bluuebunny/crossref_metadata_2025 huggingface dataset:
Inertial flow transitions of a suspension in Taylor–Couette geometry
Authors: Majji Madhu V. , Banerjee Sanjoy , Morris Jeffrey F.
Published: November 2017

Experiments on the inertial flow transitions of a particle–fluid suspension in the concentric cylinder (Taylor–Couette) flow with rotating inner cylinder and stationary outer cylinder are reported. The radius ratio of the apparatus was $\unicode[STIX]{x1D702}=d_{i}/d_{o}=0.877$, where $d_{i}$ and $d_{o}$ are the diameters of inner and outer cylinders. The ratio of the axial length to the radial gap of the annulus $\unicode[STIX]{x1D6E4}=L/\unicode[STIX]{x1D6FF}=20.5$, where $\unicode[STIX]{x1D6FF}=(d_{o}-d_{i})/2$. The suspensions are formed of non-Brownian particles of equal density to the suspending fluid, of two sizes such that the ratio of annular gap to the mean particle diameter $d_{p}$ was either $\unicode[STIX]{x1D6FC}=\unicode[STIX]{x1D6FF}/d_{p}=30$ or $100$. For the experiments with $\unicode[STIX]{x1D6FC}=100$, the particle volume fraction was $\unicode[STIX]{x1D719}=0.10$ and for the experiments with $\unicode[STIX]{x1D6FC}=30$, $\unicode[STIX]{x1D719}$ was varied over $0\leqslant \unicode[STIX]{x1D719}\leqslant 0.30$. The focus of the work is on determining the influence of particle loading and size on inertial flow transitions. The primary effects of the particles were a reduction of the maximum Reynolds number for the circular Couette flow (CCF) and several non-axisymmetric flow states not seen for a pure fluid with only inner cylinder rotation; here the Reynolds number is $Re=\unicode[STIX]{x1D6FF}d_{i}\unicode[STIX]{x1D6FA}\unicode[STIX]{x1D70C}/2\unicode[STIX]{x1D707}_{s}$, where $\unicode[STIX]{x1D6FA}$ is the rotation rate of the inner cylinder and $\unicode[STIX]{x1D70C}$ and $\unicode[STIX]{x1D707}_{s}$ are the density and effective viscosity of the suspension. For purposes of maintaining uniform particle distribution, the rotation rate of the inner cylinder (or $Re$) was decreased slowly from a state other than CCF to probe the transitions. When $Re$ was decreased, pure fluid transitions from wavy Taylor vortex flow (WTV) to Taylor vortex flow (TVF) to CCF occurred. The suspension transitions differed. For $\unicode[STIX]{x1D6FC}=30$ and $0.05\leqslant \unicode[STIX]{x1D719}\leqslant 0.15$, with reduction of $Re$, additional non-axisymmetric flow states, namely spiral vortex flow (SVF) and ribbons (RIB), were observed between TVF and CCF. At $\unicode[STIX]{x1D719}=0.30$, the flow transitions observed were only non-axisymmetric: from wavy spiral vortices (WSV) to SVF to CCF. The values of $Re$ corresponding to each flow transition were observed to reduce with increase in particle loading for $0\leqslant \unicode[STIX]{x1D719}\leqslant 0.30$, with the initial transition away from CCF, for example, occurring at $Re\approx 120$ for the pure fluid and $Re\approx 75$ for the $\unicode[STIX]{x1D719}=0.30$ suspension. When the particle size was reduced to yield $\unicode[STIX]{x1D6FC}=100$, at $\unicode[STIX]{x1D719}=0.10$, only the RIB (and no SVF) was observed between TVF and CCF.
New material and systematic re-evaluation ofMedusaceratops lokii(Dinosauria, Ceratopsidae) from the Judith River Formation (Campanian, Montana)
Authors: Chiba Kentaro , Ryan Michael J. , Fanti Federico , Loewen Mark A. , Evans David C.
Published: November 2017

Medusaceratops lokiiRyan, Russell, and Hartman, 2010 is an enigmatic taxon of ceratopsid represented by partial parietals from the Mansfield bonebed in the Campanian Judith River Formation, Montana. Originally, all ceratopsid material collected from this bonebed was referred to the centrosaurine ceratopsidAlbertaceratops, but subsequently two parietals were designated the types of the chasmosaurine,M.lokii, in part, because they were interpreted to have three epiparietals bilaterally. Here we describe new material from the bonebed that allows a systematic revision of the taxon. A revised reconstruction of the frill, informed by newly discovered parietals, reveals thatM.lokiihad a broad midline ramus and at least five epiparietals (ep) around the margin of the frill, both traits that are characteristic of Centrosaurinae. From medial to lateral, the epiparietal ornamentation consists of a small, variably procurving epiparietal (ep 1), an anterolaterally curving pachyostotic hook (ep 2), a smaller pachyostoic process (ep 3), and two small triangular epiparietals (ep 4 and 5). A phylogenetic analysis of ceratopsids, which is the first to includeMedusaceratops, indicates thatM.lokiiis a unique, early centrosaurine ceratopsid taxon that is more closely related to Centrosaurini and Pachyrhinosaurini than Nasutoceratopsini. No unequivocal chasmosaurine bones or diagnostic material from any other ceratopsid could be identified from the Mansfield bonebed, suggesting that it represents one of the oldest occurrences of a monodominant accumulation of a centrosaurine ceratopsid on record.
Mobile phone usage does not affect sudden sensorineural hearing loss
Authors: Sagiv D , Migirov L , Madgar O , Nakache G , Wolf M , Shapira Y
Published: November 2017

