bluuebunny/crossref_metadata_2025 huggingface dataset:
1939–45—Puzzled People?
Authors: Field Clive D.
Published: November 2019

Analysis of the Second World War’s impact on religious allegiance is affected by data gaps and doubts about the accuracy of opinion polling and the rigour of membership roll revision. But the Church of England lost some market share, the Free Churches slid further towards nominalism, and the number of ‘nones’ grew, absolutely and relatively, more than in the First World War. Church membership losses were greatest in 1939–42. There were 1 million fewer Sunday scholars. Unlike the First World War, there was no temporary revival of churchgoing at the start of the Second World War, only continuous decline in Protestantism, with the index of attendance at ordinary services often reduced to ten or less, half of adults never attending or solely for rites of passage. The decrease is partly explained by wartime disruptions but churchgoing also faced competition from Sunday cinema and the BBC’s enhanced portfolio of religious broadcasts.
Intersectional Discrimination
Authors: Atrey Shreya
Published: November 2019

Why has intersectionality fallen by the wayside of discrimination law? Thirty years after Kimberlé Crenshaw coined the term ‘intersectionality’, discrimination lawyers continue to be plagued by this question across a range of jurisdictions, including the US, UK, South Africa, India, Canada, as well as the UN treaty body jurisprudence and the jurisprudence of the EU and the ECHR. Claimants continue to struggle to establish intersectional claims based on more than one ground of discrimination. This book renews the bid for realizing intersectionality in comparative discrimination law. It presents a juridical account of intersectional discrimination as a category of discrimination inspired by intersectionality theory, and distinct from other categories of thinking about discrimination including strict, substantial, capacious, and contextual forms of single-axis discrimination, multiple discrimination, additive discrimination as in combination or compound discrimination, and embedded discrimination. Intersectional discrimination, defined in these theoretical and categorial terms, then needs to be translated into doctrine, recalibrating each of the central concepts and tools of discrimination law to respond to it—including the text of non-discrimination guarantees, the idea of grounds, the test for analogous grounds, the distinction between direct and indirect discrimination, the substantive meaning of discrimination, the use of comparators, the justification analysis and standard of review, the burden of proof between parties, and the range of remedies available. With this, the book presents a granular account of intersectional discrimination in theoretical, conceptual, and doctrinal terms, and aims to transform discrimination law in the process of realizing intersectionality within its discourse.
The Project
Authors: Atrey Shreya
Published: November 2019

Chapter 1 inaugurates the project by setting out the current status of intersectionality in discrimination laws across jurisdictions, including the US, UK, South Africa, Canada, and India, and in the jurisprudence of the European Court of Human Rights, the Court of Justice of the European Union, and international human rights treaty bodies. Although each jurisdiction’s tryst with intersectionality has been unique, the survey concludes by pointing out the similarities between the continuing legislative and judicial struggles in redressing intersectional discrimination successfully. This prepares the stage for the current intervention. The chapter goes on to define the central argument of this work and the parameters within which it unfolds. In particular, it explains the choice of comparative jurisdictions and the wide range of materials employed in making a case for intersectional discrimination.
The Concept
Authors: Atrey Shreya
Published: November 2019

This chapter examines how intersectional discrimination has been understood in discrimination law. The analysis reveals that courts across jurisdictions have understood this category of discrimination not only as a matter of intersectionality, but also in various other ways, such as single-axis discrimination, multiple discrimination, additive discrimination, embedded discrimination, and compound discrimination. The chapter considers the relative position of these categories along a continuum and maps the qualitative differences between them as against the category of intersectional discrimination. It argues that the differences matter diagnostically in that only the category of intersectional discrimination properly so called, explains the causality in intersectional discrimination based on multiple grounds.
Explaining Scott’s Turn to American History
Authors: Amorosa Paolo
Published: November 2019

The first chapter, like all others in the book, is divided in three sections. Section 1 offers an analysis of the US foreign policy discourse at the turn of the century and connects it with the growing popularity of international law within the elites. Section 2 follows Scott in his work as Secretary Root’s legal advisor at the State Department, until the two moved together to lead the newly established Carnegie Endowment for International Peace. The highlight of Scott’s government stint was the 1907 Second Hague Peace Conference, where he championed the project for an international court and created a large part of the transatlantic professional connections that would be crucial to his later projects. Section 3 describes how Scott, since 1910 a powerful administrator at the Carnegie Endowment for International Peace, deployed the massive resources at his disposal.
Unequal outcomes for countries and people
Authors: Nayyar Deepak
Published: November 2019

