bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic exposure of mice to low doses of imazalil induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels
Authors: Jin Cuiyuan , Luo Ting , Fu Zhengwei , Jin Yuanxiang
Published: February 2018

Imazalil (IMZ), which is a widely used fungicide, can accumulate in the body and threaten an animal's health. However, this fungicide has adverse effects on aquatic organisms and ultimately affects human health when it leaches into the environment. Our research tried to determine that if IMZ might cause liver damage and its potential to cause‐related diseases. In this study, male adult C57BL/6 mice were exposed to 0.1, 0.5, or 2.5 mg/kg body weight IMZ in drinking water for 15 weeks. Then, we evaluated the liver damage at the physiological, biochemical, and transcriptome levels in mice after chronic IMZ exposure. We observed serious ballooning degeneration of hepatocytes in the IMZ‐treated groups. And IMZ induced oxidative stress and caused the disorders of bile acid metabolism in mice. In addition, the transcriptome data showed that IMZ has substantial influence on several pathways, including metabolic pathways for drug metabolism, RNA transport, and bile secretion. We further confirmed that the mRNA expression of the key genes involved in oxidative stress and bile acid metabolism were changed of mice exposed to IMZ. Our data suggested that chronic IMZ exposure could induce hepatotoxicity in mice at the physiological, biochemical, and transcriptome levels.
Leveraging a Leadership Development Framework for Career Readiness
Authors: Fox Kirsten F.
Published: February 2018

This chapter provides a context for how colleges and universities can prepare students for career readiness by leveraging leadership development programs to further develop knowledge, skills, and competencies that translate to the changing world of work, particularly for graduates in transition to their first jobs.
Enhancing Leadership Competencies for Career Readiness
Authors: Seemiller Corey
Published: February 2018

In order to prepare students for their future careers, it is important to understand the competencies necessary for career success. This chapter will discuss the many ways in which leadership competencies can be utilized to help enhance career readiness.
An Overview of Leadership Competencies and Assessment Considerations
Authors: Smedick Bill , Rice Eric
Published: February 2018

This chapter provides an overview of leadership competencies and ways in which colleges and universities can use competency assessment as a tool for current leadership education offerings to assist professionals in revising and expanding programming to better enable their students to become career ready.
Patient perceptions of acute pain and activity disruption following inguinal hernia repair: a propensity-matched comparison of robotic-assisted, laparoscopic, and open approaches
Authors: Bittner IV James G. , Cesnik Lawrence W. , Kirwan Thomas , Wolf Laurie , Guo Dongjing
Published: February 2018

Few publications describe the potential benefit of robotic-assisted inguinal hernia repair on acute postoperative groin pain (APGP). This study compared patients’ perceptions of APGP, activity limitation, and overall satisfaction after robotic-assisted- (R), laparoscopic (L), or open (O) inguinal hernia repair (IHR). Random samples of patients from two web-based research panels and surgical practices were screened for patients who underwent IHR between October 28, 2015 and November 1, 2016. Qualified patients were surveyed to assess perceived APGP at 1 week postoperatively, activity disruption, and overall satisfaction. Three cohorts based on operative approach were compared after propensity matching. Propensity scoring resulted in 83 R-IHR matched to 83 L-IHR respondents, while 85 R-IHR matched with 85 O-IHR respondents. R-IHR respondents recalled less APGP compared to respondents who had O-IHR (4.1 ± 0.3 vs 5.6 ± 0.3, p < 0.01) but similar APGP compared to L-IHR (4.0 ± 0.3 vs 4.4 ± 0.3, p = 0.37). Respondents recalled less activity disruption 1 week postoperatively after R-IHR versus O-IHR (6.1 ± 0.3 vs. 7.3 ± 0.2, p < 0.01) but similar levels of activity disruption after R-IHR and L-IHR (6.0 ± 0.3 vs. 6.6 ± 0.27, p = 0.32). At the time of the survey, respondents perceived less physical activity disruption after R-IHR compared to O-IHR (1.4 ± 0.2 vs. 2.8 ± 0.4, p < 0.01) but similar between R-IHR and L-IHR (1.3 ± 0.2 vs 1.2 ± 0.2, p = 0.94). Most respondents felt satisfied with their outcome regardless of operative approach. Patient perceptions of pain and activity disruption differ by approach, suggesting a potential advantage of a minimally invasive technique over open for IHR. Further studies are warranted to determine long-term outcomes regarding pain and quality of life after IHR.
Smart multifunctional nanoagents for in situ monitoring of small molecules with a switchable affinity towards biomedical targets
Authors: Shevchenko Konstantin G. , Cherkasov Vladimir R. , Nikitina Irina L. , Babenyshev Andrey V. , Nikitin Maxim P.
Published: February 2018

