bluuebunny/crossref_metadata_2025 huggingface dataset:
The Long Winter of 1880/81
Authors: Boustead Barbara Mayes , Shulski Martha D. , Hilberg Steven D.
Published: December 2019

The story of the winter of 1880/81 in the central United States has been retold in historical fiction, including Laura Ingalls Wilder’s The Long Winter, as well as in local histories and folklore. What story does the meteorological data tell, and how does it measure up when compared to the fiction and folklore? What were the contributing factors to the severity of the Long Winter, and has it been or could it be repeated? Examining historical and meteorological data, reconstructions, and reanalysis, including the Accumulated Winter Season Severity Index, the Long Winter emerges as one of the most severe since European-descended settlers arrived to the central United States and began documenting weather. Contributing factors to its severity include an extremely negative North Atlantic Oscillation pattern, a mild to moderate El Niño, and a background climate state that was much colder than the twentieth-century average. The winter began early and was particularly cold and snowy throughout its duration, with a sudden spring melt that caused subsequent record-setting flooding. Historical accounts of the winter, including The Long Winter, prove to be largely accurate in describing its severity, as well as its impacts on transportation, fuel availability, food supplies, and human and livestock health. Being just one of the most severe winters on record, there are others in the modern historical record that do compare in severity, providing opportunity for comparing and contrasting the impacts of similarly severe winters.
Competitiveness of Otolaryngology Residency Applicants without a Home Program
Authors: Wang James C. , Pillutla Pranati , Tello Nadia , Gabrilska Rebecca , Aranke Mayank , Bibb Terrell , Watkins Philip D. , Cordero Joehassin
Published: December 2019

Purpose:

Investigate if otolaryngology residency home programs (HP) are associated with advantages in National Resident Matching Program match compared to applicants without HPs.

Methods:

Surveys were distributed to fourth-year medical students applying to otolaryngology residency (2015-2016 cycle) via OHNS (2015-2016) Applicants Closed Facebook Page and Otomatch. Applicant data analyzed included HP, United States Medical Licensing Examination (USMLE) scores, number of away rotations, and matching at top choice.

Results:

Applicants were grouped: (1) HP, (2) no HP but have ENT staff (staff), and (3) no HP or staff (none). Ninety-five percent of survey participants matched into otolaryngology (n = 62). A sub-analysis of match preference among matching applicants revealed 63% of participants with HP matched to their first choice compared to 56% (staff) and 14% (none) ( P = .058). Match rate between those with any staff (HP or staff) versus those without was statistically significant ( P = .037). Applicants without HPs went on more away rotations than students with HPs (mean: 2.5 ± 0.5 vs 1.7 ± 0.07, P = .0002). No statistical significance was seen between applicants with/without HP in regards to USMLE scores, publications, or number of interviews.

Conclusion:

Applicants applying to otolaryngology residency without HPs are as competitive as those who have HPs. However, without HPs, applicants tend to participate in more away rotations and are less likely to match at their top choice.
Lithium vs valproate in the maintenance treatment of bipolar I disorder: A post- hoc analysis of a randomized double-blind placebo-controlled trial
Authors: Kang Mehar G , Qian Hong , Keramatian Kamyar , Chakrabarty Trisha , Saraf Gayatri , Lam Raymond W , Wong Hubert , Yatham Lakshmi N
Published: December 2019

Objective:

Lithium and valproate are commonly used either in monotherapy or in combination with atypical antipsychotics in maintenance treatment of bipolar I disorder; however, their comparative efficacy is not well understood. This study aimed to compare the efficacy of valproate and lithium on mood stability either in monotherapy or in combination with atypical antipsychotics.

Methods:

We performed a post hoc analysis using data from a 52-week randomized double-blind, placebo-controlled trial, that recruited 159 patients with recently remitted mania during treatment with lithium or valproate and adjunctive atypical antipsychotic therapy. Patients were randomized to discontinue adjunctive atypical antipsychotic at 0, 24 or 52 weeks.

Results:

No significant differences in efficacy were observed between valproate and lithium (hazard ratio: 0.99; 95% confidence interval: [0.66, 1.48]) in time to any mood event. Valproate with 24 weeks of atypical antipsychotic was significantly superior to valproate monotherapy in preventing any mood relapse (hazard ratio: 0.46; 95% confidence interval: [0.22, 0.97]) while lithium with 24 weeks of atypical antipsychotic was superior to lithium monotherapy in preventing mania (hazard ratio: 0.27; 95% confidence interval: [0.09, 0.85]) but not depression.

