bluuebunny/crossref_metadata_2025 huggingface dataset:
The Bible Abbreviated: Summaries in Early Modern English Bibles
Authors: Horbury Ezra
Published: April 2019

Early modern English Bibles are among the most significant texts in western Christianity. They contained the translation of the Bible into English and its authorisation, they facilitated the Protestant Reformation, and their effects on English Christianity and culture are felt vividly to this day. A vital facet of these editions are paratexts: the titles, summaries, glosses, and other non-canonical additions appended to scripture to aid its organisation and interpretation. Though neglected by literary, historical, and theological scholarship, these paratexts comprised huge portions of early modern Bibles and acted as productive vehicles to disseminate politics and theologies. One such form of paratext are the casus summarii, the chapter summaries that precede many chapters in early modern Bibles. In these summaries, significant biblical events or controversial subjects were condensed, omitted, reframed, rephrased, or otherwise represented to suit the editor’s purposes. This article provides the first survey of the chapter summaries in early modern English Bibles, with a table detailing the extent to which they were copied between editions. The article focuses on the Matthew, Geneva, and KJV Bibles, with additional discussion of the Coverdale, Great, and Bishops’ Bibles. The article addresses notable aspects of this material, including practices of translation, representations of Sodom, the anglicisation of names, and the sexualisation of Eve. By explicating the origins and influences of these summaries, this article facilitates the understanding and study of paratexts and demonstrates their importance to scholarship of early modern Christianity.
Redefining the Feminine in Kathakali
Authors: Madhavan Arya
Published: April 2019

In this article Arya Madhavan examines the significance of the female protagonist Asti from the new Kathakali play, A Tale from Magadha (2015), in the four-hundred-year-old patriarchal history of Kathakali. The play is authored by Sadanam Harikumar, a Kathakali playwright and actor, whose contemporary retelling of Hindu myths and epics afford substantial agency to the female characters, compelling radical reimagining of Kathakali’s gender norms and a reconsideration of the significance of female characters, both on the stage and in the text. Asti unsettles the conventional norms of womanhood that have defined and structured the ‘Kathakali woman’ over the last five centuries. Although several new Kathakali plays have been created in recent decades, they seldom include strong female roles, so Harikumar’s plays, and his female characters in particular, deserve a historic place in the Kathakali tradition, whose slowly changing gender norms are here analyzed for the first time. Arya Madhavan is a senior lecturer in the University of Lincoln. She has been developing the research area of women in Asian performance since 2013 and edited Women in Asian Performance: Aesthetics and Politics (Routledge, 2017). She is a performer of Kutiyattam, the oldest Sanskrit theatre form from India, and serves as associate editor for the Indian Theatre Journal.
HPV infection in semen: results from a new molecular approach
Authors: Capra G. , Schillaci R. , Bosco L. , Roccheri M. C. , Perino A. , Ragusa M. A.
Published: April 2019

Human papillomavirus (HPV) is the agent of the most common sexually transmitted diseases causing a variety of clinical manifestations ranging from warts to cancer. Oncogenic HPV infection is the major cause of cervical cancer and less frequently of penile cancers. Its presence in semen is widely known, but the effects on fertility are still controversial. We developed a new approach to evaluate virus localisation in the different semen components. We analysed also the specific genotype localisation and viral DNA quantity by qPCR. Results show that HPV DNA can be identified in every fraction of semen: spermatozoa, somatic cells and seminal plasma. Different samples can contain the HPV DNA in different fractions and several HPV genotypes can be found in the same fraction. Additionally, different fractions may contain multiple HPV genotypes in different relative quantity. We analysed the wholeness of HPV DNA in sperm cells by qPCR. In one sample more than half of viral genomes were defective, suggesting a possible recombination event. The new method allows to easily distinguish different sperm infections and to observe the possible effects on semen. The data support the proposed role of HPV in decreased fertility and prompt new possible consequences of the infection in semen.
A public announcement separation logic
Authors: Courtault J.R. , van Ditmarsch H. , Galmiche D.
Published: April 2019

We define a Public Announcement Separation Logic (PASL) that allows us to consider epistemic possible worlds as resources that can be shared or separated, in the spirit of separation logics. After studying its semantics and illustrating its interest for modelling systems, we provide a sound and complete tableau calculus that deals with resource, agent and announcement constraints and give also a countermodel extraction method.
Logic is a harsh mistress: welfare economics for economists
Authors: Leeson Peter T.
Published: April 2019

Every economic explanation assumes maximization. How strange, then, that few economists accept one of maximization's most straightforward implications:every observed institution is efficient. My aim is to persuade economists of this fact and thus to dissuade them from making illogical claims about social welfare. To frame my argument, I consider the “property rights approach” to institutions developed by Yoram Barzel. I speculate that economists resist what maximization implies about institutional efficiency because they think that efficiency-always precludes them from improving the world, and hope of improving the world is what attracted them to economics in the first place. But, besides being inconsistent, resistance is unnecessary: efficiency-always does not preclude economists, or anyone else, from improving the world.
Cognitive behavioural therapy training in Tanzania: a qualitative study of clinicians’ experiences
Authors: Stone Lydia , Arroll Megan A.
Published: April 2019