Objective:

Recent studies found that mobile phone users had a significantly greater risk of having elevated thresholds in speech frequencies. This study investigated the correlation between the laterality of sudden sensorineural hearing loss, handedness and the preferred ear for mobile phone use.

Methods:

The study included all patients who presented with sudden sensorineural hearing loss to the Department of Otolaryngology – Head and Neck Surgery in our tertiary referral medical centre between 2014 and 2016. Patients were asked to indicate their dominant hand and preferred ear for mobile phone use.

Results:

The study comprised 160 patients. No correlation was found between the dominant hand or preferred ear for mobile phone use and the side of sudden sensorineural hearing loss. There was no correlation between the side of the sudden sensorineural hearing loss (preferable or non-preferable for mobile phone use) and audiometric characteristics.

Conclusion:

No correlation was found between the laterality of ears used for mobile phone and sudden sensorineural hearing loss.
Toxoplasma gondiireorganizes the host cell architecture during spontaneous cyst formationin vitro
Authors: Paredes-Santos T. C. , Martins-Duarte E. S. , de Souza W. , Attias M. , Vommaro R. C.
Published: November 2017

Toxoplasma gondiiis an intracellular protozoan parasite that causes toxoplasmosis, a prevalent infection related to abortion, ocular diseases and encephalitis in immuno-compromised individuals. In the untreatable (and life-long) chronic stage of toxoplasmosis, parasitophorous vacuoles (PVs, containingT. gondiitachyzoites) transform into tissue cysts, containing slow-dividing bradyzoite forms. While acute-stage infection with tachyzoites involves global rearrangement of the host cell cytoplasm, focused on favouring tachyzoite replication, the cytoplasmic architecture of cells infected with cysts had not been described. Here, we characterized (by fluorescence and electron microscopy) the redistribution of host cell structures aroundT. gondiicysts, using aT. gondiistrain (EGS) with high rates of spontaneous cystogenesisin vitro. Microtubules and intermediate filaments (but not actin microfilaments) formed a ‘cage’ around the cyst, and treatment with taxol (to inhibit microtubule dynamics) favoured cystogenesis. Mitochondria, which appeared adhered to the PV membrane, were less closely associated with the cyst wall. Endoplasmic reticulum (ER) profiles were intimately associated with folds in the cyst wall membrane. However, the Golgi complex was not preferentially localized relative to the cyst, and treatment with tunicamycin or brefeldin A (to disrupt Golgi or ER function, respectively) had no significant effect on cystogenesis. Lysosomes accumulated around cysts, while early and late endosomes were more evenly distributed in the cytoplasm. The endocytosis tracer HRP (but not BSA or transferrin) reached bradyzoites after uptake by infected host cells. These results suggest thatT. gondiicysts reorganize the host cell cytoplasm, which may fulfil specific requirements of the chronic stage of infection.
A highly transmissible tuberculosis outbreak: the importance of bars
Authors: GODOY P. , ALSEDÀ M. , FALGUERA M. , PUIG T. , BACH P. , MONRABÀ M. , MANONELLES A.
Published: November 2017

The transmission of tuberculosis (TB) in bars is difficult to study. The objective was to describe a large TB outbreak in a company's bar and other leisure settings. A descriptive study of a TB outbreak was carried out. Contacts were studied in the index case's workplace bar (five circles of contacts) and other recreational areas (social network of three bars in the index case's neighbourhood). Chest X-rays were recommended to contacts with positive tuberculin skin tests (TST) (⩾5 mm). The risk of latent tuberculosis infection (LTBI) was determined using an adjusted odds ratio. The dose–response relationship was determined using the chi-square test for linear trend. We studied 316 contacts at the index case's workplace and detected five new cases of TB. The prevalence of LTBI was 57·9% (183/316) and was higher in the first circle, 96·0% (24/25), and lower in the fifth, 46·5% (20/43) (P < 0·0001). Among 58 contacts in the three neighbourhood bars, two TB cases were detected and the LTBI prevalence was 51·7% (30/58). Two children of one secondary TB company patient became ill. Bars may be transmission locations for TB and, as they are popular venues for social events, should be considered as potential areas of exposure.
Aerobic environment ensures viability and anti-oxidant capacity when seeds are wet with negative effect when moist: implications for persistence in the soil
Authors: Carta Angelino , Bottega Stefania , Spanò Carmelina
Published: November 2017

