bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal MRI to Assess an Aberrant Artery in Bronchopulmonary Sequestration: The Utility of a Single-Shot Turbo Spin Echo Sequence
Authors: Aoki Hidekazu , Miyazaki Osamu , Okamoto Reiko , Tsutsumi Yoshiyuki , Miyasaka Mikiko , Sago Haruhiko , Kanamori Yutaka , Yoshioka Takako , Nosaka Shunsuke
Published: September 2019

Detecting an aberrant artery is the key to diagnosing bronchopulmonary sequestration (BPS) on fetal MRI. Few reports describe the best sequence to use for this purpose. We compared visualization of an aberrant artery in BPS on fetal MRI using single-shot turbo spin echo (SSTSE) and balanced steady state free precession (b-SSFP) sequences. We retrospectively reviewed the fetal MRI of 27 fetuses in which BPS was diagnosed prenatally (2003–2016). From these we selected 15 fetuses with the pathological diagnosis of BPS made postnatally at operation. All fetuses were examined in 1.5 T MRI units using SSTSE and b-SSFP sequences (mean gestational age: 28.4 ± 3.4 weeks). Two pediatric radiologists compared visualization of the aberrant artery using the two sequences. The presence of an aberrant artery was confirmed by postnatal contrast-enhanced CT. The influence of arterial diameter and background heterogeneity of the lung on the diagnostic power was also evaluated. All 15 fetuses clearly showed the aberrant artery on the SSTSE sequence. Conversely, the aberrant arteries detected on the SSTSE sequence were absent in the b-SSFP sequences of eight fetuses, and the other seven fetuses showed ambiguous visualization compared with the SSTSE sequence. Arterial diameter and background heterogeneity did not affect the diagnostic power in either sequence. The SSTSE sequence was superior to the b-SSFP sequence for clear visualization of the aberrant artery in BPS, regardless of the arterial diameter and background heterogeneity.
Women in the Top of the Income Distribution: What Can We Learn From LIS-Data?
Authors: Bobilev Roman , Boschini Anne , Roine Jesper
Published: September 2019

We explore the extent to which LIS-data can be used to shed light on the presence of women in the top of the income distribution. We show developments of the share of women in top groups (P90-100 and P99-100) of the labour income distribution for 28 countries and, when possible, compare to outcomes when including capital incomes. These turn out not to matter much for the share of women in top groups with some important exceptions. Relating our findings to the existing evidence on women in the top of the income distribution based on aggregate tax data, we find that LIS-data give a relatively accurate picture of the basic findings. However, we also note that once we divide the top1 group further, samples quickly become too small to allow further study. For countries where data allows such analysis, we find that having a partner and having children are positively associated with being in top income groups for men, but negatively associated for women. However, time interactions suggest that these differences have decreased over time. Also, top income men are more likely to have partners who are not in the top of the income distribution while this is not the case for top income women. All these results are surprisingly consistent across country groups.
A Review on Deterministic Lateral Displacement for Particle Separation and Detection
Authors: Salafi Thoriq , Zhang Yi , Zhang Yong
Published: September 2019

The separation and detection of particles in suspension are essential for a wide spectrum of applications including medical diagnostics. In this field, microfluidic deterministic lateral displacement (DLD) holds a promise due to the ability of continuous separation of particles by size, shape, deformability, and electrical properties with high resolution. DLD is a passive microfluidic separation technique that has been widely implemented for various bioparticle separations from blood cells to exosomes. DLD techniques have been previously reviewed in 2014. Since then, the field has matured as several physics of DLD have been updated, new phenomena have been discovered, and various designs have been presented to achieve a higher separation performance and throughput. Furthermore, some recent progress has shown new clinical applications and ability to use the DLD arrays as a platform for biomolecules detection. This review provides a thorough discussion on the recent progress in DLD with the topics based on the fundamental studies on DLD models and applications for particle separation and detection. Furthermore, current challenges and potential solutions of DLD are also discussed. We believe that a comprehensive understanding on DLD techniques could significantly contribute toward the advancements in the field for various applications. In particular, the rapid, low-cost, and high-throughput particle separation and detection with DLD have a tremendous impact for point-of-care diagnostics.
The intersectionality of identity‐based victimization in Adolescence:A person‐centered examination of mental health and academic achievement in a U.S. high school
Authors: Price Maggi , Polk Whitney , Hill Nancy E. , Liang Belle , Perella John
Published: September 2019

Introduction

Growing evidence indicates that identity‐based victimization (IBV; e.g., discrimination) is traumatic, and associated with mental health and academic concerns. Youth with multiple stigmatized identities face a higher risk of both victimization and poor mental health. The current study enhances a growing research base on intersectional IBV by examining 1) identity, rather than attribution, 2) a range of IBV experiences, 3) both mental health and academic achievement, 4) the mediating role of discrimination across multiple social identities, and 5) including gender expansive youth within a diverse sample representative of a high school population in the U.S.