The great diversity of nanomaterials provides ample opportunities for constructing effective agents for biomedical applications ranging from biosensing to drug delivery. Multifunctional nanoagents that combine several features in a single particle are of special interest due to capabilities that substantially exceed those of molecular drugs. An ideal theranostic agent should simultaneously be an advanced biosensor to identify a disease and report the diagnosis and a biomedical actuator to treat the disease. While many approaches were developed to load a nanoparticle with various drugs for actuation of the diseased cells (e.g., to kill them), the nanoparticle-based approaches for the localized biosensing with real-time reporting of the marker concentration severely lag behind. Here, we show a smart in situ nanoparticle-based biosensor/actuator system that dynamically and reversibly changes its structural and optical properties in response to a small molecule marker to allow real-time monitoring of the marker concentration and adjustment of the system ability to bind its biomedical target. Using the synergistic combination of signal readout based on the localized surface plasmon resonance and an original method of fabrication of smart ON/OFF-switchable nanoagents, we demonstrate reversible responsiveness of the system to a model small molecule marker (antibiotic chloramphenicol) in a wide concentration range. The proposed approach can be used for the development of advanced multifunctional nanoagents for theranostic applications.
200 ka of glacial events in NW Svalbard: an emergence cycle facies model and regional correlations
Authors: Alexanderson Helena , Henriksen Mona , Ryen Heidi T. , Landvik Jon Y. , Peterson Gustaf
Published: February 2018

Late Quaternary sedimentary units at Kongsfjordhallet, NW Svalbard, represent five cycles of glaciations and subsequent deglaciations during high relative sea levels. The high sea level events are interpreted as glacioisostatically induced and imply preceding regional glaciations, which we constrain in time by luminescence and radiocarbon ages to just prior to ~ 195, ~ 130, ~ 85, ~ 60, and ~ 15 ka. Combined with the stratigraphical record from nearby Leinstranda we identify six, possibly seven, major glacial advances during the last 200 ka in the Kongsfjorden region. Two of these occurred during the Saalian and at least four during the Weichselian. The results are based on detailed sedimentological, stratigraphical and chronological investigations of the uppermost 15 m of the 40-m-high Kongsfjordhallet coastal sections. The succession is dominated by sediments of marine and littoral origin, representing partial shallowing-upward sequences due to isostatic rebound. Only one subglacial till was recognised. Interestingly, alluvial and periglacial deposits, not commonly recognised in this type of setting, occur in the sequence. These include weathered coarse alluvium, sandy channel fills as well as cryoturbated sediments and solifluction deposits, which are positive evidence of a non-glacial environment. The sequence of sediments that represents an emergence cycle has been formalised in a facies model.
Irreversible Electroporation in Hepatopancreaticobiliary Tumours
Authors: Ruarus A.H. , Vroomen L.G.P.H. , Puijk R.S. , Scheffer H.J. , Zonderhuis B.M. , Kazemier G. , van den Tol M.P. , Berger F.H. , Meijerink M.R.
Published: February 2018

Hepatopancreaticobiliary tumours are often diagnosed at an advanced disease stage, in which encasement or invasion of local biliary or vascular structures has already occurred. Irreversible electroporation (IRE) is an image-guided tumour ablation technique that induces cell death by exposing the tumour to high-voltage electrical pulses. The cellular membrane is disrupted, while sparing the extracellular matrix of critical tubular structures. The preservation of tissue integrity makes IRE an attractive treatment option for tumours in the vicinity of vital structures such as splanchnic blood vessels and major bile ducts. This article reviews current data and discusses future trends of IRE for hepatopancreaticobiliary tumours.
Análise biomecânica da reconstrução do ligamento cruzado anterior
Authors: Completo António , Noronha José Carlos , Oliveira Carlos , Fonseca Fernando
Published: February 2018

Objetivo A reconstrução do ligamento cruzado anterior é aconselhável sobretudo em atletas de alta demanda física. Diversas técnicas são usadas na reconstrução, mas a grande questão é qual o melhor posicionamento para o enxerto. Analisar o efeito biomecânico da posição dos túneis ósseos na repartição de carga e cinemática da articulação, bem como os resultados funcionais em médio prazo, após reconstrução do ligamento cruzado anterior.

Métodos Fez-se um estudo de simulação biomecânica computacional com modelos de elementos finitos do joelho original e com reconstrução do ligamento cruzado anterior (Neo-LCA) em quatro combinações de posição dos túneis ósseos (femoral central-tibial central, femoral anterior-tibial central, femoral posterossuperior-tibial anterior e femoral central-tibial anterior) com o mesmo tipo de enxerto. Para cada modelo, foram comparadas a pressão de contato na cartilagem, a rotação e translação do fêmur e dos meniscos e a deformação nos ligamentos.

Resultados Nenhum modelo de Neo-LCA foi capaz de reproduzir, na íntegra, o modelo do joelho original. Quando o túnel femoral era colocado em posição mais posterior, observaram-se pressões na cartilagem 25% mais baixas e translação dos meniscos superiores entre 12% e 30% relativamente ao modelo intacto. Quando o túnel femoral estava em posição mais anterior, observou-se uma rotação interna do fêmur 50% inferior ao modelo intacto.

Conclusão Os resultados evidenciam que uma localização do túnel femoral mais distante da posição central parece ser mais preponderante para um comportamento mais díspar relativamente à articulação intacta. Na posição mais anterior existe um aumento da instabilidade rotatória.
Un curieux emploi de la négation en français canadien
Authors: Follette James E. La ,   en collaboration avec, Valin Roch
Published: February 2018

Le Français commun dit régulièrement, comme chacun sait, C’est le plus beau blé qu’il yAITsur le marché, construisant au subjonctif le verbe de la proposition subordonnée. Un trait du parler populaire de la région de Québec — observé aussi ailleurs au Canada français — consiste à substituer ici au subjonctif, lorsque le verbe est un verbe d’existence, un indicatif accompagné de la négation (réduite à pas) et à dire: C’est le plus beau blé qu’il y A PAS sur le marché.

