bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing- and Dose-Specific Associations of Prenatal Smoke Exposure With Newborn DNA Methylation
Authors: Monasso Giulietta S , Jaddoe Vincent W V , de Jongste Johan C , Duijts Liesbeth , Felix Janine F
Published: April 2020

Introduction

Fetal changes in DNA methylation may underlie associations of maternal smoking during pregnancy with adverse outcomes in children. We examined critical periods and doses of maternal smoking during pregnancy in relation to newborn DNA methylation, and associations of paternal smoking with newborn DNA methylation.

Aims and Methods

This study was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onwards. We assessed parental smoking during pregnancy using questionnaires. We analyzed associations of prenatal smoke exposure with newborn DNA methylation at 5915 known maternal smoking-related cytosine-phosphate-guanine sites (CpGs) in 1261 newborns using linear regression. Associations with false discovery rate-corrected p-values < .05 were taken forward.

Results

Sustained maternal smoking was associated with newborn DNA methylation at 1391 CpGs, compared with never smoking. Neither quitting smoking early in pregnancy nor former smoking was associated with DNA methylation, compared with never smoking. Among sustained smokers, smoking ≥5, compared with <5, cigarettes/d was associated with DNA methylation at seven CpGs. Paternal smoking was not associated with DNA methylation, independent of maternal smoking status.

Conclusions

Our results suggest that CpGs associated with sustained maternal smoking are not associated with maternal smoking earlier in pregnancy or with paternal smoking. Some of these CpGs show dose–response relationships with sustained maternal smoking. The third trimester may comprise a critical period for associations of smoking with newborn DNA methylation, or sustained smoking may reflect higher cumulative doses. Alternatively, maternal smoking limited to early pregnancy and paternal smoking may be associated with DNA methylation at specific other CpGs not studied here.

Implications

Our results suggest that quitting maternal smoking before the third trimester of pregnancy, and possibly lowering smoking dose, may prevent differential DNA methylation in the newborns at CpGs associated with sustained smoking. If the relevance of DNA methylation for clinical outcomes is established, these results may help in counseling parents-to-be about quitting smoking.
Linda Hutcheon
Authors: Lernout Geert
Published: April 2020

Linda Hutcheon (b. 1947 as Linda Bortolotti) grew up in Toronto, where she did her honors bachelor of arts in modern languages and literatures, and where, after a master of arts in Romance studies at Cornell University, she also defended her doctorate in comparative literature. Hutcheon spent her early academic career as a professor of English at McMaster University before moving back to the University of Toronto in 1988, to the department of English and the Centre for Comparative Literature; she was made University Professor in 1996 and became emeritus in 2010. The impact of her work is felt in a number of distinct but related fields: in literary theory and history, in the study of Canadian literature and culture, in the definition(s) of postmodernism, and most recently, in collaboration with her husband Michael Hutcheon in the scholarly study of opera. Hutcheon’s main contribution to literary criticism may well be her work on the theory and practice of postmodernism, starting with her dissertation on what she then called narcissistic narrative. From a wide and varied theoretical background, she has defined and redefined the contours of postmodernism, doing so on the basis of the close study of postmodernist works in different disciplines: not just literature, but also architecture, music, and the visual arts. What distinguishes Hutcheon’s contribution to literary criticism and art theory is the width of her frame of reference, in terms of both the variety of the works that she has studied and of the critical approaches that she addresses in her own thinking. This width is also reflected in the numerous collaborative initiatives in which she has been involved during her long career: she is one of the few literary critics of her generation to have fully engaged in collaboration with many others, including her husband. With other scholars, she has written articles, published books, and edited special issues of journals and essay collections.
Theatre of the Absurd
Authors: Bennett Michael Y.
Published: April 2020

Coined and first theorized by BBC Radio drama critic Martin Esslin in a 1960 article and a 1961 book of the same name, the “Theatre of the Absurd” is a literary and theatrical term used to describe a disparate group of avant-garde plays by a number of mostly European or American avant-garde playwrights whose theatrical careers, generally, began in the 1950s and 1960s. Of the playwrights and writers (whether or not accurately) associated with this movement that has not been self-proclaimed, four were awarded Nobel Prizes in Literature: Samuel Beckett, Harold Pinter, Albert Camus, and Jean-Paul Sartre (who refused the award). Other major playwrights associated with the absurd are Edward Albee, Eugène Ionesco, and Jean Genet (among other important and minor playwrights). Often misconstrued as existentialist or nihilistic plays, they signaled the end of theatrical “modernism.” As such, some of these plays are considered among the most important and influential plays of the 20th century in their own right. As a group of plays, the Theatre of the Absurd, or known more casually as “absurd theater” or “absurd drama,” is widely considered, if not the most, certainly one of the most important theatrical movements of the second half of the 20th century. Besides leaving a treasure trove of important avant-garde plays, absurd drama and dramatists have left as possibly their greatest legacy, namely, that the tragicomic worldview of these plays has been subsumed by mainstream plays. Indeed, tragicomedy has become the default theatrical genre over the past five or so decades.
Federico Barocci
Authors: Verstegen Ian
Published: April 2020

