bluuebunny/crossref_metadata_2025_split huggingface dataset:
OxyR Is a Convergent Target for Mutations Acquired during Adaptation to Oxidative Stress-Prone Metabolic States
Authors: Anand Amitesh , Chen Ke , Catoiu Edward , Sastry Anand V , Olson Connor A , Sandberg Troy E , Seif Yara , Xu Sibei , Szubin Richard , Yang Laurence , Feist Adam M , Palsson Bernhard O 
Published: October 2019

AbstractOxidative stress is concomitant with aerobic metabolism. Thus, bacterial genomes encode elaborate mechanisms to achieve redox homeostasis. Here we report that the peroxide-sensing transcription factor, oxyR, is a common mutational target using bacterial species belonging to two genera, Escherichia coli and Vibrio natriegens, in separate growth conditions implemented during laboratory evolution. The mutations clustered in the redox active site, dimer interface, and flexible redox loop of the protein. These mutations favor the oxidized conformation of OxyR that results in constitutive expression of the genes it regulates. Independent component analysis of the transcriptome revealed that the constitutive activity of OxyR reduces DNA damage from reactive oxygen species, as inferred from the activity of the SOS response regulator LexA. This adaptation to peroxide stress came at a cost of lower growth, as revealed by calculations of proteome allocation using genome-scale models of metabolism and macromolecular expression. Further, identification of similar sequence changes in natural isolates of E. coli indicates that adaptation to oxidative stress through genetic changes in oxyR can be a common occurrence.
Comparative analysis of different nuclear transfer techniques to prevent the transmission of mitochondrial DNA variants
Authors: Tang M , Guggilla R R , Gansemans Y , Van der Jeught M , Boel A , Popovic M , Stamatiadis P , Ferrer-Buitrago M , Thys V , Van Coster R , Deforce D , De Sutter P , Van Nieuwerburgh F , Heindryckx B 
Published: October 2019

Abstract
Prevention of mitochondrial DNA (mtDNA) diseases may currently be possible using germline nuclear transfer (NT). However, scientific evidence to compare efficiency of different NT techniques to overcome mtDNA diseases is lacking. Here, we performed four types of NT, including first or second polar body transfer (PB1/2T), maternal spindle transfer (ST) and pronuclear transfer (PNT), using NZB/OlaHsd and B6D2F1 mouse models. Embryo development was assessed following NT and mtDNA carry-over levels were measured by next generation sequencing (NGS). Moreover, we explored two novel protocols (PB2T-a and PB2T-b) to optimize PB2T using mouse and human oocytes. Chromosomal profiles of NT-generated blastocysts were evaluated using NGS. In mouse, our findings reveal that only PB2T-b successfully leads to blastocysts. There were comparable blastocyst rates amongst PB1T, PB2T-b, ST and PNT embryos. Furthermore, PB1T and PB2T-b had lower mtDNA carry-over levels than ST and PNT. After extrapolation of novel PB2T-b to human in vitro matured (IVM) oocytes and in vivo matured oocytes with smooth endoplasmic reticulum aggregates (SERa) oocytes, the reconstituted embryos successfully developed to blastocysts at a comparable rate to ICSI controls. PB2T-b embryos generated from IVM oocytes showed a similar euploidy rate to ICSI controls. Nevertheless, our mouse model with non-mutated mtDNAs is different from a mixture of pathogenic and non-pathogenic mtDNAs in a human scenario. Novel PB2T-b requires further optimization to improve blastocyst rates in human. Although more work is required to elucidate efficiency and safety of NT, our study suggests that PBT may have the potential to prevent mtDNA disease transmission.
SEA version 3.0: a comprehensive extension and update of the Super-Enhancer archive
Authors: Chen Chuangeng , Zhou Dianshuang , Gu Yue , Wang Cong , Zhang Mengyan , Lin Xiangyu , Xing Jie , Wang Hongli , Zhang Yan 
Published: October 2019