Methods

A cluster analysis was conducted to provide a nuanced depiction of intersectionality in a diverse sample of high school students (N = 946; ages 14–20, 44% cisgender boys, 53% cisgender girls, 3% gender expansive youth). Outcome and IBV differences across clusters were examined, in addition to the mediation of cluster membership and outcomes by discrimination.

Results

Three distinct profiles of identity emerged: LGBTQ Youth (24%), Heterosexual Youth of Color (37%), and Heterosexual White Youth (39%). LGBTQ Youth and Heterosexual Youth of Color experienced the most IBV, and had higher levels of depression, lower wellbeing, and lower GPAs. Finally, discrimination partially mediated the association between identity and outcomes for LGBTQ youth, and fully mediated this association for Heterosexual Youth of Color.

Conclusions

The disproportionately of IBV, poor mental health, and lower academic achievement faced by LGBTQ youth and youth with intersecting stigmatized identities suggests that they may benefit from tailored and targeted treatments.
On taphonomy: collages and collections at the Geiseltalmuseum
Authors: GÓMEZ LÓPEZ ANA MARÍA
Published: September 2019

German palaeontologist Johannes Weigelt (1890–1948) was the first proponent of taphonomy – the study of the decay, burial and fossilization of plants, animals and other organisms across geological time. Thousands of his fossil specimens, many recovered from coal fields in central Germany, are stored within the Geiseltalmuseum – a palaeontological collection at the Martin Luther University Halle-Wittenberg, founded by Weigelt in 1934. A significant portion of Weigelt's papers and extensive photographic production related to his taphonomic research are also within the museum's holdings. Amidst these documents, museum curator Dr Meinholf Hellmund and I discovered over forty photo-collages attributable to Weigelt. This visual essay exposes the through-lines between Weigelt's unpublished collages and his academic activities on taphonomy, suggesting the museum archive as a site of ideological fault lines crossing concomitant artistic and scientific production.
Emergency department use in people who experience imprisonment in Ontario, Canada
Authors: Tuinema John , Orkin Aaron M. , Cheng Stephanie Y. , Fung Kinwah , Kouyoumdjian Fiona G.
Published: September 2019

Objectives

The aims of this study were to describe emergency department (ED) utilization by people in provincial prison and on release, and to compare with ED utilization for the general population.

Methods

We linked correctional and health administrative data for people released from provincial prison in Ontario in 2010. We matched each person by age and sex with four people in the general population. We compared ED utilization rates using generalized estimating equations, by sex and for high urgency and ambulatory care sensitive conditions.

Results

People who experienced imprisonment (N = 48,861) had higher ED utilization rates compared with the general population (N = 195,444), with rate ratios of 3.2 (95% CI 3.0–4.4) for men and 6.5 (95% CI 5.6–7.5) for women in prison and a range of rate ratios between 3.1 and 7.7 for men and 4.2 and 8.8 for women over the 2 years after release. Most ED visits were high urgency, and between 1.0% and 5.1% of visits were for ambulatory care sensitive conditions. ED utilization rates increased on release from prison.

Conclusions

People experiencing imprisonment in Ontario have higher ED utilization compared with matched people in the general population, primarily for urgent issues, and particularly in women and in the week after release. Providing high-quality ED care and implementing prison- and ED-based interventions could improve health for this population and prevent the need for ED use.
When ethnic prejudice is political: an experiment in beliefs and hostility toward immigrant out-groups in Italy
Authors: Barisione Mauro
Published: September 2019

When the immigration issue has been strongly politicized, prejudice toward minority out-groups can be profoundly imbued with politics, to the point that citizen responses to partisan cues about immigrants tend to operate on the basis of a ‘political sympathy/antipathy bias’. This article demonstrates that there is a direct causal relation between the nature (i.e. contents and sources) of political communication over immigrants and voters' responses. Drawing on an experimental design based on ITANES (Italian National Election Studies) 2018 election survey data, it isolates the effect that the voters' ideology and party alignments, as well as the partisan source of a message, exert on manifestations of ethnic prejudice, operationalized as the refusal to accept a plausibile and counter-stereotypical statement about immigrants. It concludes that even a mere symbolic change in communication by those party actors (i.e. the League) which ‘own’ the issue would suffice to attenuate hostility toward out-groups, to the extent that it results from sustained partisan rhetoric and mobilization.
Stokes waves with constant vorticity: folds, gaps and fluid bubbles
Authors: Dyachenko Sergey A. , Hur Vera Mikyoung
Published: September 2019