Conclusion:

Overall, this study did not find significant differences in efficacy between the two mood-stabilizing agents when used as monotherapy or in combination with atypical antipsychotics. However, study design and small sample size might have precluded from detecting an effect if true difference in efficacy existed. Further head-to-head investigations with stratified designs are needed to evaluate maintenance therapies.
‘No One . . . Saves Black Girls’: Black University Women’s Understanding of Sexual Violence
Authors: Zounlome Nelson O. O. , Wong Y. Joel , Klann Elyssa M. , David Jessica L. , Stephens Nat J.
Published: December 2019

Although research has found that sexual violence is a serious issue on college campuses, the lack of diversity in previous samples calls into question the findings’ generalizability to non-White populations. Consequently, little is known about how Students of Color conceptualize sexual violence. Using an intersectional and phenomenological approach, we examined how Black/African American university women understand sexual violence, as well as their perceptions of cultural barriers to help-seeking and reporting this violence. Seven themes emerged: (a) Historical Legacy of Racialized Trauma Against Black Women, (b) Stereotypes of Hypersexualized Black Women, (c) Silence and Community Protection, (d) Duality of Black Spirituality and/or Religiosity, (e) Racial Injustice and Systemic Barriers to Help-Seeking and Reporting, (f) Stereotypes of Strong Black Women, and (g) Grassroots Healing and Empowerment of Black Communities. We provide recommendations for counselors and university staff to develop culturally grounded campus prevention initiatives for Black women.
Diasporic still life: Midnight at the Dragon Café and the cultural politics of stasis
Authors: August Timothy K
Published: December 2019

This article revisits and reevaluates the role that “stasis” can play as a literary technique in diasporic Chinese Canadian writing. To these ends I read Chinese Canadian author Judy Fong Bates’s debut novel Midnight at the Dragon Café (2005) as an important and intimate map of the social geography of a small Canadian town that illuminates how diasporic Chinese life is both constructed and constricted by the institution of the Chinese restaurant. I propose that having a narrative of restaurant life that centres around Chinese Canadian waiters and cooks exposes how socioeconomic institutions reproduce dominant social relations by limiting movement and representational possibilities for immigrant populations.

In the book, sedentariness is presented alongside the social and political institutions that generate these diasporic subjects, which, I argue, creates a scene of stasis — where diasporic subjects work to achieve an equilibrium between competing cultural regimes. Bates’s book is remarkable insofar as it maps the unevenness brought on by diasporic globality but in a very "fastened" way — showing how the characters’ global outlooks are shrunk and slowly withered away by the small-town space. This article considers, then, what writing about diasporic stasis achieves in an age that is often characterized by global mobility.
Global Migration, Local Communities and the Absent State: Resentment and Resignation on the Italian Island of Lampedusa
Authors: Franceschelli Michela
Published: December 2019

This article draws on the case of the Italian island of Lampedusa to explore how global migration nurtures populist discourses at the local community level. Lampedusa, a key transitory site for migrants crossing the Mediterranean Sea to reach Europe, revealed strong concerns about the neglect of local public services and the mismanagement of migration. These concerns fed a deep sense of resentment that the islanders addressed toward the Italian state, resonating with the experiences of other communities around the world and reifying populist ideas. Based on interviews and ethnographic fieldwork, and disseminated by a film documentary, the article reveals how apparently similar global populist experiences disclose different local worries and long-term historical processes. In doing so, it unfolds the socially situated nature of Lampedusa’s populist resentment and so it contributes to a more thorough understanding of the relation between local communities and the national state as it is being reflected through debates on migration.
Price adjustment in the London housing market
Authors: Webb Robert , Watson Duncan , Cook Steven
Published: December 2019

Recent research into the dynamic adjustment of prices within the London housing market is extended via the application of a novel two-step procedure. Combining the non-parametric analysis of the ranking distributions of the levels and changes in house prices with the application of a cross-sectional convergence technique results in the detection of a three-tier system in which highly significant convergence clubs are identified within borough-level data. These findings contrast with both the divergence apparent when considering all boroughs and the failure of previous research to identify convergent groupings. The novelty of the empirical methods is supplemented by a discussion of various theoretical factors such as gentrification, displaced demand, immigration, foreign investment and criminal activity in relation to the findings obtained.
Renewable energy, sustainability paradox and the post-urban question
Authors: Arabindoo Pushpa
Published: December 2019