Rapid economic growth in Asia was associated with an unequal distribution of its benefits among countries and between people. There was, in fact, a widening gap in per capita income levels within the Asian-14, while the gap between the richest and poorest countries in Asia was awesome. Much of the income inequality between countries in Asia was attributable to inequality between, rather than within, countries. Yet, there was also a significant increase in inequality between people within countries, just as there was a marked increase in inequality between regions within countries, both of which were more pronounced in countries that experienced rapid growth. Even so, rapid growth did lead to a substantial reduction in absolute poverty. However, the scale of absolute poverty that persists, despite unprecedented growth, is just as striking as the sharp reduction therein. The poverty reduction could have been much greater, were it not for the rising inequality.
Asian development and the world economy
Authors: Nayyar Deepak
Published: November 2019

During the post-colonial era, the relationship between Asia and the world was shaped by a geopolitics in which economics and politics, juxtaposed with history and geography, were closely intertwined. East and Southeast Asia became the main arena for contesting political ideologies—capitalism versus communism—in the Cold War, while West Asia was the stage where strategic interests driven by oil played out. Both were associated with conflicts and wars that shaped trajectories of development. Rapid economic growth in Asia has implications, both positive and negative, for the world, industrialized countries, and developing countries, which are analysed in the chapter. The international economic and political architecture for global governance was created around 1945. Asia had no voice in that process. The shifting balance of power provides Asian countries with an opportunity to exercise collective influence now, but co-ordination and co-operation among them has not surfaced yet, possibly because of economic and political rivalry.
Contemplating the future
Authors: Nayyar Deepak
Published: November 2019

This chapter concludes. It outlines the contours of change to recapitulate the essentials of the transformation in Asia, and highlights the major analytical conclusions that relate to contemporary debates on development. It considers prospects, in terms of opportunities and challenges, for countries that have led the process so far and for those that might follow in their footsteps. It reflects on the future, with reference to the past, to speculate how the changed international context, and new challenges on the horizon, might shape, or be influenced by, development in Asia over the next twenty-five years, addressing specific questions. Do recent changes in the global political economy have any longer-term implications for Asia? What is the likely impact of the profound technological changes on the horizon for development in Asia? How would the leading industrialized countries respond or adjust to the erosion of their economic dominance and political hegemony? Is this going to be an Asian century?
The Policy Effects of the Decisions of European Courts on Targeted Sanctions
Authors: Istrefi Kushtrim
Published: November 2019

This chapter examines the policy effects of decisions by European courts on Security Council targeted sanctions as regards the two concerns that triggered their judicial responses, namely due process reform and genuine realization of human rights. This consequentialist assessment argues that a more Herculean form of judicial activism, as seen in Kadi II before the Court of Justice of the European Union (CJEU), cannot alone uphold human rights and may be counterproductive to the Security Council reform process. This submission suggests that a form of judicial restraint as exercised by the European Court of Human Rights (ECtHR or Strasbourg Court) in Al-Dulimi may prove to be more effective. In particular, the arbitrariness test introduced by the Strasbourg Court in that case with regard to Security Council measures may achieve two policy objectives. First, through a timely review by national courts of arbitrary listings it may encourage the realization of human rights. Second, by demanding that states secure appropriate evidence for listings, it may revitalize reform of the sanction decision-making process. These effects of Al-Dulimi are examined in the context of earlier engagement by national authorities with Security Council measures, including in the Sayadi and Vinck and Nada cases. Despite these consequences, this chapter warns of some limitations inherent in the approach applied by the Strasbourg Court in cases where national executives turn out to be uncooperative.
Respiratory Biology of Animals
Authors: Perry Steven F. , Lambertz Markus , Schmitz Anke
Published: November 2019

The aim of this book is to shed light on one of the most fundamental processes of life in the various lineages of animals: respiration. It provides a certain background on the physiological side of respiration, but it clearly focuses on the morphological aspects. In general, the intention of this book is to illustrate the impressive diversity of respiratory faculties (form–function complexes) rather than serving as an encyclopaedic handbook. It takes the reader on a journey through the entire realm of animals and discusses the structures involved in gas exchange, how they work, and most importantly, how all of this may be connected on an evolutionary scale. Due to the common problem, namely oxygen uptake and carbon dioxide release, and the limited number of solutions, basically surface area, barrier thickness, and physical exchange model of the respiratory organ, it is not surprising that one finds a huge number of convergences. These include, for instance, the repeated origin of tubular tracheae among several lineages of arthropods, similar lung structures in snails and amphibians, and counter-current exchange gills in bivalves and fish. However, there are certain phylogenetic constraints evident and the respiratory faculty appears as a yet to be adequately exploited source of information for systematic considerations. The ultimate goal of this book is to stimulate further research in respiratory biology, because a huge number of questions remain to be tackled on all levels, ranging from molecular through functional to especially the evolutionary aspects.
The evolution of water-breathing respiratory faculties in invertebrates
Authors: Perry Steven F. , Lambertz Markus , Schmitz Anke
Published: November 2019