Federico Barocci (b. c. 1532–d. 1612) was the most famous and well-paid Italian artist of the later 16th and early 17th centuries. Born in Urbino to a prosperous artisan family, he traveled to Rome in the early 1950s and then again in the early 1560s, receiving a papal commission through his elder countryman Taddeo Zuccaro. In the meantime, he began to receive local commissions, leading to his breakthrough Deposition in Perugia Cathedral in 1569. The work announced Barocci’s mature, reforming style, which disciplined latent Maniera (Mannerist) influences in Italy at the time in favor of life observation and careful construction of the painting through numerous stages of drawing. Barocci went on to provide a series of important altarpieces in Arezzo (Madonna del Popolo, 1579) and Ravenna (Martyrdom of St. Vitalis, 1583), leading to a series of important Roman commissions that cemented his reputation (Visitation, 1586; Presentation, 1603, both Chiesa Nuova; and Communion of the Apostles, 1608, Santa Maria sopra Minerva). Barocci’s reputation was strong in the 17th century but dropped off in the 18th, perhaps due to the sentimentality of his painting. Therefore, literature about the artist is not large, in spite of the fact that research has picked up substantially over the last few years. Today, Barocci is recognized for his importance for his time and also—in spite of ideas about his painting style—one of the most brilliant draftsmen of the Early Modern period. For a review of Barocci’s recent change in critical acceptance, see “‘Maniera sfumata, dolce, e vaga’: The Recent Canonization of Federico Barocci.” Perspective 1 (2015): 161–168 (cited under Monographs).
Jansenism
Authors: O'Connor Thomas
Published: April 2020

One of a number of theological tendencies within early modern Catholicism, Jansenism derives its name from Cornelius Jansen (b. 1585–d. 1638), bishop of Ypres. The term, coined by Jansen’s Jesuit critics, came into general use only in the 1640s, when his Augustinus (1640) was posthumously published in Leuven. Its appearance marked a fresh outbreak of an ancient dispute within Western Christianity concerning the nature of divine grace and its operation in both the individual believer and the Christian community. Jansen’s supporters intended the book as a rebuttal of a doctrine of grace, which was traced to the 5th-century heretic Pelagius, and which they ascribed to the Jesuits and their sympathizers. The Augustinus, and the reaction to it, crystalized a range of theological positions that, over the following decades, garnered support among clerical and lay Catholic groups in Flanders, France, Rome, and further afield. It is impossible to reduce those either accused of or professing Jansenism to a common set of doctrines, but they did share certain attitudes. The doctrinal authority of the Church Fathers, particularly Augustine, was supreme; their religious anthropology was pessimistic; their moral views were rigorist; and they were sensitive to issues of authority and conscience. Over the following two centuries, the efforts by theologians, pastors, and spiritual directors to define the role of individual conscience under the influence of divine grace involved Jansenists in successive contestations of papal, episcopal, regal, and civil authority. Although Jansenism’s cradle was Flanders, it is more usually associated with France, where it influenced religious and political life until the Revolution. Rome was another Jansenist theater, where pressure groups alternately supported and anathematized it, leading to a number of ill-conceived, politically motivated, and highly publicized papal condemnations of Jansenist texts. The movement found sympathizers all over Catholic Europe, especially in zones of religious tension like England, Holland, and Ireland. Later, versions of Jansenism became popular with reforming Catholic administrations in the Holy Roman Empire, Spain, and Portugal. In the late 18th century, French clerics and laity with Jansenist sympathies contributed to the suppression of the Jesuits. They also supported religious reforms intended to undermine both royal and papal authority. The failure of these schemes, together with the success of Napoleon’s 1801 Concordat, ended Jansenist-inspired political activities. Jansenist sympathies, however, survived; the 19th century saw the literary retrieval of the movement, especially in its Port-Royal version. From the mid-20th century, the study of Jansenism shed some of its denominational and romantic baggage to become a useful if not always well-used category for the study of early modern Catholicism.
Slavery in New England
Authors: Warren Wendy
Published: April 2020

In popular imagination, the history of chattel slavery in North America is largely linked to the southeastern quarter of the continent, and focused on the 19th century. But the slave trade and institution of chattel slavery functioned in other regions and at other times. One region that has drawn much scholarly attention is New England; the first records of enslaved Africans in that region (in the Massachusetts Bay Colony) appear in 1638, and the region’s enslaved African population grew steadily throughout that century and well into the 18th. Numbering less than two thousand in 1700, there were more than fifteen thousand people of African descent, both free and enslaved, in the region by 1770. Neither the slave trade to New England nor the institution of slavery itself, consisted only of Africans and people of African descent; historians have increasingly paid attention to the ways that commodified enslavement ensnared Native Americans, who worked as unfree labor in the region and were also exported to the West Indies and elsewhere as chattel slaves in the Atlantic slave trade. Indeed, studies of slavery in New England, by focusing on a region seemingly relatively marginal to the greater Atlantic economy and one mostly lacking (save a few areas of Rhode Island) a stereotypical plantation economy, have usefully emphasized the various ways that chattel slavery could be experienced, and have also emphasized the broad reach of Atlantic racial hierarchies and labor systems. Slavery in New England was not the monocrop plantation slavery typical of the 19th-century US South; enslaved people in New England worked in a more varied labor system. The small holdings of New England also meant the slave market worked differently than the antebellum South. Enslaved women in New England were valued differently than in other regions; for example, their reproductive capacities meant less than they would in societies with large-scale holdings of enslaved people. Enslaved children could be a liability rather than an investment. Emancipation in the region was truly gradual: though laws were passed in the late 18th century that sought to outlaw slavery, enslaved people were still legally held in New England as late as the 1840s.
Voter Support for Women Candidates
Authors: Cooperman Rosalyn
Published: April 2020

