bluuebunny/crossref_metadata_2025 huggingface dataset:
Prisms of Distance and Power: Viewing the U.S. Regulatory Tradition
Authors: Gerber David J.
Published: January 2020

Distorted images of American regulatory ideas and practices frame foreign responses to these practices as well as foreign views of the economic policies of the United States. U.S. power both embeds and contributes to these distorted images. This article highlights the evolution of these distortions and the ways in which business history has intertwined with legal and political history throughout the evolution. It focuses on a specific area of regulation—antitrust or competition law—in order to ground the more general discussion. The article provides insights into the relationship between cognitive distance and power and into its pernicious effects on transnational discussions and decisions involving competition law.
A Premature Postmortem on the Chicago School of Antitrust
Authors: Crane Daniel A.
Published: January 2020

The Chicago School of antitrust is often thought to have killed off antitrust enforcement beginning in the late 1970s. In fact, although Chicago school prescriptions were significantly more laissez-faire than the structuralist school Chicago replaced, antitrust enforcement did not die under Chicago's influence. Rather, by directing antitrust to focus on technical economic analysis, Chicago contributed to the creation of a large and entrenched class of antitrust professionals—economists and lawyers—with a vested interest in preserving antitrust as a legal and regulatory enterprise. Today, Chicago School's consumer welfare standard and specific enforcement prescriptions are coming increasingly under political pressure and may be replaced or supplemented in the near term. But Chicago's redirection of antitrust toward technical economic analysis and technocratic reasoning seems likely to remain a durable legacy.
Institutional Economics and the Progressive Movement for the Social Control of American Business
Authors: Novak William J.
Published: January 2020

This article investigates the history of the Progressive Era effort to develop new techniques and technologies of control over American business and corporations in the late nineteenth and early twentieth centuries. A revolution in Progressive economic regulation was rooted in the intellectual work of the so-called institutional economists—particularly in the context of what economists and lawyers like Richard Ely, John Commons, and Walton Hamilton ultimately talked about as the movement for the “social control” of business, with distinct emphasis on the legal and regulatory “foundations” of modern capitalism. With increased attention to dynamics rather than statics, the real social economy rather than ideal rational actors, and historical and institutional rather than theoretical and abstract renderings of business, industry, and the market, the institutionalists were directly concerned with problems of control, particularly those mechanisms of control available through law, politics, the state, and new technologies of legislative and administrative regulation.
Comment on William J. Novak: Institutional Economics and the Progressive Movement for the Social Control of American Business
Authors: Pak Susie J.
Published: January 2020

William J. Novak's engaging historiography is at once a recovery project and a prolegomenon to a revised history of political economy. His article chronicles the achievements of Progressive Era institutional economists and critiques the way they have been obscured by the shadow of the Chicago School of economics. Why do the Progressives deserve to be recovered and remembered? According to Novak, it is because they “underwrote one of the more fundamental governmental revolutions in modern times” and created the foundations for the “social control of business” (pp. 676, 672).
A TRANSREGIONAL PERSIANATE LIBRARY: THE PRODUCTION AND CIRCULATION OFTADHKIRAS OF PERSIAN POETS IN THE 18THAND 19THCENTURIES
Authors: Schwartz Kevin L.
Published: January 2020

Thetadhkira(biographical anthology) represents one of the most prolific and prevalent categories of texts produced in Islamicate societies, yet few studies have sought to understand the larger processes that governed their production and circulation on a transregional basis. This article examines and maps the production, circulation, and citation networks oftadhkiras of Persian poets in the 18thand 19thcenturies. It understandstadhkiras of Persian poets as a transregional library that served as a repository of accessible and circulating texts meant to be incorporated, reworked, and repackaged by a cadre of authors separated by space and time. By relying on a macroanalytical approach, quantifiable data, and digital mapping, this article highlights the overall construction of the transregional library itself, the impact of state disintegration and formation on its constitution, and the different ways authors on opposite ends of the Persianate world came to view this library by the end of the 19thcentury.
Education, Labour, and Discipline: New Perspectives on Imperial Practices and Indigenous Children in Colonial Asia
Authors: Kamphuis Kirsten , van Nederveen Meerkerk Elise
Published: January 2020

This article provides an introduction to the two articles in this Special Theme on education, labour, and discipline in colonial Asia. It offers a brief historiography of education to indigenous children in the colonial context provided by non-state as well as state actors. We argue that while many studies have separated the motives behind, and actions of, these different actors in relation to education and “civilizing missions”, it is worthwhile connecting these histories. Moreover, apart from looking at motives, the articles in this Special Theme aim to show the value of studying educationalpracticesin a colonial context. Finally, this introduction identifies several opportunities for future – comparative as well as transnational – studies into the topic of education, child labour, and discipline.
Dis/ordering politics: urban riots and the socio-political configuration of contemporary Niger
Authors: Schritt Jannik
Published: January 2020