This chapter aims at piecing together the evolution of water breathing in invertebrates. Dedicated respiratory faculties, consisting of an external exchanger, an internal transport system (circulatory system or an equivalent), and some control element are first clearly recognizable among invertebrates in annelids, which excel in the number of different respiratory proteins they display. Molluscs and arthropods use primarily haemocyanin, each group showing evolutionary trends in respiratory proteins that have some bearing on the phylogenetic position. Each major group of molluscs has its own evolutionary story, but in general we see a reduction in the number of gills and often a release from bilateral symmetry. Among arthropods, crustaceans can develop gills on various parts of the legs and the body wall, each group showing a taxon-specific type. Arachnids and hexapods are primarily terrestrial, but several groups have independently and secondarily developed mechanisms for even long-term survival under water.
War By Agreement
Authors: Benbaji Yitzhak , Statman Daniel
Published: November 2019

In the last two decades, traditional just war theory has been under attack. Critics, known as ‘revisionists’, have argued that its most fundamental principles are morally suspect. However, so far they have failed to propose a convincing alternative. These developments have resulted in a stalemate. While almost everybody would like to maintain the legal order set by the UN Charter and by the Geneva Conventions, there is currently no moral outlook that convincingly substantiates it. The purpose of the present book is to forge a way through this stalemate and show that wars can be morally justified at both the jus ad bellum level (the political decision to go to war) and the jus in bello level (its actual conduct by the military). It does so by developing a contractarian account of the rules governing war, according to which they are best interpreted as a mutually beneficial and fair agreement between the relevant players. The book relies on the long social contract tradition and illustrates its fruitfulness in understanding the morality and the law of war.
When the Agreement Collapses
Authors: Benbaji Yitzhak , Statman Daniel
Published: November 2019

What happens when one of the parties to the war contract deliberately ignores it? This typically occurs when one of the parties violates the jus in bello rules by bombing civilian targets, murdering POWs and so on. This chapter argues that the normative implications of breaching the war contract are themselves part of the contract. In the absence of an international body that can enforce the contract on those violating it, the parties have the right to respond to violations of the in bello rules. These remedies—these counter-violations—should be cautious and restrained, with a constant eye on the goal of reinstituting the parties’ commitment to the broken rules. The in bello violations that call for retaliation are of three general kinds: (a) violating prohibitions whose source is merely conventional, such as those outlawing certain weapons; (b) violating the prohibition against targeting civilians in cases in which the civilians attacked bear responsibility for the enemy war effort, such as politicians or party members; and (c) carrying out indiscriminate attacks on civilians. The chapter argues that retaliation in kind is licensed by the war contract in all three categories. Ex ante, decent and partial parties would see the need to deter disobedient parties and to make them realize that they would pay too high a price for violations of the war agreement. Thus, a war ethic of the kind the chapter proposes will make the world a safer place in which to live.
Incarceration
Authors: Park Yoosun
Published: November 2019

Hastily built on existing sites such as race tracks and fair grounds, the temporary Wartime Civil Control Administration (WCCA) detention camps in which the Nikkei were first incarcerated were unfit for human habitation. Given the economic devastation wreaked by the removal, the need for financial and other types of aid soon became obvious, but no system of aid had been established at the centers. The more permanent War Relocation Authority camps to which the Nikkei were then transferred were no better in facilities or services. Social work departments in camps were ill-planned, underfunded, poorly staffed, and inconsistently administered. Recruiting trained social workers to staff the remote and inclement camps was a constant problem. The complicated and conflicted role of the Nikkei workers who comprised the bulk of the social work staff should be understood in the context of the generally fraught dynamic that existed between the Nikkei inmates and the Caucasian staff.
To what extent do socioeconomic inequalities in SRH reflect inequalities in burden of disease? The HELIUS study
Authors: Galenkamp Henrike , van Oers Hans , Stronks Karien
Published: November 2019

Background

Self-rated health (SRH), an attractive measure for health monitoring, shows persistent inequalities with regard to socioeconomic status (SES). However, knowledge on the extent to which inequalities in SRH reflect inequalities in disease burden is lacking.

Methods

Data come from the multi-ethnic HEalthy LIfe in an Urban Setting study (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish or Moroccan origin, N = 19 379, aged 18–70). SES was defined by educational and occupational level. Disease burden was operationalized as chronic diseases, physical and mental functioning (measured with SF-12) and depressive symptoms (measured with PHQ-9). We applied logistic regression analyses and reported average marginal effects (AME).

Results

Dutch origin participants with low educational or low occupational level had higher probabilities of reporting fair/poor SRH, compared to the highest levels (AME = 0.20 95% CI: 0.13;0.27; and 0.12 (0.09;0.15), respectively). Associations were attenuated after adjusting for all disease burden indicators, to AME = 0.03 (0.01;0.04) and AME = 0.02 (−0.00;0.04). In all the non-Dutch origin groups, a larger part of the inequalities remained after adjustment.

