bluuebunny/crossref_metadata_2025 huggingface dataset:
Fox’s Choice: Founding a Secular College in Oxford
Authors: Burgess Clive
Published: September 2019

This chapter discusses the powerful impact of education on the service of the British state and empire. It had been reasonably clear, in 1390, what skills an education in the Oxford and Cambridge schools could bring to the service of the crown and the high nobility—the ability to see the weak points of an argument and to put the case against it persuasively, and for those with a training in the learned laws, to deploy an accepted code of practice in a way favourable to the Crown’s or another patron’s cause. As a result, England had been represented by intelligent graduates, canonists, and theologians with a broad outlook and forensic skills, both at the Council of Constance and in the diplomacy of the Lancastrian kings. The chapter then looks at Dr. Thomas Chaundler’s pedagogy and its influence on graduates in the service of the crown.
Church, State, and Corpus: The Founder’s Years
Authors: Cavill Paul
Published: September 2019

This chapter examines Richard Fox’s establishment of a secular college in Oxford. Fox’s initial intention had been to establish a monastic college in Oxford which, without question, looks to have been a distinctly conservative choice. His wish was to benefit, in the main, the Benedictine monks of St. Swithun’s priory who served the cathedral church of Winchester and, as such, formed the community at the heart of the see that he served for the last twenty years of his life. However, he changed his mind and opted instead for a secular establishment. The chapter then considers the ramifications of his decision to establish a secular college and sets his plans for Corpus Christi College within the broader environment of collegiate foundation in the English Church in the decades that preceded the Reformation.
Corpus Christi College’s ‘Trilingual Library’: A Historical Assessment
Authors: Weinberg Joanna
Published: September 2019

This chapter assesses Corpus Christi College before Erasmus. The first promoters of humanism at the start of the Quattrocento had positioned themselves as counter-cultural. Humanism, that is to say, did not require institutional recognition to thrive, and, in England as elsewhere, it carved out space for itself in the fifteenth-century cultural landscape, within and beyond institutions. Yet, humanists proved a quarrelsome tribe: where the early Quattrocento trailblazers laid their path, others sometimes refused to follow. Over the century, the identity of humanism developed, ramified, and splintered, drawing strength from its conflicts, not only with those it characterized as its implacable opponents, but also among its own proponents. Corpus could draw on these plural identities, and the implication is that the affiliation to Erasmus and his own formulation of humanism was only one possible inspiration among several.
Brian Twyne: University History and the Traditions of English Antiquarianism
Authors: Grafton Antony
Published: September 2019

This chapter focuses on Brian Twyne, who, by 1625, was a recognized authority on Oxford’s medieval documents. In 1633, he would become Oxford University’s first archivist. Even more important were the archives themselves: especially his own collections, which would serve as the basis for every history of Oxford for centuries. Brian Twyne’s official education took place at Corpus Christi College, to which he came as a scholar in 1594, at the age of 14. From his twenties until his death in 1644, Twyne was fascinated by the history of Oxford. However, his training in the techniques of documentary scholarship had little to do with his official education. Rather, quite early in life, he encountered three distinct traditions of antiquarian scholarship. Each was embodied in a person or a text, and from each he took away ideas and practices that went into the finished body of his work.
Two Kinds of Flexibility
Authors: Aase Tor H.
Published: September 2019

The chapter outlines the theoretical approach applied in the empirical chapters (Chapters 4–9). It defines ‘adaptive capacity’ as a function of flexibility, resilience, and innovation. Special emphasis is given to flexibility. ‘Flexibility of alternation’ is defined as the ability to alternate between known crops and technologies, while ‘flexibility of retention’ refers to the practice of not utilizing production factors maximally in normal years.
Minor Crops and Major Opportunities in Dolakha, Nepal
Authors: Holmelin Nina B.
Published: September 2019

The village Maina Pokhari in Nepal has experienced a substantial degree of return migration after years of out-migration. Returned migrants take up farming and experiment with new cash crops. These positive signs of development may however be circumscribed by a projected decrease of future precipitation, especially affecting winter crops. A change of crop composition or extended water storage capacity could help the positive development to proceed.
The WIPO Treaty for the Visually Impaired as a Double Movement
Authors: Thomas Pradip Ninan
Published: September 2019

The WIPO Treaty for the Visually Impaired was preceded by the Indian government amending its copyright laws in support of the rights of the visually impaired. This chapter explores the nature of Indian advocacy in relation to one of the best global success stories linked to the expansion of communication rights. The chapter highlights issues related to access to knowledge against the background of global media advocacy, beginning with the MacBride Report and the WSIS. It highlights the role of the Indian State in both national and global advocacy—its commitment to the rights of people with disabilities in the context of the ‘book famine’, in contrast with countries such as the USA and the regional bloc, the EU, that opted to support the interests of the copyright industries. It uses Polanyi’s concept of the ‘double movement’ to illustrate the State’s role in correcting an imperfect market.
Procedure
Authors: Govindaraj V.C.
Published: September 2019