Abstract
Super-enhancers (SEs) are critical for the transcriptional regulation of gene expression. We developed the super-enhancer archive version 3.0 (SEA v. 3.0, http://sea.edbc.org) to extend SE research. SEA v. 3.0 provides the most comprehensive archive to date, consisting of 164 545 super-enhancers. Of these, 80 549 are newly identified from 266 cell types/tissues/diseases using an optimized computational strategy, and 52 have been experimentally confirmed with manually curated references. We now support super-enhancers in 11 species including 7 new species (zebrafish, chicken, chimp, rhesus, sheep, Xenopus tropicalis and stickleback). To facilitate super-enhancer functional analysis, we added several new regulatory datasets including 3 361 785 typical enhancers, chromatin interactions, SNPs, transcription factor binding sites and SpCas9 target sites. We also updated or developed new criteria query, genome visualization and analysis tools for the archive. This includes a tool based on Shannon Entropy to evaluate SE cell type specificity, a new genome browser that enables the visualization of SE spatial interactions based on Hi-C data, and an enhanced enrichment analysis interface that provides online enrichment analyses of SE related genes. SEA v. 3.0 provides a comprehensive database of all available SE information across multiple species, and will facilitate super-enhancer research, especially as related to development and disease.
Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum
Authors: Hoeijmakers Wieteke Anna Maria , Miao Jun , Schmidt Sabine , Toenhake Christa Geeke , Shrestha Sony , Venhuizen Jeron , Henderson Rob , Birnbaum Jakob , Ghidelli-Disse Sonja , Drewes Gerard , Cui Liwang , Stunnenberg Hendrik Gerard , Spielmann Tobias , Bártfai Richárd 
Published: October 2019

Abstract
Epigenetic regulatory mechanisms are central to the development and survival of all eukaryotic organisms. These mechanisms critically depend on the marking of chromatin domains with distinctive histone tail modifications (PTMs) and their recognition by effector protein complexes. Here we used quantitative proteomic approaches to unveil interactions between PTMs and associated reader protein complexes of Plasmodium falciparum, a unicellular parasite causing malaria. Histone peptide pull-downs with the most prominent and/or parasite-specific PTMs revealed the binding preference for 14 putative and novel reader proteins. Amongst others, they highlighted the acetylation-level-dependent recruitment of the BDP1/BDP2 complex and identified an PhD-finger protein (PHD 1, PF3D7_1008100) that could mediate a cross-talk between H3K4me2/3 and H3K9ac marks. Tagging and interaction proteomics of 12 identified proteins unveiled the composition of 5 major epigenetic complexes, including the elusive TBP-associated-factor complex as well as two distinct GCN5/ADA2 complexes. Furthermore, it has highlighted a remarkable degree of interaction between these five (sub)complexes. Collectively, this study provides an extensive inventory of PTM-reader interactions and composition of epigenetic complexes. It will not only fuel further explorations of gene regulation amongst ancient eukaryotes, but also provides a stepping stone for exploration of PTM-reader interactions for antimalarial drug development.
A distinct class of eukaryotic MT-A70 methyltransferases maintain symmetric DNA N6-adenine methylation at the ApT dinucleotides as an epigenetic mark associated with transcription
Authors: Wang Yuanyuan , Sheng Yalan , Liu Yongqiang , Zhang Wenxin , Cheng Ting , Duan Lili , Pan Bo , Qiao Yu , Liu Yifan , Gao Shan 
Published: October 2019

AbstractRediscovered as a potential eukaryotic epigenetic mark, DNA N6-adenine methylation (6mA) varies across species in abundance and its relationships with transcription. Here we characterize AMT1—representing a distinct MT-A70 family methyltransferase—in the ciliate Tetrahymena thermophila. AMT1 loss-of-function leads to severe defects in growth and development. Single Molecule, Real-Time (SMRT) sequencing reveals that AMT1 is required for the bulk of 6mA and all symmetric methylation at the ApT dinucleotides. The detection of hemi-methylated ApT sites suggests a semi-conservative mechanism for maintaining symmetric methylation. AMT1 affects expression of many genes; in particular, RAB46, encoding a Rab family GTPase involved in contractile vacuole function, is likely a direct target. The distribution of 6mA resembles H3K4 methylation and H2A.Z, two conserved epigenetic marks associated with RNA polymerase II transcription. Furthermore, strong 6mA and nucleosome positioning in wild-type cells is attenuated in ΔAMT1 cells. Our results support that AMT1-catalyzed 6mA is an integral part of the transcription-associated epigenetic landscape. AMT1 homologues are generally found in protists and basal fungi featuring ApT hyper-methylation associated with transcription, which are missing in animals, plants, and true fungi. This dichotomy of 6mA functions and the underlying molecular mechanisms may have implications in eukaryotic diversification.
TSEA-DB: a trait–tissue association map for human complex traits and diseases
Authors: Jia Peilin , Dai Yulin , Hu Ruifeng , Pei Guangsheng , Manuel Astrid Marilyn , Zhao Zhongming 
Published: October 2019