Cet emploi en apparence aberrant de la négation est-il une innovation du français canadien ou représente-t-il, au contraire, l’usage ancien d’un des divers parlers régionaux français apportés en Nouvelle-France aux XVIIe et XVIIIe siècles? Ce n’est pas notre intention d’éclairer ce point d’histoire. Notre propos est tout différent. Prenant acte des deux usages observés et de leur divergeance, nous démontrerons—en nous appuyant, pour ce faire, sur l’analyse psychomécanique du langage du linguiste français Gustave Guillaume — que, en face de la nuance de pensée à exprimer, les deux manières de dire s’équipollent, la négation d’une forme verbale indicative produisant en l’occurrence le même effet de sens que l’emploi affirmatif d’une forme de subjonctif.
Auditory discrimination of French vowels by English speakers
Authors: Politzer Robert L.
Published: February 2018

The concept that the auditory discrimination of phonemic differences in a foreign language is influenced by the phonemic contrast of the native language is certainly not new. A considerable amount of research has been done in the general area of auditory discrimination and the results of such research tend to prove the more or less expected: Those sound differences which are utilized by the phonemic system of the native language are perceived more easily than those which do not correspond to a native phonemic opposition. The pedagogical applications of this principle are fairly obvious and far reaching. In the learning of a second language, particular emphasis must be placed on the development of auditory discrimination between sounds which have no acoustic counterpart or near relative in the system of the learner. Thus one of the prerequisites of the teaching of pronunciation is the comparison of the sound system of the native language with that of the language to be learned and the development of auditory discrimination drills involving the phonemes revealed as difficult by the comparison. Usually the auditory discrimination drills take the form of listening to and repeating minimal pairs differentiated by the difficult sounds.
A structure-function description of Terena phrases
Authors: Bendor-Samuel John T.
Published: February 2018

The object of this article is to illustrate a particular model of grammatical description by using it to describe the Terena phrase. This model can, for convenience, be given the label “structure-function.” Like any model it employs certain interrelated categories and terms which are mutually defining. Each category can only be understood in reference to the model as a whole.

This model sets up grammatical units which are hierarchically arranged. The hierarchy consists of a series of levels of description. At each level there is a grammatical unit and this grammatical unit gives its name to the level concerned. At a given level there is only one grammatical unit. Each such grammatical unit consists of one or more of the units next below it in the hierarchy.
Eléments …: A. Martinet or G. Rondeau?
Authors: Wittman Henri
Published: February 2018

In 1961 G. Rondeau published in this journal an article entitled “Les unités linguistiques de base chez A. Martinet,” in which his intention was to discuss, “aussi objectivement que possible,” the basic linguistic units as they appear in A. Martinet’s handbook for beginners in linguistics.

Objectivity? A. Martinet states in his preface that certain novel elements are to be found in chapter IV, the chapter dealing with morphology and syntax. And since G. Rondeau’s article discusses Martinet’s principles of morphology rather than the “unités linguistiques” in general, one would have expected that Rondeau would have aimed his arguments mainly against these forty-nine pages of chapter IV. But it appears that the reviewer has been unwilling to extend his interest into this chapter.
Valeurs sémantiques du verbe en français et en anglais
Authors: Darbelnet J.
Published: February 2018

La Stylistique Comparée commence seulement à prendre conscience de son champ d’action et de ses méthodes. Aussi les spécialistes des disciplines voisines n’aperçoivent-ils pas toujours clairement quels sont ses buts et ses moyens. Pour se justifier à ce stade de son développement, il est important qu’elle choisisse des secteurs nettement délimités où elle puisse mettre sa méthode au point et obtenir des résultats auxquels la grammaire et la linguistique descriptive n’arrivent pas aussi facilement.

C’est dans cet esprit que la présente étude se propose de comparer le verbe anglais et le verbe français dans leurs façons de satisfaire certains besoins d’expression, et, plus particulièrement, d’examiner dans les deux langues le comportement du verbe par rapport à deux dichotomies, celle qui oppose le langage propre au langage figuré et celle du mouvement et du déplacement. Pour ce faire, elle sera obligée de se placer tantôt sur le plan des signifiés et tantôt sur celui des signifiants. Dans les deux cas, certains termes seront employés dans un sens qu’il importe de préciser.
South China Sea Arbitration and its Application to Dokdo
Authors: LEE Seokwoo , BERNARD Leonardo
Published: February 2018

On 12 July 2016, the Arbitral Tribunal formed under Annex VII of the 1982 United Nations Convention on the Law of the Sea issued its decision on the proceeding brought by the Philippines against China relating to certain activities in the South China Sea. The Tribunal’s decision was hotly anticipated as it dealt with various important issues relating to law of the sea and the interpretation of the Convention. It dealt with issues including the jurisdiction of the Tribunal, the legal status of maritime features, historic rights, and duty to preserve the marine environment. Although it remains to be seen whether states will follow the Tribunal’s precedent, questions arose on whether such precedent can be applied to other unresolved issues in other parts of the world. This paper looks at the application of the precedent established by the South China Sea arbitration to the situation involving Dokdo between Korea and Japan.
Enforcement Options and Paths to Compliance: Disputants and Global Stakeholders inPhilippines v. China
Authors: DESIERTO Diane A.
Published: February 2018