Cognitive behaviour therapy (CBT) in an effective technique used widely in Western countries. However, there is limited evidence as to the utility, perception and understanding of CBT in developing countries. This study describes and investigates the experience of CBT training and practice in a group of practitioners in Tanzania. A qualitative approach to the investigation was used, and seven participants from Tanzania’s only psychiatric hospital who had completed CBT training were interviewed. The resulting verbatim transcripts were analysed via interpretative phenomenological analysis. Five superordinate themes emerged from the analysis: ‘the medical model’, ‘novelty’, ‘practicalities’, ‘process’ and ‘therapist effects’. The two themes ‘therapist effects’ and ‘process’ are discussed in detail as these may be particularly relevant to the clinical application of the therapy in a new culture and context. The implications for future development of CBT in Tanzania are considered. In developing CBT for dissemination in Tanzania, specific cultural and clinical issues highlighted by indigenous clinicians need consideration.

Key learning aims

(1)

To identify what range of factors may influence clinicians’ perception of and learning about CBT when CBT training is delivered in a mental health setting in Tanzania, or to those with East African origins.

(2)

To consider the use of qualitative research approaches to inform the early stages of adapting CBT for use in new settings and applications.

(3)

To be able to apply knowledge about cultural differences to standard CBT in order to promote culturally sensitive practice.
The Role of Zinc in Thyroid Hormones Metabolism
Authors: Severo Juliana Soares , Morais Jennifer Beatriz Silva , de Freitas Taynáh Emannuelle Coelho , Andrade Ana Letícia Pereira , Feitosa Mayara Monte , Fontenelle Larissa Cristina , de Oliveira Ana Raquel Soares , Cruz Kyria Jayanne Clímaco , do Nascimento Marreiro Dilina
Published: April 2019

Abstract. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.
The Slow Slip of Viscous Faults
Authors: Viesca Robert C. , Dublanchet Pierre
Published: April 2019

We examine a simple mechanism for the spatiotemporal evolution of transient, slow slip. We consider the problem of slip on a fault that lies within an elastic continuum and whose strength is proportional to sliding rate. This rate dependence may correspond to a viscously deforming shear zone or the linearization of a nonlinear, rate‐dependent fault strength. We examine the response of such a fault to external forcing, such as local increases in shear stress or pore fluid pressure. We show that the slip and slip rate are governed by a type of diffusion equation, the solution of which is found using a Green's function approach. We derive the long‐time, self‐similar asymptotic expansion for slip or slip rate, which depend on both time t and a similarity coordinate η = x/t, where x denotes fault position. The similarity coordinate shows a departure from classical diffusion and is owed to the nonlocal nature of elastic interaction among points on an interface between elastic half‐spaces. We demonstrate the solution and asymptotic analysis of several example problems. Following sudden impositions of loading, we show that slip rate ultimately decays as 1/t while spreading proportionally to t, implying both a logarithmic accumulation of displacement and a constant moment rate. We discuss the implication for models of postseismic slip as well as spontaneously emerging slow slip events.
Upscaling and Prediction of Lagrangian Velocity Dynamics in Heterogeneous Porous Media
Authors: Hakoun Vivien , Comolli Alessandro , Dentz Marco
Published: April 2019

The understanding of the dynamics of Lagrangian velocities is key for the understanding and upscaling of solute transport in heterogeneous porous media. The prediction of large‐scale particle motion in a stochastic framework implies identifying the relation between the Lagrangian velocity statistics and the statistical characteristics of the Eulerian flow field and the hydraulic medium properties. In this paper, we approach both challenges from numerical and theoretical points of view. Direct numerical simulations of Darcy‐scale flow and particle motion give detailed information on the evolution of the statistics of particle velocities both as a function of travel time and distance along streamlines. Both statistics evolve from a given initial distribution to different steady‐state distributions, which are related to the Eulerian velocity probability density function. Furthermore, we find that Lagrangian velocities measured isochronally as a function of travel time show intermittency dominated by low velocities, which is removed when measured equidistantly as a function of travel distance. This observation gives insight into the stochastic dynamics of the particle velocity series. As the equidistant particle velocities show a regular random pattern that fluctuates on a characteristic length scale, it is represented by two stationary Markov processes, which are parametrized by the distribution of flow velocities and a correlation distance. The velocity Markov models capture the evolution of the Lagrangian velocity statistics in terms of the Eulerian flow properties and a characteristics length scale and shed light on the role of the initial conditions and flow statistics on large‐scale particle motion.
High‐Speed Quantification of Pore‐Scale Multiphase Flow of Water and Supercritical CO2 in 2‐D Heterogeneous Porous Micromodels: Flow Regimes and Interface Dynamics
Authors: Li Yaofa , Blois Gianluca , Kazemifar Farzan , Christensen Kenneth T.
Published: April 2019