Abstract
Assessing the causal tissues of human traits and diseases is important for better interpreting trait-associated genetic variants, understanding disease etiology, and improving treatment strategies. Here, we present a reference database for trait-associated tissue specificity based on genome-wide association study (GWAS) results, named Tissue-Specific Enrichment Analysis DataBase (TSEA-DB, available at https://bioinfo.uth.edu/TSEADB/). We collected GWAS summary statistics data for a wide range of human traits and diseases followed by rigorous quality control. The current version of TSEA-DB includes 4423 data sets from the UK Biobank (UKBB) and 596 from other resources (GWAS Catalog and literature mining), totaling 5019 unique GWAS data sets and 15 770 trait-associated gene sets. TSEA-DB aims to provide reference tissue(s) enriched with the genes from GWAS. To this end, we systematically performed a tissue-specific enrichment analysis using our recently developed tool deTS and gene expression profiles from two reference tissue panels: the GTEx panel (47 tissues) and the ENCODE panel (44 tissues). The comprehensive trait–tissue association results can be easily accessed, searched, visualized, analyzed, and compared across the studies and traits through our web site. TSEA-DB represents one of the many timely and comprehensive approaches in exploring human trait–tissue association.
Role of sodium-glucose cotransporter 2 inhibition to mitigate diabetic kidney disease risk in type 1 diabetes
Authors: van Raalte Daniël H , Bjornstad Petter 
Published: October 2019

AbstractDiabetic kidney disease (DKD) is a common complication of type 1 diabetes (T1D) and a major risk factor for premature death from cardiovascular disease (CVD). Current treatments, such as control of hyperglycaemia and hypertension, are beneficial, but only partially protect against DKD. Finding new, safe and effective therapies to halt nephropathy progression has proven to be challenging. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated, in addition to glycaemic lowering, impressive protection against DKD and CVD progression in people with type 2 diabetes. Although these beneficial cardiorenal effects may also apply to people with T1D, supporting data are lacking. Furthermore, the increased rates of euglycaemic diabetic ketoacidosis may limit the use of this class in people with T1D. In this review we highlight the pathophysiology of DKD in T1D and the unmet need that exists. We further detail the beneficial and adverse effects of SGLT2 inhibitors based on their mechanism of action. Finally, we balance the effects in people with T1D and indicate future lines of research.
Predictors of Outcomes After Focused Ultrasound Thalamotomy
Authors: Krishna Vibhor , Sammartino Francesco , Cosgrove Rees , Ghanouni Pejman , Schwartz Michael , Gwinn Ryder , Eisenberg Howard , Fishman Paul , Chang Jin Woo , Taira Takaomi , Kaplitt Michael , Rezai Ali , Rumià Jordi , Gedroyc Wady , Igase Keiji , Kishima Haruhiko , Yamada Kazumichi , Ohnishi Hideyuki , Halpern Casey 
Published: October 2019

Abstract

BACKGROUND
Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET).

OBJECTIVE
To determine the predictors of outcomes after FUS-T.

METHODS
Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables.

RESULTS
A total of 179 patients completed the 12-mo evaluation. The significant predictors of tremor outcomes were patient age, disease duration, peak temperature, and number of sonications. A greater improvement in hand tremor scores was observed in the postpivotal group at all time points, including 12 mo (61.9% ± 24.9% vs 52.1% ± 24.9%, P = .009). In the postpivotal group, higher energy was used, resulting in higher peak temperatures (56.7 ± 2.5 vs 55.6 ± 2.8°C, P = .004). After adjusting for age, years of disease, number of sonications, and maximum temperature, the treatment group was a significant predictor of outcomes (F = 7.9 [1,165], P = .005).