This article focuses on ‘generic moments of becoming’, historical sedimentation and patterns of recurrent protests to explain the structural drivers that sparked the dramatic increase in urban protests and riots in Niger between 2013 and 2018. It identifies several factors in the country's socio-political configuration as particularly important for understanding the protests: new media and politics by proxy, political machines, the social and political embeddedness of civil society, ethnicity and regional political strongholds, the legacy ofFrançafrique, religious reform movements, and male youth violence. In examining these drivers, the article aims to provide an informative overview of contemporary politics and society in Niger and to counter culturalist, ahistoric and Eurocentric notions of ‘African disorder’.
Parodies of whiteness: Die Antwoord and the politics of race, gender, and class in South Africa
Authors: Bekker Ian , Levon Erez
Published: January 2020

The dramatic reconfiguration of the social, political, and ideological order in South Africa since 1990/1994 has demanded a concomitant reconceptualization of (white) Afrikaner notions of self and belonging in the (new) nation. In this article, we draw on recent developments in the study of varidirectional voicing (polyphony), performance, and mediatization to examine how the South African rap-rave group Die Antwoord makes use of parody and metaparody in their music to critique emerging ‘new Afrikaner’ identities and the racial, class, and gender configurations on which they are based. We also discuss the structural limits of these critiques and the political potential of (meta)parodic performance more generally. ((Meta)parody, polyphony, performance, race, class, gender, South Africa)*
Stunting: an overlooked problem in Myanmar – an economic evaluation
Authors: Aye San Kyu Kyu , Mar Swe Le , Lwin Nyi Nyi , Hnin Zar Lwin , Hlaing Lwin Mar , Washington Michael L. , Harris Julie R.
Published: January 2020

Objectives

Stunting increases a child's susceptibility to diseases, increases mortality, and is associated over long term with reduced cognitive abilities, educational achievement, and productivity. We aimed to assess the most effective public health nutritional intervention to reduce stunting in Myanmar.

Methods

We searched the literature and developed a conceptual framework for interventions known to reduce stunting. We focused on the highest impact and most feasible interventions to reduce stunting in Myanmar, described policies to implement them, and compared their costs and projected effect on stunting using data-based decision trees. We estimated costs from the government perspective and calculated total projected cases of stunting prevented and cost per case prevented (cost-effectiveness). All interventions were compared to projected cases of stunting resulting from the current situation (e.g., no additional interventions).

Results

Three new policy options were identified. Operational feasibility for all three options ranged from medium to high. Compared to the current situation, two were similarly cost-effective, at an additional USD 598 and USD 667 per case of stunting averted. The third option was much less cost-effective, at an additional USD 27,741 per case averted. However, if donor agencies were to expand their support in option three to the entire country, the prevalence of 22.5 percent would be reached by 2025 at an additional USD 667 per case averted.

Conclusions

A policy option involving immediate expansion of the current implementation of proven nutrition-specific interventions is feasible. It would have the highest impact on stunting and would approach the WHO 2025 target.
Alin: improving interactive ontology matching by interactively revising mapping suggestions
Authors: Da Silva Jomar , Revoredo Kate , Baião Fernanda , Euzenat Jérôme
Published: January 2020

Ontology matching aims at discovering mappings between the entities of two ontologies. It plays an important role in the integration of heterogeneous data sources that are described by ontologies. Interactive ontology matching involves domain experts in the matching process. In some approaches, the expert provides feedback about mappings between ontology entities, that is, these approaches select mappings to present to the expert who replies which of them should be accepted or rejected, so taking advantage of the knowledge of domain experts towards finding an alignment. In this paper, we present Alin, an interactive ontology matching approach which uses expert feedback not only to approve or reject selected mappings but also to dynamically improve the set of selected mappings, that is, to interactively include and to exclude mappings from it. This additional use for expert answers aims at increasing in the benefit brought by each expert answer. For this purpose, Alin uses four techniques. Two techniques were used in the previous versions of Alin to dynamically select concept and attribute mappings. Two new techniques are introduced in this paper: one to dynamically select relationship mappings and another one to dynamically reject inconsistent selected mappings using anti-patterns. We compared Alin with state-of-the-art tools, showing that it generates alignment of comparable quality.
EQUILIBRIUM VALUATION OF CURRENCY OPTIONS UNDER A DISCONTINUOUS MODEL WITH CO-JUMPS
Authors: Xing Yu , Xu Yuhua , Niu Huawei
Published: January 2020

In this paper, we study the equilibrium valuation for currency options in a setting of the two-country Lucas-type economy. Different from the continuous model in Bakshi and Chen [1], we propose a discontinuous model with jump processes. Empirical findings reveal that the jump components in each country's money supply can be decomposed into the simultaneous co-jump component and the country-specific jump component. Each of the jump components is modeled with a Poisson process whose jump intensity follows a mean reversion stochastic process. By solving a partial integro-differential equation (PIDE), we get a closed-form solution to the PIDE for a European call currency option. The numerical results show that the derived option pricing formula is efficient for practical use. Importantly, we find that the co-jump has a significant impact on option price and implied volatility.
Process of therapeutic changes in Meaning-Centered Group Psychotherapy adapted to the Portuguese language: A narrative analysis
Authors: da Ponte Guida , Ouakinin Sílvia , Santo Jorge Espírito , Amorim Inês , Gameiro Zita , Fitz-Henley Mindi , Breitbart William
Published: January 2020

Objective

The aim was to understand the processes of therapeutic changes in Meaning-Centered Group Psychotherapy (MCGP) in a Portuguese sample.