ThePhilippines v. Chinaarbitration award has been praised as a landmark victory setting forth illuminating jurisprudence interpreting the UN Convention on the Law of the Sea [UNCLOS], but it has also been repeatedly excoriated as an “unenforceable” decision—a Pyrrhic victory—due to China’s repeated refusal to date to acknowledge the binding effect of the award. China’s withdrawal from Scarborough Shoal—hailed by the new Duterte government as a hallmark of its diplomatic efforts—is one instance of state practice that still remains equivocal on theopinio jurisof China’s acceptance (or rejection) of the arbitration award.
Homework Expectancy Value Scale for Undergraduates in Online	Environments
Authors: Xu Jianzhong , Fan Xitao , Du Jianxia , Cai Zhihui
Published: February 2018

Abstract. The goal of the current study was to validate the Homework Expectancy Value Scale (HEVS) for undergraduates in online learning environments. After randomly splitting the sample in halves, we conducted exploratory factor analysis (EFA) with the first half ( n = 306) and confirmatory factor analysis (CFA) with the second half ( n = 306). Both EFA and CFA results indicated that HEVS consisted of two factors: Expectancy and Value. Given an adequate level of measurement invariance, we further examined the latent mean difference across gender for the entire sample ( n = 612). Our findings showed no statistically significant mean differences in Expectancy and Value across gender. Finally, consistent with theoretical expectations, Expectancy and Value were negatively correlated with homework distraction and the frequency of attending online classes without homework, and positively correlated with homework emotion regulation and homework completion.
Psychometric Properties of the Spanish Version of the Child	Problematic Traits Inventory in 3- to 12-Year-Old Spanish	Children
Authors: López-Romero Laura , Molinuevo Beatriz , Bonillo Albert , Andershed Henrik , Colins Olivier F. , Torrubia Rafael , Romero Estrella
Published: February 2018

Abstract. The aim of this study was to test the reliability and validity of the Spanish teacher-rated Child Problematic Traits Inventory (CPTI) in two community samples of 3- to 12-year-old children. Confirmatory Factor Analysis (CFA) supported the three-factor structure of the CPTI (Grandiose-Deceitful: GD; Callous-Unemotional: CU; Impulsive-Need for Stimulation: INS), being invariant across gender and age groups. The CPTI total and factor scores showed excellent internal consistencies (> .90) in the total group, and across gender and age groups. In support of their criterion validity, the CPTI scores were positively related to psychopathy scores as measured by an alternative teacher-rated measure. In support of their convergent validity, the CPTI scores showed the expected relations to variables that have been linked to psychopathic personality, including fearlessness, conduct problems, aggression, and low prosocial behavior. Overall, these findings suggest that the Spanish teacher-rated version of the CPTI has good psychometric properties and seems to be a promising tool for studying psychopathic traits in children.
Planetary Dune Workshop Expands to Include Subaqueous Processes
Authors: Titus Timothy , Rubin David , Bryant Gerald
Published: February 2018

The Fifth International Planetary Dunes Workshop: From the Bottom of the Oceans to the Outer Limits of the Solar System; St. George, Utah, 16–19 May 2017
Expanding frontiers in materials chemistry and physics with multiple anions
Authors: Kageyama Hiroshi , Hayashi Katsuro , Maeda Kazuhiko , Attfield J. Paul , Hiroi Zenji , Rondinelli James M. , Poeppelmeier Kenneth R.
Published: February 2018

During the last century, inorganic oxide compounds laid foundations for materials synthesis, characterization, and technology translation by adding new functions into devices previously dominated by main-group element semiconductor compounds. Today, compounds with multiple anions beyond the single-oxide ion, such as oxyhalides and oxyhydrides, offer a new materials platform from which superior functionality may arise. Here we review the recent progress, status, and future prospects and challenges facing the development and deployment of mixed-anion compounds, focusing mainly on oxide-derived materials. We devote attention to the crucial roles that multiple anions play during synthesis, characterization, and in the physical properties of these materials. We discuss the opportunities enabled by recent advances in synthetic approaches for design of both local and overall structure, state-of-the-art characterization techniques to distinguish unique structural and chemical states, and chemical/physical properties emerging from the synergy of multiple anions for catalysis, energy conversion, and electronic materials.
Timescales of water accumulation in magmas and implications for short warning times of explosive eruptions
Authors: Petrelli M. , El Omari K. , Spina L. , Le Guer Y. , La Spina G. , Perugini D.
Published: February 2018

Water plays a key role in magma genesis, differentiation, ascent and, finally, eruption. Despite the recognized crucial function of water, there are still several issues that continue to blur our view about its role in magmatic systems. What are the timescales of H2O accumulation in crystallizing magmas? What are the ascent rates of water-rich residual melts leading to explosive eruptions? Here, we track the timescale of water accumulation in a residual melt resulting from crystallization of a hydrous CO2-bearing magmatic mass stored at mid- to deep-crustal levels in a subduction-related geodynamic setting. Our results indicate that, after a repose period ranging from few to several thousand years, water-rich melts with water concentrations larger than 6–9 wt.% can migrate towards the Earth surface in very short timescales, on the order of days or even hours, possibly triggering explosive eruptions with short warning times and devoid of long-term geophysical precursors.
Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility
Authors: Behera Vivek , Evans Perry , Face Carolyne J. , Hamagami Nicole , Sankaranarayanan Laavanya , Keller Cheryl A. , Giardine Belinda , Tan Kai , Hardison Ross C. , Shi Junwei , Blobel Gerd A.
Published: February 2018

Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants of in vivo TF binding and chromatin accessibility, we introduce an approach that compares ChIP-seq and DNase-seq data sets from genetically divergent murine erythroid cell lines. The impact of discriminatory single-nucleotide variants on TF ChIP signal enables definition at single base resolution of in vivo binding characteristics of nuclear factors GATA1, TAL1, and CTCF. We further develop a facile complementary approach to more deeply test the requirements of critical nucleotide positions for TF binding by combining CRISPR-Cas9-mediated mutagenesis with ChIP and targeted deep sequencing. Finally, we extend our analytical pipeline to identify nearby contextual DNA elements that modulate chromatin binding by these three TFs, and to define sequences that impact kb-scale chromatin accessibility. Combined, our approaches reveal insights into the genetic basis of TF occupancy and their interplay with chromatin features.
Active colloids as mobile microelectrodes for unified label-free selective cargo transport
Authors: Boymelgreen Alicia M. , Balli Tov , Miloh Touvia , Yossifon Gilad
Published: February 2018

Utilization of active colloids to transport both biological and inorganic cargo has been widely examined in the context of applications ranging from targeted drug delivery to sample analysis. In general, carriers are customized to load one specific target via a mechanism distinct from that driving the transport. Here we unify these tasks and extend loading capabilities to include on-demand selection of multiple nano/micro-sized targets without the need for pre-labelling or surface functionalization. An externally applied electric field is singularly used to drive the active cargo carrier and transform it into a mobile floating electrode that can attract (trap) or repel specific targets from its surface by dielectrophoresis, enabling dynamic control of target selection, loading and rate of transport via the electric field parameters. In the future, dynamic selectivity could be combined with directed motion to develop building blocks for bottom-up fabrication in applications such as additive manufacturing and soft robotics.
Landscape topography structures the soil microbiome in arctic polygonal tundra
Authors: Taş Neslihan , Prestat Emmanuel , Wang Shi , Wu Yuxin , Ulrich Craig , Kneafsey Timothy , Tringe Susannah G. , Torn Margaret S. , Hubbard Susan S. , Jansson Janet K.
Published: February 2018

In the Arctic, environmental factors governing microbial degradation of soil carbon (C) in active layer and permafrost are poorly understood. Here we determined the functional potential of soil microbiomes horizontally and vertically across a cryoperturbed polygonal landscape in Alaska. With comparative metagenomics, genome binning of novel microbes, and gas flux measurements we show that microbial greenhouse gas (GHG) production is strongly correlated to landscape topography. Active layer and permafrost harbor contrasting microbiomes, with increasing amounts of Actinobacteria correlating with decreasing soil C in permafrost. While microbial functions such as fermentation and methanogenesis were dominant in wetter polygons, in drier polygons genes for C mineralization and CH4 oxidation were abundant. The active layer microbiome was poised to assimilate N and not to release N2O, reflecting low N2O flux measurements. These results provide mechanistic links of microbial metabolism to GHG fluxes that are needed for the refinement of model predictions.
HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130
Authors: Göder Anja , Emmerich Claudia , Nikolova Teodora , Kiweler Nicole , Schreiber Maria , Kühl Toni , Imhof Diana , Christmann Markus , Heinzel Thorsten , Schneider Günter , Krämer Oliver H.
Published: February 2018

Checkpoint kinases sense replicative stress to prevent DNA damage. Here we show that the histone deacetylases HDAC1/HDAC2 sustain the phosphorylation of the checkpoint kinases ATM, CHK1 and CHK2, activity of the cell cycle gatekeeper kinases WEE1 and CDK1, and induction of the tumour suppressor p53 in response to stalled DNA replication. Consequently, HDAC inhibition upon replicative stress promotes mitotic catastrophe. Mechanistically, HDAC1 and HDAC2 suppress the expression of PPP2R3A/PR130, a regulatory subunit of the trimeric serine/threonine phosphatase 2 (PP2A). Genetic elimination of PR130 reveals that PR130 promotes dephosphorylation of ATM by PP2A. Moreover, the ablation of PR130 slows G1/S phase transition and increases the levels of phosphorylated CHK1, replication protein A foci and DNA damage upon replicative stress. Accordingly, stressed PR130 null cells are very susceptible to HDAC inhibition, which abrogates the S phase checkpoint, induces apoptosis and reduces the homologous recombination protein RAD51. Thus, PR130 controls cell fate decisions upon replicative stress.
EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase
Authors: Kasahara Kousuke , Aoki Hiromasa , Kiyono Tohru , Wang Shujie , Kagiwada Harumi , Yuge Mizuki , Tanaka Toshio , Nishimura Yuhei , Mizoguchi Akira , Goshima Naoki , Inagaki Masaki
Published: February 2018