This chapter begins with a brief discussion of the jurisprudential distinction between substance and procedure. Substance relates to rights and obligations of the parties to a dispute, whereas procedure is the means employed to determine such rights and obligations. Matters of substantive law are governed by the lex causae (that is, the law that governs the cause of action), the law found applicable under the concerned country’s rules for the choice of law. Matters of procedure, on the other hand, are governed by the lex fori (that is, the law of the forum), the law of country where the action is brought. The chapter covers procedural matters of interlocutory character; remedial measures for enforcing a right; conflict of laws and the law of limitations; matters of enforcement; underlying norms and principles of stay of proceedings; and proof of foreign law.
M.G. Ranade and Bhakti as a New Grammar for Indian Political Life
Authors: Devare Aparna
Published: September 2019

This chapter focuses on M.G. Ranade’s (re)interpretation of bhakti writings in light of the colonial encounter in nineteenth-century India. Ranade used the teachings of bhakti saints, among them Eknath and Tukaram, to assert values such as egalitarianism, compassion and co-existence in the emerging public sphere. This was in sharp contrast to the incipient voices of hyper-masculinity that were trying to fashion a more aggressive Hinduism and nationalism in response to the colonial encounter. Although Ranade was an upper-caste reformer, he pushed for a more just and inclusive Hinduism that spoke strongly against caste injustices and promoted religious tolerance. In doing so, he argued for a ‘softer’ Hinduism, not Hindutva. In many ways, he fashioned a new grammar for Indian public life that anticipated Gandhi’s use of bhakti in modern politics. This chapter teases out some of the major strands of Ranade’s use of bhakti and links it to Gandhi, arguing that Ranade laid some of the important groundwork for Gandhi’s introduction of spirituality in politics.
The Transformative Power of the One World Vision of Sri Narayana Guru
Authors: Thadathil George
Published: September 2019

This chapter focuses on the life and achievements of Sri Narayana Guru, a transformative figure in the social, political, and intellectual landscape of modern Kerala whose impact has been felt across all communities even as he remains a largely unknown figure in north India. The manner in which one person's intervention in one community is receiving attention from individuals and groups beyond the shores of Kerala and outside the original community within which he had his receptivity is shown as providing the transformative power to effect social change not only in Kerala but even beyond. Narayana Guru and his successors in the Gurukula Foundation lineage provide the vantage point for the potential of the movement. The unique approach of the Guru in challenging domination without antagonizing the other nor deprecating the elegance of the self, cutting through the societal sham, offers a renewed 'advaita' accessible to all, as argued in this chapter.
General Square Lattice Vertex Models
Authors: Eckle Hans-Peter
Published: September 2019

Vertex models more general than the ice model are possible and often have physical applications. The square lattice admits the general sixteen-vertex model of which the special cases, the eight- and the six-vertex model, are the most relevant and physically interesting, in particular through their connection to the one-dimensional integrable quantum mechanical models and the Bethe ansatz. This chapter introduces power- ful tools to examine vertex models, including the R- and L-matrices to encode the Boltzmann vertex weights and the monodromy and transfer matrices, which encode the integrability of the vertex models (i.e. that transfer matrices of different spectral parameters commute). This integrability is ultimately expressed in the Yang–Baxter relations.
Quantum Tavis–Cummings Model
Authors: Eckle Hans-Peter
Published: September 2019

This chapter extends the algebraic Bethe ansatz to the quantum Tavis–Cummings model, an N atom generalization of the Jaynes–Cummings model to describe the strong interaction between light and quantum matter. In the case of the quantum Tavis–Cum- mings model there is no underlying vertex model to suggest the constituent building blocks of the algebraic Bethe ansatz approach, e.g.like the L-matrix or ultimately the transfer matrix. The algebraic Bethe ansatz is then first applied to the Tavis–Cummings Hamiltonian with an added Stark term using a conjecture for the transfer matrix. The original Tavis–Cummings model and its algebraic Bethe ansatz are obtained in the limit of vanishing Stark term, which requires considerable care.
Bethe Ansatz for the Anisotropic Heisenberg Quantum Spin Chain
Authors: Eckle Hans-Peter
Published: September 2019

This chapter verifies the conjecture for the wave function, the Bethe ansatz wave function, of the anisotropic Heisenberg quantum spin chain by examining first the cases for one, two, and three spin deviations. The equations determining the quasi- momenta are the Bethe ansatz equations, now obtained from the coordinate Bethe ansatz. The Bethe ansatz equations derive from the eigenvalue equation in combination with boundary conditions, here periodic boundary conditions. These quasi-momenta also determine the energy eigenvalue. However, solving the Bethe ansatz equations to obtain a particular state requires more considerations. New variables, called rapidities, are useful. The consideration of the thermodynamic limit then allows to extract information about the ground state and low-lying excitations of the anisotropic quantum spin chain from the Bethe ansatz equations. Furthermore, complex solutions of the Bethe ansatz equations, called strings, are considered.
Thermodynamics of the Repulsive Lieb–Liniger Model
Authors: Eckle Hans-Peter
Published: September 2019

This chapter discusses how the Bethe ansatz solution of the one-dimensional Bose gas with repulsive δ-function interaction is extended to finite temperatures, the thermody- namic Bethe ansatz. The excitations of this system consist of particle and hole excitations, which can be described by the corresponding densities of Bethe ansatz roots. It shows how these Bethe ansatz root densities are used to define an appropriate expression for the entropy of the system of Bose particles, which is the main ingredient for the extension of the Bethe ansatz method to finite temperature.
Interaction Rituals and Embodied Choice Theory
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