Conclusion

Socioeconomic inequalities in SRH are for a large part explained by higher disease burden in lower socioeconomic groups, but less so in those with non-Dutch origin. Future research should examine if our conclusions also hold for trend data on inequalities in SRH.
President Trump and health care: a content analysis of misleading statements
Authors: Hatcher William
Published: November 2019

Background

This study examines President Trump’s misleading language in the area of health care. According to ‘The Washington Post’, President Trump has made over 10 000 misleading or false statements about public policy.

Methods

We use content analysis to examine the 662 health-related statements made over the period from his inauguration on 20 January 2017 to 27 April 2019.

Results

Analysis of these statements identified seven themes, and we also found that a plurality of the statements spreads false information about the Affordable Care Act or Obamacare.

Discussion

President Trump’s misleading statements about health care are unprecedented and potentially damaging to public health. The communications may adversely affect the public’s knowledge about their health care, their understanding of the health care system and their understanding of health care procedures.
National Philology, Imperial Hierarchies, and the ‘Defective’ Book of Sir John Mandeville
Authors: White Tom
Published: November 2019

This article examines when and how the ‘Defective’ version of the Book of Sir John Mandeville came to be called ‘defective’. It describes the use of this name by Sir George F. Warner in an edition produced in 1889 for the elite bibliographic society the Roxburghe Club. Drawing on recent work in disability studies, it argues that the philological use of ‘defective’ be read in conjunction with its broader use in the elaboration of hierarchies of class, race, and gender. Far from a neutral descriptor, ‘defective’ provides a compelling example of the imbrication of medieval studies, imperialism, and Social Darwinist principles in the late nineteenth century. The article closes with the call not only to rename the ‘Defective’ version the ‘Common’ version, but also for a broader reappraisal of this apparently discrete version of Mandeville’s Book. However, it also argues that amid the increasing marketization of higher education and the concomitant insecurity of academic labour, digital editing does not provide a straightforward answer to the question of how best to map and display the complex textual history of Mandeville’s Book.
The power of economic models: the case of the EU’s fiscal regulation framework
Authors: Heimberger Philipp , Huber Jakob , Kapeller Jakob
Published: November 2019

This article is concerned with the impact of economic ideas on political processes and decision-making. We argue that economic models can serve as a transmission device between economic paradigms and policy programs, which allow actors drawing on the model to exercise power in decision-making. We illustrate this argument by focusing on the European Commission’s ‘potential output’ model, which represents a core pillar of EU fiscal governance as it provides estimates of ‘structural deficits’ for evaluating fiscal policies. We combine an analysis of the history and content of the model at stake with insights derived from policy documents, legal provisions, speeches and interviews. Our findings imply that economic models (a) allow for exerting power only under specific conditions, (b) align paradigmatic priors with policy proposals and (c) may constitute mutual feedback loops where political decisions are coined by technicalities and, as a consequence, seemingly innocent technical assumptions become objects of political demands.
Toward an economic sociology of race
Authors: Hirschman Daniel , Garbes Laura
Published: November 2019

Race is central to economic life, but race is not central to economic sociology. We argue that economic sociologists should treat racism as a constitutive, structuring force, analytically co-equal with capitalism, patriarchy and nationalism. Our article has three aims. First, we document how canonical and award-winning works of economic sociology do not discuss race and racism, and do not engage with the contemporary sociology of race. Second, we identify six key insights from the sociology of race and suggest how they could influence economic sociology: the emergence of race out of racism, an understanding of racism as structural, the role of whiteness, the intersections between racism and other systems of oppression, the ideology of colorblind racism and the fundamental connections between racism and capitalism. Third, we conclude by discussing recent research that bridges the two subfields and lays the groundwork for an understanding of ‘racialized markets’ and ‘racialized economies’.
A new contribution to the taxonomy and molecular phylogeny of three, well-known freshwater species of the ciliate genus Spirostomum (Protozoa: Ciliophora: Heterotrichea)
Authors: Chi Yong , Duan Lili , Luo Xiaotian , Cheng Ting , Warren Alan , Huang Jie , Chen Xiangrui
Published: November 2019

Members of the heterotrich genus Spirostomum are commonly found in freshwater or low salinity biotopes. In the present study, three species (S. minus, S. subtilis and S. teres) collected from freshwater habitats in Qingdao, China, are investigated using morphological and molecular methods. Detailed morphometric data are documented and improved diagnosis are supplied based on a combination of previous and present studies. In addition, small subunit ribosomal DNA (SSU rDNA) sequences are obtained from the clonal cultures. Phylogenetic analyses show that all three species are placed in the Spirostomum clade. However, isolates of the morphospecies S. minus are divided into two paraphyletic clades, while ‘populations’ of the nominal species, S. teres, are placed in at least four separate groups in the tree. After comparing morphological and molecular differences in closely related forms available, we hypothesized that S. minus and S. teres might represent species complexes. A key to the identification of the ten valid species of Spirostomum is also supplied.
openPrimeR for multiplex amplification of highly diverse templates
Authors: Kreer Christoph , Döring Matthias , Lehnen Nathalie , Ercanoglu Meryem S. , Gieselmann Lutz , Luca Domnica , Jain Kanika , Schommers Philipp , Pfeifer Nico , Klein Florian
Published: November 2019