The pore‐scale flow of CO2 and water in 2‐D heterogeneous porous micromodels over a Ca range of nearly three orders of magnitude was explored experimentally. The porous geometry is a close reprint of real sandstone, and the experiments were performed under reservoir‐relevant conditions (i.e., 8 MPa and 21 °C), thus ensuring relevance to practical CO2 operations. High‐speed fluorescent microscopy and image processing were employed to achieve temporally and spatially resolved data, providing a unique view of the dynamics underlying this multiphase flow scenario. Under conditions relevant to CO2 sequestration, final CO2 saturation was found to decrease and increase logarithmically with Ca within the capillary and viscous‐fingering regimes, respectively, with a minimum occurring during regime crossover. Specific interfacial length generally scales linearly with CO2 saturation, with higher slopes noted at high Ca due to stronger viscous and inertial forces, as supported by direct pore‐scale observations. Statistical analysis of the interfacial movements revealed that pore‐scale events are controlled by their intrinsic dynamics at low Ca, but overrun by the bulk flow at high Ca. During postfront flow, while permeability is typically correlated with total CO2 saturation in the porous domain (regardless of its mobility), the saturation of active CO2 pathways in the current study correlated very well with permeability. This alternate approach to characterize relative permeability could serve to mitigate hysteresis in relative permeability curves. Taken together, these results provide unique insights that address inconsistent observations in the literature and previously unanswered questions about the underlying flow dynamics of this important multiphase flow scenario.
ESCRT-III is necessary for the integrity of the nuclear envelope in micronuclei but is aberrant at ruptured micronuclear envelopes generating damage
Authors: Willan Jessica , Cleasby Alexa J. , Flores-Rodriguez Neftali , Stefani Flavia , Rinaldo Cinzia , Pisciottani Alessandra , Grant Emma , Woodman Philip , Bryant Helen E. , Ciani Barbara
Published: April 2019

Micronuclei represent the cellular attempt to compartmentalize DNA to maintain genomic integrity threatened by mitotic errors and genotoxic events. Some micronuclei show aberrant nuclear envelopes (NEs) that collapse, generating damaged DNA that can promote complex genome alterations. However, ruptured micronuclei also provide a pool of cytosolic DNA that can stimulate antitumor immunity, revealing the complexity of micronuclear impact on tumor progression. The ESCRT-III (Endosomal Sorting Complex Required for Transport-III) complex ensures NE reseals during late mitosis and is repaired in interphase. Therefore, ESCRT-III activity maybe crucial for maintaining the integrity of other genomic structures enclosed by a NE. ESCRT-III activity at the NE is coordinated by the subunit CHMP7. We show that CHMP7 and ESCRT-III protect against the genomic instability associated with micronuclei formation. Loss of ESCRT-III activity increases the population of micronuclei with ruptured NEs, revealing that its NE repair activity is also necessary to maintain micronuclei integrity. Surprisingly, aberrant accumulation of ESCRT-III are found at the envelope of most acentric collapsed micronuclei, suggesting that ESCRT-III is not recycled efficiently from these structures. Moreover, CHMP7 depletion relieves micronuclei from the aberrant accumulations of ESCRT-III. CHMP7-depleted cells display a reduction in micronuclei containing the DNA damage marker RPA and a sensor of cytosolic DNA. Thus, ESCRT-III activity appears to protect from the consequence of genomic instability in a dichotomous fashion: ESCRT-III membrane repair activity prevents the occurrence of micronuclei with weak envelopes, but the aberrant accumulation of ESCRT-III on a subset of micronuclei appears to exacerbate DNA damage and sustain proinflammatory pathways.
MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2
Authors: Ren Weihua , Wu Shuangting , Wu Yabin , Liu Tan , Zhao Xingpeng , Li Yawei
Published: April 2019

microRNAs (miRNAs) play essential roles in progression of hepatocellular carcinoma (HCC). However, the roles of miR-196a and miR-196b as well as mechanism in HCC progression remain poorly understood. The expressions of miR-196a, miR-196b and suppressor of cytokine signaling 2 (SOCS2) were measured in HCC tissues and cells by quantitative real-time polymerase chain reaction or immunohistochemistry. HCC progression was investigated by cell proliferation, glycolysis, cycle, clones, apoptosis, and necrosis. The interaction between SOCS2 and miR-196a or miR-196b was explored by luciferase activity and RNA immunoprecipitation analyses. The expressions of proteins in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway were measured by western blot. A xenograft model was established to investigate the roles of miR-196a or miR-196b in vivo. We found that miR-196a and miR-196b were highly expressed in HCC tissues and cells. High expression of miR-196a or miR-196b was correlated with tumor size, tumor-node-metastasis stage, lymph node metastasis, albumin–bilirubin grade and poor 5-year survival. Knockdown of miR-196a or miR-196b suppressed cell proliferation, glycolysis, cell cycle process, colony formation but induced apoptosis or necrosis in HCC cells. SOCS2 was targeted by miR-196a and miR-196b and its interference ablated abrogation of miR-196a or miR-196b-mediated inhibitory effect on HCC progression. SOCS2 was negatively associated with activation of the JAK/STAT pathway. Besides, knockdown of miR-196a or miR-196b limited xenograft tumor growth by blocking the JAK/STAT pathway. We concluded that downregulation of miR-196a or miR-196b inhibited HCC progression through regulating the JAK/STAT pathway via targeting SOCS2, providing novel targets for prognosis and therapeutics of HCC.
Ferritinophagy is required for the induction of ferroptosis by the bromodomain protein BRD4 inhibitor (+)-JQ1 in cancer cells
Authors: Sui Shiyao , Zhang Jian , Xu Shouping , Wang Qin , Wang Peiyuan , Pang Da
Published: April 2019