Method

Adult cancer patients with distress motivated to participate in MCGP were identified; descriptive and narrative analyses were performed on the session content.

Results

The sample had 24 participants (mean age: 63.43 years); the majority were females (75%), with a median academic degree (54%). Breast cancer was most frequent (67%) at the localized stage (71%). The narrative analysis defined seven categories according to the MCGP themes. In “Moments with Meaning (MwM),” the most relevant dimensions were related to interpersonal relations, the moment of diagnosis, and personal achievements. This category established relations with almost all other categories, as did the category “historical sources of meaning (SoM).” The category “identity before and after cancer diagnosis” was only related to “attitudinal SoM” and “transitions.” Historical SoM had two dimensions, “past” and “present and future” legacies, in which prominent topics related to family, childhood, achieved goals, and values to pass to others explored. Attitudinal SoM established relations only with the category “creative SoM,” in which “courage” and “responsibility” were the main dimensions, which were also related to “MwM,” “historical,” and “attitudinal SoM.” Experiential SoM, with the main dimension “love,” was related to “MwM” and “historical SoM.” Transitions only established relations with “historical SoM” and “identity before and after cancer.”

Significance of results

The findings that “MwM” and “historical SoM” were the categories which established a solid pattern of relations suggest that these are the main psychotherapy topics that can have more influence for the participants; one explanation is that these categories imply a concrete way of thinking, which is easier to understand. This process of therapeutic changes must be integrated in a cultural context, as it is well known to have an impact upon the “meaning” of life.
Reassessing the dependence of capitalism on democracy – the case of Imperial Germany and the Weimar Republic
Authors: Wegner Gerhard
Published: January 2020

The paper interrogates the argument put forward by Acemoglu and Robinson or Northet al.that capitalism and democracy are supportive to each other. It analyzes the development of political and economic institutions in Germany before and after World War I. It is shown that the lack of democracy in Imperial Germany furthered a liberal economic order and gives reasons why the transition to full-scale parliamentarianism would have impaired the quality of economic institutions. This also explains why such a transition was not completed. The Weimar Republic established a modern democracy but was unable to secure the quality of economic institutions achieved before. Not only in Germany did the politicization of the economy impair the economic order. This empirical outcome helps to explain why Eucken and other liberals identified democracy as part of the economic problem during the interwar period. It also gives reasons to rethink the complex relationship between capitalism and democracy.
Qualitative research methods for institutional analysis
Authors: Skarbek David
Published: January 2020

How can economists use qualitative evidence – such as archival materials, interviews, and ethnography – to study institutions? While applied economists typically rely on quantitative evidence and statistical estimation, many important aspects of institutions and institutional change appear in the form of qualitative evidence. This raises the question if, and how, social scientists trained in quantitative methods can exploit and analyze this evidence. This paper discusses two qualitative research methods that are both commonly used outside of economics: comparative case studies and process tracing. Drawing on existing research about crime and political revolutions, it discusses these two methods and how to implement them to improve institutional analysis.
“The Forests Cannot Be Commons”
Authors: Woolley Christopher
Published: January 2020

This article examines the sylvan political ecology of late colonial New Spain and the colonial government's attempt to address deforestation through the Council on Forests, the first body in the kingdom's history dedicated to the conservation of natural resources. Drawing primarily from the corpus of documents produced by and remitted to the council, this article gives a trans-regional perspective on colonial forest use and argues that the Spanish crown's usurpation of indigenous communities’ eminent domain over forests was the first step in a process that over centuries progressively severed the cultural ties that bound communities and forests by converting common-pool resources into open-access commons. The catastrophic mortality of the Spanish invasion was the second step, which rendered conservation measures seemingly unnecessary among both woodcutters and officials. But it was during the eighteenth century that older Habsburg notions of protectionism intersected with economic and political changes associated with Bourbon rule to further compel this cultural severance. While previous works have studied the ecological impacts of mining, ranching, and flood control, this article moves beyond the study of a single industry to suggest some of the larger ecological consequences of Spanish colonialism.
Locating the Filipino as Malay: A Reassertion of Historical Identity from the Regional Periphery
Authors: Gomez José Edgardo Abaya
Published: January 2020