Interchangeable effects of temperature, moisture content and oxygen on seed longevity have been mostly examined to estimate seed viability during long-term dry storage, whereas few experiments have studied seed viability under near-natural conditions to evaluate seed persistence in the soil. To this end, we artificially aged seeds ofRanunculus baudotii, a hydrophyte widely distributed in temporary ponds constituting an abundant soil seed bank. Seeds were exposed to controlled ageing at three different relative humidities (RH) under both aerobic and anoxic conditions. Their viability, water content, membrane damage, oxidative stress and anti-oxidant enzymatic defence activity were evaluated. Seed survival was longer at higher relative humidity (97% RH), and lowest at a relative humidity (90% RH) simulating moist but not waterlogged soils. Anoxic conditions showed a protective role on viability at lower moisture contents (70% RH). Seed viability was negatively associated with hydrogen peroxide content and correlated with anti-oxidant enzyme activities, but not with membrane damage. Altogether, these results suggest negative roles for moist soils and anoxia in determining seed persistence in the field, but at higher moisture contents the negative effects of anaerobia diminished. The anti-oxidant system activation, even under unfavourable conditions, might recover seeds once all protective processes can operate, pointing out the plasticity of mechanisms involved in seed loss viability.
SPECIES IDENTIFICATION OF VACHELLIA PACHYCERAS FROM KUWAIT AND ITS RELATIVES VACHELLIA GERRARDII AND VACHELLIA TORTILIS, BASED ON MULTILOCUS PLASTID GENE SEQUENCES
Authors: Suleiman M. K. , Quoreshi A. M. , Bhat N. R. , Manuvel A. J.
Published: November 2017

The genus Acacia Miller is species-rich, and species discrimination is challenging owing to morphological similarities between closely related species. Naming of specimens is particularly difficult in the Middle East, where confusion in taxonomic identification exists within the context of a wider international debate on the generic systematics of Acacia sensu lato. At least five segregate genera for Acacia s.l. have been advocated: Acacia sensu stricto, Vachellia, Senegalia, Acaciella and Mariosousa. Furthermore, identification to species of the only remaining native Acacia s.l. tree in Kuwait is still a matter of controversy. The present study used multilocus chloroplast DNA sequence data analyses following maximum likelihood (ML) and Bayesian approaches to: 1) test the species concepts of Vachellia pachyceras (≡ Acacia pachyceras O.Schwartz) from the Middle East, and Vachellia tortilis (Forssk.) Galasso & Banfi (≡ Acacia tortilis (Forssk.) Hayne) and Vachellia gerrardii (Benth.) P.J.H.Hurter (≡ Acacia gerrardii Benth.) from Kenya, as well as to investigate species divergence times; and 2) identify the only remaining native Acacia s.l. tree in Kuwait (known as the Lonely Tree), as well as other unidentified Acacia s.l. specimens in cultivation. The Bayesian and ML topologies clearly differentiated Vachellia pachyceras, V. tortilis and V. gerrardii, and demonstrated that the three species are distinct. Divergence time estimates using the ML topology suggested that Vachellia gerrardii diverged from a common ancestor no later than the early Pliocene (3.3 Mya), whereas V. pachyceras originated at least 2.0 Mya (Pliocene). The unknown remaining native Acacia s.l. tree in Kuwait and other specimens collected from the nursery were identified as Vachellia pachyceras. These results stress the need to use plastid DNA barcodes complemented by population genetics approaches to address systematic issues in this complex of Acacia s.l. species in the Middle East and the Arabian Peninsula.
A chemical compound based on methylxanthine–polyphenols lowers nitric oxide levels and increases post-thaw human sperm viability
Authors: Werner Cleiton , Cadoná Francine Carla , da Cruz Ivana Beatrice Mânica , Flôres Eliza Ribas da Silveira , Machado Alencar Kolinski , Fantinel Mara Rejane , Weis Grazielle Castagna Cezimbra , Assmann Charles Elias , Alves Audrei de Oliveira , Bonadiman Beatriz da Silva Rosa , Ribeiro Euler Esteves , Montano Marco Aurélio Echart
Published: November 2017

We produced a new chemical compound based on methylxanthines and polyphenols (CCMP) present in the chemical matrix of guaraná (Paullinia cupana), a seed extract with antioxidant properties. After supplementation with the standard extract of resveratrol, a well documented antioxidant found in other plant sources, we investigated whether this resveratrol-enriched compound could improve sperm viability and modulate differentially reactive oxygen species (ROS) and nitric oxide (NO) levels in thawed sperm. Sperm samples obtained from healthy young donors were treated with different concentrations of guaraná extract (0.1, 1, 5 or 10 mg/ml) and cells were frozen at −80°C for 24 h. In addition, the potential protective effects of guaraná treatment on sperm treated with pro-oxidant compound (200 µM hydrogen peroxide, H2O2) were assessed. Samples were also exposed to three concentrations of CCMP before being frozen in liquid nitrogen (−196°C) or in an ultrafreezer (−80°C) for 24 h, and both pre-freezing and post-thaw measurements of viability and oxidative stress were performed. Guaraná supplementation at 10 mg/ml significantly increased post-thaw viability and decreased oxidative metabolism of the sperm. Moreover, selected concentrations of CCMP improved viability and oxidative metabolism in sperm samples pre-freezing. Furthermore, CCMP showed cryoprotective activity by increasing viability and decreasing oxidative stress in post-thaw samples. In summary, these findings suggested that CCMP supplementation acts as a cryoprotectant to modulate ROS and NO levels in thawed sperm. CCMP could be used to enhance sperm quality and reproductive success.
Three Ways to Improve Religious Epistemology
Authors: Schellenberg J. L.
Published: November 2017