The Stokes wave problem in a constant vorticity flow is formulated, by virtue of conformal mapping techniques, as a nonlinear pseudodifferential equation, involving the periodic Hilbert transform, which becomes the Babenko equation in the irrotational flow setting. The associated linearized operator is self-adjoint, whereby the modified Babenko equation is efficiently solved by the Newton-conjugate gradient method. For strong positive vorticity, a ‘fold’ appears in the wave speed versus amplitude plane, and a ‘gap’ as the vorticity strength increases, bounded by two touching waves, whose profile contacts with itself at the trough line, enclosing a bubble of air. More folds and gaps follow for stronger vorticity. Touching waves at the beginnings of the lowest gaps tend to the limiting Crapper wave as the vorticity strength increases indefinitely or, equivalently, gravitational acceleration vanishes, while the profile encloses a circular bubble of fluid in rigid body rotation at the ends of the gaps. Touching waves at the beginnings of the second gaps tend to the circular vortex wave on top of the limiting Crapper wave in the infinite vorticity limit, or the zero gravity limit, and the circular vortex wave on top of itself at the ends of the gaps. Touching waves for higher gaps accommodate more circular bubbles of fluid.
Tiptoeing the Line Between National Security and Protectionism: A Comparative Approach to Foreign Direct Investment Screening in the United States and European Union
Authors: Jacobs Jason
Published: September 2019

Weaponization of state-backed, foreign investments by China is an emerging national security threat in the United States and the European Union. The U.S. and E.U. have espoused similar policy goals—to address the threat without closing their markets to foreign direct investment—while fostering increased cooperation between allied partners in screening transactions.

On the surface, the recent, China-specific measures taken by the U.S. and the investment screening framework adopted by the E.U. appear reflective of an alignment of those policy goals. Indeed, many commentators have suggested that is exactly what is happening. However, closer examination reveals a stark divergence. The U.S. has a robust screening mechanism that has evolved into a weapon of economic warfare. The E.U. meanwhile, remains a patchwork of conflicting—or nonexistent—national regulations overlaid by a comparatively toothless investment screening framework.

There is a tendency to attribute this divergence to structural differences between the United States and European Union. This in-depth comparison of U.S. and E.U. investment screening mechanisms exposes a split that goes beyond application and into actual policy. This revelation should temper expectations that the E.U. is equipping itself to block transactions that are of concern to the U.S.
The Role of Precedent and Stare Decisis in the World Trade Organization's Dispute Settlement Body
Authors: Flowers Zachary
Published: September 2019

The World Trade Organization was established in 1995 and brought together countries from around the world for the purpose of fairly regulating the trade of goods, services, and intellectual property between its member states. While treaties and other trade agreements have existed between countries for hundreds of years, the WTO's most significant innovation is its dispute settlement process through the Dispute Settlement Body. Countries agree to be bound to the decisions of the DSB upon their admittance into the WTO. The DSB is a two-tiered adjudicative system consisting of the lower panels and the higher Appellate Body.

The United States, under both the Obama and Trump administrations, has blocked the appointment of AB judges. This tactic has limited the number of active judges to three. The AB normally has seven members. The United States has listed a number of reasons for their boycott of the system, among them is that the AB is functioning as if its reports are to be binding precedent on the lower panel and to future DSB cases, in a manner similar to stare decisis. This issue has been observed over the years and there is conflict between interpretations of precedent under Article 3:2 of the Dispute Settlement Understanding and Article IX:2 of the WTO Agreement. Caselaw of the DSB from over the years has also raised interesting questions and the appearance of the use of precedent.

This article will be examining the historical fundamentals and use of precedent and the doctrine of stare decisis. It will then turn into an examination of the institutional and regulatory framework of the WTO, particularly Article 3:2 of the DSU and Article IX:2 of the WTO Agreement, and whether it allows or leaves room for a system of binding precedent. Finally, jurisprudence of the DSB will be surveyed for evidence of this system. Reports that will be examined are Japan-Alcoholic Beverages, India-Patents, India-Autos, and Australia-Plain Packaging Tobacco.
Provincial, Proletarian, and Multinational: The Antibureaucratic Revolution in Late 1980s Priboj, Serbia
Authors: Musić Goran
Published: September 2019

Moving the focus away from the epicenters of the antibureaucratic revolution, this article looks at the echoes of this movement in the provincial, multinational, working-class community of Priboj, Serbia. A microstudy of Fabrika automobila Priboj, the town’s largest employer, and its surrounding community through records of self-management and party meetings and through the local press reveals some of the less-researched aspects of the social mobilizations in Serbia in the late 1980s. Without downplaying the spread of national grievances, this study highlights parallel phenomena taking place on the ground, such as labor solidarity, growing socioeconomic grievances, and the participation of non-Serb (in this case, Muslim) populations. The argument is that the presence of a large factory with a multinational workforce in the center of the municipality as the organizational core of the mobilizations and their focus on local problems helped Priboj’s antibureaucratic bevolution resemble the proletarian, pro-Yugoslav image that the leadership of the Serbian party often hoped to project.
Misruling the Masses: The Consequences of Cracking Down in Kyrgyzstan
Authors: Sullivan Charles
Published: September 2019