Amidst the hype of a ‘new’ energy regime in India with a singular focus on renewable energy, this paper offers a more scrupulous reading of renewables to set up a critical energy discourse. It offers a three-part analysis where it begins by questioning the entrenched idea of ‘renewables as science’ and its instrumental use of metrics and measurements to convey an unbelievable reach and significance. Highlighting the consistent invocation of a calculative ethos, it shows how an ‘empirics of targets’ relying largely on the lure and lore of a single numeric, installed capacity, is persuasively employed to gloss over the crucial distinction between the potential and reality of renewables. An associated consequence is not only its pegging to the speculative value of market-based energy production but also that it remains rooted in the assumptions of an existing system, that is, the logic of a carbon lifeworld. Renewables, as a result, display the tell-tale sign of a sustainability paradox, raising questions about their ability to master a transition to a post-fossil performativity, exasperated as they are by internal contradictions embedded within their core characteristics – efficiency/sufficiency and, more importantly, tensions between utilities and infrastructure. With loose connections to parallel initiatives such as the Smart Cities Mission, the transformative potential of renewables is undercut as it remains embedded within an abstract grid imaginary, challenging any effort to actualise it in and through the urban.
Moderating Role of Emotional Intelligence on Personality– Employee Creativity Relationship
Authors: Jafri Md. Hassan
Published: December 2019

Creativity has gained increased significance by organizations in current time. Both individual and organizational factors contribute to it. This study explored the relationship between the Five Factor Model (FFM) of personality and employee creativity. Emotional intelligence (EI) is presented as a moderator in the relationship between the FFM and employee creativity. Using random sampling approach, the study was conducted on 232 regular employees from three service sector organizations. Respondents consisted of both genders working at different levels. Regression analyses showed that three dimensions of the model (FFM), namely, conscientiousness, extraversion and openness to experience influenced employee creativity positively and significantly. In addition, moderated regression analysis revealed that EI significantly strengthened the relationships between the three dimensions of the FFM and creativity of employees. The insinuations of the study are explained.
Moseley’s “Macro-Monetary” Reading of Capital: Rejoinder and Further Discussion
Authors: Skillman Gilbert L.
Published: December 2019

Moseley (2018) offers a partial reply to my review of his Money and Totality, addressing one comment at length while mentioning a second in passing and ignoring the third. In this rejoinder, I respond to his replies and develop the three main arguments of my review in greater detail, with particular focus on the logical consistency of Moseley’s “algebraic summary” of his macro-monetary reading of Marx’s transformation analysis.
On the Ambivalence of the Aphorism in Sociological Theory
Authors: Crosbie Thomas , Guhin Jeffrey
Published: December 2019

Sociologists have long been taken by certain pithy expressions from the founders of the discipline. We propose here both a new explanation for the endurance of these statements as well as an analysis of the power, limitations, and possibilities of aphorisms. By drawing from the critical scholarship concerned with aphorisms, we demonstrate that some of the allure of the classical sociological texts derives from their form, and particularly their reliance on the relative autonomy of the aphorism. Through examining Marx’s “opiate of the people,” Weber’s “iron cage,” and, briefly, two more contemporary sociological aphorisms, we suggest that aphorisms have an ambivalent role in sociological theory: they make claims memorable even as they potentially oversimplify complex arguments. Yet that very simplification can provide a point of focus for productive misreading and reinterpretation.
Is Religious Liberty under Threat? An Introduction to the Symposium
Authors: Anderson Matthew Lee
Published: December 2019

This introduction surveys the contributions to this issue, which were originally delivered at Oxford University in 2018. By exploring the interconnections and shared motifs, this article suggests that the answer to this symposium is a tentative ‘yes’, but that the sources of those threats arise from the background culture within which these papers are situated.
The dual causes of fragmentation: Democratic security and the communitarian state in Colombian politics
Authors: Pardo Neyla G
Published: December 2019