Religious epistemology is widely regarded as being in a flourishing condition. It is true that some very sharp analytical work on religion has been produced by philosophers in the past few decades. But this work, for various cultural and historical reasons, has been kept within excessively narrow bounds, and the result is that the appearance of flourishing is to a considerable extent illusory. Here I discuss three important ways in which improvements to this situation might be made.
To each their own: case studies of four successful, small-scale organic vegetable farmers with distinct weed management strategies
Authors: Brown Bryan , Gallandt Eric R.
Published: November 2017

Organic vegetable farmers execute weed management using many overall philosophies, including focusing management during the early-season critical period, managing the weed seedbank with a ‘zero seed rain’ strategy, or physically suppressing weeds with plastic or natural mulches. While these strategies vary in their ecological and economic implications, farmers’ reasons for adopting specific weed management approaches, and the related practical implications of each approach remain unclear. To better understand farmer motivations and ecological impacts of broad weed management philosophies, we conducted case studies of four successful organic vegetable farmers with specialization in different management approaches. The farmers were interviewed about their experiences and soil samples were collected for weed community and soil organic matter (SOM) analysis. The farmer who controls weed seedlings primarily during the critical period has appreciated the associated weeding labor savings, but late-season weeds have contributed to a large weed seedbank (38,482 seeds m−2), which is necessitating a change in his management. Conversely, the zero seed rain strategy of another farmer required a large amount of labor in the initial years, but weeding labor requirements have lessened every year due to decreased weed emergence from his diminishing weed seedbank (3065 seeds m−2). Another farmer utilizes plastic mulch in many crops in order to reduce weeding labor during the busy spring planting season. Finally, the farmer that uses natural mulches has high labor costs, but they are offset by the benefits of weed suppression, soil moisture conservation and increases to SOM. The two farmers utilizing mulch had the greatest portion of monocotyledonous weeds, perhaps relating to their morphology allowing them to emerge through the mulch. In ranking management criteria based on their importance, the case study farmers generally valued the criteria that are benefited by their strategy, indicating a strong relationship between their priorities and their management. Overall, there was no ‘best’ weed management strategy, but farmers may benefit from the consideration of how their management priorities match the practical tradeoffs of each strategy.
Defining and delivering minimum incomes in China
Authors: Adler Michael
Published: November 2017

This paper combines an empirical analysis of national and international attempts to deal with the problem of poverty in China with a normative analysis of capability theory, as developed by Amartya Sen and Martha Nussbaum. In this way, it attempts to highlight the centrality of normative approaches to poverty and its elimination. The paper is in five parts. Section I analyses the history, development and effectiveness of social assistance under the Minimum Living Standards Scheme (MLSS) in China; Section II provides an outline of capability theory; Section III analyses the history, development and effectiveness of the United Nations Development Program's (UNDP) Millennium Development Goals, with a focus on the elimination of poverty in China; Section IV emphasises the importance of a capability approach to the measurement of poverty and outlines what needs to be done to reduce poverty in China; while Section V discusses what still needs to be done to promote an effective anti-poverty strategy in China.
Geschlechts- und situationsspezifische Stressverarbeitung und Lebensqualität bei Kindern und Jugendlichen
Authors: Hampel Petra , Petermann Franz
Published: November 2017

Zusammenfassung. In der vorliegenden Studie sollten insbesondere die wenigen Befunde zum alleinigen Einfluss der Art der Belastungssituation und dessen kombinierte Einflüsse mit dem Geschlecht auf die Stressverarbeitung erweitert werden. Hierfür bearbeiteten N = 1 087 Kinder und Jugendliche im Alter zwischen 7 und 16 Jahren den Stressverarbeitungsfragebogen für Kinder und Jugendliche (SVF-KJ). Darüber hinaus wurde die Vorhersagekraft der situationsspezifischen Stressverarbeitung auf die gesundheitsbezogene Lebensqualität an einer Teilstichprobe von N = 442 Kindern und Jugendlichen zwischen 9 und 16 Jahren untersucht. Die alleinigen Situationseinflüsse sprechen für erhöhte Ausprägungen in der Ablenkung, Situationskontrolle und Aggression für soziale Belastungssituationen. Mädchen verarbeiteten vor allem soziale Belastungssituationen ungünstig. Die Stressverarbeitung konnte die gesundheitsbezogene Lebensqualität unter Kontrolle des Alters, Geschlechts, chronischer Erkrankungen und der psychischen Stressreaktivität signifikant vorhersagen. Die Befunde unterstützen erneut, geschlechtssensible, altersangepasste Gesundheitsförderprogramme im Kindes- und Jugendalter zu implementieren, die insbesondere die Bagatellisierung, positiven Selbstinstruktionen, Vermeidung und Resignation modifizieren sollten.
Do They Rate in the Same Way?
Authors: Rogge Jana , Koglin Ute , Petermann Franz
Published: November 2017