(+)-JQ1 is an inhibitor of the tumor-driver bromodomain protein BRD4 and produces satisfactory effects because it efficiently increases apoptosis. Ferroptosis is an oxidative cell death program differing from apoptosis. Ferroptosis is characterized by high levels of iron and reactive oxygen species and has been confirmed to suppress tumor growth. In this study, BRD4 expression in cancer and its influence on the prognosis of cancer patients were analyzed using data from public databases. In addition, the effect of the BRD4 inhibitor (+)-JQ1 on ferroptosis was investigated via a series of in vitro assays. A nude mouse model was used to evaluate the function of (+)-JQ1 in ferroptosis in vivo. The potential mechanisms by which (+)-JQ1 regulates ferroptosis were explored. The results showed that BRD4 expression levels were higher in cancer tissues than in normal tissues and were related to poor prognosis in cancer patients. Furthermore, ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition. Moreover, the anticancer effect of (+)-JQ1 was enhanced by ferroptosis inducers. Further studies confirmed that (+)-JQ1 induced ferroptosis via ferritinophagy, which featured autophagy enhancement by (+)-JQ1 and increased iron levels. Subsequently, the reactive oxygen species levels were increased by iron via the Fenton reaction, leading to ferroptosis. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 may regulate ferroptosis by controlling the expression of ferroptosis-associated genes regulated by BRD4. Finally, (+)-JQ1 regulated ferritinophagy and the expression of ferroptosis-associated genes via epigenetic inhibition of BRD4 by suppressing the expression of the histone methyltransferase G9a or enhancing the expression of the histone deacetylase SIRT1. In summary, the BRD4 inhibitor (+)-JQ1 induces ferroptosis via ferritinophagy or the regulation of ferroptosis-associated genes through epigenetic repression of BRD4.
Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruses
Authors: Xiao Haixia , Guo Tianling , Yang Mi , Qi Jianxun , Huang Chaobin , Hong Yuanyuan , Gu Jinjin , Pang Xuefei , Liu William Jun , Peng Ruchao , McCauley John , Bi Yuhai , Li Shihua , Feng Junxia , Zhang Hailiang , Zhang Xupei , Lu Xishan , Yan Jinghua , Chen Liling , Shi Yi , Chen Weizhi , Gao George Fu
Published: April 2019

The isolation of human monoclonal antibodies with broadly neutralizing breadth can provide a promising countermeasure for influenza A viruses infection. Most broadly neutralizing antibodies against influenza A viruses bind to the conserved stem region or the receptor-binding cavity of hemagglutinin and the interaction is dominated by the heavy chain. The light chain, however, contributes few or no direct contacts to the antigen. Here we report an H3-clade neutralizing human monoclonal antibody, AF4H1K1, which recognizes the hemagglutinin glycoproteins of all group 2 influenza A viruses. This human monoclonal antibody has been obtained through the screening by pairing different heavy and light chains from an H7N9-infected patient based on the next-generation sequencing technology. Further structural studies revealed that light chains modulate the neutralizing spectrum by affecting the local conformation of heavy chains, instead of direct interaction with the antigen. These findings provide important clues to understand the molecular basis of light chains in antigen recognition and to explore the strategies in particular of the use of light chain modification to develop broadly protective monoclonal antibodies against influenza A viruses and other emerging viruses.
Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors
Authors: Lux Michaelyn C. , Standke Lisa C. , Tan Derek S.
Published: April 2019

Adenylate-forming enzymes are a mechanistic superfamily that are involved in diverse biochemical pathways. They catalyze ATP-dependent activation of carboxylic acid substrates as reactive acyl adenylate (acyl-AMP) intermediates and subsequent coupling to various nucleophiles to generate ester, thioester, and amide products. Inspired by natural products, acyl sulfonyladenosines (acyl-AMS) that mimic the tightly bound acyl-AMP reaction intermediates have been developed as potent inhibitors of adenylate-forming enzymes. This simple yet powerful inhibitor design platform has provided a wide range of biological probes as well as several therapeutic lead compounds. Herein, we provide an overview of the nine structural classes of adenylate-forming enzymes and examples of acyl-AMS inhibitors that have been developed for each.
Accelerating dynamics of collective attention
Authors: Lorenz-Spreen Philipp , Mønsted Bjarke Mørch , Hövel Philipp , Lehmann Sune
Published: April 2019