This chapter analyzes speeches delivered by former Colombian President, Álvaro Uribe Vélez, between August 2002 and August 2009, which can be found on the official website of the presidency: ( http://web.presidencia.gov.co/discursos/ ). We attempt to identify the webs of meaning surrounding the concepts of ‘Democratic Security’ and ‘Communitarian State’ with awareness of the relationship between discourse, ideology and power. The aim is to better understand the political power of the plans, programs and projects developed by Uribe’s administration, and how this was affected by widespread deployment of the media. These policies are conditioned by a set of colonialist principles that are embodied in symbolic-discursive strategies that result in representations, by means of which mechanisms of marginalization, discrimination and polarized hierarchy are legitimized from the different social spheres. During the 7-year period analyzed there were controversial debates over the commission of crimes against humanity by national security agents, as well as corruption scandals over topics like ‘para-politics’, ‘false positives’, selective arrests, extrajudicial killings and violations of the sovereignty of bordering countries. Within this political context, we attempt to identify the inherent tensions and social conflicts. It is argued that the analyzed discourses reproduce colonialist thoughts, in relation to neoliberal principles and the application of global policies. Using the principles of Critical Discourse Analysis (CDA), we explore the strategies and resources used in Uribe’s speeches and how major themes are positioned to reproduce systems of beliefs, values and attitudes.
Cancer Hazard Identification Integrating Human Variability: The Case of Coumarin
Authors: Hsieh ChingYi Jennifer , Sun Meng , Osborne Gwendolyn , Ricker Karin , Tsai Feng C. , Li Kate , Tomar Rajpal , Phuong Jimmy , Schmitz Rose , Sandy Martha S.
Published: December 2019

Coumarin is a naturally occurring sweet-smelling benzopyrone that may be extracted from plants or synthesized for commercial uses. Its uses include as a flavoring agent, fragrance enhancer, and odor-masking additive. We reviewed and evaluated the scientific evidence on the carcinogenicity of coumarin, integrating information from carcinogenicity studies in animals with mechanistic and other relevant data, including data from toxicogenomic, genotoxicity, and metabolism studies, and studies of human variability of a key enzyme, CYP2A6. Increases in tumors were observed in multiple studies in rats and mice in multiple tissues. Our functional pathway analysis identified several common cancer-related biological processes/pathways affected by coumarin in rat liver following in vivo exposure and in human primary hepatocytes exposed in vitro. When coumarin 7-hydroxylation by CYP2A6 is compromised, this can lead to a shift in metabolism to the 3,4-epoxidation pathway and increased generation of electrophilic metabolites. Mechanistic data align with 3 key characteristics of carcinogens, namely formation of electrophilic metabolites, genotoxicity, and induction of oxidative stress. Considerations of metabolism, human variability in CYP2A6 activity, and coumarin hepatotoxicity in susceptible individuals provide additional support for carcinogenicity concern. Our analysis illustrates the importance of integrating information on human variability in the cancer hazard identification process.
Pathological findings in central nervous system demyelination associated with infliximab
Authors: Kalinowska-Lyszczarz Alicja , Fereidan-Esfahani Mahboobeh , Guo Yong , Lucchinetti Claudia F , Tobin W Oliver
Published: December 2019

Background:

Tumor necrosis factor alpha (TNF-alpha) inhibitors, such as infliximab, are commonly used to treat rheumatoid arthritis (RA) and other immune-mediated disorders.

Objective:

To determine whether infliximab-associated central nervous system (CNS) demyelination can be differentiated from multiple sclerosis (MS).

Methods:

We present a case of pathologically proven CNS demyelination in a patient treated with infliximab and describe clinical–radiographic–neuropathological findings. Putative mechanisms of TNF-alpha inhibitor-associated CNS demyelination are described.

Results and conclusion:

Infliximab treatment is associated with CNS inflammatory demyelinating activity, which is histopathologically indistinguishable from MS.
Dubai’s Private K-12 Education Sector: In Search of Bilingual Education
Authors: Azzam Ziad
Published: December 2019