Ciliogenesis is generally inhibited in dividing cells, however, it has been unclear which signaling cascades regulate the phenomenon. Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells. These phosphorylations elevate the deubiquitinase activity, which then stabilizes the trichoplein-Aurora A pathway, an inhibitory mechanism of ciliogenesis. EGFR knockdown and serum starvation result in ciliogenesis through downregulation of the USP8-trichoplein-Aurora A signal. Moreover, primary cilia abrogation, which is induced upon IFT20 or Cep164 depletion, ameliorates the cell cycle arrest of EGFR knockdown cells. The present data reveal that the EGFR-USP8-trichoplein-Aurora A axis is a critical signaling cascade that restricts ciliogenesis in dividing cells, and functions to facilitate cell proliferation. We further show that usp8 knockout zebrafish develops ciliopathy-related phenotypes including cystic kidney, suggesting that USP8 is a regulator of ciliogenesis in vertebrates.
Reshaping the phonon energy landscape of nanocrystals inside a terahertz plasmonic nanocavity
Authors: Jin Xin , Cerea Andrea , Messina Gabriele C. , Rovere Andrea , Piccoli Riccardo , De Donato Francesco , Palazon Francisco , Perucchi Andrea , Di Pietro Paola , Morandotti Roberto , Lupi Stefano , De Angelis Francesco , Prato Mirko , Toma Andrea , Razzari Luca
Published: February 2018

Phonons (quanta of collective vibrations) are a major source of energy dissipation and drive some of the most relevant properties of materials. In nanotechnology, phonons severely affect light emission and charge transport of nanodevices. While the phonon response is conventionally considered an inherent property of a nanomaterial, here we show that the dipole-active phonon resonance of semiconducting (CdS) nanocrystals can be drastically reshaped inside a terahertz plasmonic nanocavity, via the phonon strong coupling with the cavity vacuum electric field. Such quantum zero-point field can indeed reach extreme values in a plasmonic nanocavity, thanks to a mode volume well below λ3/107. Through Raman measurements, we find that the nanocrystals within a nanocavity exhibit two new “hybridized” phonon peaks, whose spectral separation increases with the number of nanocrystals. Our findings open exciting perspectives for engineering the optical phonon response of functional nanomaterials and for implementing a novel platform for nanoscale quantum optomechanics.
Wetter summers can intensify departures from natural variability in a warming climate
Authors: Mahony Colin R. , Cannon Alex J.
Published: February 2018

Climate change can drive local climates outside the range of their historical year-to-year variability, straining the adaptive capacity of ecological and human communities. We demonstrate that dependencies between climate variables can produce larger and earlier departures from natural variability than is detectable in individual variables. Using the example of summer temperature (Tx) and precipitation (Pr), we show that this departure intensification effect occurs when the bivariate climate change trajectory is misaligned with the dominant mode of joint historical variability. Departure intensification is evident in all six CMIP5 models that we examined: 23% (9–34%) of the global land area of each model exhibits a pronounced increase in 2σ anomalies in the Tx-Pr regime relative to Tx or Pr alone. Observational data suggest that summer Tx-Pr correlations in distinct regions on all continents are sufficient to produce departure intensification. Precipitation can be an important driver of multivariate climate change signals relative to natural variability, despite typically having a much weaker univariate signal than temperature.
An ancient family of lytic polysaccharide monooxygenases with roles in arthropod development and biomass digestion
Authors: Sabbadin Federico , Hemsworth Glyn R. , Ciano Luisa , Henrissat Bernard , Dupree Paul , Tryfona Theodora , Marques Rita D. S. , Sweeney Sean T. , Besser Katrin , Elias Luisa , Pesante Giovanna , Li Yi , Dowle Adam A. , Bates Rachel , Gomez Leonardo D. , Simister Rachael , Davies Gideon J. , Walton Paul H. , Bruce Neil C. , McQueen-Mason Simon J.
Published: February 2018

Thermobia domestica belongs to an ancient group of insects and has a remarkable ability to digest crystalline cellulose without microbial assistance. By investigating the digestive proteome of Thermobia, we have identified over 20 members of an uncharacterized family of lytic polysaccharide monooxygenases (LPMOs). We show that this LPMO family spans across several clades of the Tree of Life, is of ancient origin, and was recruited by early arthropods with possible roles in remodeling endogenous chitin scaffolds during development and metamorphosis. Based on our in-depth characterization of Thermobia’s LPMOs, we propose that diversification of these enzymes toward cellulose digestion might have endowed ancestral insects with an effective biochemical apparatus for biomass degradation, allowing the early colonization of land during the Paleozoic Era. The vital role of LPMOs in modern agricultural pests and disease vectors offers new opportunities to help tackle global challenges in food security and the control of infectious diseases.
Directed gas phase formation of silicon dioxide and implications for the formation of interstellar silicates
Authors: Yang Tao , Thomas Aaron M. , Dangi Beni B. , Kaiser Ralf I. , Mebel Alexander M. , Millar Tom J.
Published: February 2018

Interstellar silicates play a key role in star formation and in the origin of solar systems, but their synthetic routes have remained largely elusive so far. Here we demonstrate in a combined crossed molecular beam and computational study that silicon dioxide (SiO2) along with silicon monoxide (SiO) can be synthesized via the reaction of the silylidyne radical (SiH) with molecular oxygen (O2) under single collision conditions. This mechanism may provide a low-temperature path—in addition to high-temperature routes to silicon oxides in circumstellar envelopes—possibly enabling the formation and growth of silicates in the interstellar medium necessary to offset the fast silicate destruction.
Spatial organization of bacterial populations in response to oxygen and carbon counter-gradients in pore networks
Authors: Borer Benedict , Tecon Robin , Or Dani
Published: February 2018