In Malaysia, Brunei, Singapore, and Indonesia, being Malay usually means being a practitioner of Islam and a speaker of standard Bahasa. However, such understandings no longer comprehend other members of the so-called brown-skinned race who were once united with the Malay aggrupation: numerous Filipinos (and East Timorese), who inhabit the same broad geopolitical region. Challenging the recent narrowly defined conceptions of who is, or was Malay, this study recalls an inclusive borderless understanding acquired in antiquity by the Filipino nation, whose peoples were considered by Spanish and American colonisers and educated by their government to consider themselves as part of a pre-modern “Malay” world. Geohistorical evidence shows how such auto-consciousness evolved and preceded the entry of the term into the nearby British colonisers’ lexicon, before its social-reconstruction for the perpetuation of post-colonial polities as well. The author interweaves his textual survey with the problematisation of the location of ethnicity, and points out the seemingly neglected corpus of Iberian works that demonstrate how the knowledge of Malayness could only have been approached by Europeans from a geographic periphery, of which the Philippine archipelago was very much a part, especially the Mindanao area. The author builds on and constructively critiques work by one scholar who had initiated the claims of the Filipino to Malayness. It is shown how sociocultural and geopolitical priorities can help or hinder the relaxation of definitions of who is Malay and where Malays are properly situated, if only because these counter perceptual rigidities, and allow the creation of hybrid third spaces that admit new possibilities of coexistence.
Potential yield loss in grain sorghum (Sorghum bicolor) with weed interference in the United States
Authors: Dille J. Anita , Stahlman Phillip W. , Thompson Curtis R. , Bean Brent W. , Soltani Nader , Sikkema Peter H.
Published: January 2020

Potential yield losses in grain sorghum due to weed interference based on quantitative data from the major grain sorghum-growing areas of the United States are reported by the WSSA Weed Loss Committee. Weed scientists and extension specialists who researched weed control in grain sorghum provided data on grain sorghum yield loss due to weed interference in their region. Data were requested from up to 10 individual experiments per calendar year over 10 yr between 2007 and 2016. Based on the summarized information, farmers in Arkansas, Kansas, Missouri, Nebraska, South Dakota, and Texas would potentially lose an average of 37%, 38%, 30%, 56%, 61%, and 60% of their grain sorghum yield with no weed control, and have a corresponding annual monetary loss of US $19 million, 302 million, 7 million, 32 million, 25 million, and 314 million, respectively. The overall average yield loss due to weed interference was estimated to be 47% for this grain sorghum-growing region. Thus, US farmers would lose approximately 5,700 million kg of grain sorghum valued at approximately US $953 million annually if weeds are not controlled. With each dollar invested in weed management (based on estimated weed control cost of US $100 ha−1), there would be a return of US $3.80, highlighting the return on investment in weed management and the importance of continued weed science research for sustaining high grain sorghum yield and profitability in the United States.
The USP21/YY1/SNHG16 axis contributes to tumor proliferation, migration, and invasion of non-small-cell lung cancer
Authors: Xu Pei , Xiao Haibo , Yang Qi , Hu Rui , Jiang Lianyong , Bi Rui , Jiang Xueyan , Wang Lei , Mei Ju , Ding Fangbao , Huang Jianbing
Published: January 2020

Deubiquitinases (DUBs) and noncoding RNAs have been the subjects of recent extensive studies regarding their roles in lung cancer, but the mechanisms involved are largely unknown. In our study, we used The Cancer Genome Atlas data set and bioinformatics analyses and identified USP21, a DUB, as a potential contributor to oncogenesis in non-small-cell lung cancer (NSCLC). We further demonstrated that USP21 was highly expressed in NSCLCs. We then conducted a series of in vitro and in vivo assays to explore the effect of USP21 on NSCLC progression and the underlying mechanism involved. USP21 promoted NSCLC cell proliferation, migration, and invasion and in vivo tumor growth by stabilizing a well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination. Furthermore, YY1 transcriptionally regulates the expression of SNHG16. Moreover, StarBase bioinformatics analyses predicted that miR-4500 targets SNHG16 and USP21. A series of in vitro experiments indicated that SNHG16 increased the expression of USP21 through miR-4500. In summary, the USP21/YY1/SNHG16 axis plays a role in promoting the progression of NSCLC. Therefore, the USP21/YY1/SNHG16/miR-4500 axis may be a potential therapeutic target in NSCLC treatment.
BMP4 and perivascular cells promote hematopoietic differentiation of human pluripotent stem cells in a differentiation stage-specific manner
Authors: Jeong Suji , An Borim , Kim Jung-Hyun , Han Hyo-Won , Kim Jung-Hyun , Heo Hye-Ryeon , Ha Kwon-Soo , Han Eun-Taek , Park Won Sun , Hong Seok-Ho
Published: January 2020