With news pushed to smart phones in real time and social media reactions spreading across the globe in seconds, the public discussion can appear accelerated and temporally fragmented. In longitudinal datasets across various domains, covering multiple decades, we find increasing gradients and shortened periods in the trajectories of how cultural items receive collective attention. Is this the inevitable conclusion of the way information is disseminated and consumed? Our findings support this hypothesis. Using a simple mathematical model of topics competing for finite collective attention, we are able to explain the empirical data remarkably well. Our modeling suggests that the accelerating ups and downs of popular content are driven by increasing production and consumption of content, resulting in a more rapid exhaustion of limited attention resources. In the interplay with competition for novelty, this causes growing turnover rates and individual topics receiving shorter intervals of collective attention.
Supersonic plasma turbulence in the laboratory
Authors: White T. G. , Oliver M. T. , Mabey P. , Kühn-Kauffeldt M. , Bott A. F. A. , Döhl L. N. K. , Bell A. R. , Bingham R. , Clarke R. , Foster J. , Giacinti G. , Graham P. , Heathcote R. , Koenig M. , Kuramitsu Y. , Lamb D. Q. , Meinecke J. , Michel Th. , Miniati F. , Notley M. , Reville B. , Ryu D. , Sarkar S. , Sakawa Y. , Selwood M. P. , Squire J. , Scott R. H. H. , Tzeferacos P. , Woolsey N. , Schekochihin A. A. , Gregori G.
Published: April 2019

The properties of supersonic, compressible plasma turbulence determine the behavior of many terrestrial and astrophysical systems. In the interstellar medium and molecular clouds, compressible turbulence plays a vital role in star formation and the evolution of our galaxy. Observations of the density and velocity power spectra in the Orion B and Perseus molecular clouds show large deviations from those predicted for incompressible turbulence. Hydrodynamic simulations attribute this to the high Mach number in the interstellar medium (ISM), although the exact details of this dependence are not well understood. Here we investigate experimentally the statistical behavior of boundary-free supersonic turbulence created by the collision of two laser-driven high-velocity turbulent plasma jets. The Mach number dependence of the slopes of the density and velocity power spectra agree with astrophysical observations, and supports the notion that the turbulence transitions from being Kolmogorov-like at low Mach number to being more Burgers-like at higher Mach numbers.
Engineering Auger recombination in colloidal quantum dots via dielectric screening
Authors: Hou Xiaoqi , Kang Jun , Qin Haiyan , Chen Xuewen , Ma Junliang , Zhou Jianhai , Chen Liping , Wang Linjun , Wang Lin-Wang , Peng Xiaogang
Published: April 2019

Auger recombination is the main non-radiative decay pathway for multi-carrier states of colloidal quantum dots, which affects performance of most of their optical and optoelectronic applications. Outstanding single-exciton properties of CdSe/CdS core/shell quantum dots enable us to simultaneously study the two basic types of Auger recombination channels—negative trion and positive trion channels. Though Auger rates of positive trion are regarded to be much faster than that of negative trion for II-VI quantum dots in literature, our experiments find the two rates can be inverted for certain core/shell geometries. This is confirmed by theoretical calculations as a result of geometry-dependent dielectric screening. By varying the core/shell geometry, both types of Auger rates can be independently tuned for ~ 1 order of magnitude. Experimental and theoretical findings shed new light on designing quantum dots with necessary Auger recombination characteristics for high-power light-emitting-diodes, lasers, single-molecular tracking, super-resolution microscope, and advanced quantum light sources.
SWITCH 1/DYAD is a WINGS APART-LIKE antagonist that maintains sister chromatid cohesion in meiosis
Authors: Yang Chao , Hamamura Yuki , Sofroni Kostika , Böwer Franziska , Stolze Sara Christina , Nakagami Hirofumi , Schnittger Arp
Published: April 2019

Mitosis and meiosis both rely on cohesin, which embraces the sister chromatids and plays a crucial role for the faithful distribution of chromosomes to daughter cells. Prior to the cleavage by Separase at anaphase onset, cohesin is largely removed from chromosomes by the non-proteolytic action of WINGS APART-LIKE (WAPL), a mechanism referred to as the prophase pathway. To prevent the premature loss of sister chromatid cohesion, WAPL is inhibited in early mitosis by Sororin. However, Sororin homologs have only been found to function as WAPL inhibitors during mitosis in vertebrates and Drosophila. Here we show that SWITCH 1/DYAD defines a WAPL antagonist that acts in meiosis of Arabidopsis. Crucially, SWI1 becomes dispensable for sister chromatid cohesion in the absence of WAPL. Despite the lack of any sequence similarities, we found that SWI1 is regulated and functions in a similar manner as Sororin hence likely representing a case of convergent molecular evolution across the eukaryotic kingdom.
A universal state and its relaxation mechanisms of long-range interacting polygons
Authors: Shen Hongchuan , Tong Hua , Tan Peng , Xu Lei
Published: April 2019

Using polygonal magnetic particles, we conduct experiments to explore the space-filling properties of anisotropic blocks with long-range interactions. In contrast to previous studies, we obtain the surprising finding that our systems’ structures do not depend on the shape of building blocks: a single state, the hexagonal plastic crystal, appears as a universal attractor for a wide range of different polygons. This robust particle-shape independency appears as the interactions go beyond nearest neighbors. Particle shape plays an essential role in system relaxation, and determines the basic relaxation dynamics through a microscopic control parameter, internal roughness, produced by particle vertices. Thus our study reveals a new pattern-forming paradigm, in which particle shape plays little role in the static structure but determines the essential relaxation dynamics. Due to the ubiquity of long-range interactions and anisotropic building blocks, our discovery may shed new light on diverse problems involving structure formation, self-assembly, and packing.
Gene discovery informatics toolkit defines candidate genes for unexplained infertility and prenatal or infantile mortality
Authors: Dawes Ruebena , Lek Monkol , Cooper Sandra T.
Published: April 2019

