bluuebunny/crossref_metadata_2025 huggingface dataset:
Coda
Authors: Small Helen
Published: August 2020

A brief Coda wrestles with the scope of the claims made for a strategic cynicism. It begins with the uncomfortable play between sceptical cynicism and much more impoverished cynicisms in Dinaw Mengestu’s novel How to Read the Air (2010). It then turns to Bernard Williams’s Truth and Truthfulness, a book that sought to clarify the virtues of truthfulness as our main resource against cynicism. It takes Williams’s reworking of the Nietzschean genealogy as a prompt to think critically about the strengths and limitations of cynicism’s corrective or recalibrating role for today.
Natural Selection in Large Populations
Authors: Hartl Daniel L.
Published: August 2020

This chapter includes selection in haploid and diploid organisms, hard and soft selective sweeps, background selection, and the probability of ultimate survival of a new favorable mutation in a large population. It considers overdominance and heterozygote inferiority in detail as well as different types of equilibria and the fundamental theorem of natural selection. Various types of balancing selection are examined including mutation–selection balance, migration–selection balance, meiotic drive and gametic selection, and the theory of CRISPR-mediated gene drive to control natural populations. It closes with a discussion of other modes of selection and their implications.
Family-Run Universities in Japan
Authors: Breaden Jeremy , Goodman Roger
Published: August 2020

Globally, private universities enrol one in three of all higher education students, while in Japan (which has the second largest higher education system in the world in terms of overall expenditure) almost 80 per cent of all university students attend private institutions. According to some estimates up to 40 per cent of these institutions are family businesses in the sense that members of a single family have substantive ownership or control over their operation. This book offers a detailed historical, sociological and ethnographic analysis of this important, but largely under-studied, category of private universities as family business. It examines how such universities in Japan have negotiated a period of major demographic decline since the 1990s: their experiments in restructuring and reform, the diverse experiences of those who worked and studied within them and, above all, their unexpected resilience. It argues that this resilience derives from a number of ‘inbuilt’ strengths of family business which are often overlooked in conventional descriptions of higher education systems and in predictions regarding the capacity of universities to cope with dramatic changes in their operating environment. The book offers a new perspective on recent changes in the Japanese higher education sector and contributes to an emerging literature on private higher education and family business across the world.
Private Universities as Family Business
Authors: Breaden Jeremy , Goodman Roger
Published: August 2020

This chapter explains how Japanese family businesses in general, and family-run universities in particular, operate in practice and some of the negative and positive tropes with which they are frequently associated. These features include a high level of centralization, little voice for employees, top-down decision-making, and a particular concern over succession. The chapter develops the argument that family-run universities benefit from an ‘inbuilt resilience’, deriving from a preference for dealing with problems in-house and with the absolute minimum of disruption to the existing modus operandi; resilience built on a network of educational operations extending beyond a single university and allowing for significant cross-subsidies; robust connections with local business interests; and above all, an overriding concern with maintaining the integrity of the family business. This inbuilt resilience is a key to understanding the unexpected ability of Japan’s private universities to adapt to the dramatic demographic changes of the 1990s and 2000s. The chapter ends with a short discussion of possible outcomes of the next period of demographic decline from 2018 to 2030, suggesting that it may well be that the private university sector in Japan, with its inbuilt resilience and long experience of reacting to crises, will survive not only better than the current gloomy predictions but indeed than the public sector overall.
The Modern State and the Society of Hyper-Order to 1939
Authors: Wilson T. K.
Published: August 2020

For the past 200 years the defining feature of most domestic contests between Western governments and armed opponents has tended to be their lopsided asymmetry. Since the later nineteenth century a recurrent phenomenon of Western societies have been hopeless micro-insurrections mounted against stable societies: the armed utopianism of the violently delusional. Time and again, it is only society’s dreamers and deranged who have dared to mount any kind of sustained violent challenge to the state. This chapter traces the emergence of such dominant state power from the late eighteenth century up until the eve of the Second World War.
The Modern State and the Society of Hyper-Order from 1939
Authors: Wilson T. K.
Published: August 2020

This chapter serves as a companion to its predecessor. It surveys the temporary dislocation of state power across much of Europe during the Second World War: before turning to its reinforcement and enhancement in the decades that followed. It examines the unfolding consequences of the 1968 crisis of legitimacy across Western societies: before noting the apparently unassailable position of the Western State against all violent challengers in the post-Cold War Brave New World of the early 1990s. Finally, it introduces the strikingly open-ended juncture of the early twenty-first century, setting up a more in-depth discussion in Chapter Three.
The Means of Destruction
Authors: Wilson T. K.
Published: August 2020

Chapter Five disaggregates political violence not by cause or group, but by basic technique. It identifies the key means that underpin violent repertoires: and attempt to trace their evolution in conjunction with some reference to other major social and technological changes. At heart, this is a structural approach that leans towards identifying emerging opportunities for violence. Yet, paradoxically, such a structuralist approach can also help to highlight the key roles of agency and contingency. Again and again, new and shocking trends in political violence turn out to be exploiting ideas that are not fundamentally new, though they may indeed be adapted or transformed in importantly novel ways. Likewise, violent techniques may be practised in a very limited way—and then very suddenly achieve widespread imitation. In short, contagion patterns can be very dramatic.
Gandhi’s Marvellous Revolution
Authors: Coovadia Imraan
Published: August 2020