United Arab Emirates nationals (‘Emiratis’) constitute less than 10% of the resident population of Dubai. Despite having access to free education in the public sector, where Arabic is the medium of instruction, more Emirati families in Dubai choose to enrol their children in private schools (specifically English-medium schools) than public ones, believing that they offer better teaching and learning, better English instruction, and better school leadership. There is growing concern among policy makers and Emirati parents that young Emiratis are in danger of becoming detached from their national language and culture. The regulatory authority for private schools, the Knowledge and Human Development Authority (KHDA), is encouraging the private sector to explore bilingual educational models. This study seeks to establish the type of Arabic-English bilingual educational model that would suit the needs of Emirati families, and to explore the circumstances in which it can take root in Dubai’s private K-12 sector. The design follows a mixed methods sequential two-phased design utilising multiple sources of data generated through: written essays by a sample of 12 Emirati students selected from two schools (the qualitative phase), and a questionnaire directed at a broader set of Emirati students (the quantitative phase). Findings suggest a model built on four core principles: (1) explicit mention of bilingualism as a stated goal; (2) the use of both Arabic and English as mediums of instruction, with subjects divided more or less equally between them; (3) the deployment of first language Arabic and English teachers in equal measure or, alternatively, the utilisation of bilingual teachers; and (4) the promotion and use of Arabic in everyday tasks, both at home and in school. The findings also advocate that the model could assume any of multiple variants of Baker’s (2011) four strong bilingual types: immersion, maintenance, dual language, or mainstream. To bring the model to fruition the government of Dubai should consider investing in the initial training and retraining of Emirati teachers with the end goal that these teachers should populate Dubai’s Arabic-English bilingual schools, while also partially funding scholarship programmes that would encourage Emirati parents to select bilingual schools over other types.
Explaining the College Choice Decisions of International Students at a Regional University in the United States
Authors: Van Alebeek Wouter , Wilson Kristin Bailey
Published: December 2019

Numerous institutions list hosting and recruiting international students as an important aspect of their internationalization mission. Reasons include the financial benefit to the institution and the local economy; job creation; recruitment of high-quality graduate assistants; increased diversity in the classroom and on campus; and creating international partnerships. However, new changes to immigration laws in the USA have had a negative impact on international college student enrollment. The purpose of this case study is to integrate the Hossler and Gallagher (1987) three-phase model of college student choice with the push and pull factors relating to how international students choose US colleges, to arrive at a descriptive understanding of how international students make their college choice decision.
Optical mapping of electromechanics in intact organs
Authors: Nesmith Haley W , Zhang Hanyu , Rogers Jack M
Published: December 2019

Optical mapping has become a widely used and important method in cardiac electrophysiology. The method typically uses voltage-sensitive fluorescent dyes and high-speed cameras to image propagation of electrical waves. However, signals are highly susceptible to artifact caused by motion of the target organ. Consequently, cardiac optical mapping is traditionally performed in isolated, perfused organs whose contraction has been pharmacologically arrested. This has prevented optical mapping from being used to study interactions between electrical and mechanical motion. However, recently, a number of groups have developed methods to implement cardiac optical mapping in the presence of motion. These methods employ two basic strategies: (1) compensate for motion by measuring it or (2) ratiometry. In ratiometry, two signals are recorded from each site. The signals have differing sensitivity to membrane potential, but common motion artifact, which can be cancelled by taking the ratio of the two signals. Some methods use both of these strategies. Methods that measure motion have the additional advantage that this information can be used to quantify the organ’s mechanical function. Doing so enables combined “electromechanical mapping,” which allows optical study of electromechanical interactions. By allowing recording in the presence of motion, the new methods open the door to optical recording in in-vivo preparations. In addition, it is possible to implement electromechanical optical mapping techniques in organ systems other than the heart. For example, it was recently shown that optical mapping of slow wave propagation in the swine stomach is feasible. Such studies have the potential to uncover new information on the role of dysrhythmic slow wave propagation in gastric motility disorders.

Impact statement

Electrical and mechanical functions in the heart are bidirectionally coupled, yet are usually studied separately because of the different instrumentation technologies that are used in the two areas. Optical mapping is a powerful and widespread tool for imaging electrical propagation, but has traditionally required mechanical function to be arrested. Recently new methods have been devised that enable optical mapping to be performed in beating hearts and also to simultaneously quantify mechanical function. These new technologies promise to yield new information about electromechanical interactions in normal and pathological settings. They are also beginning to find application in other organ systems such as the gastrointestinal tract where they may provide new insight into motility disorders.
Intersections in Subaltern Urbanism: The narratives of women in urban occupations in Brazil
Authors: Cruz Mariana de Moura , Silva Natália Alves da
Published: December 2019