To study the diversity of immune receptors and pathogens, multiplex PCR has become a central approach in research and diagnostics. However, insufficient primer design against highly diverse templates often prevents amplification and therefore limits the correct understanding of biological processes. Here, we present openPrimeR, an R-based tool for evaluating and designing multiplex PCR primers. openPrimeR provides a functional and intuitive interface and uses either a greedy algorithm or an integer linear program to compute the minimal set of primers that performs full target coverage. As proof of concept, we used openPrimeR to find optimal primer sets for the amplification of highly mutated immunoglobulins. Comprehensive analyses on specifically generated immunoglobulin variable gene segment libraries resulted in the composition of highly effective primer sets (oPR-IGHV, oPR-IGKV and oPR-IGLV) that demonstrated to be particularly suitable for the isolation of novel human antibodies.
Neural correlates of evidence and urgency during human perceptual decision-making in dynamically changing conditions
Authors: Yau Y. , Dadar M. , Taylor M. , Zeighami Y. , Fellows L.K. , Cisek P. , Dagher A.
Published: November 2019

Current models of decision-making assume that the brain gradually accumulates evidence and drifts towards a threshold which, once crossed, results in a choice selection. These models have been especially successful in primate research, however transposing them to human fMRI paradigms has proved challenging. Here, we exploit the face-selective visual system and test whether decoded emotional facial features from multivariate fMRI signals during a dynamic perceptual decision-making task are related to the parameters of computational models of decision-making. We show that trial-by-trial variations in the pattern of neural activity in the fusiform gyrus reflect facial emotional information and modulate drift rates during deliberation. We also observed an inverse-urgency signal based in the caudate nucleus that was independent of sensory information but appeared to slow decisions, particularly when information in the task was ambiguous. Taken together, our results characterize how decision parameters from a computational model (i.e., drift rate and urgency signal) are involved in perceptual decision-making and reflected in the activity of the human brain.
Context-dependent role of vinculin in neutrophil adhesion, motility and trafficking
Authors: Wilson Zachary S. , Witt Hadley , Hazlett Lauren , Harman Michael , Neumann Brittany M. , Whitman Andrew , Patel Mohak , Ross Robert S. , Franck Christian , Reichner Jonathan S. , Lefort Craig T.
Published: November 2019

Neutrophils are innate immune effector cells that traffic from the peripheral blood to extravascular sites of inflammation. β2 integrins are involved during multiple phases of neutrophil recruitment, including the transition from rolling to arrest, firm attachment and motility within the vasculature. Following neutrophil arrest, adhesion stabilization occurs as the neutrophil interacts with the endothelial surface and crawls into a favorable position for extravasation. The cytoskeletal protein vinculin has been implicated in other cell types as a regulator of adhesion strength by promoting focal adhesion maturation and as a sensor of the mechanical properties of the microenvironment. Neutrophils express vinculin but do not form mature focal adhesions. Here, we characterize the role of vinculin in β2 integrin-dependent neutrophil adhesion, motility, mechanosensing, and recruitment. We observe that knockout of vinculin attenuates, but does not completely abrogate, neutrophil adhesion, spreading, and crawling under static conditions. In the presence of forces from fluid flow, vinculin was not required for neutrophil adhesion or migration. Vinculin deficiency only mildly attenuated neutrophil traction stresses and spreading on stiff, but not soft, polyacrylamide gels indicating a minor role for vinculin in the mechanosensing of the neutrophil as compared to slower moving mesenchymal cells that form mature focal adhesions. Consistent with these findings, we observe in vivo neutrophil recruitment into the inflamed peritoneum of mice remains intact in the absence of vinculin. Together, these data suggest that while vinculin regulates some aspects of neutrophil adhesion and spreading, it may be dispensable for neutrophil recruitment and motility in vivo.
Signal to Noise Ratio as a Cross-Platform Metric for Intraoperative Fluorescence Imaging
Authors: Gharia Asmaysinh , Papageorgiou Efthymios P. , Giverts Simeon , Park Catherine , Anwar Mekhail
Published: November 2019