We propose an embodied choice theory, which argues that people make reasonable choices based on the needs and demands of human experience. These choices are driven by cognitive systems that rely heavily upon information that comes from the body’s affective systems including affective somatic markers attached to prior experiences. Megachurches are successful because they meet human emotional needs by providing emotionally powerful interaction rituals. These rituals satisfy people’s individual desires while merging them with the desires of the group. In particular, for many people, megachurches meet six desires: acceptance, a sense of awe, a reliable leader, deliverance, purpose, and a community in which to belong.
Desire for a Reliable Leader
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

In this chapter, we show how megachurches meet attendees’ desire for a reliable leader. In megachurches, for those who attend, their desire and the force of feeling, the zenith of emotional energy, is squarely centered on the megachurch pastor. We identify how the charismatic bond between the attendees and their senior pastor is solidified through the demonstration of his perceived extraordinary and ordinary qualities. Allowing followers to see their human side makes charismatic leaders more relatable, authentic, and trustworthy. The pastor is both the central figure around which most activities, and in some sense the lives of individuals, revolve, and the mouthpiece for the explicit articulation of the values, beliefs, morals, and symbols that will define the group. The pastor is the “mutual focus of attention” that contributes to binding the group together and amplifying the emotional energy experienced by attendees.
Desire for Purpose in Service
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

In this chapter, we demonstrate how megachurches provide individuals with purpose through service. The genius in megachurch socialization is that it not only encourages service to others, but also conceptually roots this service as an expression of one’s “gifts.” It makes individuals feel as though their service—their gifts—are specifically and uniquely needed. Encouraging their attendees to engage in service results in a community overflowing with ministries for members and the community. Megachurches are like small towns—communities that welcome all and where every conceivable form of care is given, which includes hospital clinics for “every sinner and sickness.”
Dissecting Megachurch Scandals
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

This chapter examines the dark side of megachurches by quantifying and theorizing megachurch scandals. We collected data on megachurch scandals and identified fifty-six such scandals discussed in forty-eight online newspaper articles for the years 2006 to 2017. Most of the scandals that we studied came from the malfeasance of megachurch senior pastors, and the vast majority were sexual in nature. The charismatic bond that megachurch pastors form with their attendees and the power that stems from it can be used for their own personal gain. We theorize a form of soft patriarchalism as a way to name this power differential. We contend that the model of soft patriarchalism gives power to men and creates opportunities for them to manipulate and ruin the lives of women under their care. These scandals often lead to the implosion of megachurches, where the charismatic bond between the pastor and congregation is irrevocably broken.
The Problem of the Border
Authors: Schain Martin A.
Published: September 2019

This introductory chapter examines questions that have been raised about the evolving importance of the border, from whether global trade has made borders less relevant, to whether states still possess the capability (or the will) to control borders. A great deal has been written about border policies in Europe and the United States, but very little about how and why policies change, both over time and across space. In the United States, even during the most severe period of immigration restriction, borders were a minor focus of attention, and the northern and southern borders remained relatively open and only lightly patrolled. In Europe, even after the dismantling of the internal borders when the Schengen Agreement was implemented after 1995, the external borders still remained the responsibility of the member states, with relatively little coordination at the EU level. Therefore, why have borders become an important focus of politics?
A high-mass-ratio red-dwarf contact binary with an extremely cool close-in red dwarf
Authors: Fang Xiao-Hui , Qian Shengbang , Zejda Miloslav , Boonrucksar Soonthornthum , Zhou Xiao , Zhu Liying , Liao Wen Ping
Published: September 2019

1SWASP J161335.80$-$284722.2 (hereafter J161335) is an eclipsing red-dwarf binary with an orbital period of $0.229778\:$d, which is around the short-period limit for contact binaries. Three sets of multi-color light curves of J161335 were obtained from different telescopes in 2015 and 2016 and are analyzed using the Wilson–Devinney method. We discovered that the system is a W-type contact system with a contact degree of 19% and a high mass ratio of 0.91. By using all available eclipse times, we found that the observed $-$ calculated $(O-C)$ diagram displays a cyclic oscillation with an amplitude of 0.00196($\pm 0.00006)\:$d and a period of 4.79($\pm 0.14)\:$yr while it undergoes a downward parabolic change. This downward variation corresponds to a continuous decrease in the orbital period at a rate of $dP/dt = -4.26(\pm$0.01) $\times$ 10$^{-7}\:$d$\:$yr$^{-1}$. The small-amplitude oscillation is explained as the light travel-time effect from the gravitational influence of a third body with a lowest mass of $M _{3}$ = 0.15($\pm 0.01)M_{\,\odot }$. In solving the light curves, we found that the third light is increasing, with the wavelength suggesting that the third body may be a cool red dwarf. This is in agreement with the results obtained by analyzing the $O-C$ diagram. The tertiary red dwarf is orbiting the central red-dwarf binary at an orbital separation of 2.8($\pm 0.2$) au. These results suggest that the J161335 system may be formed through early dynamical interaction where the original low-mass component was replaced by a higher-mass third body and the lower-mass component was kicked out to a wider orbit. In this way, a hierarchical triple system similar to J161335 with a high-mass-ratio binary and a small close-in third body is formed.
Physiologically Based Pharmacokinetic Modeling of Salivary Concentrations for Noninvasive Biomonitoring of 2,4-Dichlorophenoxyacetic Acid (2,4-D)
Authors: Han Alice A , Timchalk Charles , Carver Zana A , Weber Thomas J , Tyrrell Kimberly J , Sontag Ryan L , Gibbins Teresa , Chrisler William B , Weitz Karl K , Du Dan , Lin Yuehe , Smith Jordan N
Published: September 2019