Can nondemocratic leaders initiate a crackdown against mass protesters and suffer little in the way of political-reputational costs? In conceptualizing a “crackdown” as a government-orchestrated violent restriction of civil society involving the killing of civilians, this article analyzes how the use of force is perceived by ordinary citizens when their government represses a portion of the populace. In analyzing the findings of a 2016 survey that gauges contemporary attitudes toward the overthrow of presidents Askar Akaev (in 2005) and Kurmanbek Bakiev (in 2010), this article argues that Kyrgyzstanis evaluate the Bakiev administration more negatively than they do the Akaev administration because of the former’s resort to forceful measures in attempting to quell mass protesters in April 2010. Such findings imply that nondemocratic leaders who employ force against mass protesters incur significant political-reputational costs, irrespective as to whether the wider public views the mass protests as legitimate or not.
Love, Truth and Moral Judgement
Authors: Carr David
Published: September 2019

A famous section of 1 Corinthians and some influential passages in the work of Iris Murdoch seem to suppose a significant connection between the higher human love of agape and moral knowledge: that, perhaps, the former may provide access to the latter. Following some sceptical attention to this possibility, this paper turns to a more modest suggestion of Plato's Symposium that the ‘lower’ human love of eros might be a transitional stage to higher moral love or knowledge of the good. Still, while conceding that this may be so, the present paper argues that any moral transformations of such loves would need to be informed by moral wisdom or knowledge rather than vice versa. However, the paper concludes that there are ultimately deep and perhaps irreconcilable tensions between the epistemic and agapeic dimensions of moral life.
A model-driven approach to better identify older people at risk of depression
Authors: Gennaro Chiara , Paccagnella Omar , Zaninotto Paola
Published: September 2019

Depression in later life is one of the most common mental disorders. Several instruments have been developed to detect the presence or the absence of certain symptoms or emotional disorders, based on cut-off points. However, the use of a cut-off does not allow identification of depression sub-types or distinguish between mild and severe depression. As a result, depression may be under- or over-diagnosed in older people. This paper aims to apply a model-driven approach to classify individuals into distinct sub-groups, based on different combinations of depressive and emotional conditions. This approach is based on two distinct statistical solutions: first, a latent class analysis is applied to the items collected by the depression scale and, according to the final model, the probability of belonging to each class is calculated for every individual. Second, a factor analysis of these classes is performed to obtain a reduced number of clusters for easy interpretation. We use data collected through the EURO-D scale in a large sample of older individuals, participants of the sixth wave of the Survey of Health, Ageing and Retirement in Europe. We show that by using such a model-based approach it is possible to classify individuals in a more accurate way than the simple dichotomisation ‘depressed’ versus ‘non-depressed’.
A Critical Analysis of Joseph Fins’ Mosaic Decisionmaking: A Response to “Mosaic Decisionmaking and Reemergent Agency after Severe Brain Injury” (CQ 27 (1))
Authors: PETERSON ANDREW
Published: September 2019

In this paper, the author argues that Joseph Fins’ mosaic decisionmaking model for brain-injured patients is untenable. He supports this claim by identifying three problems with mosaic decisionmaking. First, that it is unclear whether a mosaic is a conceptually adequate metaphor for a decisionmaking process that is intended to promote patient autonomy. Second, that the proposed legal framework for mosaic decisionmaking is inappropriate. Third, that it is unclear how we ought to select patients for participation in mosaic decisionmaking.
Detention, Capacity, and Treatment in the Mentally Ill—Ethical and Legal Challenges
Authors: CHIN H. PAUL
Published: September 2019

For individuals whose mental illness impair their ability to accept appropriate care—the depressed, acutely suicidal mother, or the psychotic lawyer too paranoid to eat any food—statutes exist to permit involuntary hospitalization, a temporary override of paternalistic benefice over personal autonomy. This exception to the primacy of personal autonomy at the core of bioethics has the aim of restoring the mental health of the temporarily incapacitated individual, and with it, their autonomy.
New suburbia, now: The possibilities of modular construction
Authors: Latham Mark , Sookhoo Dhruv
Published: September 2019

Mark Latham is an advocate of modern methods of construction in residential design and development. He reflects upon how contemporary approaches to modular housing can reshape residents’ experiences of suburban settings.
The Early Growth and Development Study: A Dual-Family Adoption Study from Birth Through Adolescence
Authors: Leve Leslie D. , Neiderhiser Jenae M. , Ganiban Jody M. , Natsuaki Misaki N. , Shaw Daniel S. , Reiss David
Published: September 2019

The Early Growth and Development Study (EGDS) is a prospective adoption study of birth parents, adoptive parents and adopted children (n= 561 adoptees). The original sample has been expanded to include siblings of the EGDS adoptees who were reared by the birth mother and assessed beginning at age 7 years (n= 217 biological children), and additional siblings in both the birth and adoptive family homes, recruited when the adoptees were 8–15 years old (n= 823). The overall study aims are to examine how family, peer and contextual processes affect child and adolescent adjustment, and to examine their interplay (mediation, moderation) with genetic influences. Adoptive and birth parents were originally recruited through adoption agencies located throughout the USA following the birth of a child. Assessments are ongoing and occurred in 9 month’s intervals until the adoptees turned 3 years of age, and in 1 to 2 year intervals thereafter through age 15. Data collection includes the following primary constructs: child temperament, behavior problems, mental health, peer relations, executive functioning, school performance and health; birth and adoptive parent personality characteristics, mental health, health, context, substance use, parenting and marital relations; and the prenatal environment. Findings highlight the power of the adoption design to detect environmental influences on child development and provide evidence of complex interactions and correlations between genetic, prenatal environmental and postnatal environmental influences on a range of child outcomes. The study sample, procedures and an overview of findings are summarized and ongoing assessment activities are described.
A New Proxy for Past Precipitation
Authors: Wheeling Kate
Published: September 2019