The chapter examines Gandhi’s mature conceptions of decolonization and social change, which he developed alongside his interpretation of Tolstoy and Tolstoy’s understanding of colonialism. Gandhi seems to have expected social transformation to come immediately, as a kind of miracle of consciousness, yet he also imagined change as an indefinitely protracted process, dominated by delay and reversion, as a counter to the clarity and swiftness of revolutionary upheaval. He was particularly concerned with conversion of the adversary and control of the self as the motors of social change. The chapter considers the arguments of Hind Swaraj and the ways in which Gandhi referred to the example of South Africa even when in India, as well as the extent to which questions posed by Tolstoy in the ‘Letter to a Hindoo’ shaped Gandhi’s thinking.
Motivated Delusional Beliefs
Authors: Bortolotti Lisa
Published: August 2020

In this chapter, the author argues that monothematic delusions that have been construed as responses to trauma or adversity have the potential for epistemic innocence. So-called ‘motivated’ delusions are irrational because they are the output of a mechanism enabling an agent’s desires to influence the agent’s beliefs, independent of the evidence available. Two examples are discussed in the chapter, erotomania and anosognosia. It is found that the adoption of motivated delusions contributes to managing negative emotions that could otherwise become overwhelming and negatively affect the agent’s epistemic functionality by causing depression. By presenting reality as better than it is, the motivated delusion prevents the agent’s disengagement from the surrounding environment and can be seen as temporarily beneficial.
Gender and Transformation
Authors: Sharrock Alison
Published: August 2020

Ovid often displays a remarkable attention to the psychology of female actors, but the question is to what extent this attention can be regarded as truly sympathetic and empathetic, and to what extent it is objectifying. Rather than treating this question in one or a few passages, this chapter approaches the problem systematically. The chapter explores the rules which seem to apply to gender through transformation, including those instances that are actually metamorphosis of gender. Thus, not only a well-known example like Teiresias but a number of others are summoned to detail how Ovid does in a variety of ways sensitively represent female subjectivity—but only in negative contexts. Metamorphosis of gender goes almost exclusively in one direction. The chapter suggests the possibility of holding in tension both sympathy and objectification, arguing that there is a disproportionate emphasis on women’s (as opposed to men’s) experience of metamorphosis and that this is combined with the power relations which make certain kinds of metamorphosis a negatively feminizing process.
Naso Deus
Authors: Hanses Mathias
Published: August 2020

Chapter 6 comments on the rarely observed telestich at Met. 1.452–5, spelling out the noun Naso. The chapter posits that it ought to be connected to the acrostic deus, noted by Isidor Hilberg at 1.29–32. Together, the two so-named intexts form the authorial signature Naso deus, which resembles Ovid’s references to himself elsewhere in his poetry and invites a number of playful interpretations ranging from the metapoetic to the political. By including intexts in his poetry, Ovid inserts himself into a tradition of literary sophistication that reaches back ultimately to the Hellenistic era. Yet Ovid’s signature also highlights the poet’s role as the demiurge who created the cosmos of the Metamorphoses. The deus acrostic occurs in a passage describing the formation of the universe, and the Naso telestich marks the famous Primus amor Phoebi episode, which narrates the world’s transformation into a truly Ovidian realm of illicit sexual affairs between humans and gods. For this literary creation, the signature suggests, Ovid can claim the title of Naso deus.
Latent Transformations
Authors: Asztalos Monika
Published: August 2020

In Ovid’s stories one finds metamorphoses where the outward appearance is transformed while the inner being remains the same. This chapter argues that the reverse can occasionally be detected in the poetic language: when an expression is repeated, the appearance (word) is the same while the inner being (meaning) is not. In three cases, from the stories of Echo, Pygmalion, and the plague in Aegina, it is shown that the hidden transformations are subtly signalled by the poet. In the first and third cases, the poet’s hints to the readers have been overlooked; as a result, lines containing one or both of the expressions have been considered interpolations by some critics. Arguments are presented in support of their authenticity, and it is suggested that textual problems which may have arisen from early readers’ failure to catch a hint by the poet can be eliminated in two cases by means of conjectures rather than by bracketing entire lines. In the third case the meaning of a repeated expression undergoes a transformation by reappearing in a different generic surrounding.
The Metamorphoses of Sin
Authors: Hardie Philip
Published: August 2020

Ovid’s Metamorphoses, the encyclopedia of pagan mythology for later centuries, was also pressed into the service of Christian theology. This chapter shows how three Christian poets—Prudentius, Dante, and John Milton—reworked metamorphosis into a snake, each in his own specific way. The central text is Metamorphoses 4.569–603, where Cadmus and his wife Harmonia are transformed into snakes in fulfilment of a supernatural prophecy, the ultimate consequence of Cadmus’ slaying of the serpent of Mars on the site of Thebes. While the metamorphosed Cadmus falls physically to the ground, in the Christian authors serpentine metamorphosis signifies a theological and spiritual fall. In the late fourth century, Prudentius projects the transformation on to Satan, while Dante in the early fourteenth century exploits Ovidian metamorphosis into snakes for the punishment of sinners in Inferno. Milton, a reader of both Prudentius and Dante, applies the metamorphosis to Satan, but in a very different way from Prudentius. Each of these Christian poets explores the motif of serpentine metamorphosis in their own language, and within their own culture. The demonic repetition of falls into serpentine metamorphosis also figures the repetitive migration of the Ovidian motif through the Christian centuries.
Foreword
Authors: Wright Crispin
Published: August 2020