Saliva has become a favorable sample matrix for biomonitoring due to its noninvasive attributes and overall flexibility in collection. To ensure measured salivary concentrations reflect the exposure, a solid understanding of the salivary transport mechanism and relationships between salivary concentrations and other monitored matrices (ie, blood, urine) is needed. Salivary transport of a commonly applied herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), was observed in vitro and in vivo and a physiologically based pharmacokinetic (PBPK) model was developed to translate observations from the cell culture model to those in animal models and further evaluate 2,4-D kinetics in humans. Although apparent differences in experimental in vitro and in vivo saliva:plasma ratios (0.034 and 0.0079) were observed, simulations with the PBPK model demonstrated dynamic time and dose-dependent saliva:plasma ratios, elucidating key mechanisms affecting salivary transport. The model suggested that 2,4-D exhibited diffusion-limited transport to saliva and was additionally impacted by protein binding saturation and permeability across the salivary gland. Consideration of sampling times post-exposure and potential saturation of transport mechanisms are then critical aspects for interpreting salivary 2,4-D biomonitoring observations. This work utilized PBPK modeling in in vitro to in vivo translation to explore benefits and limitations of salivary analysis for occupational biomonitoring.
IDH2 reprograms mitochondrial dynamics in cancer through a HIF‐1α‐regulated pseudohypoxic state
Authors: Wang Yuan , Agarwal Ekta , Bertolini Irene , Ghosh Jagadish C. , Seo Jae Ho , Altieri Dario C.
Published: September 2019

The role of mitochondria in cancer continues to be debated and paradoxically implicated in opposing functions in tumor growth and tumor suppression. To understand this dichotomy, we explored the function of mitochondrial isocitrate dehydrogenase (IDH)2, a tricarboxylic acid cycle enzyme mutated in subsets of acute leukemias and gliomas, in cancer. Silencing of IDH2 in prostate cancer cells impaired oxidative bioenergetics, elevated reactive oxygen species (ROS) production, and promoted exaggerated mitochondrial dynamics. This was associated with increased subcellular mitochondrial trafficking, turnover of membrane focal adhesion complexes, and enhanced tumor cell migration and invasion, without changes in cell cycle progression. Mechanistically, loss of IDH2 caused ROS‐dependent stabilization of hypoxia‐inducible factor‐1α in normoxia, which was required for increased mitochondrial trafficking and tumor cell movements. Therefore, IDH2 is a dual regulator of cancer bioenergetics and tumor cell motility. This pathway may reprogram mitochondrial dynamics to differentially adjust energy production or promote tumor cell invasion in response to microenvironment conditions.—Wang, Y., Agarwal, E., Bertolini, I., Ghosh, J. C., Seo, J. H., Altieri, D. C. IDH2 reprograms mitochondrial dynamics in cancer through a HIF‐1α‐regulated pseudohypoxic state. FASEB J. 33, 13398–13411 (2019). www.fasebj.org
What information do healthcare professionals need to inform premenopausal women about risk-reducing salpingo-oophorectomy?
Authors: Hickey Martha , Rio Ines , Trainer Alison , Marino Jennifer L , Wrede C. David , Peate Michelle
Published: September 2019

Objective:

The aim of this study was to identify the unmet information needs of healthcare professionals managing risk-reducing bilateral salpingo-oophorectomy (RRBSO) in premenopausal women.

Methods:

A cross-sectional survey of healthcare professionals managing high-risk women in Victoria, Australia. Questions included roles and responsibilities around RRBSO, perceived barriers to uptake of RRBSO, and unmet information needs.

Results:

One hundred eighteen healthcare professionals across 10 different disciplines and specialties were approached to participate, of whom 47 completed the survey. Most respondents were genetic counselors (47%) or nurses (19%) and all worked in the public health system. Almost all (81%) provided information about RRBSO, but there was considerable uncertainty about who was responsible for making decisions with high-risk women about RRBSO. Most (85%) were “quite a bit” or “extremely” confident about informing high-risk women about ovarian cancer risk reduction from RRBSO and the surgical procedure (47%), but only one-third were “quite a bit” or “extremely” confident about discussing (36%) or managing (31%) surgical menopause. Furthermore, surgical menopause was considered the main barrier (88%, “quite a bit” or “extremely”) to RRBSO. Most healthcare professionals (78%) wanted more information and resources about surgical menopause for high-risk women.

Conclusions:

There is uncertainty around the roles and responsibilities of healthcare professionals managing high-risk women around RRBSO. Surgical menopause is perceived as a major barrier to RRBSO and healthcare professionals lack confidence in managing this outcome.