Real-time molecular imaging to guide curative cancer surgeries is critical to ensure removal of all tumor cells, however visualization of microscopic tumor foci remains challenging. Wide variation in both imager instrumentation and molecular labeling agents demands a common metric conveying the ability of a system to identify tumor cells. Microscopic disease, comprised of a small number of tumor cells, has a signal on par with the background, making the use of signal (or tumor) to background ratio inapplicable in this critical regime. Therefore, a metric that incorporates the ability to subtract out background, evaluating the signal itself relative to the sources of uncertainty, or noise is required. Here we introduce the signal-to-noise ratio (SNR) to characterize the ultimate sensitivity of an imaging system, and optimize factors such as pixel size. Variation in the background (noise) are due to electronic sources, optical sources, and spatial sources (heterogeneity in tumor marker expression, fluorophore binding, diffusion). Here we investigate the impact of these noise sources and ways to limit its effect on SNR. We use empirical tumor and noise measurements to procedurally generate tumor images and run a monte carlo simulation of microscopic disease imaging to optimize parameters such as pixel size.
Branch point control at malonyl-CoA node: A computational framework to uncover the design principles of an ideal genetic-metabolic switch
Authors: Xu Peng
Published: November 2019

Living organism is an intelligent system encoded by hierarchically-organized information to perform precisely-controlled biological functions. Biophysical models are important tools to uncover the design rules underlying complex genetic-metabolic circuit interactions. Based on a previously engineered synthetic malonyl-CoA switch (Xu et al, PNAS 2014), we have formulated nine differential equations to unravel the design principles underlying an ideal metabolic switch to improve fatty acids production in E. coli. By interrogating the physiologically accessible parameter space, we have determined the optimal controller architecture to configure both the metabolic source pathway and metabolic sink pathway. We determined that low protein degradation rate, medium strength of metabolic inhibitory constant, high metabolic source pathway induction rate, strong binding affinity of the transcriptional activator toward the metabolic source pathway, weak binding affinity of the transcriptional repressor toward the metabolic sink pathway, and a strong cooperative interaction of transcriptional repressor toward metabolic sink pathway benefit the accumulation of the target molecule (fatty acids). The target molecule (fatty acid) production is increased from 50% to 10-folds upon application of the autonomous metabolic switch. With strong metabolic inhibitory constant, the system displays multiple steady states. Stable oscillation of metabolic intermediate is the driving force to allow the system deviate from its equilibrium state and permits bidirectional ON-OFF gene expression control, which autonomously compensates enzyme level for both the metabolic source and metabolic sink pathways. The computational framework may facilitate us to design and engineer predictable genetic-metabolic switches, quest for the optimal controller architecture of the metabolic source/sink pathways, as well as leverage autonomous oscillation as a powerful tool to engineer cell function.
Wolbachia successfully replicate in a newly established horn fly, Haematobia irritans irritans (L.) (Diptera: Muscidae) cell line
Authors: Madhav Mukund , Brown Geoff , Morgan Jess A.T. , Asgari Sassan , McGraw Elizabeth A. , Munderloh Ulrike G. , Kurtti Timothy J. , James Peter
Published: November 2019

BACKGROUND

Haematobia spp., horn flies (HF) and buffalo flies (BF), are economically important ectoparasites of dairy and beef cattle. Control of these flies relies mainly on the treatment of cattle with chemical insecticides. However, the development of resistance to commonly used compounds is compromising the effectiveness of these treatments and alternative methods of control are required. Wolbachia are maternally transmitted endosymbiotic bacteria of arthropods that cause various reproductive distortions and fitness effects, making them a potential candidate for use in the biological control of pests.

RESULTS

Here we report the successful establishment of a continuous HF cell line (HIE-18) from embryonic cells and its stable transinfection with Wolbachia strain wAlbB native to mosquitoes, and wMel and wMelPop native to Drosophila melanogaster. The established HIE-18 cells are typically round and diploid with ten chromosomes (2n = 10) or tetraploid with 20 chromosomes (4n=20) having a doubling time of 67.2 hours. Wolbachia density decreased significantly in the HIE-18 cells in the first 48 hours of infection, possibly due to overexpression of antimicrobial peptides through the Imd immune signalling pathway. However, density recovered after this time and stably Wolbachia-infected HIE-18 cell lines have now all been subcultured more than 50 times as persistently infected lines.

