng , Zeng Ji , Liu Zheng , Thaker Hatim , Wang Siyu , Tian Songhai , Zhang Jie , Tao Liang , Gutierrez Craig B. , Xing Li , Gerhard Ralf , Huang Lan , Dong Min , Jin Rongsheng
Published: June 2021

C. difficile is a major cause of antibiotic-associated gastrointestinal infections. Two C. difficile exotoxins (TcdA and TcdB) are major virulence factors associated with these infections, and chondroitin sulfate proteoglycan 4 (CSPG4) is a potential receptor for TcdB, but its pathophysiological relevance and the molecular details that govern recognition remain unknown. Here, we determine the cryo-EM structure of a TcdB–CSPG4 complex, revealing a unique binding site spatially composed of multiple discontinuous regions across TcdB. Mutations that selectively disrupt CSPG4 binding reduce TcdB toxicity in mice, while CSPG4-knockout mice show reduced damage to colonic tissues during C. difficile infections. We further show that bezlotoxumab, the only FDA approved anti-TcdB antibody, blocks CSPG4 binding via an allosteric mechanism, but it displays low neutralizing potency on many TcdB variants from epidemic hypervirulent strains due to sequence variations in its epitopes. In contrast, a CSPG4-mimicking decoy neutralizes major TcdB variants, suggesting a strategy to develop broad-spectrum therapeutics against TcdB.
Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer
Authors: Takayama Ken-ichi , Kosaka Takeo , Suzuki Takashi , Hongo Hiroshi , Oya Mototsugu , Fujimura Tetsuya , Suzuki Yutaka , Inoue Satoshi
Published: June 2021

Interactive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC). Investigation of the transcriptome in castration-resistant PC (CRPC) revealed OCT4 as a key TF in the disease pathology. OCT4 confers epigenetic changes by promoting complex formation with FOXA1 and androgen receptor (AR), the central signals for the progression to CRPC. Meanwhile, OCT4 facilitates a distinctive complex formation with nuclear respiratory factor 1 (NRF1) to gain chemo-resistance in the absence of AR. Mechanistically, we reveal that OCT4 increases large droplet formations with AR/FOXA1 as well as NRF1 in vitro. Disruption of TF collaborations using a nucleoside analogue, ribavirin, inhibited treatment-resistant PC tumor growth. Thus, our findings highlight the formation of TF collaborations as a potent therapeutic target in advanced cancer.
Immunological imprinting of the antibody response in COVID-19 patients
Authors: Aydillo Teresa , Rombauts Alexander , Stadlbauer Daniel , Aslam Sadaf , Abelenda-Alonso Gabriela , Escalera Alba , Amanat Fatima , Jiang Kaijun , Krammer Florian , Carratala Jordi , García-Sastre Adolfo
Published: June 2021

In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.
FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes
Authors: Miyoshi Goichi , Ueta Yoshifumi , Natsubori Akiyo , Hiraga Kou , Osaki Hironobu , Yagasaki Yuki , Kishi Yusuke , Yanagawa Yuchio , Fishell Gord , Machold Robert P. , Miyata Mariko
Published: June 2021

Abnormalities in GABAergic inhibitory circuits have been implicated in the aetiology of autism spectrum disorder (ASD). ASD is caused by genetic and environmental factors. Several genes have been associated with syndromic forms of ASD, including FOXG1. However, when and how dysregulation of FOXG1 can result in defects in inhibitory circuit development and ASD-like social impairments is unclear. Here, we show that increased or decreased FoxG1 expression in both excitatory and inhibitory neurons results in ASD-related circuit and social behavior deficits in our mouse models. We observe that the second postnatal week is the critical period when regulation of FoxG1 expression is required to prevent subsequent ASD-like social impairments. Transplantation of GABAergic precursor cells prior to this critical period and reduction in GABAergic tone via Gad2 mutation ameliorates and exacerbates circuit functionality and social behavioral defects, respectively. Our results provide mechanistic insight into the developmental timing of inhibitory circuit formation underlying ASD-like phenotypes in mouse models.
Static-state particle fabrication via rapid vitrification of a thixotropic medium
Authors: Kim Sang Yup , Liu Shanliangzi , Sohn Sungwoo , Jacobs Jane , Shattuck Mark D. , O’Hern Corey S. , Schroers Jan , Loewenberg Michael , Kramer-Bottiglio Rebecca
Published: June 2021

Functional particles that respond to external stimuli are spurring technological evolution across various disciplines. While large-scale production of functional particles is needed for their use in real-life applications, precise control over particle shapes and directional properties has remained elusive for high-throughput processes. We developed a high-throughput emulsion-based process that exploits rapid vitrification of a thixotropic medium to manufacture diverse functional particles in large quantities. The vitrified medium renders stationary emulsion droplets that preserve their shape and size during solidification, and energetic fields can be applied to build programmed anisotropy into the particles. We showcase mass-production of several functional particles, including low-melting point metallic particles, self-propelling Janus particles, and unidirectionally-magnetized robotic particles, via this static-state particle fabrication process.
A global analysis of extreme coastal water levels with implications for potential coastal overtopping
Authors: Almar Rafael , Ranasinghe Roshanka , Bergsma Erwin W. J. , Diaz Harold , Melet Angelique , Papa Fabrice , Vousdoukas Michalis , Athanasiou Panagiotis , Dada Olusegun , Almeida Luis Pedro , Kestenare Elodie
Published: June 2021