Voter support for women candidates in American politics may best be summed up by the often-repeated phrase, “when women run, women win.” This statement indicates that when compared to male candidates running in a similar capacity, such as candidates for open seats in which no incumbent is present, female candidates are equally likely to win elected office. Voters, therefore, seem equally likely at face value to support female candidates. However, the literature on voter support for women candidates suggests that this voter support may be more conditional in nature. A central research thread on voters and women candidates is how voters perceive women candidates and, in turn, their electability. Research on gender stereotypes and candidates examines voter perceptions of the traits they typically associate with men and women, candidates, and officeholders and the circumstances under which these traits make gender and political candidacy more or less attractive. The literature on political party and voter support for women candidates explores how gender and party affect levels of voter support and is offered as one explanation for the party imbalance in women’s representation with female Democrats significantly outnumbering female Republicans as candidates and officeholders. Researchers have also examined how voters evaluate other components of women’s candidacies, including their party affiliation, race, ethnicity, and sexual orientation. In addition to personal characteristics, scholars have explored how the type or level of office impacts voter support of women candidates with certain types of elected positions often considered more or less well suited for women candidates. More recently, a thread of research on voter support for women candidates has focused on women’s absence from the nation’s highest elected position—the US presidency. Scholars, and the candidate herself, have assessed voter support for or opposition to Hillary Clinton’s unsuccessful presidential bids in 2008 and 2016. This line of research includes public opinion polling that measures both the abstract idea of electing a woman president as well as electing a specific woman president, namely Clinton.
IANPHI and National Public Health Institutes
Authors: Whitney Ellen , Seib Katherine , Blackburn Jessica , Clemente Jacob , Dusenbury Courtenay M. , Koplan Jeffrey P.
Published: April 2020

More than one hundred countries around the world have established national public health institutes (NPHIs) to coordinate and lead their public health systems. Some NPHIs, such as the US Centers for Disease Control and Prevention (CDC), South African National Institute for Communicable Diseases (NICD), Brazilian Oswaldo Cruz Foundation (FIOCRUZ), and Chinese Center for Disease Control and Prevention, have developed over time. Others, such as the Public Health Agency of Canada (PHAC), emanated in response to more recent global public health threats like severe acute respiratory syndrome (SARS). NPHI functionalities range from combatting primarily infectious diseases to comprehensive mandates to lead national efforts for prevention and control of both infectious and noncommunicable disease threats. The International Association of National Public Health Institutes (IANPHI), envisioned in 2001 and chartered in 2006, serves to link and catalyze the capacity of NPHIs around the world through a robust international professional and scientific network. IANPHI works closely with the World Health Organization (WHO) through a formal partnership agreement. The Bill & Melinda Gates Foundation, the Rockefeller Foundation, member dues and peer assistance, bilateral cooperative agreements, and private-sector partnerships support its activities. IANPHI’s members encompass more than five billion people across six continents. IANPHI is the only organization whose mission is to strengthen national public health institutes. To do this, IANPHI’s work focuses on (a) supporting a robust scientific community of NPHI directors through an annual meeting, a listserv, and collaborative activities; (b) developing and distributing guidelines and tools that strengthen NPHIs’ abilities to conduct and evaluate public health programs and efforts, including the IANPHI NPHI development framework, the Staged Development Tool, NPHI-to-NPHI evaluation guidance, and a best practices series; and (c) investing in projects designed to create NPHIs and strengthen public health systems in low-resource countries. IANPHI helps NPHIs by advocating for strong and well-supported NPHIs and providing timely information and insights for public health programs and actions.
English as a Lingua Franca
Authors: Jenkins Jennifer , Baker Will
Published: April 2020

The phenomenon of English as a lingua franca (ELF), in other words English used among speakers who have different first language backgrounds, has existed since the British began to colonize parts of Asia and Africa in the late 16th century. However, it is only during the past thirty years that ELF has spread to the rest of the world, seen a dramatic rise in its number of users, and attained its current global status. Unsurprisingly, then, research publications on the ELF phenomenon are also relatively recent. Like the phenomenon that it explores, research into ELF has also grown, particularly since the start of the current millennium, in terms of the amount being published as well as an expansion in the areas of interest being reported. Thus, whereas the original research into ELF focused entirely on linguistic forms, particularly phonological and lexico-grammatical, current ELF research explores a host of domains from tourism, to business, to higher education among many others, as well as a wider range of linguistic areas including ELF pragmatics, metaphorical language, and morpho-syntactics, along with various other English language-related topics such as intercultural communication, ELF in social contexts, humor in ELF interactions, assessment of ELF, and implications for teacher education. In addition, the first corpora of ELF use began to be collected, most notably Mauranen’s Corpus of English as a Lingua Franca in Academic Settings (ELFA) and Seidlhofer’s Vienna-Oxford International Corpus of English (VOICE), with Kirkpatrick’s Asian Corpus of English (ACE) following a few years later. Meanwhile the ELF phenomenon has been reconceptualized in line with the findings of its growing body of research. Nevertheless, ELF research is still in its infancy by comparison with most other areas of academic inquiry, and to date there is therefore only one overview publication, one journal, and no reference works, bibliographies, textbooks or the like. This bibliography is therefore divided according to the key areas in which publications on ELF have focused up to now.
Africa and Intellectual Property Rights for Plant Varieties
Authors: Adebola Titilayo
Published: April 2020