CONCLUSION

The amenability of HF to infection with different strains of Wolbachia suggests the potential for use of Wolbachia in novel approaches for the control of Haematobia spp. Further, the availability of the HIE-18 cell line will provide an important resource for the study of genetics, host-parasite interactions and chemical resistance in Haematobia populations.
Determination of Cas9/dCas9 associated toxicity in microbes
Authors: Misra Chitra Seetharam , Bindal Gargi , Sodani Megha , Wadhawan Surbhi , Kulkarni Savita , Gautam Satyendra , Mukhopadhyaya Rita , Rath Devashish
Published: November 2019

The CRISPR-Cas9 system has been used extensively in eukaryotic and prokaryotic systems for various applications. In case of the latter, a couple of previous studies had shown Cas9 protein expression associated toxicity. We studied the same in five microbes, viz Escherichia coli, Salmonella typhimurium, Mycobacterium smegmatis, Xanthomonas campestris and Deinococcus radiodurans. Transformation efficiency of plasmids carrying genes coding for Cas9 or dCas9 was used to gauge toxicity associated with Cas9 protein expression. Results showed differential levels of Cas9 toxicity among the bacteria and lower transformation efficiency for cas9/dcas9 bearing plasmids compared to controls in general. This indicated lethal effect of Cas9/dCas9 expression. While E. coli and S. typhimurium seemed to tolerate Cas9/dCas9 fairly well, in GC rich microbes, M. smegmatis, X. campestris and D. radiodurans, Cas9/dCas9 associated toxicity was acute.
Transplacental innate immune training via maternal microbial exposure: the XBP1-ERN1 axis in programming dendritic cell precursors
Authors: Mincham Kyle T. , Jones Anya C. , Bodinier Marie , Scott Naomi M. , Lauzon-Joset Jean-Francois , Stumbles Philip A. , Bosco Anthony , Holt Patrick G. , Strickland Deborah H.
Published: November 2019

We recently reported that the offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance postnatally to allergic airways inflammation, and localised the potential treatment target to the fetal cDC progenitor compartment which expands to increase the pool of precursors available at birth, enabling accelerated postnatal seeding of the lung mucosal cDC network required for establishment of immunological homeostasis in the airways. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis, that are hallmarks of classical “immune training”. In addition, the cDC progenitor compartment displayed treatment-associated activation of the XBP1-ERN1 signalling axis which has previously been shown to be essential for tissue survival of cDC, particularly within the lung microenvironment. Our forerunner studies indicate uniquely rapid turnover of airway mucosal cDCs at baseline, with further large-scale upregulation of population dynamics during aeroallergen and/or pathogen challenge. XBP1-ERN1 signalling plays a key role in mitigation of ER stress-associated toxicity which frequently accompanies DC hyper-activation during intense immunoinflammatory responses, and we suggest that enhanced capacity for XBP1-ERN1-dependent cDC survival within the airway mucosal tissue microenvironment may be a crucial element of the OM-85-mediated transplacental “innate immune training” process which results in enhanced resistance to airway inflammatory disease during the high-risk early postnatal period.
Toxin-antitoxin gene pairs found in Tn3family transposons appear to be an integral part of the transposition module
Authors: Lima-Mendez Gipsi , Alvarenga Danillo Oliveira , Ross Karen , Hallet Bernard , Van Melderen Laurence , Varani Alessandro M. , Chandler Michael
Published: November 2019

Much of the diversity of prokaryotic genomes is contributed by the tightly controlled recombination activity of transposons (Tn). The Tn3family is arguably one of the most widespread transposon families. Members carry a large range of passenger genes incorporated into their structures. Family members undergo replicative transposition using a DDE transposase to generate a cointegrate structure which is then resolved by site-specific recombination between specific DNA sequences (res) on each of the two Tn copies in the cointegrate. These sites also carry promoters controlling expression of the recombinase and transposase. We report here that a number of Tn3members encode a type II toxin-antitoxin (TA) system, typically composed of a stable toxin and a labile antitoxin that binds the toxin and inhibits its lethal activity. This system serves to improve plasmid maintenance in a bacterial population and, until recently, was believed to be associated with bacterial persistence. At least six different TA gene pairs are associated with various Tn3members. Our data suggest that several independent acquisition events have occurred. In contrast to most Tn3family passenger genes which are generally located away from the transposition module, the TA gene pairs abut theressite upstream of the resolvase genes. Although their role when part of Tn3family transposons is unclear, this finding suggests a potential role for the embedded TA in stabilizing the associated transposon with the possibility that TA expression is coupled to expression of transposase and resolvase during the transposition process itself.

Importance

Transposable Elements (TEs) are important in genetic diversification due to their recombination properties and their ability to promote horizontal gene transfer. Over the last decades, much effort has been made to understand TE transposition mechanisms and their impact on prokaryotic genomes. For example, the Tn3family is ubiquitous in bacteria, moulding their host genomes by thepaste-and-copymechanism. In addition to the transposition module, Tn3members often carry additional passenger genes (e.g., conferring antibiotic or heavy metal resistance and virulence) and three were previously known to carry a toxin-antitoxin (TA) system often associated with plasmid maintenance; however, the role of TA systems within the Tn3family is unknown. The genetic context of TA systems in Tn3members suggests that they may play a regulatory role in ensuring stable invasion of these Tn during transposition.
Statistical analysis and optimality of neural systems
Authors: Młynarski Wiktor , Hledík Michal , Sokolowski Thomas R. , Tkačik Gašper
Published: November 2019