This chapter is divided into four parts, corresponding to the partitioning of the essays in the volume. Part I, on neo-Fregeanism in the philosophy of mathematics develops replies to Demopolous, Heck, Rosen and Yablo, Boolos and Edwards; Part II, on vagueness, intuitionistic logic and the Sorites Paradox develops replies to Rumfitt and Schiffer; Part III, on revisionism in the philosophy of logic develops replies to Shieh and Tennant; and Part IV, on the epistemology of metaphysical possibility develops a reply to Hale. In each section, Crispin Wright offers an overview of the relevant area and outlines and refines his views on the relevant topics. Inter alia, he offers detailed replies to each of the ten contributed essays in the volume.
Introduction
Authors: P R Nisha
Published: August 2020

Circus in the subcontinent is embedded with the arrival of the modern and the recasting of body and its caste and gender structures; new trans-cultural and transnational spaces that emerged with this itinerant entertainment; technologies of the tent; and the acquisition, taming, and training of animals whose past is deeply implicated in the history of hunting, wildlife management, and forest policies of the colonial and post-colonial states in India. Subcontinental regions such as Kerala and Maharashtra have rich histories of circus acrobatics and animal training that span over a century. However, autobiographies, personal histories, and memoirs are very rare. While looking at the history of Indian circus, the major challenge is the lack of archival sources, both public and private. Memories and memorabilia of the circus community have been rich sources for the author. The book explores some key moments and aspects in the different spaces of the circus in this part of the world, spanning over a hundred years.
Animals, Circus, and the State
Authors: P R Nisha
Published: August 2020

Wild animals have always been an indispensable part of circus around the world. This chapter traces their trajectory from the ‘wild’ to the ‘submissive’. It also discusses in detail the attitudes of the colonial and post-colonial states towards animals in general and the changes over the period in relation to circus animals. This section examines such statist double standards focusing at the ban of wild animals in Indian circus by the environment ministry, which proved to be fatal to both circus people and the animals. This chapter also explores how the present ‘conservation’ ideas excludes and thus jeopardizes certain historical practices of animal taming, training, and performance.
Coda
Authors: P R Nisha
Published: August 2020

This chapter discusses the 2011 Supreme Court ban on children and adolescent youth under eighteen from performing in Indian circus, and its aftermath. It also examines the various attempts within the community and government institutions to establish circus training centres at various points of time, as well as the idea of the ‘new circus’, which has been gaining popularity in the West over the last few decades.
Paediatric injuries due to falls from windows and balconies: an 8-year prospective and retrospective review
Authors: Rajagopal Manasi , Kundra Manu , Mabood Neelam , Ali Samina , Rankin Tara , Dow Nadia , Craig William
Published: August 2020

Background

Unintentional falls from windows and balconies pose a serious health risk to children. Limited Canadian data describing such falls currently exist. This study aimed to describe the frequency, demographic characteristics, injury patterns, and risk factors associated with paediatric falls from windows and balconies.

Methods

This study employed both prospective data collection and retrospective medical record review. Prospectively, consenting families were enrolled from February 2015 to February 2017; retrospectively, charts from January 2009 to December 2014 were reviewed. Children 0 to 16 years of age, who presented to the Stollery Children’s Hospital (Edmonton, Alberta) emergency department due to a fall from a window or balcony, were included.

Results

A total of 102 children were included; thirty were enrolled prospectively and 72 retrospectively. Median age was 4.5 years (interquartile range 2.83 to 6.83) with 63.7% (65 of 102) males. About 87.2% (89 of 102) of falls were from windows and 12.8% (13 of 102) from balconies. The median estimated height of fall was 4.1 m (interquartile range 3.04 to 4.73). About 58.4% (59 of 101) had at least one major injury (i.e., concussion, fractured skull, internal injury, fractured limb, severe laceration), 36.6% had minor injuries only (i.e., abrasions, contusions, sprains), and 5.0% had no documented injuries. There were no fatalities. About 30.4% (31 of 102) were admitted, with 48.4% of these children (15 of 31) requiring surgery.