In the past decade in Brazil, we have witnessed the rise of a new subaltern space, which has prompted a new theoretical category, incorporated in the contemporary epistemologies of Subaltern Urbanism: Urban Occupations. These new terrains of livelihood and self-organization have prompted a series of new resistance strategies, everyday practices and narratives that must be understood and decodified. The Metropolitan Region of Belo Horizonte—third largest in the country—accounts for over 25 housing occupations in its territory, more than half of which settled in the last five years. Occupation Rosa Leão, established in 2013, is one of them. As it happens in many other occupations, most of its dwellers are black women. They constitute majority in the coordination groups and are often more closely involved in the collective necessities of the community. The present article draws upon the experiences of these women as subjects of their own history to showcase urban occupation as a powerful place for understanding and dismantling the always existing but often overlooked intersection between coloniality and gender. It relies on the activist and academic engagement of both authors in these territories, and specifically in the experience with a women-only self-construction workshop organized in October 2017. Through this workshop, we sought to understand how “usually male” construction knowledge was employed (or not) by women, how it could be used as a tool for domination/emancipation and how gender relations intertwined with such issues in the process.
The friction and wear properties of RGO/3Y-TZP composites under dry sliding
Authors: Liu Liqi , Shi Lei , Guo Xiaofeng , Li Aijun , Zhang Fangzhou
Published: December 2019

The graphene oxide (GO)/yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) composites were fabricated by impregnating the GO dispersion into the zirconium oxide ceramic and sintered by microwave method. The wear and friction properties of the composites were tested by pan-on-disk method, and the results showed that the coefficient of friction and the wear rate decreased and the wear rate of silicon carbide ball was nearly similar with the increase of GO volume fraction. The microstructure of wear surface of the reduced graphene oxide (RGO)/3Y-TZP composite and the 3Y-TZP were investigated by using scanning electron microscopy, respectively. It was indicated that plastic deformation was occurred and the carbon-rich tribofilm was formed in the RGO/3Y-TZP composite, and the tribofilm of the RGO/3Y-TZP composite showed better wear performance than the 3Y-TZP.
Deconvoluting the diversity of within-host pathogen strains in a multi-locus sequence typing framework
Authors: Gan Guo Liang , Willie Elijah , Chauve Cedric , Chindelevitch Leonid
Published: December 2019

Background

Bacterial pathogens exhibit an impressive amount of genomic diversity. This diversity can be informative of evolutionary adaptations, host-pathogen interactions, and disease transmission patterns. However, capturing this diversity directly from biological samples is challenging.

Results

We introduce a framework for understanding the within-host diversity of a pathogen using multi-locus sequence types (MLST) from whole-genome sequencing (WGS) data. Our approach consists of two stages. First we process each sample individually by assigning it, for each locus in the MLST scheme, a set of alleles and a proportion for each allele. Next, we associate to each sample a set of strain types using the alleles and the strain proportions obtained in the first step. We achieve this by using the smallest possible number of previously unobserved strains across all samples, while using those unobserved strains which are as close to the observed ones as possible, at the same time respecting the allele proportions as closely as possible. We solve both problems using mixed integer linear programming (MILP). Our method performs accurately on simulated data and generates results on a real data set of Borrelia burgdorferi genomes suggesting a high level of diversity for this pathogen.

Conclusions

Our approach can apply to any bacterial pathogen with an MLST scheme, even though we developed it with Borrelia burgdorferi, the etiological agent of Lyme disease, in mind. Our work paves the way for robust strain typing in the presence of within-host heterogeneity, overcoming an essential challenge currently not addressed by any existing methodology for pathogen genomics.
ShiF acts as an auxiliary factor of aerobactin secretion in meningitis Escherichia coli strain S88
Authors: Genuini Mathieu , Bidet Philippe , Benoist Jean-François , Schlemmer Dimitri , Lemaitre Chloé , Birgy André , Bonacorsi Stéphane
Published: December 2019

Background

The neonatal meningitis E. coli (NMEC) strain S88 carries a ColV plasmid named pS88 which is involved in meningeal virulence. Transcriptional analysis of pS88 in human serum revealed a strong upregulation of an ORF of unknown function: shiF, which is adjacent to the operon encoding the siderophore aerobactin. The aim of this work is to investigate the role of shiF in aerobactin production in strain S88.