The entry into force of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) on 1 January 1995 reversed Africa’s relationship with intellectual property rights for Plant Varieties. Except for Kenya, South Africa, and Zimbabwe, no other African country had intellectual property rights systems for plant varieties before TRIPS. However, the obligation set out in Article 27.3(b) of TRIPS for all World Trade Organization (WTO) members to protect plant varieties through patents, an effective sui generis system, or a combination of systems, heralded revisions to the intellectual property laws and policies on the continent. Africa’s response to Article 27.3(b) of TRIPS was the Organization for African Unity (now African Union—AU) African Model Law for the Protection of the Rights of Local Communities, Farmers, and Breeders, and for the Regulation of Access to Biological Resources (African Model Law), adopted in 2000. Grounded on the dynamic social, economic, and political realities in Africa, the African Model Law seeks to balance small-scale farmers’, farming communities’, and commercial plant breeders’ interests. The African Model Law rejects patents for plant varieties and the wholesale adoption of the 1991 version of the International Convention on the Protection of New Varieties of Plants (UPOV). Instead, it presents a TRIPS-compliant model sui generis option that provides for access and benefit-sharing principles from the Convention on Biological Diversity (CBD), farmers’ rights from the International Undertaking on Plant Genetic Resources for Food and Agriculture (IUPGRFA), and plant breeders’ rights from UPOV 1978 and UPOV 1991. Despite the commendable efforts at creatively designing the Model Law and its historical significance as an African-rooted response to the international debates on the overlapping and conflicting international treaties for plant varieties, the Model Law failed to gain traction in Africa. No African country has adopted it. On the contrary, there is increasing pressure through a coalition of Global North countries, international organizations, and multinational firms for African countries to adopt UPOV-1991-styled plant breeders’ rights systems.
Thoracic paravertebral involvement in patients with IgG4-related disease: CT and MR imaging findings
Authors: Zhang Zaizhu , Guan Wenmin , Lin Qiang , Yu Wei
Published: April 2020

Objectives

To retrospectively evaluate CT and magnetic resonance (MR) imaging thoracic paravertebral findings at baseline and follow-up in patients with IgG4-related disease.

Methods

The study consisted of 36 patients with IgG4-related disease involving thoracic paravertebral regions (32 men and four women; mean age, 58 years; range, 25–78 years). A total of 36 patients underwent CT or MR imaging at baseline; 20 patients underwent follow-up. CT and MR images were reviewed and analysed in consensus by two radiologists for the various features of thoracic paravertebral lesions.

Results

All lesions were located around two or more thoracic vertebrae, particularly the lower thoracic vertebrae (n = 36). The right side of vertebrae was predominantly affected in all cases (n = 36). Radiologically, IgG4-related thoracic paravertebral lesions were categorized into three types: solitary or multiple saddle-like masses type (32 patients); multiple nodules type (three patients); and invasively irregular mass type (three patients). All the types showed soft-tissue density on CT images, isointense on T1- and T2-weighted images, and homogeneous enhancement with penetration of small arteries in the lesions on contrast-enhanced CT and MR images. Steroid therapy administered to 20 patients dramatically diminished the mean maximum thickness in 18 patients. One patient with T7-12 vertebrae involved improved after steroid therapy.

Conclusion

IgG4-related paravertebral lesions occur mainly around the right side of the lower thoracic vertebrae and manifest as three major patterns of CT and MR imaging findings. Recognition of these diagnostic features will assist in the diagnosis and treatment of IgG4-related disease.
Behavior science in the evolving world of digital health: considerations on anticipated opportunities and challenges
Authors: Sucala Madalina , Cole-Lewis Heather , Arigo Danielle , Oser Megan , Goldstein Stephanie , Hekler Eric B , Diefenbach Michael A
Published: April 2020