Despite a recent surge in novel gene discovery, genetic causes of prenatal-lethal phenotypes remain poorly defined. To advance gene discovery in prenatal-lethal disorders, we created an easy-to-mine database integrating known human phenotypes with inheritance pattern, scores of genetic constraint, and murine and cellular knockout phenotypes—then critically assessed defining features of known prenatal-lethal genes, among 3187 OMIM genes, and relative to 16,009 non-disease genes. While around one-third (39%) of protein-coding genes are essential for murine development, we curate only 3% (624) of human protein-coding genes linked currently to prenatal/infantile lethal disorders. 75% prenatal-lethal genes are linked to developmental lethality in knockout mice, compared to 54% for all OMIM genes and 34% among non-disease genes. Genetic constraint correlates with inheritance pattern (autosomal recessive <<autosomal dominant 90% of recessive genes show neither missense nor loss-of-function constraint, even for prenatal-lethal genes. Detailed ontology mapping for 624 prenatal-lethal genes shows marked enrichment among dominant genes for nuclear proteins with roles in RNA/DNA biology, with recessive genes enriched in cytoplasmic (mitochondrial) metabolic proteins. We conclude that genes without genetic constraint should not be excluded as potential novel disease genes, and especially for recessive conditions (<10% constrained). Prenatal lethal genes are 5.9-fold more likely to be associated with a lethal murine phenotype than non-disease genes. Cell essential genes are largely a subset of mouse-lethal genes, notably under-represented among known OMIM genes, and strong candidates for gamete/embryo non-viability. We therefore curate 3435 ‘candidate developmental lethal’ human genes: essential for murine development or cellular viability, not yet linked to human disorders, presenting strong candidates for unexplained infertility and prenatal/infantile mortality.
Medusozoan genomes inform the evolution of the jellyfish body plan
Authors: Khalturin Konstantin , Shinzato Chuya , Khalturina Maria , Hamada Mayuko , Fujie Manabu , Koyanagi Ryo , Kanda Miyuki , Goto Hiroki , Anton-Erxleben Friederike , Toyokawa Masaya , Toshino Sho , Satoh Noriyuki
Published: April 2019

Cnidarians are astonishingly diverse in body form and lifestyle, including the presence of a jellyfish stage in medusozoans and its absence in anthozoans. Here, we sequence the genomes of Aurelia aurita (a scyphozoan) and Morbakka virulenta (a cubozoan) to understand the molecular mechanisms responsible for the origin of the jellyfish body plan. We show that the magnitude of genetic differences between the two jellyfish types is equivalent, on average, to the level of genetic differences between humans and sea urchins in the bilaterian lineage. About one-third of Aurelia genes with jellyfish-specific expression have no matches in the genomes of the coral and sea anemone, indicating that the polyp-to-jellyfish transition requires a combination of conserved and novel, medusozoa-specific genes. While no genomic region is specifically associated with the ability to produce a jellyfish stage, the arrangement of genes involved in the development of a nematocyte—a phylum-specific cell type—is highly structured and conserved in cnidarian genomes; thus, it represents a phylotypic gene cluster.
Morphology and genome of a snailfish from the Mariana Trench provide insights into deep-sea adaptation
Authors: Wang Kun , Shen Yanjun , Yang Yongzhi , Gan Xiaoni , Liu Guichun , Hu Kuang , Li Yongxin , Gao Zhaoming , Zhu Li , Yan Guoyong , He Lisheng , Shan Xiujuan , Yang Liandong , Lu Suxiang , Zeng Honghui , Pan Xiangyu , Liu Chang , Yuan Yuan , Feng Chenguang , Xu Wenjie , Zhu Chenglong , Xiao Wuhan , Dong Yang , Wang Wen , Qiu Qiang , He Shunping
Published: April 2019

It is largely unknown how living organisms—especially vertebrates—survive and thrive in the coldness, darkness and high pressures of the hadal zone. Here, we describe the unique morphology and genome ofPseudoliparis swirei—a recently described snailfish species living below a depth of 6,000 m in the Mariana Trench. Unlike closely related shallow sea species,P. swireihas transparent, unpigmented skin and scales, thin and incompletely ossified bones, an inflated stomach and a non-closed skull. Phylogenetic analyses show thatP. swireidiverged from a close relative living near the sea surface about 20 million years ago and has abundant genetic diversity. Genomic analyses reveal that: (1) the bone Gla protein (bglap) gene has a frameshift mutation that may cause early termination of cartilage calcification; (2) cell membrane fluidity and transport protein activity inP. swireimay have been enhanced by changes in protein sequences and gene expansion; and (3) the stability of its proteins may have been increased by critical mutations in the trimethylamineN-oxide-synthesizing enzyme and hsp90 chaperone protein. Our results provide insights into the morphological, physiological and molecular evolution of hadal vertebrates.
Ni(OH)2-decorated nitrogen doped MWCNT nanosheets as an efficient electrode for high performance supercapacitors
Authors: Ramesh Sivalingam , Karuppasamy K. , Yadav Hemraj M. , Lee Jae-Joon , Kim Hyun-Seok , Kim Heung-Soo , Kim Joo-Hyung
Published: April 2019