Results

Study of the prevalence of shiF and aerobactin operon in a collection of 100 extra-intestinal pathogenic E. coli strains (ExPEC) and 50 whole genome-sequenced E. coli strains revealed the colocalization of these two genes for 98% of the aerobactin positive strains. We used Datsenko and Wanner’s method to delete shiF in two S88 mutants. A cross-feeding assay showed that these mutants were able to excrete aerobactin meaning that shiF is dispensable for aerobactin excretion. Our growth assays revealed that the shiF-deleted mutants grew significantly slower than the wild-type strain S88 in iron-depleted medium with a decrease of maximum growth rates of 23 and 28% (p < 0.05). Using Liquid Chromatography-Mass Spectrometry, we identified and quantified siderophores in the supernatants of S88 and its shiF deleted mutants after growth in iron-depleted medium and found that these mutants secreted significantly less aerobactin than S88 (− 52% and - 49%, p < 0.001).

Conclusions

ShiF is physically and functionally linked to aerobactin. It provides an advantage to E. coli S88 under iron-limiting conditions by increasing aerobactin secretion and may thus act as an auxiliary virulence factor.
SPAR – a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial
Authors: Jameson Michael B. , Gormly Kirsten , Espinoza David , Hague Wendy , Asghari Gholamreza , Jeffery Grahame Mark , Price Timothy Jay , Karapetis Christos Stelios , Arendse Michael , Armstrong James , Childs John , Frizelle Frank A. , Ngan Sam , Stevenson Andrew , Oostendorp Martinus , Ackland Stephen P.
Published: December 2019

Background

Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG).

Methods

A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1–2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4–5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018.

Discussion

When completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations.

Trial registration

ANZ Clinical Trials Register ACTRN12617001087347.

(www.anzctr.org.au, registered 26/7/2017)

Protocol Version: 1.1 (June 2017).
Increased songbird nest depredation due to Aleppo pine (Pinus halepensis) encroachment in Mediterranean shrubland
Authors: Ben-David Asaf , Shamon Hila , Izhaki Ido , Efronny Ronny , Maor Roi , Dayan Tamar
Published: December 2019

Background

In recent decades, a decrease of passerine densities was documented in Mediterranean shrublands. At the same time, a widespread encroachment of Aleppo pines (Pinus halepensis) to Mediterranean shrubland occurred. Such changes in vegetation structure may affect passerine predator assemblage and densities, and in turn impact passerine densities. Depredation during the nesting season is an important factor to influence passerine population size. Understanding the effects of changes in vegetation structure (pine encroachment) on passerine nesting success is the main objective of this study. We do so by assessing the effects of Aleppo pine encroachment on Sardinian warbler (Sylvia melanocephala) nest depredation in Mediterranean shrublands. We examined direct and indirect predation pressures through a gradients of pine density, using four methods: (1) placing dummy nests; (2) acoustic monitoring of mobbing events; (3) direct observations on nest predation using cameras; and (4) observation of Eurasian jay (Garrulus glandarius) behaviour as indirect evidence of predation risk.

Results

We found that Aleppo pine encroachment to Mediterranean shrublands increased nest predation by Eurasian jays. Nest predation was highest in mixed shrubland and pines. These areas are suitable for warblers but had high occurrence rate of Eurasian jays.

Conclusions

Encroaching pines directly increase activity of Eurasian jays in shrubland habitats, which reduced the nesting success of Sardinian warblers. These findings are supported by multiple methodologies, illustrating different predation pressures along a gradient of pine densities in natural shrublands. Management of Aleppo pine seedlings and removal of unwanted trees in natural shrubland might mitigate arrival and expansion of predators and decrease the predation pressure on passerine nests.
Region-specific blood–brain barrier transporter changes leads to increased sensitivity to amisulpride in Alzheimer’s disease
Authors: Sekhar Gayathri Nair , Fleckney Alice L. , Boyanova Sevda Tomova , Rupawala Huzefa , Lo Rachel , Wang Hao , Farag Doaa B. , Rahman Khondaker Miraz , Broadstock Martin , Reeves Suzanne , Thomas Sarah Ann
Published: December 2019

Background

Research into amisulpride use in Alzheimer’s disease (AD) implicates blood–brain barrier (BBB) dysfunction in antipsychotic sensitivity. Research into BBB transporters has been mainly directed towards the ABC superfamily, however, solute carrier (SLC) function in AD has not been widely studied. This study tests the hypothesis that transporters for organic cations contribute to the BBB delivery of the antipsychotics (amisulpride and haloperidol) and is disrupted in AD.