The efficient and reproducible derivation and maturation of multipotent hematopoietic progenitors from human pluripotent stem cells (hPSCs) requires the recapitulation of appropriate developmental stages and the microenvironment. Here, using serum-, xeno-, and feeder-free stepwise hematopoietic induction protocols, we showed that short-term and high-concentration treatment of hPSCs with bone morphogenetic protein 4 (BMP4) strongly promoted early mesoderm induction followed by increased hematopoietic commitment. This method reduced variations in hematopoietic differentiation among hPSC lines maintained under chemically defined Essential 8 medium compared to those maintained under less-defined mTeSR medium. We also found that perivascular niche cells (PVCs) significantly augmented the production of hematopoietic cells via paracrine signaling mechanisms only when they were present during the hematopoietic commitment phase. A protein array revealed 86 differentially expressed (>1.5-fold) secretion factors in PVC-conditioned medium compared with serum-free control medium, of which the transforming growth factor-β inducible gene H3 significantly increased the number of hematopoietic colony-forming colonies. Our data suggest that BMP4 and PVCs promote the hematopoietic differentiation of hPSCs in a differentiation stage-specific manner. This will increase our understanding of hematopoietic development and expedite the development of hPSC-derived blood products for therapeutic use.
Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1
Authors: Park Hye-Kyung , Yoon Nam Gu , Lee Ji-Eun , Hu Sung , Yoon Sora , Kim So Yeon , Hong Jun-Hee , Nam Dougu , Chae Young Chan , Park Jong Bae , Kang Byoung Heon
Published: January 2020

The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity.
Role of interleukin-23 in the development of nonallergic eosinophilic inflammation in a murine model of asthma
Authors: Lee Hyun Seung , Park Da-Eun , Lee Ji-Won , Sohn Kyung Hee , Cho Sang-Heon , Park Heung-Woo
Published: January 2020

Nonallergic eosinophilic asthma (NAEA) is a clinically distinct subtype of asthma. Thus far, the pathophysiologic mechanisms underlying NAEA have not been fully elucidated. This study aimed to determine the role of IL-23 in the pathogenesis of NAEA. We developed a murine model of NAEA using recombinant IL-23 (rIL-23) plus a nonspecific airway irritant [polyinosinic-polycytidylic acid (polyI:C) or diesel exhaust particles (DEPs)] and investigated whether IL-23 plays an important role in the development of NAEA. Intranasal administration of rIL-23 (0.1 μg/mouse) plus polyI:C (0.01 μg/mouse) or DEPs (10 μg/mouse) without allergen resulted in methacholine bronchial hyperresponsiveness and eosinophilic airway inflammation in mice, which are characteristic features of NAEA. rIL-23 plus a low dose nonspecific airway irritants induced the release of innate cytokines from airway epithelium, including IL-33, thymic stromal lymphopoietin and IL-1β; these factors activated types 2 and 3 innate lymphoid cells (ILC2s and ILC3s). ILC2s and ILC3s, but not CD4+ T cells (i.e., adaptive immune cells), were important in the development of NAEA. In addition, we observed that IL-23 receptor expressions increased in airway epithelial cells, which suggests the existence of a positive autocrine loop in our murine model of NAEA. To our knowledge, this is the first report in which administration of rIL-23 plus a nonspecific airway irritant (polyI:C or DEPs) without allergen resulted in features of NAEA in mice similar to those found in humans. IL-23 may constitute a therapeutic target for NAEA in humans.
Amino acid transporters as tetraspanin TM4SF5 binding partners
Authors: Jung Jae Woo , Kim Ji Eon , Kim Eunmi , Lee Jung Weon
Published: January 2020

Transmembrane 4 L6 family member 5 (TM4SF5) is a tetraspanin that has four transmembrane domains and can be N-glycosylated and palmitoylated. These posttranslational modifications of TM4SF5 enable homophilic or heterophilic binding to diverse membrane proteins and receptors, including growth factor receptors, integrins, and tetraspanins. As a member of the tetraspanin family, TM4SF5 promotes protein-protein complexes for the spatiotemporal regulation of the expression, stability, binding, and signaling activity of its binding partners. Chronic diseases such as liver diseases involve bidirectional communication between extracellular and intracellular spaces, resulting in immune-related metabolic effects during the development of pathological phenotypes. It has recently been shown that, during the development of fibrosis and cancer, TM4SF5 forms protein-protein complexes with amino acid transporters, which can lead to the regulation of cystine uptake from the extracellular space to the cytosol and arginine export from the lysosomal lumen to the cytosol. Furthermore, using proteomic analyses, we found that diverse amino acid transporters were precipitated with TM4SF5, although these binding partners need to be confirmed by other approaches and in functionally relevant studies. This review discusses the scope of the pathological relevance of TM4SF5 and its binding to certain amino acid transporters.
Correction: TiO2 nanotube stimulate chondrogenic differentiation of limb mesenchymal cells by modulating focal activity
Authors: Kim Dongkyun , Choi Bohm , Song Jinsoo , Kim Sunhyo , Oh Seunghan , Jin Eun-Heui , Kang Shin-Sung , Jin Eun-Jung
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Correction to: Graft immaturity and safety concerns in transplanted human kidney organoids
Authors: Nam Sun Ah , Seo Eunjeong , Kim Jin Won , Kim Hyung Wook , Kim Hong Lim , Kim Kyuryung , Kim Tae-Min , Ju Ji Hyeon , Gomez Ivan G. , Uchimura Kohei , Humphreys Benjamin D. , Yang Chul Woo , Lee Jae Yeon , Kim Jin , Cho Dong Woo , Freedman Benjamin S. , Kim Yong Kyun
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Parallelized volumetric fluorescence microscopy with a reconfigurable coded incoherent light-sheet array
Authors: Ren Yu-Xuan , Wu Jianglai , Lai Queenie T. K. , Lai Hei Ming , Siu Dickson M. D. , Wu Wutian , Wong Kenneth K. Y. , Tsia Kevin K.
Published: January 2020