Microbial activity in soil is spatially heterogeneous often forming spatial hotspots that contribute disproportionally to biogeochemical processes. Evidence suggests that bacterial spatial organization contributes to the persistence of anoxic hotspots even in unsaturated soils. Such processes are difficult to observe in situ at the microscale, hence mechanisms and time scales relevant for bacterial spatial organization remain largely qualitative. Here we develop an experimental platform based on glass-etched micrometric pore networks that mimics resource gradients postulated in soil aggregates to observe spatial organization of fluorescently tagged aerobic and facultative anaerobic bacteria. Two initially intermixed bacterial species, Pseudomonas putida and Pseudomonas veronii, segregate into preferential regions promoted by opposing gradients of carbon and oxygen (such persistent coexistence is not possible in well-mixed cultures). The study provides quantitative visualization and modeling of bacterial spatial organization within aggregate-like hotspots, a key step towards developing a mechanistic representation of bacterial community organization in soil pores.
The structure of iPLA2β reveals dimeric active sites and suggests mechanisms of regulation and localization
Authors: Malley Konstantin R. , Koroleva Olga , Miller Ian , Sanishvili Ruslan , Jenkins Christopher M. , Gross Richard W. , Korolev Sergey
Published: February 2018

Calcium-independent phospholipase A2β (iPLA2β) regulates important physiological processes including inflammation, calcium homeostasis and apoptosis. It is genetically linked to neurodegenerative disorders including Parkinson’s disease. Despite its known enzymatic activity, the mechanisms underlying iPLA2β-induced pathologic phenotypes remain poorly understood. Here, we present a crystal structure of iPLA2β that significantly revises existing mechanistic models. The catalytic domains form a tight dimer. They are surrounded by ankyrin repeat domains that adopt an outwardly flared orientation, poised to interact with membrane proteins. The closely integrated active sites are positioned for cooperative activation and internal transacylation. The structure and additional solution studies suggest that both catalytic domains can be bound and allosterically inhibited by a single calmodulin. These features suggest mechanisms of iPLA2β cellular localization and activity regulation, providing a basis for inhibitor development. Furthermore, the structure provides a framework to investigate the role of neurodegenerative mutations and the function of iPLA2β in the brain.
A regulatory circuit of two lncRNAs and a master regulator directs cell fate in yeast
Authors: Moretto Fabien , Wood N. Ezgi , Kelly Gavin , Doncic Andreas , van Werven Folkert J.
Published: February 2018

Transcription of long noncoding RNAs (lncRNAs) regulates local gene expression in eukaryotes. Many examples of how a single lncRNA controls the expression of an adjacent or nearby protein-coding gene have been described. Here we examine the regulation of a locus consisting of two contiguous lncRNAs and the master regulator for entry into yeast meiosis, IME1. We find that the cluster of two lncRNAs together with several transcription factors form a regulatory circuit by which IME1 controls its own promoter and thereby promotes its own expression. Inhibition or stimulation of this unusual feedback circuit affects timing and rate of IME1 accumulation, and hence the ability for cells to enter meiosis. Our data demonstrate that orchestrated transcription through two contiguous lncRNAs promotes local gene expression and determines a critical cell fate decision.
Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation
Authors: Khayachi Anouar , Gwizdek Carole , Poupon Gwénola , Alcor Damien , Chafai Magda , Cassé Frédéric , Maurin Thomas , Prieto Marta , Folci Alessandra , De Graeve Fabienne , Castagnola Sara , Gautier Romain , Schorova Lenka , Loriol Céline , Pronot Marie , Besse Florence , Brau Frédéric , Deval Emmanuel , Bardoni Barbara , Martin Stéphane
Published: February 2018

Fragile X syndrome (FXS) is the most frequent inherited cause of intellectual disability and the best-studied monogenic cause of autism. FXS results from the functional absence of the fragile X mental retardation protein (FMRP) leading to abnormal pruning and consequently to synaptic communication defects. Here we show that FMRP is a substrate of the small ubiquitin-like modifier (SUMO) pathway in the brain and identify its active SUMO sites. We unravel the functional consequences of FMRP sumoylation in neurons by combining molecular replacement strategy, biochemical reconstitution assays with advanced live-cell imaging. We first demonstrate that FMRP sumoylation is promoted by activation of metabotropic glutamate receptors. We then show that this increase in sumoylation controls the homomerization of FMRP within dendritic mRNA granules which, in turn, regulates spine elimination and maturation. Altogether, our findings reveal the sumoylation of FMRP as a critical activity-dependent regulatory mechanism of FMRP-mediated neuronal function.
Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246
Authors: Cooks Tomer , Pateras Ioannis S. , Jenkins Lisa M. , Patel Keval M. , Robles Ana I. , Morris James , Forshew Tim , Appella Ettore , Gorgoulis Vassilis G. , Harris Curtis C.
Published: February 2018