Normative theories and statistical inference provide complementary approaches for the study of biological systems. A normative theory postulates that organisms have adapted to efficiently solve essential tasks, and proceeds to mathematically work out testable consequences of such optimality; parameters that maximize the hypothesized organismal function can be derived ab initio, without reference to experimental data. In contrast, statistical inference focuses on efficient utilization of data to learn model parameters, without reference to any a priori notion of biological function, utility, or fitness. Traditionally, these two approaches were developed independently and applied separately. Here we unify them in a coherent Bayesian framework that embeds a normative theory into a family of maximum-entropy “optimization priors.” This family defines a smooth interpolation between a data-rich inference regime (characteristic of “bottom-up” statistical models), and a data-limited ab inito prediction regime (characteristic of “top-down” normative theory). We demonstrate the applicability of our framework using data from the visual cortex, the retina, and C. elegans, and argue that the flexibility it affords is essential to address a number of fundamental challenges relating to inference and prediction in complex, high-dimensional biological problems.
Robotic light touch assists human balance control during maximum forward reaching
Authors: Johannsen Leif , Potwar Karna , Saveriano Matteo , Endo Satoshi , Lee Dongheui
Published: November 2019

Objective

We investigated how light interpersonal touch (IPT) provided by a robotic system supports human individuals performing a challenging balance task compared to IPT provided by a human partner.

Background

IPT augments the control of body balance in contact receivers without a provision of mechanical body weight support. The nature of the processes governing the social haptic interaction, whether they are predominantly reactive or predictive, is uncertain.

Method

Ten healthy adult individuals performed maximum forward reaching (MFR) without visual feedback while standing upright. We evaluated their control of reaching behaviour and of body balance during IPT provided by either another human individual or by a robotic system in two alternative control modes (reactive vs predictive).

Results

Changes in reaching behaviour under the robotic IPT, such as lower speed and straighter direction were linked to reduced body sway. MFR of the contact receiver was influenced by the robotic control mode such as that a predictive mode reduced movement variability and increased postural stability to a greater extend in comparison to human IPT. The effects of the reactive robotic system, however, more closely resembled the effects of IPT provided by human contact provider.

Conclusion

The robotic IPT system was as supportive as human IPT. Robotic IPT seemed to afford more specific adjustments, such as trading reduced speed for increased accuracy, to meet the intrinsic demands and constraints of the robotic system. Possibly, IPT provided by a human contact provider reflected reactive interpersonal postural coordination more similar to the robotic system’s follower mode.

Précis

Interpersonal touch support by a robotic system was evaluated against support provided a human partner during maximum forward reaching.

Human contact receivers showed comparable benefits in their reaching postural performance between the support conditions.

Coordination with the robotic system, nevertheless, afforded specific adaptations in the reaching behaviour.
DoUble resin casting micro computed tomography (DUCT) reveals biliary and vascular pathology in a mouse model of Alagille syndrome
Authors: Hankeova Simona , Salplachta Jakub , Zikmund Tomas , Kavkova Michaela , Van Hul Noemi , Brinek Adam , Smekalova Veronika , Laznovsky Jakub , Jaros Josef , Bryja Vitezslav , Lendahl Urban , Ellis Ewa , Hannezo Edouard , Kaiser Jozef , Andersson Emma R
Published: November 2019

BACKGROUND AND AIMS

Alagille syndrome, like several other liver diseases, is characterized by malformation of lumenized structures, such as the circulatory or biliary systems. Liver architecture has typically been studied through 2D sections and, more recently, using thick tissue sections combined with immunofluorescence. We aimed to develop a robust method to image, digitalize and quantify 3D architecture of the biliary and vascular systems in tandem.

METHODS

The biliary and portal vein trees of the mouse liver were injected with Microfil resin, followed by microCT scanning. Tomographic data was segmented and analyzed using a MATLAB script we wrote to investigate length, volume, tortuosity, branching, and the relation between the vascular and biliary systems. Double resin casting micro computed tomography (DUCT) was applied to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), in which the biliary system is absent at postnatal stages, but regenerates by adulthood. Phenotypes discovered using DUCT were validated with cumbersome consecutive liver sections from mouse and human liver including patients with Alagille syndrome.

RESULTS

DUCT revealed tortuous bile ducts either placed further from portal veins, or ectopically traversing the parenchyma and connecting two portal areas, in Jag1Ndr/Ndr mice. Furthermore, bile ducts either ended abruptly, or branched independently of portal vein branching, with bifurcations placed hilar or peripheral to portal vein branches. The branching defects, parenchymal bile ducts, and blunt endings were confirmed in patient samples.

CONCLUSION

DUCT is a powerful technique, which provides computerized 3D reconstruction of casted networks. It exposes and quantifies previously unknown vascular and biliary phenotypes in mouse models, revealing new phenotypes in patients.

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