Researchers used luminescence signals from marine sediment cores to bolster estimates of precipitation levels on land over the past 30,000 years.
AMPKα1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation
Authors: Wang Ying-Nan , Lu Yun-Xin , Liu Jie , Jin Ying , Bi Hui-Chang , Zhao Qi , Liu Ze-Xian , Li Ying-Qin , Hu Jia-Jia , Sheng Hui , Jiang Yi-Ming , Zhang Chao , Tian Feng , Chen Yang , Pan Zhi-Zhong , Chen Gong , Zeng Zhao-Lei , Liu Kai-Yan , Ogasawara Marcia , Yun Jin-Ping , Ju Huai-Qiang , Feng Jian-Xiong , Xie Dan , Gao Song , Jia Wei-Hua , Kopetz Scott , Xu Rui-Hua , Wang Feng
Published: September 2019

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction–oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.
ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942
Authors: Sava Georgina P. , Fan Hailing , Fisher Rosemary A. , Lusvarghi Sabrina , Pancholi Sunil , Ambudkar Suresh V. , Martin Lesley-Ann , Charles Coombes R. , Buluwela Lakjaya , Ali Simak
Published: September 2019

The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become resistant to CDK7i. Resistant lines were established through continuous drug selection. ABC-transporter copy number, expression and activity were examined using real-time PCR, immunoblotting and flow cytometry. Drug responses were measured using growth assays. ABCB1 was upregulated in ICEC0942-resistant cells and there was cross-resistance to THZ1. THZ1-resistant cells upregulated ABCG2 but remained sensitive to ICEC0942. Drug resistance in both cell lines was reversible upon inhibition of ABC-transporters. CDK7i response was altered in adriamycin- and mitoxantrone-resistant cell lines demonstrating ABC-transporter upregulation. ABCB1 expression correlated with ICEC0942 and THZ1 response, and ABCG2 expression with THZ2 response, in a panel of cancer cell lines. We have identified ABCB1 upregulation as a common mechanism of resistance to ICEC0942 and THZ1, and confirmed that ABCG2 upregulation is a mechanism of resistance to THZ1. The identification of potential mechanisms of CDK7i resistance and differences in susceptibility of ICEC0942 and THZ1 to ABC-transporters, may help guide their future clinical use.
NRXN1 is associated with enlargement of the temporal horns of the lateral ventricles in psychosis
Authors: Alliey-Rodriguez Ney , Grey Tamar A. , Shafee Rebecca , Asif Huma , Lutz Olivia , Bolo Nicolas R. , Padmanabhan Jaya , Tandon Neeraj , Klinger Madeline , Reis Katherine , Spring Jonathan , Coppes Lucas , Zeng Victor , Hegde Rachal R. , Hoang Dung T. , Bannai Deepthi , Nawaz Uzma , Henson Philip , Liu Siyuan , Gage Diane , McCarroll Steven , Bishop Jeffrey R. , Hill Scot , Reilly James L. , Lencer Rebekka , Clementz Brett A. , Buckley Peter , Glahn David C. , Meda Shashwath A. , Narayanan Balaji , Pearlson Godfrey , Keshavan Matcheri S. , Ivleva Elena I. , Tamminga Carol , Sweeney John A. , Curtis David , Badner Judith A. , Keedy Sarah , Rapoport Judith , Liu Chunyu , Gershon Elliot S.
Published: September 2019

Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles (THLV) is associated with an intronic SNP of the gene NRXN1 (rs12467877,P = 6.76E–10), which accounts for 4.5% of the variance in size. Enlarged THLV is associated with psychosis in this sample, and with reduction of the hippocampus and enlargement of the choroid plexus and caudate. Eight other suggestively significant associations (P < 5.5E–8) were identified with THLV and 5 other brain structures. Although rare deletions of NRXN1 have been previously associated with psychosis, this is the first report of a common SNP variant of NRXN1 associated with enlargement of the THLV in psychosis.
The lytic activity of VSV-GP treatment dominates the therapeutic effects in a syngeneic model of lung cancer
Authors: Schreiber Liesa-Marie , Urbiola Carles , Das Krishna , Spiesschaert Bart , Kimpel Janine , Heinemann Fabian , Stierstorfer Birgit , Müller Philipp , Petersson Monika , Erlmann Patrik , von Laer Dorothee , Wollmann Guido
Published: September 2019

Background

Oncolytic virotherapy is thought to result in direct virus-induced lytic tumour killing and simultaneous activation of innate and tumour-specific adaptive immune responses. Using a chimeric vesicular stomatitis virus variant VSV-GP, we addressed the direct oncolytic effects and the role of anti-tumour immune induction in the syngeneic mouse lung cancer model LLC1.