Abstract. The internal structure of the Strengths and Difficulties Questionnaire (SDQ) has been widely discussed in the literature. The first purpose of this study was, therefore, to analyze the internal structure of the SDQ as completed by German parents and teachers. Parents and teachers of 1,135 children between the ages of 3 and 6 years in German daycare facilities were asked to complete the SDQ. Using confirmatory factor analysis (CFA), we found that the original five-factor model with added correlations between items with similar content and allowing cross-loads of reverse-worded items to the prosocial behavior factor is the model that fits the data the best. Additionally, we found significant mean differences between parents and teachers in four of the five SDQ subscales. Nevertheless, to compare the scores across both groups, it is necessary that the SDQ measures social-emotional and behavioral difficulties for both parents and teachers in the same way. Hence, the second purpose of this study was to test for measurement invariance of the SDQ across both groups. Using multigroup confirmatory factor analysis (MGCFA), we found that strict measurement invariance is tenable. Therefore, the observed means of the SDQ scores from parents and teachers are readily comparable and interpretable.
Measurement Invariance of a Universal Behavioral Screener Across	Samples From the USA and Germany
Authors: Casale Gino , Volpe Robert J. , Daniels Brian , Hennemann Thomas , Briesch Amy M. , Grosche Michael
Published: November 2017

Abstract. The current study examines the item and scalar equivalence of an abbreviated school-based universal screener that was cross-culturally translated and adapted from English into German. The instrument was designed to assess student behavior problems that impact classroom learning. Participants were 1,346 K-6 grade students from the US (n = 390, Mage = 9.23, 38.5% female) and Germany (n = 956, Mage = 8.04, 40.1% female). Measurement invariance was tested by multigroup confirmatory factor analysis (CFA) across students from the US and Germany. Results support full scalar invariance between students from the US and Germany (df = 266, χ2 = 790.141, Δχ2 = 6.9, p < .001, CFI = 0.976, ΔCFI = 0.000, RMSEA = 0.052, ΔRMSEA = −0.003) indicating that the factor structure, the factor loadings, and the item thresholds are comparable across samples. This finding implies that a full cross-cultural comparison including latent factor means and structural coefficients between the US and the German version of the abbreviated screener is possible. Therefore, the tool can be used in German schools as well as for cross-cultural research purposes between the US and Germany.
Exact Moonlight Measurements Could Aid Earth-Observing Missions
Authors: Loomis Ilima
Published: November 2017

A new telescope’s unprecedented study of subtle variations in lunar light could finally give Earth-facing satellites a common reference point for their observations.
IFT proteins spatially control the geometry of cleavage furrow ingression and lumen positioning
Authors: Taulet Nicolas , Vitre Benjamin , Anguille Christelle , Douanier Audrey , Rocancourt Murielle , Taschner Michael , Lorentzen Esben , Echard Arnaud , Delaval Benedicte
Published: November 2017

Cytokinesis mediates the physical separation of dividing cells and, in 3D epithelia, provides a spatial landmark for lumen formation. Here, we unravel an unexpected role in cytokinesis for proteins of the intraflagellar transport (IFT) machinery, initially characterized for their ciliary role and their link to polycystic kidney disease. Using 2D and 3D cultures of renal cells, we show that IFT proteins are required to correctly shape the central spindle, to control symmetric cleavage furrow ingression and to ensure central lumen positioning. Mechanistically, IFT88 directly interacts with the kinesin MKLP2 and is essential for the correct relocalization of the Aurora B/MKLP2 complex to the central spindle. IFT88 is thus required for proper centralspindlin distribution and central spindle microtubule organization. Overall, this work unravels a novel non-ciliary mechanism for IFT proteins at the central spindle, which could contribute to kidney cyst formation by affecting lumen positioning.
Distributed neural representation of saliency controlled value and category during anticipation of rewards and punishments
Authors: Zhang Zhihao , Fanning Jennifer , Ehrlich Daniel B. , Chen Wenting , Lee Daeyeol , Levy Ifat
Published: November 2017