In this study, nickel hydroxide nanoparticles (NPs) decorated with nitrogen doped multiwalled carbon nanotubes (N-MWCNT) hybrid composite was synthesized by thermal reduction process in the presence of cetyl ammonium bromide (CTAB) and urea. The as-synthesized Ni(OH)2@N-MWCNT hybrid composite was characterized by FTIR, Raman, XRD, BET, BJH and FE-TEM analyses. These prepared porous carbon hybrid composite materials possessed high specific surface area and sheet like morphology useful for active electrode materials. The maximum specific capacitance of Ni(OH)2@N-MWCNT hybrid nanocomposite in the two electrode system showed 350 Fg−1 at 0.5 A/g,energy density ~43.75 Wkg−1 and corresponds to power density 1500 W kg−1 with excellent capacity retention after 5000 cycles. The results suggest that the prepared two-dimensional hybrid composite is a promising electrode material for electrochemical energy storage applications.
Oscillatory shear potentiates latent TGF-β1 activation more than steady shear as demonstrated by a novel force generator
Authors: Kouzbari Karim , Hossan Mohammad R. , Arrizabalaga Julien H. , Varshney Rohan , Simmons Aaron D. , Gostynska Sandra , Nollert Matthias U. , Ahamed Jasimuddin
Published: April 2019

Cardiovascular mechanical stresses trigger physiological and pathological cellular reactions including secretion of Transforming Growth Factor β1 ubiquitously in a latent form (LTGF-β1). While complex shear stresses can activate LTGF-β1, the mechanisms underlying LTGF-β1 activation remain unclear. We hypothesized that different types of shear stress differentially activate LTGF-β1. We designed a custom-built cone-and-plate device to generate steady shear (SS) forces, which are physiologic, or oscillatory shear (OSS) forces characteristic of pathologic states, by abruptly changing rotation directions. We then measured LTGF-β1 activation in platelet releasates. We modeled and measured flow profile changes between SS and OSS by computational fluid dynamics (CFD) simulations. We found a spike in shear rate during abrupt changes in rotation direction. OSS activated TGF-β1 levels significantly more than SS at all shear rates. OSS altered oxidation of free thiols to form more high molecular weight protein complex(es) than SS, a potential mechanism of shear-dependent LTGF-β1 activation. Increasing viscosity in platelet releasates produced higher shear stress and higher LTGF-β1 activation. OSS-generated active TGF-β1 stimulated higher pSmad2 signaling and endothelial to mesenchymal transition (EndoMT)-related genes PAI-1, collagen, and periostin expression in endothelial cells. Overall, our data suggest variable TGF-β1 activation and signaling occurs with competing blood flow patterns in the vasculature to generate complex shear stress, which activates higher levels of TGF-β1 to drive vascular remodeling.
In situ response of Antarctic under-ice primary producers to experimentally altered pH
Authors: Cummings Vonda J. , Barr Neill G. , Budd Rod G. , Marriott Peter M. , Safi Karl A. , Lohrer Andrew M.
Published: April 2019

Elevated atmospheric CO2 concentrations are contributing to ocean acidification (reduced seawater pH and carbonate concentrations), with potentially major ramifications for marine ecosystems and their functioning. Using a novel in situ experiment we examined impacts of reduced seawater pH on Antarctic sea ice-associated microalgal communities, key primary producers and contributors to food webs. pH levels projected for the following decades-to-end of century (7.86, 7.75, 7.61), and ambient levels (7.99), were maintained for 15 d in under-ice incubation chambers. Light, temperature and dissolved oxygen within the chambers were logged to track diurnal variation, with pH, O2, salinity and nutrients assessed daily. Uptake of CO2 occurred in all treatments, with pH levels significantly elevated in the two extreme treatments. At the lowest pH, despite the utilisation of CO2 by the productive microalgae, pH did not return to ambient levels and carbonate saturation states remained low; a potential concern for organisms utilising this under-ice habitat. However, microalgal community biomass and composition were not significantly affected and only modest productivity increases were noted, suggesting subtle or slightly positive effects on under-ice algae. This in situ information enables assessment of the influence of future ocean acidification on under-ice community characteristics in a key coastal Antarctic habitat.
Ectopic miR-975 induces CTP synthase directed cell proliferation and differentiation in Drosophila melanogaster
Authors: Woo Wai Kan , Dzaki Najat , Thangadurai Shallinie , Azzam Ghows
Published: April 2019