Methods

To study a tumour system with limited antiviral effects, we generated interferon receptor-deficient cells (LLC1-IFNAR1−/−). Therapeutic efficacy of VSV-GP was assessed in vivo in syngeneic C57BL/6 and athymic nude mice bearing subcutaneous tumours. VSV-GP treatment effects were analysed using bioluminescent imaging (BLI), immunohistochemistry, ELISpot, flow cytometry, multiplex ELISA and Nanostring® assays.

Results

Interferon insensitivity correlated with VSV-GP replication and therapeutic outcome. BLI revealed tumour-to-tumour spread of viral progeny in bilateral tumours. Histological and gene expression analysis confirmed widespread and rapid infection and cell killing within the tumour with activation of innate and adaptive immune-response markers. However, treatment outcome was increased in the absence of CD8+T cells and surviving mice showed little protection from tumour re-challenge, indicating limited therapeutic contribution by the activated immune system.

Conclusion

These studies present a case for a predominantly lytic treatment effect of VSV-GP in a syngeneic mouse lung cancer model.
Identification of significant chromatin contacts from HiChIP data by FitHiChIP
Authors: Bhattacharyya Sourya , Chandra Vivek , Vijayanand Pandurangan , Ay Ferhat
Published: September 2019

HiChIP/PLAC-seq is increasingly becoming popular for profiling 3D chromatin contacts among regulatory elements and for annotating functions of genetic variants. Here we describe FitHiChIP, a computational method for loop calling from HiChIP/PLAC-seq data, which jointly models the non-uniform coverage and genomic distance scaling of contact counts to compute statistical significance estimates. We also develop a technique to filter putative bystander loops that can be explained by stronger adjacent loops. Compared to existing methods, FitHiChIP performs better in recovering contacts reported by Hi-C, promoter capture Hi-C and ChIA-PET experiments and in capturing previously validated promoter-enhancer interactions. FitHiChIP loop calls are reproducible among replicates and are consistent across different experimental settings. Our work also provides a framework for differential HiChIP analysis with an option to utilize ChIP-seq data for further characterizing differential loops. Even though designed for HiChIP, FitHiChIP is also applicable to other conformation capture assays.
Neural JNK3 regulates blood flow recovery after hindlimb ischemia in mice via an Egr1/Creb1 axis
Authors: Kant Shashi , Craige Siobhan M. , Chen Kai , Reif Michaella M. , Learnard Heather , Kelly Mark , Caliz Amada D. , Tran Khanh-Van , Ramo Kasmir , Peters Owen M. , Freeman Marc , Davis Roger J. , Keaney John F.
Published: September 2019

Diseases related to impaired blood flow such as peripheral artery disease (PAD) impact nearly 10 million people in the United States alone, yet patients with clinical manifestations of PAD (e.g., claudication and limb ischemia) have limited treatment options. In ischemic tissues, stress kinases such as c-Jun N-terminal kinases (JNKs), are activated. Here, we show that inhibition of the JNK3 (Mapk10) in the neural compartment strikingly potentiates blood flow recovery from mouse hindlimb ischemia. JNK3 deficiency leads to upregulation of growth factors such asVegfa,Pdgfb,Pgf,HbegfandTgfb3in ischemic muscle by activation of the transcription factors Egr1/Creb1. JNK3 acts through Forkhead box O3 (Foxo3a) to suppress the activity of Egr1/Creb1 transcription regulators in vitro. In JNK3-deficient cells, Foxo3a is suppressed which leads to Egr1/Creb1 activation and upregulation of downstream growth factors. Collectively, these data suggest that the JNK3-Foxo3a-Egr1/Creb1 axis coordinates the vascular remodeling response in peripheral ischemia.
Evolution of acoustic communication in blind cavefish
Authors: Hyacinthe Carole , Attia Joël , Rétaux Sylvie
Published: September 2019

Acoustic communication allows the exchange of information within specific contexts and during specific behaviors. The blind, cave-adapted and the sighted, river-dwelling morphs of the species Astyanax mexicanus have evolved in markedly different environments. During their evolution in darkness, cavefish underwent a series of morphological, physiological and behavioral changes, allowing the study of adaptation to drastic environmental change. Here we discover that Astyanax is a sonic species, in the laboratory and in the wild, with sound production depending on the social contexts and the type of morph. We characterize one sound, the “Sharp Click”, as a visually-triggered sound produced by dominant surface fish during agonistic behaviors and as a chemosensory-, food odor-triggered sound produced by cavefish during foraging. Sharp Clicks also elicit different reactions in the two morphs in play-back experiments. Our results demonstrate that acoustic communication does exist and has evolved in cavefish, accompanying the evolution of its behaviors.
Visualization of supercritical water pseudo-boiling at Widom line crossover
Authors: Maxim Florentina , Contescu Cristian , Boillat Pierre , Niceno Bojan , Karalis Konstantinos , Testino Andrea , Ludwig Christian
Published: September 2019