Conclusion

Most falls from windows and balconies occurred in children under the age of 5 years and were associated with serious morbidity, high admission rates, and need for surgery. Child supervision as well as installation of key safety features in windows may help minimize paediatric fall-related injuries.
Household Inequality, Entrepreneurial Dynamism, and Corporate Financing
Authors: Braggion Fabio , Dwarkasing Mintra , Ongena Steven
Published: August 2020

Economic theories posit conflicting hypotheses on how wealth inequality affects entrepre-neurial dynamism. We investigate the impact of wealth inequality on business dynamics by constructing local measures of household wealth inequality based on financial rents, home equity, and 1880 farmland. We then identify the effect of wealth inequality on entrepre-neurship by instrumenting it with land distribution under the 1862 Homestead Act. Wealth inequality decreases firm entry and exit, and the proportion of high-tech businesses across metropolitan statistical areas. Wealth inequality also lowers the supply of public goods, such as education. Growth in income per capita consequently lags.
Society of Behavioral Medicine (SBM) position statement: support increased knowledge and efforts to address the financial burden associated with cancer treatment
Authors: Asche Carl V , Watson Karriem , Baumgartner Meredith Greer , Buscemi Joanna , Fitzgibbon Marian , Simon Melissa , Winn Robert , Henley Candace , Glenn Joanne , Hong Susan
Published: August 2020

Millions of individuals and their families struggle with both treatment-related and out-of-pocket (OOP) economic repercussions of a cancer diagnosis, an effect increasingly referred to as “financial toxicity.” In 2014, the Agency for Healthcare Research and Quality (AHRQ) estimated the total U.S. expenditures for cancer at $87.8 billion dollars with patient OOP costs accounting for $3.9 billion dollars (2014). These figures do not take into account indirect costs, such as those from lost earnings. As a result, financial toxicity can extend well beyond the active treatment phase and have a substantial impact on a household’s economic reserve and financial resilience well into the future. Of the 9.5 million U.S. adults aged 50 years and older diagnosed with cancer (2000–2012), 42.2% have depleted their assets at 2 years and 38.2% were financially insolvent in 4 years. Bankruptcy rates are 2.65 times higher among cancer survivors than matched controls. A full 70% of Americans want to have conversations about the costs of care with their health care providers, but only 28% report doing so. Delaying or deferring these conversations can have major financial consequences for patients. According to a polling conducted for the Robert Wood Johnson Foundation (RWJF) by Avalere Health, almost 20% of patients report forgoing care when they have questions about costs. A critical element to achieve this is to have accurate cost information, including health care insurance coverage policies. Specifically, while patients and their families look to their health care providers to help them better navigate the cost implication of their treatment choices, most who are willing to undertake this challenging task need to have accessible and comprehensive (including direct and indirect) cost information to facilitate the discussion.
Patient Feedback on the Effectiveness of Auricular Acupuncture on Pain in Routine Clinical Care
Authors: Zeliadt Steven B. , Thomas Eva R. , Olson Juli , Coggeshall Scott , Giannitrapani Karleen , Ackland Princess E. , Reddy Kavitha P. , Federman Daniel G. , Drake David F. , Kligler Benjamin , Taylor Stephanie L.
Published: August 2020

Objectives:

Veterans Health Administration (VHA) launched a national initiative to train providers in a specific, protocolized auricular acupuncture treatment (also called Battlefield Acupuncture or BFA) as a nonpharmacological approach to pain management. This evaluation assessed the real-world effectiveness of BFA on immediate pain relief and identified subgroups of patients for whom BFA is most effective.

Research Design:

In a cross-sectional cohort study, electronic medical record data for 11,406 Veterans treated with BFA at 57 VHA medical centers between October 2016 and September 2018 was analyzed. The multivariate analysis incorporated data on pain history, change in pain level on an 11-point scale, complications, and demographic information.

Methods:

A total of 11,406 Veterans were treated with BFA at 57 VHA medical centers between October 2016 and September 2018 and had effectiveness data recorded in their electronic medical record.

Results:

More than 3 quarters experienced immediate decreases in pain following administration of BFA, with nearly 60% reported experiencing a minimal clinically important difference in pain intensity. The average decrease in pain intensity was −2.5 points (SD=2.2) at the initial BFA treatment, and −2.2 points (SD=2.0) at subsequent treatments. BFA was effective across a wide range of Veterans with many having preexisting chronic pain, or physical, or psychological comorbid conditions. Veterans with opioid use in the year before BFA experienced less improvement, with pain intensity scores improving more among Veterans who had not recently used opioids.

Conclusion:

VHA’s rapid expansion of training providers to offer BFA as a nonpharmacological approach to pain management has benefited many Veterans.
Physical Therapy in Pediatric and Young Adult Patients With Sickle Cell Disease: Assessing Potential Benefits and Barriers
Authors: Callaway Daniel , Chawla Anjulika , Sprinz Philippa
Published: August 2020

Background:

Despite advances in the treatment of sickle cell disease (SCD) in pediatric and young adult patients, pain remains a significant cause of disease-related morbidity. Physical therapy has been shown to be useful for the treatment of pain in young patients with chronic illnesses, however, limited data exists regarding potential benefits of physical therapy in patients with SCD.

Materials and Methods:

We conducted a web-based survey of health care providers and support staff in the New England area to identify potential benefits of and barriers to outpatient physical therapy in this patient population.

Results:

Nearly 92% of survey participants felt that physical therapy had the potential to be beneficial in pediatric and young adult patients with SCD. A majority of physicians reported having referred patients with SCD for physical therapy. Perceived potential benefits included improved functional mobility, improved chronic pain symptoms, decreased opiate use, improved mood symptoms, improved acute pain symptoms, and improved adherence with medications and clinic visits. Significant perceived barriers identified included lack of transportation, time constraints, patient lack of understanding, and difficulty with insurance coverage.