Video Summary:
http://links.lww.com/MENO/A477.
Extended Prophylaxis With Nevirapine Does Not Affect Growth in HIV-Exposed Infants
Authors: Onyango-Makumbi Carolyne , Owora Arthur H. , Mwiru Ramadhani S. , Mwatha Anthony , Young Alicia M. , Moodley Dhayendre , Coovadia Hoosen M. , Stranix-Chibanda Lynda , Manji Karim , Maldonado Yvonne , Richardson Paul , Andrew Philip , George Kathleen , Fawzi Wafaie , Fowler Mary Glenn
Published: September 2019

Background:

Effects of prolonged nevirapine prophylaxis exposure on growth among HIV-exposed uninfected (HEU) infants are unknown. This study examines the impact of extended nevirapine prophylaxis from 6 weeks to 6 months on the growth of HEU infants followed for 18 months and also identifies correlates of incident wasting, stunting, underweight, and low head circumference in the HPTN 046 trial.

Methods:

Intention-to-treat analysis examined the effect of extended nevirapine exposure on: weight-for-age Z-score, length-for-age Z-score, weight-for-length Z-score, and head circumference-for-age Z-score. Multivariable linear mixed-effects and Cox proportional hazard models were used to compare growth outcomes between the study arms and identify correlates of incident adverse growth outcomes, respectively.

Results:

Compared to placebo, extended prophylactic nevirapine given daily from 6 weeks to 6 months did not affect growth in HEU breastfeeding (BF) infants over time (treatment × time: P > 0.05). However, overall growth declined over time (time effect: P < 0.01) when compared with WHO general population norms. Male sex was associated with higher risk of all adverse growth outcomes (P < 0.05), whereas short BF duration was associated with wasting (P = 0.03). Maternal antiretroviral therapy exposure was protective against underweight (P = 0.02). Zimbabwe tended to have worse growth outcomes especially stunting, compared to South Africa, Uganda and Tanzania (P < 0.05).

Conclusions:

It is reassuring that prolonged exposure to nevirapine for prevention-of-mother-to-child HIV transmission does not restrict growth. However, targeted interventions are needed to improve growth outcomes among at-risk HEU infants (i.e., male sex, short BF duration, lack of maternal antiretroviral therapy exposure, and resident in Zimbabwe).
Effects of neighbour location and nutrient distributions on root foraging behaviour of the common sunflower
Authors: Ljubotina Megan K. , Cahill James F.
Published: September 2019

Plants regularly encounter patchily distributed soil nutrients. A common foraging response is to proliferate roots within high-quality patches. The influence of the social environment on this behaviour has been given limited attention, despite important fitness consequences of competition for soil resources among plants. Using the common sunflower (Helianthus annuusL.), we compared localized root proliferation in a high-quality patch by plants grown alone to that of plants in two different social environments: with a neighbouring plant sharing equal access to the high-quality patch, and with a neighbouring plant present but farther from the high-quality patch such that the focal individual was in closer proximity to the high-quality patch. Sunflowers grown alone proliferated more roots within high-nutrient patches than lower-nutrient soil. Plants decreased root proliferation within a high-nutrient patch when it was equidistant to a neighbour. Conversely, plants increased root proliferation when they were in closer proximity to the patch relative to a nearby neighbour. Such contingent responses may allow sunflowers to avoid competition in highly contested patches, but to also pre-empt soil resources from neighbours when they have better access to a high-quality patch. We also compared patch occupancy by sunflowers grown alone with two equidistant high-quality patches to occupancy by sunflowers grown with two high-quality patches and a neighbour. Plants grown with a neighbour decreased root length within shared patches but did not increase root length within high-quality patches they were in closer proximity to, perhaps because resource pre-emption may be less important for individuals when resources are more abundant. These results show that nutrient foraging responses in plants can be socially contingent, and that plants may account for the possibility of pre-empting limited resources in their foraging decisions.
Family history and polygenic risk of cardiovascular disease: independent factors associated with secondary cardiovascular events in patients undergoing carotid endarterectomy
Authors: Timmerman Nathalie , de Kleijn Dominique P.V. , de Borst Gert J. , den Ruijter Hester M. , Asselbergs Folkert W. , Pasterkamp Gerard , Haitjema Saskia , van der Laan Sander W.
Published: September 2019

Background

Family history (FHx) of cardiovascular disease (CVD) is a risk factor for CVD and a proxy for cardiovascular heritability. Polygenic risk scores (PRS) summarizing >1 million variants for coronary artery disease (CAD) are associated with incident and recurrent CAD events. However, little is known about the influence of FHx or PRS on secondary cardiovascular events (sCVE) in patients undergoing carotid endarterectomy (CEA).

Methods

We included 1,788 CEA patients from the Athero-Express Biobank. A weighted PRS for CAD including 1.7 million variants was calculated (MetaGRS). The composite endpoint of sCVE during three years follow-up included coronary, cerebrovascular and peripheral events and cardiovascular death. We assessed the impact of FHx and MetaGRS on sCVE and carotid plaque composition.

Results

Positive FHx was associated with a higher 3-year risk of sCVE independent of cardiovascular risk factors and MetaGRS (adjusted HR 1.40, 95%CI 1.07-1.82, p=0.013). Patients in the highest MetaGRS quintile had a higher 3-year risk of sCVE compared to the rest of the cohort independent of cardiovascular risk factors including FHx (adjusted HR 1.35, 95%CI 1.01-1.79, p=0.043), and their atherosclerotic plaques contained more fat (adjusted OR 1.59, 95%CI, 1.11-2.29, p=0.013) and more macrophages (OR 1.49, 95%CI 1.12-1.99, p=0.006).