An extensive literature from cognitive neuroscience examines the neural representation of value, but interpretations of these existing results are often complicated by the potential confound of saliency. At the same time, recent attempts to dissociate neural signals of value and saliency have not addressed their relationship with category information. Using a multi-category valuation task that incorporates rewards and punishments of different nature, we identify distributed neural representation of value, saliency, and category during outcome anticipation. Moreover, we reveal category encoding in multi-voxel blood-oxygen-level-dependent activity patterns of the vmPFC and the striatum that coexist with value signals. These results help clarify ambiguities regarding value and saliency encoding in the human brain and their category independence, lending strong support to the neural “common currency” hypothesis. Our results also point to potential novel mechanisms of integrating multiple aspects of decision-related information.
The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand
Authors: Chan John D. , Cupit Pauline M. , Gunaratne Gihan S. , McCorvy John D. , Yang Yang , Stoltz Kristen , Webb Thomas R. , Dosa Peter I. , Roth Bryan L. , Abagyan Ruben , Cunningham Charles , Marchant Jonathan S.
Published: November 2017

Schistosomiasis is a debilitating tropical disease caused by infection with parasitic blood flukes. Approximately 260 million people are infected worldwide, underscoring the clinical and socioeconomic impact of this chronic infection. Schistosomiasis is treated with the drug praziquantel (PZQ), which has proved the therapeutic mainstay for over three decades of clinical use. However, the molecular target(s) of PZQ remain undefined. Here we identify a molecular target for the antischistosomal eutomer — (R)-PZQ — which functions as a partial agonist of the human serotoninergic 5HT2B receptor. (R)-PZQ modulation of serotoninergic signaling occurs over a concentration range sufficient to regulate vascular tone of the mesenteric blood vessels where the adult parasites reside within their host. These data establish (R)-PZQ as a G-protein-coupled receptor ligand and suggest that the efficacy of this clinically important anthelmintic is supported by a broad, cross species polypharmacology with PZQ modulating signaling events in both host and parasite.
Van der Waals epitaxial growth and optoelectronics of large-scale WSe2/SnS2 vertical bilayer p–n junctions
Authors: Yang Tiefeng , Zheng Biyuan , Wang Zhen , Xu Tao , Pan Chen , Zou Juan , Zhang Xuehong , Qi Zhaoyang , Liu Hongjun , Feng Yexin , Hu Weida , Miao Feng , Sun Litao , Duan Xiangfeng , Pan Anlian
Published: November 2017

High-quality two-dimensional atomic layered p–n heterostructures are essential for high-performance integrated optoelectronics. The studies to date have been largely limited to exfoliated and restacked flakes, and the controlled growth of such heterostructures remains a significant challenge. Here we report the direct van der Waals epitaxial growth of large-scale WSe2/SnS2 vertical bilayer p–n junctions on SiO2/Si substrates, with the lateral sizes reaching up to millimeter scale. Multi-electrode field-effect transistors have been integrated on a single heterostructure bilayer. Electrical transport measurements indicate that the field-effect transistors of the junction show an ultra-low off-state leakage current of 10−14 A and a highest on–off ratio of up to 107. Optoelectronic characterizations show prominent photoresponse, with a fast response time of 500 μs, faster than all the directly grown vertical 2D heterostructures. The direct growth of high-quality van der Waals junctions marks an important step toward high-performance integrated optoelectronic devices and systems.
ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice
Authors: Batenburg Nicole L. , Walker John R. , Noordermeer Sylvie M. , Moatti Nathalie , Durocher Daniel , Zhu Xu-Dong
Published: November 2017

CSB, a member of the SWI2/SNF2 superfamily, is implicated in DNA double-strand break (DSB) repair. However, how it regulates this repair process is poorly understood. Here we uncover that CSB interacts via its newly identified winged helix domain with RIF1, an effector of 53BP1, and that this interaction mediates CSB recruitment to DSBs in S phase. At DSBs, CSB remodels chromatin by evicting histones, which limits RIF1 and its effector MAD2L2 but promotes BRCA1 accumulation. The chromatin remodeling activity of CSB requires not only damage-induced phosphorylation on S10 by ATM but also cell cycle-dependent phosphorylation on S158 by cyclin A-CDK2. Both modifications modulate the interaction of the CSB N-terminal region with its ATPase domain, the activity of which has been previously reported to be autorepressed by the N-terminal region. These results suggest that ATM and CDK2 control the chromatin remodeling activity of CSB in the regulation of DSB repair pathway choice.
Targeted kinase inhibition relieves slowness and tremor in a Drosophila model of LRRK2 Parkinson’s disease
Authors: Cording Amy C. , Shiaelis Nicolas , Petridi Stavroula , Middleton C. Adam , Wilson Laurence G. , Elliott Christopher J. H.
Published: November 2017