CONCLUSION
We observed an improvement in outcomes in the postpivotal group compared to the pivotal group potentially reflecting a learning curve with FUS-T. The other associations of tremor outcomes included patient age, disease duration, peak temperature, and number of sonications.
On the ratifiability of efficient cartel mechanisms in first-price auctions with participation costs and information leakage
Authors: Cao Xiaoyong , Hsueh Shao-Chieh , Tian Guoqiang 
Published: October 2019

Abstract
This paper addresses the ratifiability of an efficient cartel mechanism in a first-price auction. When a seller uses a first-price sealed-bid auction, the efficient all-inclusive cartel mechanism will no longer be ratifiable in the presence of both participation costs and potential information leakage. A bidder whose value is higher than a cut-off in the cartel will have an incentive to leave the cartel, thereby sending a credible signal of his high value, which discourages other bidders from participating in the seller’s auction. However, the cartel mechanism is still ratifiable where either the participation cost or information leakage is absent.
Tweeted Heresies
Authors: Hamidaddin Abdullah 
Published: October 2019

AbstractHow should we understand religion in Saudi Arabia? To what extent does religion control the various aspects of Saudi life? Why are more and more Saudis and generally Muslims leaning toward heresy? Why are many others exhibiting an indifference toward religion? And how does our understanding of the state of religion in Saudi Arabia inform us about the state of religion in other Islamic communities? This book explores the emergence of nonbelief and the response to it from the Salafi-Wahhabi religious institutions of Saudi Arabia. While previous studies have focused on particular institutions and their role in religious change, this study focuses on individuals that have criticized religion by taking advantage of the virtual space of social media. In doing so, they have questioned the most fundamental aspects of Saudi society: politics, religion, social justice, gender, sexuality, and the future of the country. Just as importantly, these individuals, who emerged first on the Internet, have mounted a frontal challenge to religious orthodoxy, whether through calls for religious reform or, even more provocatively, through debates over concepts of deity, duty to Allah, and morality.
Criticizing Religion
Authors: Hamidaddin Abdullah 
Published: October 2019

AbstractThis chapter defines the scope of this volume. It explores the impact of modernity on religion in general, and some key aspects of the Muslim response to modernity. The chapter highlights the difference between two ways of understanding the impact of modernity on Muslim religiosity: the first is the disengagement from religion in ways similar to modernity’s impact on religion in other societies; the second is the evolution of religion into a social and political identity, an evolution that has had serious consequences most notably the rise of the politics of cultural authenticity and the growth of political Islam. The book claims that the second way has had a monopoly on our understanding of Muslims and instead chooses to focus on the first way. The chapter also explores the ways Islam in Saudi has been understood, and how that has limited our understanding of society and religion in that country. Most importantly the chapter discusses some of the key social theories that highlight the reasons individuals disengage from religion and revert to either indifference towards religion, or heresy or even nonbelief.
Possessive Individualism
Authors: Bromley Daniel W. 
Published: October 2019

Abstract
The emergence of authoritarian governments in much of Europe, the British vote to leave the European Union, and widespread political anger in the United States suggest that anxiety and uncertainty now threaten to undermine stable democracies. Decades of stagnant household incomes and growing inequality are casting doubt on the benefits of capitalism. Meanwhile, millions of desperate migrants streaming north out of Latin America, the Middle East, and Africa further jeopardize political stability in the wealthy metropole. We have here an explanation for why the world finds itself in widespread dysfunction. First, there is a dominant culture of possessive individualism. This attitude has fostered political opposition to taxes, to higher wages for vast numbers of workers, and to various programs that would ease the economic burden on beleaguered households. Meanwhile, a culture of managerial capitalism suppresses wages and salaries, embraces automation, and moves jobs overseas. Voters have taken the measure of contemporary capitalism and are unimpressed. Many of the disillusioned have turned to authoritarian braggarts to rescue them from their misery. Xenophobia stalks the land. Escape from this crisis requires that the isolated acquisitive individual rediscover a sense of loyalty to others—as neighbors, as colleagues, and as participants in a shared social process of living rather than merely consuming. Escape also requires that the private firm be reimagined as a public trust in which the economic well-being of employees becomes a central part of its purpose. In the absence of these dual transformations, capitalism as we know it cannot endure.
Act 1 of Berg’s Lulu
Authors: Notley Margaret 
Published: October 2019