Supercritical water is a green solvent used in many technological applications including materials synthesis, nuclear engineering, bioenergy, or waste treatment and it occurs in nature. Despite its relevance in natural systems and technical applications, the supercritical state of water is still not well understood. Recent theories predict that liquid-like (LL) and gas-like (GL) supercritical water are metastable phases, and that the so-called Widom line zone is marking the crossover between LL and GL behavior of water. With neutron imaging techniques, we succeed to monitor density fluctuations of supercritical water while the system evolves rapidly from LL to GL as the Widom line is crossed during isobaric heating. Our observations show that the Widom line of water can be identified experimentally and they are in agreement with the current theory of supercritical fluid pseudo-boiling. This fundamental understanding allows optimizing and developing new technologies using supercritical water as a solvent.
Enhancing and controlling valley magnetic response in MoS2/WS2 heterostructures by all-optical route
Authors: Zhang Jing , Du Luojun , Feng Shun , Zhang Run-Wu , Cao Bingchen , Zou Chenji , Chen Yu , Liao Mengzhou , Zhang Baile , Yang Shengyuan A. , Zhang Guangyu , Yu Ting
Published: September 2019

Van der Waals heterostructures of transition metal dichalcogenides with interlayer coupling offer an exotic platform to realize fascinating phenomena. Due to the type II band alignment of these heterostructures, electrons and holes are separated into different layers. The localized electrons induced doping in one layer, in principle, would lift the Fermi level to cross the spin-polarized upper conduction band and lead to strong manipulation of valley magnetic response. Here, we report the significantly enhanced valley Zeeman splitting and magnetic tuning of polarization for the direct optical transition of MoS2 in MoS2/WS2 heterostructures. Such strong enhancement of valley magnetic response in MoS2 stems from the change of the spin-valley degeneracy from 2 to 4 and strong many-body Coulomb interactions induced by ultrafast charge transfer. Moreover, the magnetic splitting can be tuned monotonically by laser power, providing an effective all-optical route towards engineering and manipulating of valleytronic devices and quantum-computation.
A shared core microbiome in soda lakes separated by large distances
Authors: Zorz Jackie K. , Sharp Christine , Kleiner Manuel , Gordon Paul M. K. , Pon Richard T. , Dong Xiaoli , Strous Marc
Published: September 2019

In alkaline soda lakes, concentrated dissolved carbonates establish productive phototrophic microbial mats. Here we show how microbial phototrophs and autotrophs contribute to this exceptional productivity. Amplicon and shotgun DNA sequencing data of microbial mats from four Canadian soda lakes indicate the presence of > 2,000 species of Bacteria and Eukaryotes. We recover metagenome-assembled-genomes for a core microbiome of < 100 abundant bacteria, present in all four lakes. Most of these are related to microbes previously detected in sediments of Asian alkaline lakes, showing that common selection principles drive community assembly from a globally distributed reservoir of alkaliphile biodiversity. Detection of > 7,000 proteins show how phototrophic populations allocate resources to specific processes and occupy complementary niches. Carbon fixation proceeds by the Calvin-Benson-Bassham cycle, in Cyanobacteria, Gammaproteobacteria, and, surprisingly, Gemmatimonadetes. Our study provides insight into soda lake ecology, as well as a template to guide efforts to engineer biotechnology for carbon dioxide conversion.
Quantitative expression of MMPs 2, 9, 14, and collagen IV in LCIS and paired normal breast tissue
Authors: Nyante Sarah J. , Wang Tengteng , Tan Xianming , Ozdowski Emily F. , Lawton Thomas J.
Published: September 2019

Certain matrix metalloproteinases (MMPs) have the ability to degrade collagen IV, a main component of the breast lobular basement membrane. In this cross-sectional study, we evaluated expression of MMPs 2, 9, and 14 and collagen IV in LCIS and adjacent normal breast tissue among LCIS patients without invasive breast cancer to determine whether expression differed between benign and preinvasive breast epithelial tissue. A total of 64 LCIS patients, diagnosed 2004–2014, were included; 44 had sufficient paired normal tissue for analysis. Marker epithelial expression was measured using immunofluorescence and quantified using the H score (MMPs) or pixel intensity (collagen IV). Associations were evaluated using the Spearman correlation or the Wilcoxon signed-rank test. In LCIS and normal tissue, there was a strong correlation between MMP2 and MMP14 expression (LCIS r = 0.69, normal r = 0.81, both P < 0.01). Other pairwise correlations were moderate to weak (range: LCIS r = 0.32–0.47, normal r = 0.19–0.32). For all markers, expression was lower in LCIS vs. normal tissue (all P ≤ 0.05). In sum, collagenase MMPs were expressed in normal breast and LCIS lesions of LCIS patients. However, expression was not higher in LCIS compared with normal tissue, suggesting collagenase MMP expression does not increase as breast tissue gains a more proliferative phenotype.
Estimating the Frequency of Single Point Driver Mutations across Common Solid Tumours
Authors: Darbyshire Madeleine , du Toit Zachary , Rogers Mark F. , Gaunt Tom R. , Campbell Colin
Published: September 2019