In a number of Drosophila models of genetic Parkinson’s disease (PD) flies climb more slowly than wild-type controls. However, this assay does not distinguish effects of PD-related genes on gravity sensation, “arousal”, central pattern generation of leg movements, or muscle. To address this problem, we have developed an assay for the fly proboscis extension response (PER). This is attractive because the PER has a simple, well-identified reflex neural circuit, in which sucrose sensing neurons activate a pair of “command interneurons”, and thence motoneurons whose activity contracts the proboscis muscle. This circuit is modulated by a single dopaminergic neuron (TH-VUM). We find that expressing either the G2019S or I2020T (but not R1441C, or kinase dead) forms of human LRRK2 in dopaminergic neurons reduces the percentage of flies that initially respond to sucrose stimulation. This is rescued fully by feeding l-DOPA and partially by feeding kinase inhibitors, targeted to LRRK2 (LRRK2-IN-1 and BMPPB-32). High-speed video shows that G2019S expression in dopaminergic neurons slows the speed of proboscis extension, makes its duration more variable, and increases the tremor. Testing subsets of dopaminergic neurons suggests that the single TH-VUM neuron is likely most important in this phenotype. We conclude the Drosophila PER provides an excellent model of LRRK2 motor deficits showing bradykinesia, akinesia, hypokinesia, and increased tremor, with the possibility to localize changes in neural signaling.
Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish
Authors: Raghupathy Rakesh K. , Zhang Xun , Liu Fei , Alhasani Reem H. , Biswas Lincoln , Akhtar Saeed , Pan Luyuan , Moens Cecilia B. , Li Wenchang , Liu Mugen , Kennedy Breandan N. , Shu Xinhua
Published: November 2017

Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.
Glandular Morphometrics for Objective Grading of Colorectal Adenocarcinoma Histology Images
Authors: Awan Ruqayya , Sirinukunwattana Korsuk , Epstein David , Jefferyes Samuel , Qidwai Uvais , Aftab Zia , Mujeeb Imaad , Snead David , Rajpoot Nasir
Published: November 2017

Determining the grade of colon cancer from tissue slides is a routine part of the pathological analysis. In the case of colorectal adenocarcinoma (CRA), grading is partly determined by morphology and degree of formation of glandular structures. Achieving consistency between pathologists is difficult due to the subjective nature of grading assessment. An objective grading using computer algorithms will be more consistent, and will be able to analyse images in more detail. In this paper, we measure the shape of glands with a novel metric that we call the Best Alignment Metric (BAM). We show a strong correlation between a novel measure of glandular shape and grade of the tumour. We used shape specific parameters to perform a two-class classification of images into normal or cancerous tissue and a three-class classification into normal, low grade cancer, and high grade cancer. The task of detecting gland boundaries, which is a prerequisite of shape-based analysis, was carried out using a deep convolutional neural network designed for segmentation of glandular structures. A support vector machine (SVM) classifier was trained using shape features derived from BAM. Through cross-validation, we achieved an accuracy of 97% for the two-class and 91% for three-class classification.
Temperature Dependence in Heterogeneous Nucleation with Application to the Direct Determination of Cluster Energy on Nearly Molecular Scale
Authors: McGraw Robert L. , Winkler Paul M. , Wagner Paul E.
Published: November 2017

A re-examination of measurements of heterogeneous nucleation of water vapor on silver nanoparticles is presented here using a model-free framework that derives the energy of critical cluster formation directly from measurements of nucleation probability. Temperature dependence is correlated with cluster stabilization by the nanoparticle seed and previously found cases of unusual increasing nucleation onset saturation ratio with increasing temperature are explained. A necessary condition for the unusual positive temperature dependence is identified, namely that the critical cluster be more stable, on a per molecule basis, than the bulk liquid to exhibit the effect. Temperature dependence is next examined in the classical Fletcher model, modified here to make the energy of cluster formation explicit in the model.  The contact angle used in the Fletcher model is identified as the microscopic contact angle, which can be directly obtained from heterogeneous nucleation experimental data by a recently developed analysis method. Here an equivalent condition, increasing contact angle with temperature, is found necessary for occurrence of unusual temperature dependence. Our findings have immediate applications to atmospheric particle formation and nanoparticle detection in condensation particle counters (CPCs).
A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
Authors: Lai John , Moya Leire , An Jiyuan , Hoffman Andrea , Srinivasan Srilakshmi , Panchadsaram Janaththani , Walpole Carina , Perry-Keene Joanna L. , Chambers Suzanne ,   Australian Prostate Cancer BioResource, Yeadon T. , Saunders P. , Eckert A. , Heathcote P. , Wood G. , Malone G. , Samaratunga H. , Collins A. , Turner M. , Kerr K. , Lehman Melanie L. , Nelson Colleen C. , Clements Judith A. , Batra Jyotsna
Published: November 2017

Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate cancer development and/or progression. We undertook RNA sequencing analysis of prostate tumors and adjacent non-malignant cells to identify polymorphic STRs that are readily expressed in these cells. Most of the expressed STRs in the clinical samples mapped to intronic and intergenic DNA. Our analysis indicated that three of these STRs (TAAA-ACTG2, TTTTG-TRIB1, and TG-PCA3) are polymorphic and differentially expressed in prostate tumors compared to adjacent non-malignant cells. TG-PCA3 STR expression was repressed by the anti-androgen drug enzalutamide in prostate cancer cells. Genetic analysis of prostate cancer patients and healthy controls (N > 2,000) showed a significant association of the most common 11 repeat allele of TG-PCA3 STR with prostate cancer risk (OR = 1.49; 95% CI 1.11–1.99; P = 0.008). A significant association was also observed with aggressive disease (OR = 2.00; 95% CI 1.06–3.76; P = 0.031) and high mortality rates (HR = 3.0; 95% CI 1.03–8.77; P = 0.045). We propose that TG-PCA3 STR has both diagnostic and prognostic potential for prostate cancer. We provided a proof of concept to be applied to other RNA sequencing datasets to identify disease-associated STRs for future clinical exploratory studies.
Water depth affects reproductive allocation and reproductive allometry in the submerged macrophyte Vallisneria natans
Authors: Li Lei , Bonser Stephen P. , Lan Zhichun , Xu Ligang , Chen Jiakuan , Song Zhiping
Published: November 2017