Parallelized fluorescence imaging has been a long-standing pursuit that can address the unmet need for a comprehensive three-dimensional (3D) visualization of dynamical biological processes with minimal photodamage. However, the available approaches are limited to incomplete parallelization in only two dimensions or sparse sampling in three dimensions. We hereby develop a novel fluorescence imaging approach, called coded light-sheet array microscopy (CLAM), which allows complete parallelized 3D imaging without mechanical scanning. Harnessing the concept of an “infinity mirror”, CLAM generates a light-sheet array with controllable sheet density and degree of coherence. Thus, CLAM circumvents the common complications of multiple coherent light-sheet generation in terms of dedicated wavefront engineering and mechanical dithering/scanning. Moreover, the encoding of multiplexed optical sections in CLAM allows the synchronous capture of all sectioned images within the imaged volume. We demonstrate the utility of CLAM in different imaging scenarios, including a light-scattering medium, an optically cleared tissue, and microparticles in fluidic flow. CLAM can maximize the signal-to-noise ratio and the spatial duty cycle, and also provides a further reduction in photobleaching compared to the major scanning-based 3D imaging systems. The flexible implementation of CLAM regarding both hardware and software ensures compatibility with any light-sheet imaging modality and could thus be instrumental in a multitude of areas in biological research.
An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder
Authors: Pu Juncai , Liu Yiyun , Zhang Hanping , Tian Lu , Gui Siwen , Yu Yue , Chen Xiang , Chen Yue , Yang Lining , Ran Yanqin , Zhong Xiaogang , Xu Shaohua , Song Xuemian , Liu Lanxiang , Zheng Peng , Wang Haiyang , Xie Peng
Published: January 2020

Major depressive disorder (MDD) is a serious mental illness, characterized by high morbidity, which has increased in recent decades. However, the molecular mechanisms underlying MDD remain unclear. Previous studies have identified altered metabolic profiles in peripheral tissues associated with MDD. Using curated metabolic characterization data from a large sample of MDD patients, we meta-analyzed the results of metabolites in peripheral blood. Pathway and network analyses were then performed to elucidate the biological themes within these altered metabolites. We identified 23 differentially expressed metabolites between MDD patients and controls from 46 studies. MDD patients were characterized by higher levels of asymmetric dimethylarginine, tyramine, 2-hydroxybutyric acid, phosphatidylcholine (32:1), and taurochenodesoxycholic acid and lower levels of l-acetylcarnitine, creatinine, l-asparagine, l-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, l-serine, oleic acid, myo-inositol, dodecanoic acid, l-methionine, hypoxanthine, palmitic acid, l-tryptophan, kynurenic acid, taurine, and 25-hydroxyvitamin D compared with controls. l-tryptophan and kynurenic acid were consistently downregulated in MDD patients, regardless of antidepressant exposure. Depression rating scores were negatively associated with decreased levels of l-tryptophan. Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan–kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients. Taken together, our integrated results revealed that metabolic changes in the peripheral blood were associated with MDD, particularly decreased l-tryptophan and kynurenic acid levels, and alterations in the tryptophan–kynurenine and fatty acid metabolism pathways. Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.
The importance of a developmental perspective in Psychiatry: what do recent genetic-epidemiological findings show?
Authors: Thapar Anita , Riglin Lucy
Published: January 2020

There is growing appreciation that a developmental perspective is helpful in Psychiatry. However, clinical practice and research, especially in an era of very large sample sizes, often ignore the developmental context. In this perspective piece, we discuss why a developmental view is important in Psychiatry and how recent genetic-epidemiological findings further highlight this. DSM-5 childhood neurodevelopmental disorders such as ADHD, typically onset in early childhood but can persist into adult life; the same ADHD genetic loading appears to contribute across the life course. However, recent longitudinal studies have observed that ADHD symptoms may emerge later during adolescence and adult life in some individuals although the etiology of this late-onset group is unclear. The epidemiology and genetics of depression do not appear to be the same in childhood, adolescence, and adult life. Recent genetic findings further highlight this. Autistic type problems and irritability also appear to show developmental variation in their genetic etiology. These findings raise the question of whether social communication and irritability have the same meaning at different ages. Schizophrenia typically onsets after adolescence. However, it is commonly preceded by childhood antecedents that do not resemble schizophrenia itself but do appear to index schizophrenia genetic liability. We conclude that there is a need for clinicians and scientists to adopt a developmental perspective in clinical practice and research by considering age-at-onset and changes over time as well as different developmental periods when interpreting clinical symptoms.
Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis
Authors: Guan Yun-feng , Huang Qiao-ling , Ai Yuan-li , Chen Qi-tao , Zhao Wen-xiu , Wang Xiao-min , Wu Qiao , Chen Hang-zi
Published: January 2020