Climate change and anthropogenic pressures are widely expected to exacerbate coastal hazards such as episodic coastal flooding. This study presents global-scale potential coastal overtopping estimates, which account for not only the effects of sea level rise and storm surge, but also for wave runup at exposed open coasts. Here we find that the globally aggregated annual overtopping hours have increased by almost 50% over the last two decades. A first-pass future assessment indicates that globally aggregated annual overtopping hours will accelerate faster than the global mean sea-level rise itself, with a clearly discernible increase occurring around mid-century regardless of climate scenario. Under RCP 8.5, the globally aggregated annual overtopping hours by the end of the 21st-century is projected to be up to 50 times larger compared to present-day. As sea level continues to rise, more regions around the world are projected to become exposed to coastal overtopping.
Mechanism of genome instability mediated by human DNA polymerase mu misincorporation
Authors: Guo Miao , Wang Yina , Tang Yuyue , Chen Zijing , Hou Jinfeng , Dai Jingli , Wang Yudong , Wang Liangyan , Xu Hong , Tian Bing , Hua Yuejin , Zhao Ye
Published: June 2021

Pol μ is capable of performing gap-filling repair synthesis in the nonhomologous end joining (NHEJ) pathway. Together with DNA ligase, misincorporation of dGTP opposite the templating T by Pol μ results in a promutagenic T:G mispair, leading to genomic instability. Here, crystal structures and kinetics of Pol μ substituting dGTP for dATP on gapped DNA substrates containing templating T were determined and compared. Pol μ is highly mutagenic on a 2-nt gapped DNA substrate, with T:dGTP base pairing at the 3ʹ end of the gap. Two residues (Lys438 and Gln441) interact with T:dGTP and fine tune the active site microenvironments. The in-crystal misincorporation reaction of Pol μ revealed an unexpected second dGTP in the active site, suggesting its potential mutagenic role among human X family polymerases in NHEJ.
The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis
Authors: Teng Liu , Feng Yu Chen , Guo Su Tang , Wang Pei Lin , Qi Teng Fei , Yue Yi Meng , Wang Shi Xing , Zhang Sheng Nan , Tang Cai Xia , La Ting , Zhang Yuan Yuan , Zhao Xiao Hong , Gao Jin Nan , Wei Li Yuan , Zhang Didi , Wang Jenny Y. , Shi Yujie , Liu Xiao Ying , Li Jin Ming , Cao Huixia , Liu Tao , Thorne Rick F. , Jin Lei , Shao Feng-Min , Zhang Xu Dong
Published: June 2021

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.
Preventing post-surgical cardiac adhesions with a catechol-functionalized oxime hydrogel
Authors: Fujita Masaki , Policastro Gina M. , Burdick Austin , Lam Hillary T. , Ungerleider Jessica L. , Braden Rebecca L. , Huang Diane , Osborn Kent G. , Omens Jeffrey H. , Madani Michael M. , Christman Karen L.
Published: June 2021

Post-surgical cardiac adhesions represent a significant problem during routine cardiothoracic procedures. This fibrous tissue can impair heart function and inhibit surgical access in reoperation procedures. Here, we propose a hydrogel barrier composed of oxime crosslinked poly(ethylene glycol) (PEG) with the inclusion of a catechol (Cat) group to improve retention on the heart for pericardial adhesion prevention. This three component system is comprised of aldehyde (Ald), aminooxy (AO), and Cat functionalized PEG mixed to form the final gel (Ald-AO-Cat). Ald-AO-Cat has favorable mechanical properties, degradation kinetics, and minimal swelling, as well as superior tissue retention compared to an initial Ald-AO gel formulation. We show that the material is cytocompatible, resists cell adhesion, and led to a reduction in the severity of adhesions in an in vivo rat model. We further show feasibility in a pilot porcine study. The Ald-AO-Cat hydrogel barrier may therefore serve as a promising solution for preventing post-surgical cardiac adhesions.
All-optical nonreciprocity due to valley polarization pumping in transition metal dichalcogenides
Authors: Guddala Sriram , Kawaguchi Yuma , Komissarenko Filipp , Kiriushechkina Svetlana , Vakulenko Anton , Chen Kai , Alù Andrea , M. Menon Vinod , Khanikaev Alexander B.
Published: June 2021

Nonreciprocity and nonreciprocal optical devices play a vital role in modern photonic technologies by enforcing one-way propagation of light. Here, we demonstrate an all-optical approach to nonreciprocity based on valley-selective response in transition metal dichalcogenides (TMDs). This approach overcomes the limitations of magnetic materials and it does not require an external magnetic field. We provide experimental evidence of photoinduced nonreciprocity in a monolayer WS2 pumped by circularly polarized (CP) light. Nonreciprocity stems from valley-selective exciton population, giving rise to nonlinear circular dichroism controlled by CP pump fields. Our experimental results reveal a significant effect even at room temperature, despite considerable intervalley-scattering, showing promising potential for practical applications in magnetic-free nonreciprocal platforms. As an example, here we propose a device scheme to realize an optical isolator based on a pass-through silicon nitride (SiN) ring resonator integrating the optically biased TMD monolayer.