Conclusion

In CEA patients, both positive FHx and higher MetaGRS were independently associated with increased risk of sCVE. Moreover, higher MetaGRS was associated with vulnerable plaque characteristics. Future studies should unravel underlying mechanisms and focus on the added value of PRS and FHx in individual risk prediction for sCVE.
Dmc1is a candidate for temperature tolerance during wheat meiosis
Authors: Draeger Tracie , Martin Azahara , Alabdullah Abdul Kader , Pendle Ali , Rey María-Dolores , Shaw Peter , Moore Graham
Published: September 2019

We have assessed the effects of high and low temperatures on meiotic chromosome synapsis and crossover formation in the hexaploid wheat (Triticum aestivumL.) variety ‘Chinese Spring’. At low temperatures, asynapsis and chromosome univalence have been observed before in Chinese Spring lines lacking the long arm of chromosome 5D (5DL), which led to the proposal that 5DL carries a gene (Ltp1) that stabilises wheat chromosome pairing at low temperatures. In the current study, Chinese Spring wild type and 5DL interstitial deletion mutant plants were exposed to low (13°C) or high (30°C) temperatures in controlled environment rooms during a period from premeiotic interphase to early meiosis I. A 5DL deletion mutant was identified whose meiotic chromosomes exhibit extremely high levels of asynapsis and chromosome univalence at metaphase I after seven days at 13°C. This suggests that the mutant, which we namettmei1(temperaturetolerance inmeiosis 1) has a deletion of a gene that, likeLtp1, normally stabilises chromosome pairing at low temperatures. Immunolocalisation of the meiotic proteins ASY1 and ZYP1 onttmei1mutants showed that low temperature results in a failure to complete synapsis at pachytene. After 24 hours at 30°C,ttmei1mutants exhibited a reduced number of crossovers and increased univalence, but to a lesser extent than at 13°C. KASP genotyping revealed thatttmei1has a 4 Mb deletion in 5DL. Of 41 genes within this deletion region, the strongest candidate for the stabilisation of chromosome pairing at low (and possibly high) temperatures is the meiotic recombination geneDmc1.

Key message

The meiotic recombination geneDmc1on wheat chromosome 5D has been identified as a candidate for the maintenance of normal chromosome synapsis and crossover at low and possibly high temperatures.
Novel insights into the regulation of chemerin expression: role of acute-phase cytokines and DNA methylation
Authors: Kwiecien Kamila , Brzoza Piotr , Majewski Pawel , Skulimowska Izabella , Bednarczyk Kamil , Cichy Joanna , Kwitniewski Mateusz
Published: September 2019

Chemerin is a chemoattractant protein with adipokine properties encoded by the retinoic acid receptor responder 2 (RARRES2) gene. It has gained more attention over the past few years due to its multilevel impact on metabolism and immune responses. The pleiotropic actions of chemerin include chemotaxis of dendritic cells, macrophages and natural killers (NK) subsets, bactericidal activity as well as regulation of adipogenesis and glucose metabolism. Therefore, reflecting the pleiotropic actions of chemerin, expression of RARRES2 is regulated by a variety of inflammatory and metabolic mediators. However, for most cell types, the molecular mechanisms controlling constitutive and regulated chemerin expression are poorly characterized. Here we show that RARRES2 mRNA levels in murine adipocytes are upregulated in vitro and in vivo by acute-phase cytokines, IL-1β and OSM. In contrast to adipocytes, these cytokines exerted a weak, if any, response in mouse hepatocytes, suggesting that the effect of IL-1β and OSM on chemerin expression is specific to fat tissue. Moreover, we show that DNA methylation controls the constitutive expression of chemerin. Bisulfite sequencing analysis showed low methylation levels within −735 to +258 bp of the murine RARRES2 gene promoter in unstimulated adipocytes and hepatocytes. In contrast to these cells, the RARRES2 promoter is highly methylated in B lymphocytes, cells that do not produce chemerin. Together, our findings reveal previously uncharacterized mediators and mechanisms controlling chemerin expression in various cells.
Identification of spatial compartments in tissue from in situ sequencing data
Authors: Partel Gabriele , Hilscher Markus M. , Milli Giorgia , Solorzano Leslie , Klemm Anna H. , Nilsson Mats , Wählby Carolina
Published: September 2019

Spatial organization of tissue characterizes biological function, and spatially resolved gene expression has the power to reveal variations of features with high resolution. Here, we propose a novel graph-based in situ sequencing decoding approach that improves recall, enabling precise spatial gene expression analysis. We apply our method on in situ sequencing data from mouse brain sections, identify spatial compartments that correspond with known brain regions, and relate them with tissue morphology.
Thinking small: next-generation sensor networks close the size gap in vertebrate biologging
Authors: Ripperger Simon P. , Carter Gerald G. , Page Rachel A. , Duda Niklas , Koelpin Alexander , Weigel Robert , Hartmann Markus , Nowak Thorsten , Thielecke Jörn , Schadhauser Michael , Robert Jörg , Herbst Sebastian , Meyer-Wegener Klaus , Wägemann Peter , Schröder-Preikschat Wolfgang , Cassens Björn , Kapitza Rüdiger , Dressler Falko , Mayer Frieder
Published: September 2019