Digital health promises to increase intervention reach and effectiveness for a range of behavioral health outcomes. Behavioral scientists have a unique opportunity to infuse their expertise in all phases of a digital health intervention, from design to implementation. The aim of this study was to assess behavioral scientists’ interests and needs with respect to digital health endeavors, as well as gather expert insight into the role of behavioral science in the evolution of digital health. The study used a two-phased approach: (a) a survey of behavioral scientists’ current needs and interests with respect to digital health endeavors (n = 346); (b) a series of interviews with digital health stakeholders for their expert insight on the evolution of the health field (n = 15). In terms of current needs and interests, the large majority of surveyed behavioral scientists (77%) already participate in digital health projects, and from those who have not done so yet, the majority (65%) reported intending to do so in the future. In terms of the expected evolution of the digital health field, interviewed stakeholders anticipated a number of changes, from overall landscape changes through evolving models of reimbursement to more significant oversight and regulations. These findings provide a timely insight into behavioral scientists’ current needs, barriers, and attitudes toward the use of technology in health care and public health. Results might also highlight the areas where behavioral scientists can leverage their expertise to both enhance digital health’s potential to improve health, as well as to prevent the potential unintended consequences that can emerge from scaling the use of technology in health care.
Columnar growth phenotype in apple results from gibberellin deficiency by ectopic expression of a dioxygenase gene
Authors: Okada Kazuma , Wada Masato , Takebayashi Yumiko , Kojima Mikiko , Sakakibara Hitoshi , Nakayasu Masaru , Mizutani Masaharu , Nakajima Masatoshi , Moriya Shigeki , Shimizu Taku , Abe Kazuyuki
Published: April 2020

The apple cultivar McIntosh Wijcik, which is a mutant of ‘McIntosh’, exhibits a columnar growth phenotype (short internodes, few lateral branches, many spurs, etc.) that is controlled by a dominant Co gene. The candidate gene (MdDOX-Co), encoding a 2-oxoglutarate-dependent dioxygenase, is located adjacent to an insertion mutation. Non-columnar apples express MdDOX-Co in the roots, whereas columnar apples express MdDOX-Co in the aerial parts as well as in the roots. However, the function of MdDOX-Co remains unknown. Here, we characterized tobacco plants overexpressing MdDOX-Co. The tobacco plants showed the typical dwarf phenotype, which was restored by application of gibberellin A3 (GA3). Moreover, the dwarf tobacco plants had low concentrations of endogenous bioactive gibberellin A1 (GA1) and gibberellin A4 (GA4). Similarly, ‘McIntosh Wijcik’ contained low endogenous GA4 concentration and its dwarf traits (short main shoot and internodes) were partially reversed by GA3 application. These results indicate that MdDOX-Co is associated with bioactive GA deficiency. Interestingly, GA3 application to apple trees also resulted in an increased number of lateral branches and a decrease in flower bud number, indicating that gibberellin (GA) plays important roles in regulating apple tree architecture by affecting both lateral branch formation (vegetative growth) and flower bud formation (reproductive growth). We propose that a deficiency of bioactive GA by ectopic expression of MdDOX-Co in the aerial parts of columnar apples not only induces dwarf phenotypes but also inhibits lateral branch development and promotes flower bud formation, and assembly of these multiple phenotypes constructs the columnar tree form.
Identification and Characterization of Dual‐Acting Small Molecule Modulators targeting Secretin Receptors
Authors: Dengler Daniela G. , Sun Qing , Kaleeckal Harikumar G. , Beutel Jannis , Holleran John , Pollari Sirkku , Ma Chen-Ting , Miller Laurence J. , Sergienko Eduard
Published: April 2020

The Secretin receptor (SCTR) has been cloned as the first member of class B G protein‐coupled receptors (GPCRs)
, giving rise to this highly important group of therapeutic targets, which are crucial for hormonal homeostasis
. Despite the wide recognition of their functional importance, the development of potent small molecule ligands for Class B GPCRs remained challenging
. To date, no ligands other than secretin peptide and its close analogs are known to interact with SCTRs, despite its therapeutic relevance in multiple diseases, such as heart failure, obesity, diabetes and cancer
. In order to enhance our chances for discovering orally bioavailable drug candidates targeting an ‚undruggable’ class B GPCR, we focused our efforts on the identification of positive allosteric modulators (PAMs), which are likely to interact via structurally distinct binding sites and potentiate effects of native hormones and neurotransmitters
.

We developed a comprehensive tool box with robust high‐throughput screening and lead characterization/optimization assays capable of identifying and characterizing biologically relevant SCTR small molecule modulators. The dominant physiological coupling of SCTRs occurs via Gs proteins. Hence, we utilized this signaling mechanism to establish diverse cAMP accumulation assays suitable for simultaneous detection of PAMs modulating secretin and its potential metabolites. We also established a TR‐FRET based binding assay to further characterize potential PAMs with respect to their kinetic properties. Since functional selectivity has been proven to be therapeutically relevant for this family of membrane proteins, we additionally designed assays to investigate signaling mechanisms beyond Gs protein coupling, such as β‐arrestin recruitment, receptor internalization and calcium flux.

High‐throughput screening (HTS) of a 360,000 compound library provided promising sets of hits, which have been further investigated regarding their allosteric activity and mechanism of action. We identified three related scaffolds with significant PAM activity at SCTRs. Selectivity studies revealed that this specific set of compounds demonstrated positive modulation not only on SCTRs but also on GLP‐1Rs (glucagon‐like peptide 1 receptors). Interestingly, dual activation of SCTRs and GLP‐1Rs has been shown to be beneficial for appetite regulation and glucose homeostasis without having proliferative effects on exocrine or total pancreas mass
.