Conclusions:

Health care providers have a positive view of the use of physical therapy in the management of this patient population. Significant barriers exist which need to be addressed.
Time Course and Management of Protracted Anaphylaxis Due to PEG-Asparaginase
Authors: Fertal Shelby A. , Bradeen Heather A. , Friesen Elizabeth , Heath Jessica L.
Published: August 2020

Polyethylene glycosylated (PEG)-asparaginase is a cornerstone of treatment for acute lymphoblastic leukemia (ALL), and effective administration is associated with better outcomes. PEG-asparaginase is associated with a uniphasic hypersensitivity reaction in ∼10% to 20% of patients. We present a 17-year-old male individual diagnosed with very high-risk pre–B-ALL, who experienced protracted anaphylaxis 1 hour following administration of his second PEG-asparaginase dose. This type of allergic reaction has yet to be described in ALL patients treated with PEG-asparaginase. Here, we outline the time course and successful management of protracted anaphylaxis in an ALL patient.
Atypical Outcomes for Hepatitis-associated Acquired Aplastic Anemia: 2 Case Studies and Review of the Literature
Authors: Lapinski Jillian , Nolfi-Donegan Deirdre , Cooper James D. , Squires Robert H.
Published: August 2020

There is little data specifically dedicated to the long-term outcomes of the hepatitis-associated variant of aplastic anemia (HAAA). A majority of patients with nonsevere (moderate) aplastic anemia progress to severe aplastic anemia, and severe aplastic anemia typically results in death if left untreated. We present 2 unique cases of HAAA that contribute to our knowledge of the natural history of this disease variant. One patient had moderate HAAA that never progressed to severe disease. The second patient had severe HAAA that spontaneously resolved without treatment. The rare possibility of moderate HAAA failing to progress to fulfill severe criteria, or of severe HAAA spontaneously improving, may complicate early treatment decisions for some patients.
Clozapine utilization at the United States Veterans Health Administration: a descriptive report of prescribing patterns and patient characteristics among Operation Enduring Freedom/Operation Iraqi Freedom Veterans
Authors: Zuschlag Zachary D. , Fowler Christopher A. , Devendorf Andrew , Panaite Vanessa , Efimova Olga , Schultz Susan K.
Published: August 2020

To identify the clozapine utilization rate at Veterans Health Administration, as well as patient characteristics, and correlates of use to garner a better understanding of the Veterans Health Administration-treated clozapine population. A longitudinal retrospective cohort analysis was conducted on all Operation Enduring Freedom/Operation Iraqi Freedom Veterans treated with clozapine prescriptions through Veterans Health Administration from 2006 to 2016. Descriptive and inferential analyses were conducted. The sample of 1.3 million veterans had 15 416 with schizophrenia-spectrum disorders, however; only 197 filled outpatient clozapine prescriptions through Veterans Health Administration, a clozapine utilization rate of 1.28%. Median days on clozapine were 305. Median number of antipsychotic medications was 12, with a median rank of clozapine being the eighth antipsychotic trialed. 59.90% of individuals had at least one period of maintenance clozapine treatment. The median number of psychiatric hospitalizations was four, and Clozapine rank was strongly associated with number of hospitalizations. There were no associations between acute versus maintenance clozapine use and either hospitalizations or mortality. Clozapine utilization was very low relative to recommended prescribing rates. Delayed initiation of clozapine was noted and was associated with increased number of hospitalizations. Lack of observed differences in mortality may be explained by low number of mortalities.
Cytoplasmic polyadenylation by TENT5A is required for proper bone formation
Authors: Gewartowska Olga , Novaliches Goretti Aranaz , Krawczyk Paweł S , Mroczek Seweryn , Kusio-Kobiałka Monika , Tarkowski Bartosz , Spoutil Frantisek , Benada Oldrich , Kofroňová Olga , Szwedziak Piotr , Cysewski Dominik , Gruchota Jakub , Szpila Marcin , Chlebowski Aleksander , Sedlacek Radislav , Prochazka Jan , Dziembowski Andrzej
Published: August 2020

Osteoblasts orchestrate bone formation by secreting dense, highly cross-linked type I collagen and other proteins involved in osteogenesis. Mutations in Col1α1, Col1α2, or collagen biogenesis factors lead to the human genetic disease, osteogenesis imperfecta (OI). Herein, we show that the TENT5A gene, whose mutation is responsible for poorly characterized type XVIII OI, encodes an active cytoplasmic poly(A) polymerase regulating osteogenesis. TENT5A is induced during osteoblast differentiation and TENT5A KO osteoblasts are defective in mineralization. The TENT5A KO mouse recapitulates OI disease symptoms such as bone fragility and hypomineralization. Direct RNA sequencing revealed that TENT5A polyadenylates and increases expression of Col1α1 and Col1α2 RNAs, as well as those of other genes mutated in OI, resulting in lower production and improper folding of collagen chains. Thus, we have identified the specific pathomechanism of XVIII OI and report for the first time a biologically relevant post-transcriptional regulator of collagen production. We further postulate that TENT5A, possibly together with its paralogue TENT5C, is responsible for the wave of cytoplasmic polyadenylation of mRNAs encoding secreted proteins occurring during bone mineralization.
Molecular tracking devices quantify antigen distribution and archiving in the lymph node
Authors: Walsh Shannon M. , Sheridan Ryan M. , Doan Thu , Lucas Erin D. , Ware Brian C. , Fu Rui , Burchill Matthew A. , Hesselberth Jay R. , Jirón Tamburini Beth A
Published: August 2020