Recent advances in animal tracking technology have ushered in a new era in biologging. However, the considerable size of many sophisticated biologging devices restricts their application to larger animals, while old-fashioned techniques often still represent the state-of-the-art for studying small vertebrates. In industrial applications, low-power wireless sensor networks fulfill requirements similar to those needed to monitor animal behavior at high resolution and at low tag weight. We developed a wireless biologging network (WBN), which enables simultaneous direct proximity sensing, high-resolution tracking, and long-range remote data download at tag weights of one to two grams. Deployments to study wild bats created social networks and flight trajectories of unprecedented quality. Our developments highlight the vast capabilities of WBNs and their potential to close an important gap in biologging: fully automated tracking and proximity sensing of small animals, even in closed habitats, at high spatial and temporal resolution.
The pneumococcal two-component system VisRH is linked to enhanced intracellular survival ofStreptococcus pneumoniaein influenza-infected pneumocytes
Authors: Reinoso-Vizcaíno Nicolás M. , Cian Melina B. , Cortes Paulo R. , Olivero Nadia B. , Hernandez-Morfa Mirelys , Piñas Germán E. , Badapanda Chandan , Rathore Ankita , Perez Daniel R. , Echenique José
Published: September 2019

The virus-bacterial synergism implicated in secondary bacterial infections caused byStreptococcus pneumoniaefollowing infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection withS. pneumoniaeleads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system VisRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔvisRandwtstrains, a list of 179 differentially expressed genes was defined. Among those, theclpLprotein chaperone gene and thepsaBMn+2transporter gene, which are involved in the stress response, are important in enhancingS. pneumoniaesurvival in influenza-infected cells. The ΔvisR,ΔclpLand ΔpsaBdeletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the VisRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival ofS. pneumoniaein IAV-infected pneumocytes.

Author summary

S. pneumoniaeis an inhabitant of the human nasopharynx that is capable of causing a variety of infections contributing to an estimated 1.6 million deaths each year. Many of these deaths occur as result of secondaryS. pneumoniaeinfections following seasonal or pandemic influenza. AlthoughS. pneumoniaeis considered a typical extracellular pathogen, an intracellular survival mechanism has been more recently recognized as significant in bacterial pathogenesis. The synergistic effects between influenza A andS. pneumoniaein secondary bacterial infection are well documented; however, the effects of influenza infections on intracellular survival ofS. pneumoniaeare ill-defined. Here, we provide evidence that influenza infection increasesS. pneumoniaeintracellular survival in pneumocytes. We demonstrate that the poorly understood VisRH signal transduction system in pneumococcus controls the expression of genes involved in the stress response thatS. pneumoniaeneeds to increase intracellular survival in influenza A-infected pneumocytes. These findings have important implications for understanding secondary bacterial pathogenesis following influenza and for the treatment of such infections in influenza-stricken patients.
Discovery and characterization of a Gram-positive Pel polysaccharide biosynthetic gene cluster
Authors: Whitfield Gregory B. , Marmont Lindsey S. , Bundalovic-Torma Cedoljub , Razvi Erum , Roach Elyse J. , Khursigara Cezar M. , Parkinson John , Howell P. Lynne
Published: September 2019

Our understanding of the biofilm matrix components utilized by Gram-positive bacteria, and the signalling pathways that regulate their production are largely unknown. In a companion study, we developed a computational pipeline for the unbiased identification of homologous bacterial operons and applied this algorithm to the analysis of synthase-dependent exopolysaccharide biosynthetic systems (https://doi.org/10.1101/769745). Here, we explore the finding that many species of Gram-positive bacteria have operons with similarity to the Pseudomonas aeruginosa pel locus. Our characterization of the pelDEADAFG operon from Bacillus cereus ATCC 10987, presented herein, demonstrates that this locus is required for biofilm formation and produces a polysaccharide structurally similar to Pel. We show that the degenerate GGDEF domain of the B. cereus PelD ortholog binds cyclic-3’,5’-dimeric guanosine monophosphate (c-di-GMP), and that this binding is required for biofilm formation. Finally, we identify a diguanylate cyclase, CdgF, and a c-di-GMP phosphodiesterase, CdgE, that reciprocally regulate the production of Pel. The discovery of this novel c-di-GMP regulatory circuit significantly contributes to our limited understanding of c-di-GMP signalling in Gram-positive organisms. Furthermore, conservation of the core pelDEADAFG locus amongst many species of Bacilli, Clostridia, Streptococci, and Actinobacteria suggests that Pel may be a common biofilm matrix component in many Gram-positive bacteria.

Author summary

The Pel polysaccharide is required for biofilm formation in P. aeruginosa and we have previously found that the genes necessary for biosynthesis of this polymer are broadly distributed across Gram-negative bacteria. Herein, we show that many species of Gram-positive bacteria also possess Pel biosynthetic genes and demonstrate that these genes are used Bacillus cereus for biofilm formation. We show that Pel production in B. cereus is regulated by c-di-GMP and have identified two enzymes, a diguanylate cyclase, CdgF, and a phosphodiesterase, CdgE, that control the levels of this bacterial signalling molecule. While Pel production in B. cereus also requires the binding of c-di-GMP to the receptor PelD, the divergence of this protein in Streptococci suggests a c-di-GMP independent mechanism of regulation is used in this species. The discovery of a Pel biosynthetic gene cluster in Gram-positive bacteria and our characterization of the pel operon in B. cereus suggests that Pel is a widespread biofilm component across all bacteria.
Chromosome-scalede novoassembly and phasing of a Chinese indigenous pig genome
Authors: Yang Yalan , Lian Jinmin , Xie Bingkun , Chen Muya , Niu Yongchao , Li Qiaowei , Liu Yuwen , Yi Guoqiang , Fan Xinhao , Tang Yijie , Li Jiang , Liachko Ivan , Sullivan Shawn T. , Nelson Bradley , Zuo Erwei , Tang Zhonglin
Published: September 2019