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Orphan nuclear receptor Nur77, which is low expressed in HCC, functions as a tumor suppressor to suppress HCC. However, the detailed mechanism is still not well understood. Here, we demonstrate that Nur77 could inhibit HCC development via transcriptional activation of the lncRNA WAP four-disulfide core domain 21 pseudogene (WFDC21P). Nur77 binds to its response elements on the WFDC21P promoter to directly induce WFDC21P transcription, which inhibits HCC cell proliferation, tumor growth, and tumor metastasis both in vitro and in vivo. In clinical HCC samples, WFDC21P expression positively correlated with that of Nur77, and the loss of WFDC21P is associated with worse prognosis. Mechanistically, WFDC21P could inhibit glycolysis by simultaneously interacting with PFKP and PKM2, two key enzymes in glycolysis. These interactions not only abrogate the tetramer formation of PFKP to impede its catalytic activity but also prevent the nuclear translocation of PKM2 to suppress its function as a transcriptional coactivator. Cytosporone-B (Csn-B), an agonist for Nur77, could stimulate WFDC21P expression and suppress HCC in a WFDC21P-dependent manner. Therefore, our study reveals a new HCC suppressor and connects the glycolytic remodeling of HCC with the Nur77-WFDC21P-PFKP/PKM2 axis.
Transmissible gastroenteritis virus targets Paneth cells to inhibit the self-renewal and differentiation of Lgr5 intestinal stem cells via Notch signaling
Authors: Wu Aimin , Yu Bing , Zhang Keying , Xu Zhiwen , Wu De , He Jun , Luo Junqiu , Luo Yuheng , Yu Jie , Zheng Ping , Che Lianqiang , Mao Xiangbing , Huang Zhiqing , Wang Lan , Zhao Jun , Chen Daiwen
Published: January 2020

Infection with transmissible gastroenteritis virus (TGEV) has been associated with villous atrophy within 48 h, which seriously disrupts intestinal homeostasis. However, the underlying mechanisms remain elusive. In this study, we found that TGEV infection severely disrupted intestinal homeostasis via inhibition of self-renewal and differentiation in Lgr5 intestinal stem cells (ISCs). Profoundly, TGEV-encoded NSP10/NSP16 protein complex-mediated the inactivation of Notch signaling provided a mechanistic explanation for this phenomenon. Initial invasions by TGEV-targeted Paneth cells through aminopeptidase N (APN) receptor, then inducing mitochondrial damage and ROS generation in them, ultimately causing Paneth cell decrease and loss of Notch factors (DII4 and Hes5), which are essential for Lgr5 ISCs self-renewal and differentiation. Interestingly, loss of Notch signaling induced goblet cells differentiation at the cost of absorptive enterocytes and promoted mucins secretion, which accelerated TGEV replication. Therefore, the more differentiation of goblet cells, the greater TGEV infection in jejunum. These results provide a detailed mechanistic pathway by which villous atrophy sharply occurs in TGEV-infected jejunum within 48 h. Thus, the pathogenesis of TGEV can be described as a “bottom up scenario”, which is contrary to the traditional “top down” hypothesis. Together, our findings provide a potential link between diarrheal virus infection and crypt cells response that regulates Paneth cells function and Lgr5 ISCs fate and could be exploited for therapeutic application.
Genome-scale CRISPR screening for potential targets of ginsenoside compound K
Authors: Yang Yuanyuan , Liu Xiaojian , Li Shuang , Chen Yanhao , Zhao Yongxu , Wei Yuda , Qiu Yan , Liu Yan , Zhou Zhihua , Han Jun , Wu Guohao , Ding Qiurong
Published: January 2020

Ginsenosides exhibit a large variety of biological activities in maintaining physical health; however, the molecule underpinnings underlining these biological activities remain to be defined. Here, we took a cellular condition that compound K (CK) induces autophagic cell death in HeLa cells, and setup a high-throughput genetic screening using CRISPR technology. We have identified a number of CK-resistant and CK-sensitive genes, and further validated PMAIP1 as a CK-resistant gene and WASH1 as a CK-sensitive gene. Compound K treatment reduces the expression of WASH1, which further accelerates the autophagic cell death, highlighting WASH1 as an interesting downstream mediator of CK effects. Overall, our study offers an easy-to-adopt platform to study the functional mediators of ginsenosides, and provides a candidate list of genes that are potential targets of CK.
Emergence of chirality and structural complexity in single crystals at the molecular and morphological levels
Authors: di Gregorio Maria Chiara , Shimon Linda J. W. , Brumfeld Vlad , Houben Lothar , Lahav Michal , van der Boom Milko E.
Published: January 2020