Live, attenuated vaccines generate humoral and cellular immune memory, increasing the duration of protective immune memory. We previously found that antigens derived from vaccination or viral infection persist within lymphatic endothelial cells (LECs) beyond the clearance of the infection, a process we termed “antigen archiving”. Technical limitations of fluorescent labeling have precluded a complete picture of antigen archiving across cell types in the lymph node. We developed a “molecular tracking device” to follow the distribution, acquisition, and retention of antigen in the lymph node. We immunized mice with an antigen conjugated to a nuclease-resistant DNA tag and used single-cell mRNA sequencing to quantify its abundance in lymph node hematopoietic and non-hematopoietic cell types. At early and late time points after vaccination we found antigen acquisition by dendritic cell populations (DCs), associated expression of genes involved in DC activation and antigen processing, and antigen acquisition and archiving by LECs as well as unexpected stromal cell types. Variable antigen levels in LECs enabled the identification of caveolar endocytosis as a mechanism of antigen acquisition or retention. Molecular tracking devices enable new approaches to study dynamic tissue dissemination of antigens and identify new mechanisms of antigen acquisition and retention at cellular resolutionin vivo.
A View of Waste Might Decrease Relaxation: The Effects of Viewing an Open Dump in a Forest Environment on the Psychological Response of Healthy Young Adults
Authors: Ernest Bielinis , Emilia Janeczko , Norimasa Takayama , Alicja Słupska , Natalia Korcz , Anna Zawadzka , Lidia Bielinis
Published: August 2020

Forest recreation can be successfully used for the psychological relaxation of respondents and can be used as a remedy for common problems with stress. The special form of forest recreation intended for restoration is forest bathing. These activities might be distracted by some factors, such as viewing buildings in the forest or using a computer in nature, which interrupt psychological relaxation. One factor that might interrupt psychological relaxation is the occurrence of an open dump in the forest during an outdoor experience. To test the hypothesis that an open dump might decrease psychological relaxation, a case study was planned that used a randomized, controlled crossover design. For this purpose, two groups of healthy young adults viewed a control forest or a forest with an open dump in reverse order and filled in psychological questionnaires after each stimulus. A pretest was used. Participants wore oblique eye patches to stop their visual stimulation before the experimental stimulation, and the physical environment was monitored. The results were analyzed using the two-way repeated measures ANOVA. The measured negative psychological indicators significantly increased after viewing the forest with waste, and the five indicators of the Profile of Mood States increased: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion. In addition, the negative aspect of the Positive and Negative Affect Schedule increased in comparison to the control and pretest. The measured positive indicators significantly decreased after viewing the forest with waste, the positive aspect of the Positive and Negative Affect Schedule decreased, and the Restorative Outcome Scale and Subjective Vitality scores decreased (in comparison to the control and pretest). The occurrence of an open dump in the forest might interrupt a normal restorative experience in the forest by reducing psychological relaxation. Nevertheless, the mechanism of these relevancies is not known, and thus, it will be further investigated. In addition, in a future study, the size of the impact of these open dumps on normal everyday experiences should be investigated. It is proposed that different mechanisms might be responsible for these reactions; however, the aim of this manuscript is to only measure this reaction. The identified psychological reasons for these mechanisms can be assessed in further studies.
Modular HUWE1 architecture serves as hub for degradation of cell-fate decision factors
Authors: Hunkeler Moritz , Jin Cyrus Y. , Ma Michelle W. , Overwijn Daan , Monda Julie K. , Bennett Eric J. , Fischer Eric S.
Published: August 2020

HECT ubiquitin ligases play essential roles in metazoan development and physiology. The HECT ligase HUWE1 is central to the cellular stress response by mediating degradation of key death or survival factors including Mcl1, p53, DDIT4, and Myc. As a step toward understanding regulation of HUWE1 engagement with its diverse substrates, we present here the cryo-EM structure of HUWE1, offering a first complete molecular picture of a HECT ubiquitin ligase. The ~4400 amino acid residue polypeptide forms an alpha solenoid-shaped assembly with a central pore decorated with protein interaction modules. This modularity enables HUWE1 to target a wide range of substrates for destruction. The locations of human mutations associated with severe neurodevelopmental disorders link functions of this essential enzyme with its three-dimensional organization.
Effect of the p75 Neurotrophin Receptor on Glycemic Control of Obese Mice during Time-Restricted Feeding
Authors: Podyma Brandon , Battin Katherine , Johnson Dove-Anna , Güler Ali D. , Deppmann Christopher D.
Published: August 2020