To conclude, HTS and the development of a diverse panel of binding and functional assays has led to the discovery of small molecules with a unique dual‐acting pharmacological profile and potential to serve as starting points for developing first‐in‐class drug candidates for the treatment of comorbid conditions obesity and diabetes.

Support or Funding Information

Funding: NHLBI award 5R01HL133501
Contemporary Treatment of Antimicrobial Resistant S. aureus, HCV and HIV infection: A Case Study.
Authors: Bassey Gertrude O. , Einstein George P , Tulp Orien Lee
Published: April 2020

The human body typically faces multiple threats of potentially infectious agents on a daily basis. As more advanced antimicrobial and antiviral agents are developed, the strains of microbes, bacteria and viruses all too often develop biochemical and immunologic strategies to survive and escape therapeutic eradication. The human immune system is generally designed to protect the body against virtually everything microscopic that may penetrate the body. The antibiotic/antimicrobial/antiviral therapies are not always as effective for patients with diabetes or other immunocompromised status.

MATERIALS AND METHODS

The integrated biophotonics method therapy was based on electron charge (“e”), and for each photon transition a probability may be obtained (biophotonic therapy, BioP). The Case Studies referenced above were conducted on infected patients with S. aureus, HIV or HVC in years 2001 – 2002 at the Einstein Clinical Laboratories in the Dominican Republic. After only 14 to 21 days of the BioP therapies the treatment was found to be highly effective in eliminating the infectious diseases, with both antibody levels and clinical evidence of continuing recovery from illness decreasing to nil. BioP therapy uses ultraviolet light, and is safe. All patients signed a medical treatment consent for the BioP treatments. The treatment was conducted in Einstein Clinical Laboratories S.A. The therapy was conducted by 7 to 10 episodes of auto‐transfusion of heparinized blood over the 14 ro 21 days of BioP treatment. In each treatment blood, from the patient was collected to a heparinized container from the vein of the upper arm in volume of 250 ml to 400 ml based on weight of the patients under sterile conditions. This blood was transmitted to the BioP apparatus and exposure to photonic quantum energy of UV light at 254 nm wavelength over a duration of 20 minutes. This blood was then returned to the patient from whom it had been obtained minutes earlier via a sterile closed circuit to the patient by auto‐transfusion. This procedure was repeated over 14 to 21 days. The macrobiotic diet, containing mixed grains, mixed vegetables and fruits was recommended to patient followed by Yoga as a complement to the BioP therapy.

RESULTS

The influence of controlled UV treatment of blood stimulates the immune system to activate cytokine induced expression of mRNA during pro‐inflammation for the HIV and HVC, and suggests a clear explanation about the decreasing of the inflammation that was observed after the photonic quantum energy BioP therapy.

Support or Funding Information

Support from University of Science Arts & Technology, Montserrat and the Einstein Medical Institute USA/ Einstein Clinical Laboratories SA.
Late embryonic skull anomalies in mice carrying the Fgfr2 W290R Crouzon mutation
Authors: Pitirri M. Kathleen , Motch Perrine Susan M. , Takenaka Risa , Marcucio Ralph , Richtsmeier Joan
Published: April 2020

FGFR2 has two major isoforms, IIIb and IIIc, generated through alternative splicing with their own temporal, spatial, and ligand‐binding specificities. Dysregulated signaling of both IIIb and IIIc isoforms of Fgfr2 contribute to the phenotypic changes seen in Crouzon patients carrying the W290R mutation. Previous postnatal studies of mice carrying a Fgfr2W290R/+ mutation have shown that heterozygote mutant mice were similar in shape at birth to their unaffected littermates but presented with dome shaped skulls, shortened snouts, and variable nasal‐septal defects leading to relatively decreased anterior‐posterior skull lengths by 8 weeks of age. In this study, we acquired microCT images of the heads of Fgfr2+/W290R mice at embryonic day 17.5 (E17.5). Using a calcium hydroxyapatite phantom, we used a threshold for bone (80 mg/cm3), and landmarked the skulls of the nine Fgfr2+/W290R and nine Fgfr2+/+ specimens in Avizo 9.4. Euclidean Distance Matrix Analysis (EDMA) and Principal Components Analysis (PCA) were performed to identify and statistically test for morphological differences between these groups. PCA results indicate a phenotypic separation of unaffected and mutant individuals, while EMDA results specify the localized differences responsible for group separation. This analysis shows that relative to Fgfr2+/+ specimens, Fgfr2+/W290R specimens present with a more rounded, domed vault with the largest magnitude differences at the most posterior aspect of the head. Additionally, at E17.5, no reduction in snout length was noted in Fgfr2+/W290R mice. Our results indicate the initiation of craniofacial dysmorphology by E17.5 in Fgfr2+/W290R mice, with the vault being most affected.