Methods

The accumulation of [3H]amisulpride (3.7–7.7 nM) and [3H]haloperidol (10 nM) in human (hCMEC/D3) and mouse (bEnd.3) brain endothelial cell lines was explored. Computational approaches examined molecular level interactions of both drugs with the SLC transporters [organic cation transporter 1 (OCT1), plasma membrane monoamine transporter (PMAT) and multi-drug and toxic compound extrusion proteins (MATE1)] and amisulpride with the ABC transporter (P-glycoprotein). The distribution of [3H]amisulpride in wildtype and 3×transgenic AD mice was examined using in situ brain perfusion experiments. Western blots determined transporter expression in mouse and human brain capillaries .

Results

In vitro BBB and in silico transporter studies indicated that [3H]amisulpride and [3H]haloperidol were transported by the influx transporter, OCT1, and efflux transporters MATE1 and PMAT. Amisulpride did not have a strong interaction with OCTN1, OCTN2, P-gp, BCRP or MRP and could not be described as a substrate for these transporters. Amisulpride brain uptake was increased in AD mice compared to wildtype mice, but vascular space was unaffected. There were no measurable changes in the expression of MATE1, MATE2, PMAT OCT1, OCT2, OCT3, OCTN1, OCTN2 and P-gp in capillaries isolated from whole brain homogenates from the AD mice compared to wildtype mice. Although, PMAT and MATE1 expression was reduced in capillaries obtained from specific human brain regions (i.e. putamen and caudate) from AD cases (Braak stage V–VI) compared to age matched controls (Braak stage 0–II).

Conclusions

Together our research indicates that the increased sensitivity of individuals with Alzheimer’s to amisulpride is related to previously unreported changes in function and expression of SLC transporters at the BBB (in particular PMAT and MATE1). Dose adjustments may be required for drugs that are substrates of these transporters when prescribing for individuals with AD.
Human bone marrow mesenchymal stem cells-derived microRNA-205-containing exosomes impede the progression of prostate cancer through suppression of RHPN2
Authors: Jiang Shuangjian , Mo Chengqiang , Guo Shengjie , Zhuang Jintao , Huang Bin , Mao Xiaopeng
Published: December 2019

Background

Human bone marrow mesenchymal stem cells (hBMSCs) are implicated in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the physiological mechanisms by which exosomal miR-205 derived from hBMSCs may modulate the growth of prostate cancer cells.

Methods

Microarray-based gene expression profiling of prostate cancer was adopted to identify differentially expressed genes and regulatory miRNAs, which identified the candidates RHPN2 and miR-205 as the study focus. Then the binding affinity between miR-205 and RHPN2 was identified using in silico analysis and luciferase activity detection. Prostate cancer cells were co-cultured with exosomes derived from hBMSCs treated with either miR-205 mimic or miR-205 inhibitor. Subsequently, prostate cancer cell proliferation, invasion, migration, and apoptosis were detected in vitro. The effects of hBMSCs-miR-205 on tumor growth were investigated in vivo.

Results

miR-205 was downregulated, while RHPN2 was upregulated in prostate cancer cells. RHPN2 was a target of miR-205, and upregulated miR-205 inhibited prostate cancer cell proliferation, invasion, and migration and promoted apoptosis by targeting RHPN2. Next, experiments demonstrated that hBMSCs-derived exosomes carrying miR-205 contributed to repressed prostate cancer cell proliferation, invasion, and migration and enhanced apoptosis. Furthermore, in vivo assays confirmed the inhibitory effects of hBMSCs-derived exosomal miR-205 on prostate cancer.

Conclusion

The hBMSCs-derived exosomal miR-205 retards prostate cancer progression by inhibiting RHPN2, suggesting that miR-205 may present a predictor and potential therapeutic target for prostate cancer.
Systematic underestimation of the epigenetic clock and age acceleration in older subjects
Authors: El Khoury Louis Y. , Gorrie-Stone Tyler , Smart Melissa , Hughes Amanda , Bao Yanchun , Andrayas Alexandria , Burrage Joe , Hannon Eilis , Kumari Meena , Mill Jonathan , Schalkwyk Leonard C.
Published: December 2019

Background

The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments.

Results

The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways.

Conclusions

The concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate.