bluuebunny/crossref_metadata_2025 huggingface dataset:
Visceral organ growth patterns in Saanen goats
Authors: Andrade M. E. B. , Härter C. J. , Gindri M. , Resende K. T. , Teixeira I. A. M. A.
Published: March 2020

Visceral organs play an important role in animals' energy requirements, so their growth must be well understood. The objective of the current study was to fit and compare growth curves that best describe body and visceral organ growth over time in Saanen goats of different sexes. Data were synthesized from seven studies in which curves were fitted to visceral organ growth over time for female, intact male and castrated male Saanen goats from 5 to 45 kg body weight. The liver, pancreas, spleen, rumen–reticulum, omasum, abomasum, small intestine, large intestine and mesenteric adipose tissue (MAT) data were fitted to eight models: simple linear regression, quadratic, monomolecular, Brody, Von Bertalanffy, logistic, Gompertz and Richards. The best-fit model was chosen based on the corrected Akaike information criterion and the concordance correlation coefficient. Model parameters for each sex were compared. Overall, the model that best described visceral organ growth was the logistic model. Sex did not influence the parameters that predicted organ growth (g), except for MAT, where females presented a lower tissue deposition rate and greater inflection point than males. Irrespective of sex, at the beginning of the growth curve, the liver accounted for 28 ± 1.1 g/kg of empty body weight, and the inflection point occurred at 1.7 months. The rumen–reticulum and large intestine presented higher growth rates in the first 2 months of life. Knowledge of the visceral organ growth curve is useful in improving the understanding of the effect of nutritional requirements for goats and must be used to optimize the nutritional plans.
On energy confinement following the onset of ‘stiff’ transport
Authors: Connor J. W. , Hastie R. J. , Richards K.
Published: March 2020

The dependence of confinement on input power for a tokamak plasma with regions having a stiff temperature profile is explored. The resilience of the confinement of the core energy to increasing power loss by core radiation from impurities in such situations, as it is anticipated will be required in a demonstration fusion reactor (DEMO) design, is examined.
Anger attacks are associated with persistently elevated irritability in MDD: findings from the EMBARC study
Authors: Jha Manish K. , Fava Maurizio , Minhajuddin Abu , Chin Fatt Cherise , Mischoulon David , Wakhlu Nausheen , Trombello Joseph M. , Cusin Cristina , Trivedi Madhukar H.
Published: March 2020

Background

This report tests the association of self-reported symptoms of irritability with overt behavior of anger attacks (uncharacteristic sudden bouts of anger that are disproportionate to situation and associated with autonomic activation).

Methods

Participants of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care study who completed Massachusetts General Hospital Anger Attacks questionnaire were included (n = 293). At each visit, the 17-item Hamilton Depression Rating Scale and the 16-item Concise Associated Symptom Tracking scale were used to measure depression, anxiety, and irritability. In those with anger attacks present v. those without anger attacks, separate t tests and mixed model analyses compared afore-mentioned symptoms at baseline and changes with treatment respectively. As anger attacks may occur without aggressive behaviors, analyses were repeated based only on the presence of aggressive behaviors.

Results

At baseline, those with anger attacks (n = 109) v. those without anger attacks (n = 184) had similar levels of depression but higher levels of irritability [effect size (d) = 0.80] and anxiety (d = 0.32). With acute-phase treatment, participants with anger attacks experienced a greater reduction in irritability (p < 0.001) but not in depression (p = 0.813) or anxiety (p = 0.771) as compared to those without anger attacks. Yet, irritability levels at week-8 were higher in those with anger attacks (d = 0.32) than those without anger attacks. Similar results were found in participants with aggressive behaviors.

Conclusions

The presence of anger attacks in outpatients with major depressive disorder may identify a sub-group of patients with persistently elevated irritability.
INTRODUCTION: TOWARDS GENDER DIVERSITY IN NEW MUSIC PRACTICE
Authors: Devenish Louise
Published: March 2020

The collection of articles in TEMPO 292 provides the opportunity to examine recent research and approaches towards gender diversity in new music from an Australian perspective. The otherwise under-recognised contributions to the development of music by women and gender-diverse artists is spotlighted through academic research, industry strategies and creative approaches to music-making. Topics explored include artistic research in free improvisation, performance analysis and performativity, presented together with research findings drawn from mentorship programmes for female composers, gender diversity strategies in tertiary music education and the positive impacts of content targets in programming. Together these articles offer a wide range of perspectives on changing creation and performance practices, listening practices and audience attitudes to music in the twenty-first century. Contributors include leading scholar-performers active at the forefront of contemporary music in Australia, artists from the UK and USA, as well as national radio programmers and not-for-profit arts organisations.
TOWARDS THE SUMMERS NIGHT: A MENTORING PROJECT FOR AUSTRALIAN COMPOSERS IDENTIFYING AS WOMEN
Authors: Hope Cat , Grant Nat , Smart Gabriella , Parr Tristen
Published: March 2020

The Summers Night Project is an ongoing composer-mentoring programme established in 2018 by musicians Cat Hope and Gabriella Smart, with the support of the Perth-based new music organisation Tura New Music. The project aims to support and mentor emerging Australian female and gender minority composers to create new compositions for performance, with the aim of growing the gender diversity of composers in music programmes across Australia. Three composers were chosen from a national call for submissions, and works were performed by an ensemble consisting of members from the Decibel and Soundstream new music ensembles. Three new works were workshopped, recorded then performed on a short tour of Perth, Adelaide and Melbourne, Australia in July 2018. The project takes its name and inspiration from Australian feminist Anne Summers, author of the ground-breaking examination of women in Australia's history Damned Whores and God's Police (1975) and was inspired by her 2017 Women's Manifesto. This article examines the rationale for such a project, the processes and results of the project itself, and plans for its future.
OF BODY, OF EMOTION: A TOOLKIT FOR TRANSFORMATIVE SOUND USE
Authors: Rosenberg Shoshana , Reardon-Smith Hannah
Published: March 2020

Much of contemporary western art music relies on objectivist and individualistic frameworks of intellect which oppose any focus on subjectivity, embodiment or emotion. These approaches deny composers, players and audiences the powerful experiences facilitated by works which are of body and of emotion. We suggest that by facilitating a return to body and emotion in sound we create potential for deep, cathartic, and transformative psychophysiological states. We argue that these states can create shared experiences that directly resist the isolating, homogenising, socially apathetic and narrowing path paved by frameworks of intellect. This refusal can facilitate collectivised movement towards an ethics of care, through mutuality, solidarity and empathy. This extends further than musical practice and builds potential inroads towards greater social and political transformation. We offer a toolkit of actions and frameworks that enable embodied and emotional sound use: intensity, stillness, improvisation, collectivised praxis and uncanoning.
Places of living and places of dying: the case for preventing suicide in residential long-term care
Authors: Jain Briony , Kalesnikava Viktoryia , Ibrahim Joseph E. , Mezuk Briana
Published: March 2020

This commentary addresses the increasing public health problem of suicide in later life and presents the case for preventing suicide in residential long-term care settings. We do so by examining this issue from the perspective of three levels of stakeholders – societal, organisational and individual – considering the relevant context, barriers and implications of each. We begin by discussing contemporary societal perspectives of ageing; the potential impact of ageism on prevention of late-life suicide; and the roles of gender and masculinity. This is followed by a historical analysis of the origin of residential long-term care; current organisational challenges; and person-centred care as a suicide prevention strategy. Finally, we consider suicide in long-term care from the perspective of individuals, including the experience of older adults living in residential care settings; the impact of suicide on residential care health professionals and other staff; and the impact of suicide bereavement on family, friends and other residents. We conclude with recommendations for policy reform and future research. This commentary aims to confront the often unspoken bias associated with preventing suicide among older adults, particularly those living with complex medical conditions, and invoke an open dialogue about suicide prevention in this population and setting.
The Principles of Triage in Emergencies and Disasters: A Systematic Review
Authors: Bazyar Jafar , Farrokhi Mehrdad , Salari Amir , Khankeh Hamid Reza
Published: March 2020

Introduction:

The use of triage systems is one of the most important measures in response to mass-casualty incidents (MCIs) caused by emergencies and disasters. In these systems, certain principles and criteria must be considered that can be achieved with a lack of resources. Accordingly, the present study was conducted as a systematic review to explore the principles of triage systems in emergencies and disasters world-wide.

Methods:

The present study was conducted as a systematic review of the principles of triage in emergencies and disasters. All papers published from 2000 through 2019 were extracted from the Web of Science, PubMed, Scopus, Cochrane Library, and Google Scholar databases. The search for the articles was conducted by two trained researchers independently.

Results:

The classification and prioritization of the injured people, the speed, and the accuracy of the performance were considered as the main principles of triage. In certain circumstances, including chemical, biological, radiation, and nuclear (CBRN) incidents, certain principles must be considered in addition to the principles of the triage based on traumatic events. Usually in triage systems, the classification of the injured people is done using color labeling. The short duration of the triage and its accuracy are important for the survival of the injured individuals. The optimal use of available resources to protect the lives of more casualties is one of the important principles of triage systems and does not conflict with equity in health.

Conclusion:

The design of the principles of triage in triage systems is based on scientific studies and theories in which attempts have been made to correctly classify the injured people with the maximum correctness and in the least amount of time to maintain the survival of the injured people and to achieve the most desirable level of health. It is suggested that all countries adopt a suitable and context-bond model of triage in accordance with all these principles, or to propose a new model for the triage of injured patients, particularly for hospitals in emergencies and disasters.
Knowledge of the Art of Governance: The Mughal and Ottoman Empires in the Early Seventeenth Century
Authors: SOOD GAGAN D. S.
Published: March 2020

This article seeks to reconstruct the prevailing concepts, images and principles that framed sovereign governance in the Mughal and Ottoman empires in the early seventeenth century. Little is known about the subject. To help fill the gap, two contemporaneous advice-to-kings treatises—one Mughal by ʿAbd al-Ḥaqq Dihlavī, one Ottoman by Koçi Bey—are analysed in juxtaposition. Such an analysis, never previously undertaken, is motivated and guided by a novel approach. In this approach, a model founded on near-universal conditions and problems is deployed within a regional perspective. The findings which result advance our understanding of the art of governance in the Mughal and Ottoman empires of the time. But they have a larger importance, too. They move us closer to achieving a break with the decline paradigm, whose logic still persists in mainstream interpretations. They also contribute to a more recent, and rapidly developing, interest in a region spanning much of South Asia and the Middle East that was formative for the global genesis of the modern world.
Age of acquisition – not bilingualism – is the primary determinant of less than nativelike L2 ultimate attainment
Authors: Bylund Emanuel , Hyltenstam Kenneth , Abrahamsson Niclas
Published: March 2020

It has recently been suggested that bilingualism, rather than age of acquisition, is what underlies less than nativelike attainment in childhood L2 acquisition. Currently, however, the empirical evidence in favor of or against this interpretation remains scarce. The present study sets out to fill this gap, implementing a novel factorial design in which the variables age of acquisition and bilingualism have been fully crossed. Eighty speakers of Swedish, who were either L1 monolinguals, L1 simultaneous bilinguals, L2 sequential monolinguals (international adoptees), or L2 sequential bilinguals (childhood immigrants), were tested on phonetic, grammatical, and lexical measures. The results indicate consistent effects of age of acquisition, but only limited effects of bilingualism, on ultimate attainment. These findings thus show that age of acquisition – not bilingualism – is the primary determinant of L2 ultimate attainment.
A SEMI-ANALYTICAL PRICING FORMULA FOR EUROPEAN OPTIONS UNDER THE ROUGH HESTON-CIR MODEL
Authors: HE XIN-JIANG , LIN SHA
Published: March 2020

We combine the rough Heston model and the CIR (Cox–Ingersoll–Ross) interest rate together to form a rough Heston-CIR model, so that both the rough behaviour of the volatility and the stochastic nature of the interest rate can be captured. Despite the convoluted structure and non-Markovian property of this model, it still admits a semi-analytical pricing formula for European options, the implementation of which involves solving a fractional Riccati equation. The rough Heston-CIR model is more general, taking both the rough Heston model and the Heston-CIR model as special cases. The influence of rough volatility and stochastic interest rate is shown to be significant through numerical experiments.
Armando Carvalho and Others v. EU: Invoking Human Rights and the Paris Agreement for Better Climate Protection Legislation
Authors: Winter Gerd
Published: March 2020

This contribution takes the form of an uncommon case report. It discusses an action brought to the Court of Justice of the European Union (CJEU) before the final decision has been rendered. The author believes this is justified because the innovative character of the procedural and substantive reasoning of the application could be of interest to a wider public. This may be the case even if the CJEU eventually dismisses the action as being inadmissible, leaving the substantive questions undecided. The applicants in Carvalho and Others v. European Union claim that European Union (EU) law does not limit greenhouse gas (GHG) emissions as strictly as is required by EU human rights and international law. The case note explains the parties in the case, the acts being challenged, the relief being sought, and the content and application of the relevant procedural and substantive law. The case is illustrative of the high barriers for direct access to the CJEU, and suggests how they might be overcome. It is also a laboratory for examining the interface of climate science, economics, and law. At this interface, available emissions budgets and the technical and economic feasibility of emissions reductions are calculated and made legally relevant. Carvalho is based on the applicants’ conviction that, where the EU assumes a regulatory competence such as that of GHG emissions reduction, it must exercise it in accordance with its human rights and international obligations.
The Linkage of Kuroshio Intrusion and Mesoscale Eddy Variability in the Northern South China Sea: Subsurface Speed Maximum
Authors: Wang Qiang , Zeng Lili , Chen Ju , He Yunkai , Zhou Weidong , Wang Dongxiao
Published: March 2020

In situ data suggest that there is a subsurface speed maximum between 70 and 120 m in the Kuroshio, which is first revealed by the directly velocity observation. The subsurface speed maximum can also be advected into the largest marginal sea in the tropics, that is, the South China Sea (SCS). As it enters the SCS, its depth shoals to between 40 and 70 m and then finally disappears in the western northern SCS. Strong subsurface speed maximum intrusion results in strong baroclinic instability, which triggers vigorous baroclinic conversion, consequently the active mesoscale eddy variability in the northern SCS, and vice versa. Our study highlights this intuitive bridge connecting the Kuroshio intrusion and the mesoscale eddy activities in the northern SCS.
Discovery of suppressors of CRMP2 phosphorylation reveals compounds that mimic the behavioral effects of lithium on amphetamine-induced hyperlocomotion
Authors: Zhao Wen-Ning , Tobe Brian T. D. , Udeshi Namrata D. , Xuan Lucius L. , Pernia Cameron D. , Zolg Daniel P. , Roberts Amanda J. , Mani Deepak , Blumenthal Sarah R. , Kurtser Iren , Patnaik Debasis , Gaisina Irina , Bishop Joshua , Sheridan Steven D. , Lalonde Jasmin , Carr Steven A. , Snyder Evan Y. , Haggarty Stephen J.
Published: March 2020

The effective treatment of bipolar disorder (BD) represents a significant unmet medical need. Although lithium remains a mainstay of treatment for BD, limited knowledge regarding how it modulates affective behavior has proven an obstacle to discovering more effective mood stabilizers with fewer adverse side effects. One potential mechanism of action of lithium is through inhibition of the serine/threonine protein kinase GSK3β, however, relevant substrates whose change in phosphorylation may mediate downstream changes in neuroplasticity remain poorly understood. Here, we used human induced pluripotent stem cell (hiPSC)-derived neuronal cells and stable isotope labeling by amino acids in cell culture (SILAC) along with quantitative mass spectrometry to identify global changes in the phosphoproteome upon inhibition of GSK3α/β with the highly selective, ATP-competitive inhibitor CHIR-99021. Comparison of phosphorylation changes to those induced by therapeutically relevant doses of lithium treatment led to the identification of collapsin response mediator protein 2 (CRMP2) as being highly sensitive to both treatments as well as an extended panel of structurally distinct GSK3α/β inhibitors. On this basis, a high-content image-based assay in hiPSC-derived neurons was developed to screen diverse compounds, including FDA-approved drugs, for their ability to mimic lithium’s suppression of CRMP2 phosphorylation without directly inhibiting GSK3β kinase activity. Systemic administration of a subset of these CRMP2-phosphorylation suppressors were found to mimic lithium’s attenuation of amphetamine-induced hyperlocomotion in mice. Taken together, these studies not only provide insights into the neural substrates regulated by lithium, but also provide novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders.
The therapeutic response of ER+/HER2− breast cancers differs according to the molecular Basal or Luminal subtype
Authors: Bertucci François , Finetti Pascal , Goncalves Anthony , Birnbaum Daniel
Published: March 2020

The genomics-based molecular classifications aim at identifying more homogeneous classes than immunohistochemistry, associated with a more uniform clinical outcome. We conducted an in silico analysis on a meta-dataset including gene expression data from 5342 clinically defined ER+/HER2− breast cancers (BC) and DNA copy number/mutational and proteomic data. We show that the Basal (16%) versus Luminal (74%) subtypes as defined using the 80-gene signature differ in terms of response/vulnerability to systemic therapies of BC. The Basal subtype is associated with better chemosensitivity, lesser benefit from adjuvant hormone therapy, and likely better sensitivity to PARP inhibitors, platinum salts and immune therapy, and other targeted therapies under development such as FGFR inhibitors. The Luminal subtype displays potential better sensitivity to CDK4/6 inhibitors and vulnerability to targeted therapies such as PIK3CA, AR and Bcl-2 inhibitors. Expression profiles are very different, showing an intermediate position of the ER+/HER2− Basal subtype between the ER+/HER2− Luminal and ER− Basal subtypes, and let suggest a different cell-of-origin. Our data suggest that the ER+/HER2− Basal and Luminal subtypes should not be assimilated and treated as a homogeneous group.
A socio-environmental geodatabase for integrative research in the transboundary Rio Grande/Río Bravo basin
Authors: Plassin Sophie , Koch Jennifer , Paladino Stephanie , Friedman Jack R. , Spencer Kyndra , Vaché Kellie B.
Published: March 2020

Integrative research on water resources requires a wide range of socio-environmental datasets to better understand human-water interactions and inform decision-making. However, in transboundary watersheds, integrating cross-disciplinary and multinational datasets is a daunting task due to the disparity of data sources and the inconsistencies in data format, content, resolution, and language. This paper introduces a socio-environmental geodatabase that transcends political and disciplinary boundaries in the Rio Grande/Río Bravo basin (RGB). The geodatabase aggregates 145 GIS data layers on five main themes: (i) Water & Land Governance, (ii) Hydrology, (iii) Water Use & Hydraulic Infrastructures, (iv) Socio-Economics, and (v) Biophysical Environment. Datasets were primarily collected from public open-access data sources, processed with ArcGIS, and documented through the FGCD metadata standard. By synthesizing a broad array of datasets and mapping public and private water governance, we expect to advance interdisciplinary research in the RGB, provide a replicable approach to dataset compilation for transboundary watersheds, and ultimately foster transboundary collaboration for sustainable resource management.
High dielectric ternary oxides from crystal structure prediction and high-throughput screening
Authors: Qu Jingyu , Zagaceta David , Zhang Weiwei , Zhu Qiang
Published: March 2020

The development of new high dielectric materials is essential for advancement in modern electronics. Oxides are generally regarded as the most promising class of high dielectric materials for industrial applications as they possess both high dielectric constants and large band gaps. Most previous researches on high dielectrics were limited to already known materials. In this study, we conducted an extensive search for high dielectrics over a set of ternary oxides by combining crystal structure prediction and density functional perturbation theory calculations. From this search, we adopted multiple stage screening to identify 441 new low-energy high dielectric materials. Among these materials, 33 were identified as potential high dielectrics favorable for modern device applications. Our research has opened an avenue to explore novel high dielectric materials by combining crystal structure prediction and high throughput screening.
Publisher Correction: Denitrification Aligns with N2 Fixation in Red Sea Corals
Authors: Tilstra Arjen , El-Khaled Yusuf C. , Roth Florian , Rädecker Nils , Pogoreutz Claudia , Voolstra Christian R. , Wild Christian
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Pure single-mode Rayleigh-Taylor instability for arbitrary Atwood numbers
Authors: Liu Wanhai , Wang Xiang , Liu Xingxia , Yu Changping , Fang Ming , Ye Wenhua
Published: March 2020

The validity of theoretical investigation on Rayleigh-Taylor instability (RTI) with nonlinearity is quite important, especially for the simplest and the commonest case of a pure single-mode RTI, while its previous explicit solution in weakly nonlinear scheme is found to have several defections. In this paper, this RTI is strictly solved by the method of the potential functions up to the third order at the weakly nonlinear stage for arbitrary Atwood numbers. It is found that the potential solution includes terms of both the stimulating and inhibiting RTI, while the terms of the decreasing RTI are omitted in the classical solution of the weakly nonlinear scheme, resulting in a big difference between these two results. For the pure single-mode cosine perturbation, comparisons among the classical result, the present potential result and numerical simulations, in which the two dimensional Euler equations are used, are carefully performed. Our result is in a better agreement with the numerical simulations than the classical one before the saturation time. To avoid the tedious expressions and improve a larger valid range of the solution, the method of the Taylor expansion is employed and the velocities of the bubble and spike are, respectively, obtained. Comparisons between the improved and the simulation results show that the improved theory can better predict the evolution of the interface from the linear to weakly nonlinear, even to later of the nonlinear stages.
A randomised controlled study shows supplementation of overweight and obese adults with lactobacilli and bifidobacteria reduces bodyweight and improves well-being
Authors: Michael D. R. , Jack A. A. , Masetti G. , Davies T. S. , Loxley K. E. , Kerry-Smith J. , Plummer J. F. , Marchesi J. R. , Mullish B. H. , McDonald J. A. K. , Hughes T. R. , Wang D. , Garaiova I. , Paduchová Z. , Muchová J. , Good M. A. , Plummer S. F.
Published: March 2020

In an exploratory, block-randomised, parallel, double-blind, single-centre, placebo-controlled superiority study (ISRCTN12562026, funded by Cultech Ltd), 220 Bulgarian participants (30 to 65 years old) with BMI 25–34.9 kg/m2 received Lab4P probiotic (50 billion/day) or a matched placebo for 6 months. Participants maintained their normal diet and lifestyle. Primary outcomes were changes in body weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), blood pressure and plasma lipids. Secondary outcomes were changes in plasma C-reactive protein (CRP), the diversity of the faecal microbiota, quality of life (QoL) assessments and the incidence of upper respiratory tract infection (URTI). Significant between group decreases in body weight (1.3 kg, p < 0.0001), BMI (0.045 kg/m2, p < 0.0001), WC (0.94 cm, p < 0.0001) and WtHR (0.006, p < 0.0001) were in favour of the probiotic. Stratification identified greater body weight reductions in overweight subjects (1.88%, p < 0.0001) and in females (1.62%, p = 0.0005). Greatest weight losses were among probiotic hypercholesterolaemic participants (−2.5%, p < 0.0001) alongside a significant between group reduction in small dense LDL-cholesterol (0.2 mmol/L, p = 0.0241). Improvements in QoL and the incidence rate ratio of URTI (0.60, p < 0.0001) were recorded for the probiotic group. No adverse events were recorded. Six months supplementation with Lab4P probiotic resulted in significant weight reduction and improved small dense low-density lipoprotein-cholesterol (sdLDL-C) profiles, QoL and URTI incidence outcomes in overweight/obese individuals.
Skeletal pathologies track body plan evolution in ichthyosaurs
Authors: Pardo-Pérez Judith M. , Kear Benjamin P. , Maxwell Erin E.
Published: March 2020

Changing predator-prey interactions during the Mesozoic Marine Revolution (MMR) profoundly altered the trajectory of marine tetrapod evolution. Here, we assess potential signatures of this landmark transition through the fossil record of skeletal pathologies in ichthyosaurs — iconic marine reptiles that developed increasingly ‘fish-like’ body plans over time. We surveyed a stratigraphically constrained sample of 200 Middle Triassic ichthyosaur specimens and compared the type, distribution and prevalence of pathologies with an approximately equivalent assemblage of Early Jurassic age. Overall, skeletal pathologies were equally prevalent in these groups, and most often manifested in species >4 m long. However, pathological bones were found to be concentrated in the hind limbs and tail of Triassic ichthyosaurs, whereas the jaws, forelimbs, and ribcage were preferentially affected in Jurassic taxa. We posit that the occurrence of ankylosed zygapophyses in the caudal peak of Triassic ichthyosaurs could represent a functional by-product of their primitive ‘eel-like’ swimming. Conversely, increased instances of broken ribs in Jurassic ichthyosaurs may infer ramming or tail strike behaviours that characterise morphologically ‘fish-like’ marine tetrapods, such as modern toothed whales. Different categories of skeletal pathologies thus evidently reflect structural modifications in the ichthyosaur body plan, and indirectly coincide with ecological turnover during the MMR.
Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts
Authors: Castro-Viñuelas R. , Sanjurjo-Rodríguez C. , Piñeiro-Ramil M. , Hermida-Gómez T. , Rodríguez-Fernández S. , Oreiro N. , de Toro J. , Fuentes I. , Blanco F. J. , Díaz-Prado S.
Published: March 2020

Knowledge and research results about hand osteoarthritis (hOA) are limited due to the lack of samples and animal models of the disease. Here, we report the generation of two induced pluripotent stem cell (iPSC)-lines from patients with radiographic hOA. Furthermore, we wondered whether these iPSC-lines carried single nucleotide polymorphisms (SNPs) within genes that have been associated with hOA. Finally, we performed chondrogenic differentiation of the iPSCs in order to prove their usefulness as cellular models of the disease. We performed a non-integrative reprogramming of dermal fibroblasts obtained from two patients with radiographic rhizarthrosis and non-erosive hOA by introducing the transcriptional factors Oct4, Sox2, Klf4 and c-Myc using Sendai virus. After reprogramming, embryonic stem cell-like colonies emerged in culture, which fulfilled all the criteria to be considered iPSCs. Both iPSC-lines carried variants associated with hOA in the four studied genes and showed differences in their chondrogenic capacity when compared with a healthy control iPSC-line. To our knowledge this is the first time that the generation of iPSC-lines from patients with rhizarthrosis and non-erosive hOA is reported. The obtained iPSC-lines might enable us to model the disease in vitro, and to deeper study both the molecular and cellular mechanisms underlying hOA.
Development and Characterization of a Benchtop Corneal Puncture Injury Model
Authors: Snider Eric J. , Cornell Lauren E. , Acevedo Jorge M. , Gross Brandon , Edsall Peter R. , Lund Brian J. , Zamora David O.
Published: March 2020

During recent military operations, eye-related injuries have risen in frequency due to increased use of explosive weaponry which often result in corneal puncture injuries. These have one of the poorest visual outcomes for wounded soldiers, often resulting in blindness due to the large variations in injury shape, size, and severity. As a result, improved therapeutics are needed which can stabilize the injury site and promote wound healing. Unfortunately, current corneal puncture injury models are not capable of producing irregularly shaped, large, high-speed injuries as seen on the battlefield, making relevant therapeutic development challenging. Here, we present a benchtop corneal puncture injury model for use with enucleated eyes that utilizes a high-speed solenoid device suitable for creating military-relevant injuries. We first established system baselines and ocular performance metrics, standardizing the different aspects of the benchtop model to ensure consistent results and properly account for tissue variability. The benchtop model was evaluated with corneal puncture injury objects up to 4.2 mm in diameter which generated intraocular pressure levels exceeding 1500 mmHg. Overall, the created benchtop model provides an initial platform for better characterizing corneal puncture injuries as seen in a military relevant clinical setting and a realistic approach for assessing potential therapeutics.
A high-throughput screening platform for Polycystic Kidney Disease (PKD) drug repurposing utilizing murine and human ADPKD cells
Authors: Asawa Rosita R. , Danchik Carina , Zakharov Alexey , Chen Yuchi , Voss Ty , Jadhav Ajit , Wallace Darren P. , Trott Josephine F. , Weiss Robert H. , Simeonov Anton , Martinez Natalia J.
Published: March 2020

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited monogenic disorders, characterized by a progressive decline in kidney function due in part to the formation of fluid-filled cysts. While there is one FDA-approved therapy, it is associated with potential adverse effects, and all other clinical interventions are largely supportive. Insights into the cellular pathways underlying ADPKD have revealed striking similarities to cancer. Moreover, several drugs originally developed for cancer have shown to ameliorate cyst formation and disease progression in animal models of ADPKD. These observations prompted us to develop a high-throughput screening platform of cancer drugs in a quest to repurpose them for ADPKD. We screened ~8,000 compounds, including compounds with oncological annotations, as well as FDA-approved drugs, and identified 155 that reduced the viability of Pkd1-null mouse kidney cells with minimal effects on wild-type cells. We found that 109 of these compounds also reduced in vitro cyst growth of Pkd1-null cells cultured in a 3D matrix. Moreover, the result of the cyst assay identified therapeutically relevant compounds, including agents that interfere with tubulin dynamics and reduced cyst growth without affecting cell viability. Because it is known that several ADPKD therapies with promising outcomes in animal models failed to be translated to human disease, our platform also incorporated the evaluation of compounds in a panel of primary ADPKD and normal human kidney (NHK) epithelial cells. Although we observed differences in compound response amongst ADPKD and NHK cell preparation, we identified 18 compounds that preferentially affected the viability of most ADPKD cells with minimal effects on NHK cells. Our study identifies attractive candidates for future efficacy studies in advanced pre-clinical models of ADPKD.
Characterization of serum small extracellular vesicles and their small RNA contents across humans, rats, and mice
Authors: Zhao Fengbo , Cheng Li , Shao Qian , Chen Zixing , Lv Xiufang , Li Jing , He Li , Sun Yufeng , Ji Qiuhong , Lu Peng , Ji Yuhua , Ji Juling
Published: March 2020

Serum small extracellular vesicles (sEVs) have recently drawn considerable interest because of the diagnostic and therapeutic potential of their miRNAs content. However, the characteristics of human, mouse and rat serum sEVs and their differences in small RNA contents are still unknown. In this study, through nanoparticle tracking analysis and small RNA sequencing, we found that human, rat, and mouse serum sEVs exhibited distinct sizes and particle numbers as well as small RNA contents. Serum sEVs contained not only abundant miRNAs but also a large number of tRNA fragments. Most serum miRNAs existed both inside and outside of sEVs but were enriched in sEVs. Common serum sEV miRNAs (188 miRNAs) and species-specific serum sEV miRNAs (265, 58, and 159 miRNAs, respectively) were identified in humans, rats, or mice. The serum sEVs contained miRNAs from tissues and organs throughout the body, with blood cells as the main contributors. In conclusion, our findings confirmed the rationality of exploring serum sEV miRNAs as noninvasive diagnostic markers and revealed great differences in serum sEV small RNAs between humans, rats, and mice. Inadequate attention to these differences and the contribution of blood cells to serum sEV miRNAs could hinder the clinical translation of basic studies.
A Modified Magnified Analysis of Proteome (MAP) Method for Super-Resolution Cell Imaging that Retains Fluorescence
Authors: Woo Jiwon , Seo Jeong-Min , Lee Mirae , Kim Juyoung , Min Sol , Kim Sang-Tae , Ku Seockmo , Park Jeong-Yoon
Published: March 2020

Biological systems consist of a variety of distinct cell types that form functional networks. Super-resolution imaging of individual cells is required for better understanding of these complex systems. Direct visualization of 3D subcellular and nano-scale structures in cells is helpful for the interpretation of biological interactions and system-level responses. Here we introduce a modified magnified analysis of proteome (MAP) method for cell super-resolution imaging (Cell-MAP) which preserves cell fluorescence. Cell-MAP expands cells more than four-fold while preserving their overall architecture and three-dimensional proteome organization after hydrogel embedding. In addition, Optimized-Cell-MAP completely preserves fluorescence and successfully allows for the observation of tagged small molecular probes containing peptides and microRNAs. Optimized-Cell-MAP further successfully applies to the study of structural characteristics and the identification of small molecules and organelles in mammalian cells. These results may give rise to many other applications related to the structural and molecular analysis of smaller assembled biological systems.
TmRelish is required for regulating the antimicrobial responses to Escherichia coli and Staphylococcus aureus in Tenebrio molitor
Authors: Keshavarz Maryam , Jo Yong Hun , Patnaik Bharat Bhusan , Park Ki Beom , Ko Hye Jin , Kim Chang Eun , Edosa Tariku Tesfaye , Lee Yong Seok , Han Yeon Soo
Published: March 2020

Relish, a transcription factor, is a critical downstream component of the immune deficiency (Imd) pathway and regulates host defense against bacterial infection by mediating antimicrobial peptide (AMP) synthesis. Understanding the immunological function of the mealworm beetle, Tenebrio molitor Relish (TmRelish) will be instructive in understanding insect immunity. In the present study, full-length ORF of TmRelish was retrieved from T. molitor-expressed sequence tags and RNA-seq database. The predicted TmRelish amino acid sequence contained an N-terminal Rel-homology domain; an Ig-like, plexin, and transcription factor domain; ankyrin repeat motifs; a nuclear localization signal; and a C-terminal death domain and shared the highly conserved structure of the Relish proteins of other insect species. TmRelish mRNA was detected in all developmental stages of the insect; however, the highest levels were detected in the larval gut tissue and adult hemocytes. TmRelish mRNA level was upregulated in the fat body, hemocyte, and gut tissue 9 h after infection of T. molitor larvae by the gram-negative bacteria, Escherichia coli. Furthermore, TmRelish knockdown led to significantly higher mortality of the E. coli-infected larvae, and significantly lower mortality of larvae infected with Staphylococcus aureus or Candida albicans. To elucidate the possible cause of mortality, we measured AMP transcription in the fat body, hemocytes, gut, and Malpighian tubules (MTs) of T. molitor larvae. TmRelish knockdown suppressed the expression of nine AMP genes in the larval fat body and gut tissue during E. coli infection, suggesting that TmRelish positively regulates AMP expression in both immune-related tissues, in response to E. coli challenge. Furthermore, negative regulation of some AMPs by TmRelish in the MTs, gut and hemocytes in response to C. albicans infection suggests a crosstalk between the Toll and Imd pathways.
Silicon amendment induces synergistic plant defense mechanism against pink stem borer (Sesamia inferens Walker.) in finger millet (Eleusine coracana Gaertn.)
Authors: Jadhao Kundansing Rajpalsing , Bansal Anuradha , Rout Gyana R.
Published: March 2020

Silicon (Si) uptake and accumulation in plants can mitigate various biotic stresses through enhanced plant resistance against wide range of herbivores. But the role of silicon in defense molecular mechanism still remains to be elucidated in finger millet. In the present study, we identified three silicon transporter genes viz.EcLsi1,EcLsi2, andEcLsi6involved in silicon uptake mechanism. In addition, the study also identified and characterized ten different Si transporters genes from finger millet through transcriptome assembly. The phylogenetic study revealed thatEcLsi1andEcLsi6 are homologs whileEcLsi2andEcLsi3 form another pair of homologs.EcLsi1andEcLsi6belong to family of NIP2s (Nod26-like major intrinsic protein),bona fidesilicon transporters, whereasEcLsi2andEcLsi3, an efflux Si transporter, belong to an uncharacterized anion transporter family having a significant identity with putative arsB transporter proteins. Further, the phylogenetic and topology analysis suggest thatEcLsi1andEcLsi2co-evolved during evolution while,EcLsi2andEcLsi3are evolved from eitherEcLsi1and/orEcLsi6by fusion or duplication event. Moreover, these silicon transporters are predicted to be localized in plasma membrane, but their structural differences indicate that they might have differences in their silicon uptake ability. Silicon amendment induces the synergistic defense mechanism by significantly increasing the transcript level of silicon transporter genes (EcLsi1,EcLsi2andEcLsi6) as well as defense hormone regulating genes (EcSAM,EcPALandEcLOX) at 72 hpi (hours of post infestation) in both stem and roots compared to non-silicon treated plants against pink stem borer in finger millet plants. This study will help to understand the molecular defense mechanism for developing strategies for insect pest management.
Second-line Hormonal Therapy for the Management of Metastatic Castration-resistant Prostate Cancer: a Real-World Data Study Using a Claims Database
Authors: Liu Jui-Ming , Lin Cheng-Chia , Liu Kuan-Lin , Lin Cheng-Feng , Chen Bing-Yu , Chen Tien-Hsing , Sun Chi-Chin , Wu Chun-Te
Published: March 2020

We evaluated the efficacy of second-line hormonal therapy for treatment of metastatic castration-resistant prostate cancer (mCRPC) in a real-world retrospective study. We conducted a population-based real-world cohort study of 258 mCRPC patients between 2014 and 2018 using the Chang Gung Research Database (CGRD) of Taiwan. The second-line hormonal therapy included abiraterone acetate and enzalutamide. The clinical efficacy outcomes were overall survival (OS) and prostate-specific antigen (PSA) doubling time. The median PSA level was also assessed. In total, 223 mCRPC patients who underwent second-line hormonal therapy met all of the inclusion and exclusion criteria for this study. Among them, 65 (29.1%) patients were in the PSA response group and 158 (70.9%) were in the non-response group. The median age was 72.9 years. The median OS was 12.3 months (range: 9.9–19.9 months) and 9.6 months (range: 5.3–15.9 months) in the response and non-response groups, respectively, and the respective PSA doubling times were 9.0 months (range: 4.4–11.6 months) and 3.9 months (range: 2.2–9.1 months), with a median follow-up period of 10.5 months. A significantly longer median OS was seen in the PSA response group. This real-world database study demonstrated that clinical outcomes of second-line hormonal therapy were better in patients with a PSA response. Further studies are warranted to achieve a better understanding of second-line hormonal therapy for mCRPC in Asian populations.
Increased genetic diversity from colony merging in termites does not improve survival against a fungal pathogen
Authors: Aguero Carlos M. , Eyer Pierre-André , Vargo Edward L.
Published: March 2020

In some species of social insects the increased genetic diversity from having multiple breeders in a colony has been shown to improve pathogen resistance. Termite species typically found colonies from single mated pairs and therefore may lack the flexibility to buffer pathogen pressure with increased genetic diversity by varying the initial number of reproductives. However, they can later increase group diversity through colony merging, resulting in a genetically diverse, yet cohesive, workforce. In this study, we investigate whether the increased group diversity from colony fusion benefits social immunity in the subterranean termite Reticulitermes flavipes. We confirm previous findings that colonies of R. flavipes will readily merge and we show that workers will equally groom nestmates and non-nestmates after merging. Despite this, the survival of these merged colonies was not improved after exposure to a fungal pathogen, but instead leveled to that of the more susceptible or the more resistant colony. Our study brings little support to the hypothesis that colony fusion may improve immunity through an increase of genetic diversity in R. flavipes. Instead, we find that following exposure to a lethal pathogen, one colony is heavily influential to the entire group’s survival after merging.