Chinese indigenous pigs differ significantly from Western commercial pig breeds in phenotypic and genomic characteristics. Thus, building a high-quality reference genome for Chinese indigenous pigs is pivotal to exploring gene function, genome evolution and improving genetic breeding in pigs. Here, we report an ultrahigh-quality phased chromosome-scale genome assembly for a male Luchuan pig, a representative Chinese domestic breed, by generating and combining data from PacBio Sequel reads, Illumina paired-end reads, high-throughput chromatin conformation capture and BioNano optical map. The primary assembly is ∼ 2.58 Gb in size with contig and scaffold N50s of 18.03 Mb and 140.09 Mb, respectively. Comparison between primary assembly and alternative haplotig reveals numerous haplotype-specific alleles, which provide a rich resource to study the allele-specific expression, epigenetic regulation, genome structure and evolution of pigs. Gene enrichment analysis indicates that the Luchuan-specific genes are predominantly enriched in Gene Ontology terms for phosphoprotein phosphatase activity, signaling receptor activity and phosphatidylinositol binding. We provide clear molecular evolutionary evidence that the divergence time between Luchuan and Duroc pigs is dated back to about 1.7 million years ago. Meanwhile, Luchuan exhibits fewer events of gene family expansion and stronger gene family contraction than Duroc. The positively selected genes (PSGs) in Luchuan pig significantly enrich for protein tyrosine kinase activity, microtubule motor activity, GTPase activator activity and ubiquitin-protein transferase activity, whereas the PSGs in Duroc pig enrich for G-protein coupled receptor activity. Overall, our findings not only provide key benchmark data for the pig genetics community, but also pave a new avenue for utilizing porcine biomedical models to study human health and diseases.
The pericardium promotes cardiac repair and remodelling post-myocardial infarction
Authors: Mylonas Katie J. , Jackson-Jones Lucy H. , Andrews Jack P. M. , Magalhaes Marlene S. , Meloni Marco , Joshi Nikhil V. , Allen Judith E. , Newby David E. , Dweck Marc R. , Gray Gillian A. , Bénézech Cécile
Published: September 2019

The pericardium is widely recognised for its lubricating and bio-mechanical properties. It also contains fat-associated lymphoid clusters (FALCs) and its immune functions have been widely overlooked. Here we aimed to assess the inflammatory activity of the pericardium in patients who suffered a recent myocardial infarction (MI) and to determine its importance for repair and remodelling in a murine MI model induced by coronary artery ligation (CAL). By comparing 18F-fluorodeoxyglucose (FDG) activity in the pericardium of patients with stable coronary artery disease and patients who had a recent MI, we demonstrate that MI is associated with increased pericardial inflammation. We confirm in mice, that pericardial FALCs undergo a major expansion following CAL. We show that despite similar initial injury, removal of the pericardium prior to MI disrupted subsequent repair, resulting in 50% mortality due to cardiac rupture, while all mice with intact pericardia survived. Removal of the pericardium also led to decreased staining for Ym1, a marker of reparative macrophages and adverse cardiac fibrosis within the infarct area. Together, this work indicates a crucial role for the pericardium in regulating inflammation, macrophage polarisation and tissue remodelling in the heart following MI.
Modelling Inoculum Availability ofPlurivorosphaerella nawaein Persimmon Leaf Litter with Bayesian Beta Regression
Authors: Martínez-Minaya Joaquín , Conesa David , López-Quílez Antonio , Mira José Luis , Vicent Antonio
Published: September 2019

Circular leaf spot (CLS), caused byPlurivorosphaerella nawae, is a serious disease of persimmon (Diospyros kaki) inducing necrotic lesions on leaves, defoliation and fruit drop. Under Mediter-ranean conditions,P. nawaeforms pseudothecia in the leaf litter during winter and ascospores are released in spring infecting susceptible leaves. Persimmon growers are advised to apply fungicides for CLS control during the period of inoculum availability, which was defined based on ascospore counts under the microscope. A model of inoculum availability ofP. nawaewas developed and evaluated as an alternative to ascospore counts. Leaf litter samples were collected weekly in L’Alcúdia from 2010 to 2015. Leaves were soaked, placed in a wind tunnel, and released ascospores ofP. nawaewere counted. Hierarchical Bayesian beta regression methods were used to fit the dynamics of ascospore production in the leaf litter. The selected model, having the lowest values of DIC, WAIC and LCPO, included accumulated degree days (ADD) andADDtaking into account the vapor pressure deficit (ADDvpd) as fixed effects, and year as a random effect. This model had a MAE of 0.042 and RMSE of 0.062. The beta regression model was evaluated in four orchards for different years from 2010 to 2015. Higher accuracy was obtained at the beginning and the end of the ascospore production period, which are the events of interest to schedule fungicide sprays for CLS control in Spain. This same modelling framework can be extended to other fungal plant pathogens whose inoculum dynamics are expressed as proportion data.