Circulating glucose regulates organismal energy homeostasis and is tightly controlled in response to feeding behavior. In overweight individuals, glucose homeostasis is often perturbed due to resistance to normal satiety signals, such as insulin and leptin, leading to type 2 diabetes and its attendant complications. An emerging dietary intervention, time-restricted feeding (TRF), aims to ameliorate the adverse metabolic consequences of obesity, however, its effectiveness on glucose control is uncertain. Here, we demonstrate that TRF is only transiently effective in reducing pre-meal serum glucose levels in obese mice lacking leptin. However, inOb/Obmice that also lack a gene known to suppress behavior associated with TRF, the p75 neurotrophin receptor (p75NTR), a sustained reduction of glucose levels is observed. These results suggest that the effectiveness of TRF on glycemic control can be enhanced with concurrent targeting of modulators of glucose homeostasis and TRF response.
Pyrethroid Resistance Intensity ofAnopheles gambiae sensu lato(Diptera: Culicidae) from Phase II Hut Trial Station in KOLOKOPE, Eastern Plateau Togo: A Potential Site to Assess the Next Generation of Long-Lasting Insecticidal Nets
Authors: Ahadji-Dabla Koffi Mensah , Chabi Joseph , Apétogbo Georges , Koffi Edoh , Hadi Melinda Patricia , Ketoh Guillaume Koffivi
Published: August 2020

Per WHO recommendations, the implementation of the next-generation of Long Lasting Insecticidal Nets (LLINs) for malaria vector control requires appropriate investigations on the insecticide resistance profile of the vector and the impact of the LLINs on the known resistant mosquitoes. The next-generation of LLINs are actually an incorporation of a mixture of pyrethroid insecticides and a synergist such as PBO. Several studies have proven the additional impact of PBO on the increase in the mortality rate ofAnopheles gambiaes.l. (Diptera: Culicidae). However, further assessments need to be done at community level in order to set a stage for the acceleration of the WHO policies on the implementation of the next-generation of LLINs. Kolokopé is a cotton-growing area in the central region of Togo characterized by an intensive use of agro pesticides and insecticides. A phase II experimental hut station for the evaluation of mosquito control tools has been built in Kolokopé. For the characterization of the site, WHO susceptibility tests using diagnostic doses of eight insecticides, PBO synergist assay and intensity assay of three pyrethroids (5x and 10x) were conducted on adult female mosquitoes obtained from larvae collected around the site.Anopheles gambiaes.l. from Kolokopé showed high resistance to pyrethroids and DDT, but in lesser extent to carbamates and organophosphates. Likewise, high intensity of resistance to pyrethroid was observed with less than 40% mortality at 10x deltamethrin, 52 and 29% mortality at 10x permethrin and 10x alphacypermethrin, respectively. Also, the addition of PBO showed a reversal mortality which was similar to mortality rate at 10x doses of pyrethroids. The high pyrethroid intensity resistance recorded at Kolokopé could be mainly due to the pressure onAn. gambiae s.l. through the excessive use of insecticide in agriculture. This can be used for the assessment of the next-generation of LLINs either in experimental hut or at a community trial.
Genetic variation for tolerance to the downy mildew pathogenPeronospora variabilisin genetic resources of quinoa (Chenopodium quinoa)
Authors: Colque-Little Carla , Abondano Miguel Correa , Lund Ole Søgard , Amby Daniel Buchvaldt , Piepho Hans-Peter , Andreasen Christian , Schmöckel Sandra , Schmid Karl
Published: August 2020

Background

Quinoa (Chenopodium quinoaWilld.) is an ancient grain crop that is tolerant to abiotic stress and has favorable nutritional properties. Downy mildew is the main disease of quinoa and is caused by infections of the biotrophic oomycetePeronospora variabilisGaüm. Since the disease causes major yield losses, identifying sources of downy mildew tolerance in genetic resources and understanding its genetic basis are important goals in quinoa breeding.

Results

We infected 132 South American genotypes, three Danish cultivars and the weedy relativeC. albumwith a single isolate ofP. variabilisunder greenhouse conditions and observed a large variation in disease traits like severity of infection, which ranged from 5% to 83%. Linear mixed models revealed a significant effect of genotypes on disease traits with high heritabilities (0.72 to 0.81). Factors like altitude at site of origin or seed saponin content did not correlate with mildew tolerance, but stomatal width was weakly correlated with severity of infection. Despite the strong genotypic effects on mildew tolerance, genome-wide association mapping with 88 genotypes failed to identify significant marker-trait associations indicating a polygenic architecture of mildew tolerance.

Conclusions

The strong genetic effects on mildew tolerance allow to identify genetic resources, which are valuable sources of resistance in future quinoa breeding.
Holocene plant diversity dynamics shows a distinct biogeographical pattern in temperate Europe
Authors: Roleček Jan , Abraham Vojtěch , Vild Ondřej , Svobodová Helena Svitavská , Jamrichová Eva , Plesková Zuzana , Pokorný Petr , Kuneš Petr
Published: August 2020

Aims

Reconstruction of the Holocene diversity changes in a biogeographically complex region. Description of major diversity patterns, testing their predictors, and their interpretation in the palaeoecological and biogeographical context. Testing the assumption that pollen record is informative with respect to plant diversity in our study area.