Support or Funding Information

R01‐DE019638, R01‐DE018234, R01‐DE022988; R01 DE027677, P01 HD078233
Biological Functions for STARD5 Assessed Using stard5−/− Mice
Authors: Clark Barbara J. , Khundmiri Syed J. , Lederer Eleanor D. , Gregg Ronald G. , Cheng Alan
Published: April 2020

STARD5 belongs to the StAR‐Related Lipid‐transfer (START) domain protein superfamily and is proposed to contribute to intracellular non‐vesicular cholesterol transport. STARD5 is a soluble sterol‐binding protein that is induced by endoplasmic reticulum (ER) stress, yet testing for a biological function needs to consider the conflicting data on whether the preferred ligand for STARD5 is cholesterol and 25‐hydroxycholesterol or bile acids, including chenodeoxycholic acid (CDCA). Our work has characterized STARD5 expression in kidney and we reported that STARD5 and cholesterol levels are increased in kidneys of the OVE diabetic mouse model compare to wild‐type controls, and that STARD5 is increased in cell culture by the ER stress inducer tunicamycin. Cholesterol accumulation in the ER is known to promote ER stress; however, the significance of the association between elevated renal cholesterol, ER stress, and STARD5 in diabetic kidney remains to be determined. We propose STARD5 indirectly controls cholesterol homeostasis via modulating farnesoid X receptor (FXR) activity. FXR is a nuclear receptor that binds CDCA and activation of FXR contributes to maintaining fatty acid and cholesterol homeostasis in diabetic kidney disease. To test whether STARD5 affects FXR signaling we generated whole body STARD5 knock‐out mice (stard5−/−) using CRISPR‐Cas9 and compared the FXR target gene expression in the knockout and WT kidney. There was no difference in body weight, liver weight/body weight ratio, or kidney weight/body weight ratio between stard5−/− mice compared to wild‐type littermate controls (WT) (male mice n = 5 WT; n= 7 stard5−/−). We will present data from current studies focused on determining whether there are differences in tissue histology, lipid accumulation, and FXR target gene expression between stard5−/− mice and WT littermate controls.

Support or Funding Information

Biochemistry & Molecular Genetics Departmental Funds to BJC
From Arabidopsis to crops: a molecular tool to increase protein content and broad disease resistance
Authors: Li Ling
Published: April 2020

Crop plants must integrate signals from the environment and prioritize responses to stresses that may occur individually or simultaneously throughout the growing season. Stress responses can adversely affect plant growth and quality traits such as protein and starch. The ability to optimize protein productivity of plant‐based foods has far‐ranging impact on world health and sustainability. Plant diseases each year cause major losses to crop production. The Arabidopsis thaliana QQS (Qua Quine Starch) orphan gene modulates carbon allocation to protein and starch
1. Ectopic QQS expression increases protein content
2 in leaf and seed in soybean, in corn and rice
3,
4. QQS transcript levels are altered in plants under stresses and in mutants of genes involved in all sorts of stress responses, indicating that QQS may integrate primary metabolism with environmental perturbations, thus adjusting the plant’s adaption to abiotic and biotic stresses
5. The QQS protein binds to a transcriptional regulator in Arabidopsis and its homologs in crops: Nuclear Factor Y subunit C4 (NF‐YC4). NF‐YC4 overexpression mimics QQS‐overexpression phenotype
4. Mutants overexpressing QQS or NF‐YC4 have significantly increased resistance to plant pathogens and pests
6,
7. We are developing a non‐transgenic strategy to create high‐protein crops and enhance broad‐spectrum disease resistance
6. Transcriptomics analyses enable new discovery to advance basic research and application in crops.

Support or Funding Information

1) Iowa Soybean Association: Non‐transgenic soybeans with broad plant disease resistance and high protein. 2) National Science Foundation MCB #0951170: Uncovering novel signaling interactions in plant metabolic networks. 3) United Soybean Board: High‐protein soybeans.
The Effect of Multiple Antenatal Courses of Corticosteroids on Neonatal Growth and Development Until Six Months
Authors: Maryam Kaveh B , Baghbahadorani Fahimeh Kaveh , Bostan Atefeh , Dehkordi Ali Hassanpour , Sedehi Morteza
Published: April 2020

PURPOSE

Preterm birth is associated with multiple complications, such as respiratory distress syndrome, intracranial hemorrhage, and arterial duct openness, resulting in high mortality in preterm infants. This study aimed to evaluate the effect of multiple antenatal courses of corticosteroids on neonatal growth and development until six months.

Methods

In our retrospective study, the history of corticosteroid exposure was extracted from the maternal medical record and history of the drug prescription. Based on the antenatal corticosteroids exposure, newborns were assigned into the first group (i. e., no exposure or exposure to a single dose of corticosteroid), the second group (exposure to one course of corticosteroid therapy), and the third group (i. e., exposure to more than one course of corticosteroid therapy). The newborn characteristics at birth and duration of hospitalization were recorded in each group. After discharge, weight, height, and head circumference were determined at two months intervals for six months. Neonatal evolution and ability were also studied based on the Milestones checklist. Data were analyzed by t‐test and expressed as Mean ± SD.

Results

There were no significant differences in the mean birth weight and Apgar scores at minutes 1 and 5 among groups (p > 0.05). Besides, mean weight, head circumference, and height at months 2, 4, and 6 were not significantly different among the studied groups (p > 0.05). The mean score of the Milestones checklist, including motion, language, activity, and social‐emotional scores, did not differ significantly between the study groups at months 2, 4, and 6 (p > 0.05). The duration of hospitalization was not significantly different among the studied groups (p > 0.05). However, the mean duration of hospitalization in the first group (9.67 days) was more than those in the second and third groups (7.05 and 6.35 days).

Conclusion

Treatment with repeated doses of corticosteroids reduced the duration of hospitalization; however, it did not significantly affect the growth and abilities of newborns.
Constructing Physical 3D Models Enhances Comprehension of Anatomical Concepts in Allopathic Medical Students: A Pilot Study
Authors: Cannell Ruslana M. , Saied Arman , Kirshman Nathalie , Panchal Dhruvi D. , Vu Baoanh , Hassan Sherif S.
Published: April 2020

Background

Studies have shown that the use of physical 3D anatomy models enhance understanding of complex anatomical structures.
1 However, these studies have been limited to specific medical and veterinary schools. This study examines whether creating physical 3D anatomy models will also provide learning enhancements to allopathic medical students at California University of Science and Medicine (CUSM) taking anatomy courses to diversify pre‐existing data.

Methods

First and second year allopathic medical students constructed physical 3D anatomy models during art workshops at the CUSM in San Bernardino, CA. Art workshops were held one to two times per course block. During the workshops, participants built physical 3D models that were relevant to the material that was being studied during the respective medical school block. At the end of workshops, participants completed a survey that asked about their learning style and how the workshops affected their understanding of the given anatomy topic. The learning styles are defined as: visual ‐‐ learn best by producing graphs, flow charts, and diagrams, aural ‐‐ learn best by listening, read/write ‐‐ learn best by reading printed words, and kinesthetic ‐‐ learn best through “multisensory learning experiences” by applying information using most of their senses.
2

Results

The majority of participants (87.5%) reported that building the physical 3D anatomy models enhanced their understanding of the associated anatomy concept. One participant reported their understanding of the anatomy concept remained unchanged. 87.5% of participants stated having a visual learning style as opposed to a read/write (25%), aural (12.5%), or kinesthetic (12.5%) learning styles
2. The discrepancy in percentages is due to students selecting multiple learning styles.

Conclusion

Our initial study shows promising results that constructing physical 3D anatomy models can enrich allopathic medical student’s learning of related anatomy concepts. Furthermore, our study revealed that the majority of participants preferred visual learning techniques which could play a role in the increased comprehension of anatomy concepts from building 3D models. In future studies, we will survey participants to gauge for depth of understanding of anatomical concepts, other than the participants’ perceived understanding. In addition, we will evaluate if specific learning styles affect the ability for allopathic medical students to grasp anatomical concepts following assembly of physical 3D models.
Roles of Mediator subunit MED26 in Regulation of Post‐initiation Events in RNA Pol II Transcription
Authors: Ranjan Amol , Chen Shiyuan , Goode Zach , Sato Shigeo , Sato Chieri , Takahashi Hidehisa , Conaway Ronald , Conaway Joan W.
Published: April 2020

Mediator is a conserved multi‐protein complex that transduces regulatory signals from gene‐specific transcription factors to RNA polymerase II and its regulatory factors to control transcription. Mediator subunit MED26 has been implicated in control of post‐initiation steps in transcription. Its N‐terminal domain binds two types of complexes containing elongation factor ELL, the Little Elongation Complexes (LECs) and Super Elongation Complexes (SECs) (
Takahashi et al., 2011). MED26 regulates expression of non‐polyadenylated snRNA genes, at least in part by recruiting LECs (
Takahashi et al., 2015). In assays using PRO‐seq to measure the location of transcribing Pol II in MED26 mutant cells, we observed an increase in mapped reads extending past the normal transcription termination sites of LEC regulated snRNA genes as well as genes encoding replication‐dependent histone transcripts, which, like snRNAs, are not polyadenylated (
Takahashi, Ranjan, et al., 2020). These observations suggest a new role for MED26‐containing Mediator in control of 3′‐end processing and transcription termination at these genes.

MED26‐containing Mediator also helps recruit SECs to c‐myc and several other protein coding genes to regulate phosphorylation of the Rpb1 CTD and, most likely, transcription elongation (
Takahashi et al., 2011); however, whether MED26 contributes to these processes globally is unknown. In this study, we used genome‐wide approaches to examine the consequences of MED26 mutation in regulation of post‐initiation events including CTD phosphorylation and elongation, assessed by measuring the distribution of transcriptionally active Pol II across gene bodies. We observed that MED26 mutation alters Pol II distribution and reduces CTD Ser2 phosphorylation (Ser2P) at many protein‐coding genes, mostly towards their 3′‐ends. Moreover, MED26 mutation is associated with a remarkable shift of Ser2P towards 5′‐ends at many protein‐coding genes. Notably, 5′‐enrichment of Ser2P in MED26 mutant cells appeared independent of changes in gene expression. We hypothesize that because of a defect in Mediator’s ability to recruit elongation complexes, MED26 mutation could generally slow Pol II elongation and trigger premature termination.

Support or Funding Information

This research was supported by the Stowers Institute for Medical Research and the Helen Nelson Medical Research Fund of the Greater Kansas City Community Foundation