TP53 mutants (mutp53) are involved in the pathogenesis of most human cancers. Specific mutp53 proteins gain oncogenic functions (GOFs) distinct from the tumor suppressor activity of the wild-type protein. Tumor-associated macrophages (TAMs), a hallmark of solid tumors, are typically correlated with poor prognosis. Here, we report a non-cell-autonomous mechanism, whereby human mutp53 cancer cells reprogram macrophages to a tumor supportive and anti-inflammatory state. The colon cancer cells harboring GOF mutp53 selectively shed miR-1246-enriched exosomes. Uptake of these exosomes by neighboring macrophages triggers their miR-1246-dependent reprogramming into a cancer-promoting state. Mutp53-reprogammed TAMs favor anti-inflammatory immunosuppression with increased activity of TGF-β. These findings, associated with poor survival in colon cancer patients, strongly support a microenvironmental GOF role for mutp53 in actively engaging the immune system to promote cancer progression and metastasis.
A quantum causal discovery algorithm
Authors: Giarmatzi Christina , Costa Fabio
Published: February 2018

Finding a causal model for a set of classical variables is now a well-established task—but what about the quantum equivalent? Even the notion of a quantum causal model is controversial. Here, we present a causal discovery algorithm for quantum systems. The input to the algorithm is a process matrix describing correlations between quantum events. Its output consists of different levels of information about the underlying causal model. Our algorithm determines whether the process is causally ordered by grouping the events into causally ordered non-signaling sets. It detects if all relevant common causes are included in the process, which we label Markovian, or alternatively if some causal relations are mediated through some external memory. For a Markovian process, it outputs a causal model, namely the causal relations and the corresponding mechanisms, represented as quantum states and channels. Our algorithm opens the route to more general quantum causal discovery methods.
Superior memory efficiency of quantum devices for the simulation of continuous-time stochastic processes
Authors: Elliott Thomas J. , Gu Mile
Published: February 2018

Continuous-time stochastic processes pervade everyday experience, and the simulation of models of these processes is of great utility. Classical models of systems operating in continuous-time must typically track an unbounded amount of information about past behaviour, even for relatively simple models, enforcing limits on precision due to the finite memory of the machine. However, quantum machines can require less information about the past than even their optimal classical counterparts to simulate the future of discrete-time processes, and we demonstrate that this advantage extends to the continuous-time regime. Moreover, we show that this reduction in the memory requirement can be unboundedly large, allowing for arbitrary precision even with a finite quantum memory. We provide a systematic method for finding superior quantum constructions, and a protocol for analogue simulation of continuous-time renewal processes with a quantum machine.
Hologenomic adaptations underlying the evolution of sanguivory in the common vampire bat
Authors: Zepeda Mendoza M. Lisandra , Xiong Zijun , Escalera-Zamudio Marina , Runge Anne Kathrine , Thézé Julien , Streicker Daniel , Frank Hannah K. , Loza-Rubio Elizabeth , Liu Shengmao , Ryder Oliver A. , Samaniego Castruita Jose Alfredo , Katzourakis Aris , Pacheco George , Taboada Blanca , Löber Ulrike , Pybus Oliver G. , Li Yang , Rojas-Anaya Edith , Bohmann Kristine , Carmona Baez Aldo , Arias Carlos F. , Liu Shiping , Greenwood Alex D. , Bertelsen Mads F. , White Nicole E. , Bunce Michael , Zhang Guojie , Sicheritz-Pontén Thomas , Gilbert M. P. Thomas
Published: February 2018

Adaptation to specialized diets often requires modifications at both genomic and microbiome levels. We applied a hologenomic approach to the common vampire bat (Desmodus rotundus), one of the only three obligate blood-feeding (sanguivorous) mammals, to study the evolution of its complex dietary adaptation. Specifically, we assembled its high-quality reference genome (scaffold N50 = 26.9 Mb, contig N50 = 36.6 kb) and gut metagenome, and compared them against those of insectivorous, frugivorous and carnivorous bats. Our analyses showed a particular common vampire bat genomic landscape regarding integrated viral elements, a dietary and phylogenetic influence on gut microbiome taxonomic and functional profiles, and that both genetic elements harbour key traits related to the nutritional (for example, vitamin and lipid shortage) and non-nutritional (for example, nitrogen waste and osmotic homeostasis) challenges of sanguivory. These findings highlight the value of a holistic study of both the host and its microbiota when attempting to decipher adaptations underlying radical dietary lifestyles.
Systemic Homeostasis in Metabolome, Ionome, and Microbiome of Wild Yellowfin Goby in Estuarine Ecosystem
Authors: Wei Feifei , Sakata Kenji , Asakura Taiga , Date Yasuhiro , Kikuchi Jun
Published: February 2018

Data-driven approaches were applied to investigate the temporal and spatial changes of 1,022 individuals of wild yellowfin goby and its potential interaction with the estuarine environment in Japan. Nuclear magnetic resonance (NMR)-based metabolomics revealed that growth stage is a primary factor affecting muscle metabolism. Then, the metabolic, elemental and microbial profiles of the pooled samples generated according to either the same habitat or sampling season as well as the river water and sediment samples from their habitats were measured using NMR spectra, inductively coupled plasma optical emission spectrometry and next-generation 16 S rRNA gene sequencing. Hidden interactions in the integrated datasets such as the potential role of intestinal bacteria in the control of spawning migration, essential amino acids and fatty acids synthesis in wild yellowfin goby were further extracted using correlation clustering and market basket analysis-generated networks. Importantly, our systematic analysis of both the seasonal and latitudinal variations in metabolome, ionome and microbiome of wild yellowfin goby pointed out that the environmental factors such as the temperature play important roles in regulating the body homeostasis of wild fish.