For cancers, such as common solid tumours, variants in the genome give a selective growth advantage to certain cells. It has recently been argued that the mean count of coding single nucleotide variants acting as disease-drivers in common solid tumours is frequently small in size, but significantly variable by cancer type (hypermutation is excluded from this study). In this paper we investigate this proposal through the use of integrative machine-learning-based classifiers we have proposed recently for predicting the disease-driver status of single nucleotide variants (SNVs) in the human cancer genome. We find that predicted driver counts are compatible with this proposal, have similar variabilities by cancer type and, to a certain extent, the drivers are identifiable by these machine learning methods. We further discuss predicted driver counts stratified by stage of disease and driver counts in non-coding regions of the cancer genome, in addition to driver-genes.
Cohesion-driven mixing and segregation of dry granular media
Authors: Jarray Ahmed , Shi Hao , Scheper Bert J. , Habibi Mehdi , Luding Stefan
Published: September 2019

Granular segregation is a common, yet still puzzling, phenomenon encountered in many natural and engineering processes. Here, we experimentally investigate the effect of particles cohesion on segregation in dry monodisperse and bidisperse systems using a rotating drum mixer. Chemical silanization, glass surface functionalization via a Silane coupling agent, is used to produce cohesive dry glass particles. The cohesive force between the particles is controlled by varying the reaction duration of the silanization process, and is measured using an in-house device specifically designed for this study. The effects of the cohesive force on flow and segregation are then explored and discussed. For monosized particulate systems, while cohesionless particles perfectly mix when tumbled, highly cohesive particles segregate. For bidisperse mixtures of particles, an adequate cohesion-tuning reduces segregation and enhances mixing. Based on these results, a simple scheme is proposed to describe the system’s mixing behaviour with important implications for the control of segregation or mixing in particulate industrial processes.
Simple 3D culture of dissociated kidney mesenchyme mimics nephron progenitor niche and facilitates nephrogenesis Wnt-independently
Authors: Dapkunas Arvydas , Rantanen Ville , Gui Yujuan , Lalowski Maciej , Sainio Kirsi , Kuure Satu , Sariola Hannu
Published: September 2019

Kidney mesenchyme (KM) and nephron progenitors (NPs) depend on WNT activity, and their culture in vitro requires extensive repertoire of recombinant proteins and chemicals. Here we established a robust, simple culture of mouse KM using a combination of 3D Matrigel and growth media supplemented with Fibroblast Growth Factor 2 (FGF2) and Src inhibitor PP2. This allows dissociated KM to spontaneously self-organize into spheres. To reassess the requirement of WNT activity in KM self-organization and NPs maintenance, cells were cultured with short pulse of high-dose GSK3β inhibitor BIO, on a constant low-dose or without BIO. Robust proliferation at 48 hours and differentiation at 1 week were observed in cultures with high BIO pulse. Importantly, dissociated KM cultured without BIO, similarly to that exposed to constant low dose of BIO, maintained NPs up to one week and spontaneously differentiated into nephron tubules at 3 weeks of culture. Our results show that KM is maintained and induced to differentiate in a simple culture system. They also imply that GSK3β/WNT-independent pathways contribute to the maintenance and induction of mouse KM. The robust and easy 3D culture enables further characterization of NPs, and may facilitate disease modeling when applied to human cells.
Comparative transcriptome analysis of the human endocervix and ectocervix during the proliferative and secretory phases of the menstrual cycle
Authors: Mukhopadhyay S. , Liang Y. , Hur H. , Villegas G. , Calenda G. , Reis A. , Millen L. , Barnable P. , Mamkina L. , Kumar N. , Kalir T. , Sperling R. , Teleshova N.
Published: September 2019

Despite extensive studies suggesting increased susceptibility to HIV during the secretory phase of the menstrual cycle, the molecular mechanisms involved remain unclear. Our goal was to analyze transcriptomes of the endocervix and ectocervix during the proliferative and secretory phases using RNA sequencing to explore potential molecular signatures of susceptibility to HIV. We identified 202 differentially expressed genes (DEGs) between the proliferative and secretory phases of the cycle in the endocervix (adjusted p < 0.05). The biofunctions and pathways analysis of DEGs revealed that cellular assembly and epithelial barrier function in the proliferative phase and inflammatory response/cellular movement in the secretory phase were among the top biofunctions and pathways. The gene set enrichment analysis of ranked DEGs (score = log fold change/p value) in the endocervix and ectocervix revealed that (i) unstimulated/not activated immune cells gene sets positively correlated with the proliferative phase and negatively correlated with the secretory phase in both tissues, (ii) IFNγ and IFNα response gene sets positively correlated with the proliferative phase in the ectocervix, (iii) HIV restrictive Wnt/β-catenin signaling pathway negatively correlated with the secretory phase in the endocervix. Our data show menstrual cycle phase-associated changes in both endocervix and ectocervix, which may modulate susceptibility to HIV.