Naturally occurring single crystals having a multidomain morphology are a counterintuitive phenonomon: the macroscopic appearance is expected to follow the symmetry of the unit cell. Growing such crystals in the lab is a great challenge, especially from organic molecules. We achieve here uniform metallo-organic crystals that exhibit single crystallinity with apparently distinct domains and chirality. The chirality is present at both the molecular and macroscopic levels, although only achiral elements are used. “Yo-yo”-like structures having opposite helical handedness evolve from initially formed seemingly achiral cylinders. This non-polyhedral morphology coexists with a continuous coordination network forming homochiral channels. This work sheds light on the enigmatic aspects of fascinating crystallization processes occurring in biological mineralization. Our findings open up opportunities to generate new porous and hierarchical chiral materials.
JMJD3 and UTX determine fidelity and lineage specification of human neural progenitor cells
Authors: Shan Yongli , Zhang Yanqi , Zhao Yuan , Wang Tianyu , Zhang Jingyuan , Yao Jiao , Ma Ning , Liang Zechuan , Huang Wenhao , Huang Ke , Zhang Tian , Su Zhenghui , Chen Qianyu , Zhu Yanling , Wu Chuman , Zhou Tiancheng , Sun Wei , Wei Yanxing , Zhang Cong , Li Chenxu , Su Shuquan , Liao Baojian , Zhong Mei , Zhong Xiaofen , Nie Jinfu , Pei Duanqing , Pan Guangjin
Published: January 2020

Neurogenesis, a highly orchestrated process, entails the transition from a pluripotent to neural state and involves neural progenitor cells (NPCs) and neuronal/glial subtypes. However, the precise epigenetic mechanisms underlying fate decision remain poorly understood. Here, we delete KDM6s (JMJD3 and/or UTX), the H3K27me3 demethylases, in human embryonic stem cells (hESCs) and show that their deletion does not impede NPC generation from hESCs. However, KDM6-deficient NPCs exhibit poor proliferation and a failure to differentiate into neurons and glia. Mechanistically, both JMJD3 and UTX are found to be enriched in gene loci essential for neural development in hNPCs, and KDM6 impairment leads to H3K27me3 accumulation and blockade of DNA accessibility at these genes. Interestingly, forced expression of neuron-specific chromatin remodelling BAF (nBAF) rescues the neuron/glia defect in KDM6-deficient NPCs despite H3K27me3 accumulation. Our findings uncover the differential requirement of KDM6s in specifying NPCs and neurons/glia and highlight the contribution of individual epigenetic regulators in fate decisions in a human development model.
Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy
Authors: Huhn Oisín , Ivarsson Martin A. , Gardner Lucy , Hollinshead Mike , Stinchcombe Jane C , Chen Puran , Shreeve Norman , Chazara Olympe , Farrell Lydia E. , Theorell Jakob , Ghadially Hormas , Parham Peter , Griffiths Gillian , Horowitz Amir , Moffett Ashley , Sharkey Andrew M. , Colucci Francesco
Published: January 2020

During early pregnancy, decidual innate lymphoid cells (dILCs) interact with surrounding maternal cells and invading fetal extravillous trophoblasts (EVT). Here, using mass cytometry, we characterise five main dILC subsets: decidual NK cells (dNK)1–3, ILC3s and proliferating NK cells. Following stimulation, dNK2 and dNK3 produce more chemokines than dNK1 including XCL1 which can act on both maternal dendritic cells and fetal EVT. In contrast, dNK1 express receptors including Killer-cell Immunoglobulin-like Receptors (KIR), indicating they respond to HLA class I ligands on EVT. Decidual NK have distinctive organisation and content of granules compared with peripheral blood NK cells. Acquisition of KIR correlates with higher granzyme B levels and increased chemokine production in response to KIR activation, suggesting a link between increased granule content and dNK1 responsiveness. Our analysis shows that dILCs are unique and provide specialised functions dedicated to achieving placental development and successful reproduction.
Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis
Authors: Olafsdottir Thorunn A. , Theodors Fannar , Bjarnadottir Kristbjorg , Bjornsdottir Unnur Steina , Agustsdottir Arna B. , Stefansson Olafur A. , Ivarsdottir Erna V. , Sigurdsson Jon K. , Benonisdottir Stefania , Eyjolfsson Gudmundur I. , Gislason David , Gislason Thorarinn , Guðmundsdóttir Steinunn , Gylfason Arnaldur , Halldorsson Bjarni V. , Halldorsson Gisli H. , Juliusdottir Thorhildur , Kristinsdottir Anna M. , Ludviksdottir Dora , Ludviksson Bjorn R. , Masson Gisli , Norland Kristjan , Onundarson Pall T. , Olafsson Isleifur , Sigurdardottir Olof , Stefansdottir Lilja , Sveinbjornsson Gardar , Tragante Vinicius , Gudbjartsson Daniel F. , Thorleifsson Gudmar , Sulem Patrick , Thorsteinsdottir Unnur , Norddahl Gudmundur L. , Jonsdottir Ingileif , Stefansson Kari
Published: January 2020

Asthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant inTNFRSF8and 3‘ UTR variant inTGFBR1. Functional studies show that theTNFRSF8variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that theTGFBR1variant acts through gain of function and together with an intronic variant in a downstream gene,SMAD3, points to defective TGFβR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.