Abstract
This chapter has to do with Berg’s interpretation of Erdgeist in Act 1 of his opera and connects it to the new, expanded understanding of censorship. Building on work by Michel Foucault and Judith Butler, Robert C. Post wrote in 1998 that censorship “establishes the practices that define us as social subjects.” Post thereby offered a frame of reference for genres that have social practices as their subject matter, two of which critics have linked to Erdgeist: when Wedekind turned the first three acts of the Ur-Lulu into the basis of Erdgeist, he made the self-censorship that allows us to function in a society thematic in his new play. Berg chose to refine Wedekind’s material, but also to emphasize passages that reveal the origins of Erdgeist in a play Wedekind had conceived as a “monster tragedy”; in doing this, Berg clearly intended to prepare the second half of the opera.
Torts
Authors: Friedman Lawrence M. 
Published: October 2019

Abstract
This chapter discusses the development of tort law in the second half of the nineteenth century. Tort law experienced its biggest growth spurt in the late nineteenth century. The legal world began to sit up and pay attention. The very first English-language treatise on torts appeared in 1859: Francis Hilliard’s book, The Law of Torts, Or Private Wrongs. Then came Charles G. Addison, Wrongs and Their Remedies in 1860, in England. By 1900, there was an immense literature on the law of torts; Joel Bishop and Thomas M. Cooley had written imposing treatises on the subject; the case law had swollen to heroic proportions. Tort law was a product of the industrial revolution; England here had a head start; problems emerged there first, and so did their tentative legal solutions.
Dissent
Authors: Zick Timothy 
Published: October 2019

Abstract
This chapter considers a concept that connects all of the previous chapters to one another: dissent. Dissent is itself a central First Amendment concern. As the book’s chapters show, the Trump Era has been marked or marred by various efforts to challenge or suppress dissent. After briefly discussing the meaning of dissent, the chapter examines the democratic and social values of dissent and current challenges to participating in active dissent. It considers the steps necessary to preserving a culture of dissent in the United States. The positive and potentially uplifting lesson of the book is that time and again, dissent and dissenters have ultimately defeated the worst authoritarian impulses. However, this process has generally taken long stretches of time, during which the American people have considered and recalculated the costs and benefits of allowing dissenting voices to be heard.
Deconstructing “Decentralization”
Authors: Walch Angela 
Published: October 2019

Abstract
This chapter first describes the current use of the term “decentralized” as applied to permissionless blockchains like Bitcoin and Ethereum. Then, it analyzes the complex, contested nature of the term, delving into issues such as the different domains where power is exercised in blockchain systems and the fluid nature of power concentration and diffusion in these systems. Next, it provides examples of events that reveal sites of concentrated power in permissionless blockchain systems, focusing on the activities of software developers and miners. Finally, it explores the significant implications for law of using a fuzzy term like “decentralized” to make legal decisions, as misunderstandings about power hidden in the term can lead to flawed decisions across a wide swath of legal fields.
What Should Be Disclosed in an Initial Coin Offering?
Authors: Brummer Chris , Kiviat Trevor I. , Massari Jai 
Published: October 2019

Abstract
This chapter unsettles the all-too-common assumption that existing Securities Act registration and disclosure requirements offer adequate remedies for the increasingly obvious shortcomings of initial coin offerings (ICOs). It argues that, as currently constituted, the Securities Act and its accompanying regulations offer, at best, only a partial remedy to the disclosure challenges that ICOs pose. Even if subject to the full panoply of disclosures operative in public offerings, ICO promoters would not necessarily disclose all factors material to evaluating and pricing their tokens. Furthermore, even where disclosures are made, they may not be done in ways that investors can easily understand, and technical disclosures would not be subject to the kind of financial statement audits common in more traditional securities offerings.