CTP synthase (CTPSyn) is an essential metabolic enzyme, synthesizing precursors required for nucleotides and phospholipids production. Previous studies have also shown that CTPSyn is elevated in various cancers. In many organisms, CTPSyn compartmentalizes into filaments called cytoophidia. In Drosophila melanogaster, only its isoform C (CTPSynIsoC) forms cytoophidia. In the fruit fly’s testis, cytoophidia are normally seen in the transit amplification regions close to its apical tip, where the stem-cell niche is located, and development is at its most rapid. Here, we report that CTPSynIsoC overexpression causes the lengthening of cytoophidia throughout the entirety of the testicular body. A bulging apical tip is found in approximately 34% of males overexpressing CTPSynIsoC. Immunostaining shows that this bulged phenotype is most likely due to increased numbers of both germline cells and spermatocytes. Through a microRNA (miRNA) overexpression screen, we found that ectopic miR-975 concurrently increases both the expression levels of CTPSyn and the length of its cytoophidia. The bulging testes phenotype was also recovered at a penetration of approximately 20%. However, qPCR assays reveal that CTPSynIsoC and miR-975 overexpression each provokes a differential response in expression of a number of cancer-related genes, indicating that the shared CTPSyn upregulation seen in either case is likely the cause of observed testicular overgrowth. This study presents the first instance of consequences of miRNA-asserted regulation upon CTPSyn in D. melanogaster, and further reaffirms the enzyme’s close ties to germline cells overgrowth.
Individual play patterns stimulated by a familiar object are group-driven
Authors: Zupan Manja , Rehn Therese , de Oliveira Daiana , Malovrh Špela , Keeling Linda
Published: April 2019

This study investigates the dynamics of play behaviour within groups of four juvenile pigs and uses a novel clustering and statistical modelling approach to describe new details in how individuals play with a familiar object (toy rope). We examined complex state sequence data collected during a 30 min home pen play test, using the package TraMineR, where the states were defined as object play, locomotor/social play and no play. From behavioural observations, and based on the relative proportion of the different types of object play observed, each individual was later categorised as an initiator or joiner type of player. Initiators were found to be more solitary and to show more object play whereas joiners were more social and showed less object play. The majority of groups did not have an initiator type of player, yet on average they played more. Despite strong group and type of player effects, we identified three general individual play patterns. On a group level, our results demonstrate differences in how a period of playing develops, that playing with the object simultaneously occurs more often in groups than expected by chance and that the number of pigs playing together is stable over time.
Heritability and genome-wide association study of benign prostatic hyperplasia (BPH) in the eMERGE network
Authors: Hellwege Jacklyn N. , Stallings Sarah , Torstenson Eric S. , Carroll Robert , Borthwick Kenneth M. , Brilliant Murray H. , Crosslin David , Gordon Adam , Hripcsak George , Jarvik Gail P. , Linneman James G. , Devi Parimala , Peissig Peggy L. , Sleiman Patrick A. M. , Hakonarson Hakon , Ritchie Marylyn D. , Verma Shefali Setia , Shang Ning , Denny Josh C. , Roden Dan M. , Velez Edwards Digna R. , Edwards Todd L.
Published: April 2019

Benign prostatic hyperplasia (BPH) results in a significant public health burden due to the morbidity caused by the disease and many of the available remedies. As much as 70% of men over 70 will develop BPH. Few studies have been conducted to discover the genetic determinants of BPH risk. Understanding the biological basis for this condition may provide necessary insight for development of novel pharmaceutical therapies or risk prediction. We have evaluated SNP-based heritability of BPH in two cohorts and conducted a genome-wide association study (GWAS) of BPH risk using 2,656 cases and 7,763 controls identified from the Electronic Medical Records and Genomics (eMERGE) network. SNP-based heritability estimates suggest that roughly 60% of the phenotypic variation in BPH is accounted for by genetic factors. We used logistic regression to model BPH risk as a function of principal components of ancestry, age, and imputed genotype data, with meta-analysis performed using METAL. The top result was on chromosome 22 in SYN3 at rs2710383 (p-value = 4.6 × 10−7; Odds Ratio = 0.69, 95% confidence interval = 0.55–0.83). Other suggestive signals were near genes GLGC, UNCA13, SORCS1 and between BTBD3 and SPTLC3. We also evaluated genetically-predicted gene expression in prostate tissue. The most significant result was with increasing predicted expression of ETV4 (chr17; p-value = 0.0015). Overexpression of this gene has been associated with poor prognosis in prostate cancer. In conclusion, although there were no genome-wide significant variants identified for BPH susceptibility, we present evidence supporting the heritability of this phenotype, have identified suggestive signals, and evaluated the association between BPH and genetically-predicted gene expression in prostate.
Epsilon-Near-Zero Grids for On-chip Quantum Networks
Authors: Vertchenko Larissa , Akopian Nika , Lavrinenko Andrei V.
Published: April 2019

Realization of an on-chip quantum network is a major goal in the field of integrated quantum photonics. A typical network scalable on-chip demands optical integration of single photon sources, optical circuitry and detectors for routing and processing of quantum information. Current solutions either notoriously experience considerable decoherence or suffer from extended footprint dimensions limiting their on-chip scaling. Here we propose and numerically demonstrate a robust on-chip network based on an epsilon-near-zero (ENZ) material, whose dielectric function has the real part close to zero. We show that ENZ materials strongly protect quantum information against decoherence and losses during its propagation in the dense network. As an example, we model a feasible implementation of an ENZ network and demonstrate that information can be reliably sent across a titanium nitride grid with a coherence length of 434 nm, operating at room temperature, which is more than 40 times larger than state-of-the-art plasmonic analogs. Our results facilitate practical realization of large multi-node quantum photonic networks and circuits on-a-chip.