Methods

Fossil pollen extracted from 18 high-quality profiles was used as a proxy of past plant diversity. Pollen counts of tree taxa were corrected by pollen productivity, and pollen assemblages were resampled to 100 grains per sample and 150 grains per 500-years time window. SiZer analysis was used to test and visualize multi-scale diversity patterns. Linear modelling was used to identify the best predictors. SiZer maps and pollen composition were analysed using non-metric multidimensional scaling. K-means clustering and indicator species analysis were used to interpret ordination results.

Results

Mean Holocene plant diversity is significantly predicted by latitude, while its temporal pattern followed the biogeographical region and elevation. Major differences were found between the Mesic and Montane Hercynia (lower diversity, increasing only in the Late Holocene) and Pannonia, the Carpathians and Warm Hercynia (higher diversity, increasing from the Early or Middle Holocene on). Low diversity in the Middle and Late Holocene is associated with the prevalence of woody and acidophilic taxa. High diversity is associated with numerous grassland and minerotrophic wetland taxa, crops and weeds. Fossil-modern pollen diversity and modern pollen-plant diversity show significant positive relationships.

Conclusions

Plant diversity and its changes during the Holocene are geographically structured across temperate Europe. Main causes appear to be differences in past dynamics of the landscape openness and vegetation composition, driven mainly by changes in climate and human impact and their different timing. Fossil pollen, if appropriately treated, is a useful proxy of past plant diversity.
Tissue-specific transcription footprinting using RNA PoI DamID (RAPID) inC. elegans
Authors: Gómez-Saldivar Georgina , Osuna-Luque Jaime , Semple Jennifer I. , Glauser Dominique A. , Jarriault Sophie , Meister Peter
Published: August 2020

Differential gene expression across cell types underlies the development and cell physiology in multicellular organisms.C. elegansis a powerful, extensively used model to address these biological questions. A remaining bottleneck relates, however, to the difficulty to obtain comprehensive tissue-specific gene transcription data, since available methods are still challenging to execute and/or require large worm populations. Here, we introduce theRNAPoI DamID(RAPID) approach, in which the Dam methyltransferase is fused to a ubiquitous RNA polymerase subunit in order to create transcriptional footprintsviamethyl marks on the DNA of transcribed genes. To validate the method, we determined the polymerase footprints in whole animals, sorted embryonic blastomeres and in different tissues from intact young adults by driving Dam fusion expression tissue-specifically. We obtained meaningful transcriptional footprints in line with RNA-seq studies in whole animals or specific tissues. To challenge the sensitivity of RAPID and demonstrate its utility to determine novel tissue-specific transcriptional profiles, we determined the transcriptional footprints of the pair of XXX neuroendocrine cells, representing 0.2% of the somatic cell content of the animals. We identified 2362 candidate genes with putatively active transcription in XXX cells, among which the few known markers for these cells. Using transcriptional reporters for a subset of new hits, we confirmed that the majority of them were expressed in XXX and identified novel XXX-specific markers. Taken together, our work establishes RAPID as a valid method for the determination of polymerase footprints in specific tissues ofC. eleganswithout the need for cell sorting or RNA tagging.

Article summary

Gene expression is a major determinant of cell fate and physiology, yet it is notoriously difficult to characterize in individual cell types for the widely used model systemC. elegans. Here, we introduce a method based on thein vivocovalent modification of DNA by transcribing RNA polymerases to determine genome-wide transcription patterns in single tissues of embryos or young adult animals. We show that the method is able to identify actively transcribed genes in tissues representing down to 0.2% of the somatic cells in adult animals. Additionally, this method can be fully performed in a single laboratory by using third generation sequencing methods (ONT).
A systems based framework to computationally predict putative transcription factors and signaling pathways regulating glycan biosynthesis
Authors: Groth Theodore , Neelamegham Sriram
Published: August 2020

Glycosylation is a common post-translational modification, and glycan biosynthesis is regulated by a set of ‘glycogenes’. The role of transcription factors (TFs) in regulating the glycogenes and related glycosylation pathways is largely unknown. This manuscript presents a multi-omics data-mining framework to computationally predict putative, tissue-specific TF regulators of glycosylation. It combines existing ChIP-Seq (Chromatin Immunoprecipitation Sequencing) and RNA-Seq data to suggest 22,519 potentially significant TF-glycogene relationships. This includes interactions involving 524 unique TFs and 341 glycogenes that span 29 TCGA (The Cancer Genome Atlas) cancer types. Here, TF-glycogene interactions appeared in clusters or ‘communities’, suggesting that changes in single TF expression during both health and disease may affect multiple carbohydrate structures. Upon applying the Fisher’s exact test along with glycogene pathway classification, we identify TFs that may specifically regulate the biosynthesis of individual glycan types. Integration with knowledge from the Reactome database provided an avenue to relate cell-signaling pathways to TFs and cellular glycosylation state. Whereas analysis results are presented for all 29 cancer types, specific focus is placed on human luminal and basal breast cancer disease progression. Overall, the computational predictions in this manuscript present a starting point for systems-wide validation of TF-glycogene relationships.