In freshwater ecosystems, shifts in hydrological regimes have profound effects on reproductive output (R), along with vegetative biomass (V) and survival of plants. Because reproductive allocation (RA) is allometric, it remains unclear whether the observed variation of RA in response to water level variability is due to fixed patterns of development or plasticity in the developmental trajectories. Here, we investigated shifts in RA of a submerged macrophyte Vallisneria natans in response to water depth to test the hypothesis that allometric trajectories of RA are highly plastic. Plants were grown at three water depths (50, 100 and 150 cm) and measured after 26 weeks of growth. The relationships between R and V among treatments were compared. Deep water affected both biomass and number of fruits produced per plant, leading to less sexual reproduction. Plants in deep water started flowering at a smaller size and despite their small mature size, had a relatively high RA. Furthermore, these plants had a much lower log R–log V relationship than shallow- or intermediate-water plants. In conclusion, reproduction of V. natans is highly variable across water depth treatments, and variations in reproductive allometry represent different strategies under an important stress gradient for these freshwater angiosperms.
DNA metabarcoding data unveils invisible pollination networks
Authors: Pornon André , Andalo Christophe , Burrus Monique , Escaravage Nathalie
Published: November 2017

Animal pollination, essential for both ecological services and ecosystem functioning, is threatened by ongoing global changes. New methodologies to decipher their effects on pollinator composition to ecosystem health are urgently required. We compare the main structural parameters of pollination networks based on DNA metabarcoding data with networks based on direct observations of insect visits to plants at three resolution levels. By detecting numerous additional hidden interactions, metabarcoding data largely alters the properties of the pollination networks compared to visit surveys. Molecular data shows that pollinators are much more generalist than expected from visit surveys. However, pollinator species were composed of relatively specialized individuals and formed functional groups highly specialized upon floral morphs. We discuss pros and cons of metabarcoding data relative to data obtained from traditional methods and their potential contribution to both current and future research. This molecular method seems a very promising avenue to address many outstanding scientific issues at a resolution level which remains unattained to date; especially for those studies requiring pollinator and plant community investigations over macro-ecological scales.
Associations between general and central obesity and hypertension among children: The Childhood Obesity Study in China Mega-Cities
Authors: Zhao Yaling , Wang Liang , Xue Bo , Wang Youfa
Published: November 2017

In this study, we examined the associations of general and central obesity and hypertension among Chinese children. Data was collected from 1626 children aged 7–16 years and their parents in four mega-cities across China. Mixed effect models examined associations of general and central obesity with hypertension, and between body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The prevalence of general obesity, central obesity, and hypertension among the children was 11.1%, 19.7%, and 9.0%, respectively. More boys had general and central obesity than girls (15.2% vs. 6.9%; 27.4% vs. 11.7%, respectively; both P < 0.0001). Sex difference in hypertension rate was not statistically significant (9.3% in boys vs. 8.8% in girls, P = 0.7341). Both SBP and DBP were positively associated with BMI, WC, and WHtR, regardless of sex and region. General obesity (OR = 5.94, 95% confidence interval [CI]: 3.69–9.55) and central obesity (OR = 3.45, 95% CI: 2.27–5.23) were strongly associated with hypertension. The prevalence of general obesity, central obesity, and hypertension was high among Chinese children in the four mega-cities across China. Children’s BMI, WC, and WHtR were positively associated with their SBP and DBP. Obese children were 3–6 times more likely to have hypertension.
Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles
Authors: Hutzler Stefan , Erbar Stephanie , Jabulowsky Robert A. , Hanauer Jan R. H. , Schnotz Jürgen H. , Beissert Tim , Bodmer Bianca S. , Eberle Regina , Boller Klaus , Klamp Thorsten , Sahin Ugur , Mühlebach Michael D.
Published: November 2017

Recombinant vaccine strain-derived measles virus (MV) is clinically tested both as vaccine platform to protect against other pathogens and as oncolytic virus for tumor treatment. To investigate the potential synergism in anti-tumoral efficacy of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor antigen, claudin-6, for pre-clinical proof of concept. To enhance immunogenicity, both antigens were presented by retroviral virus-like particle produced in situ during MV-infection. All recombinant MV revealed normal growths, genetic stability, and proper expression and presentation of both antigens. Potent antigen-specific humoral and cellular immunity were found in immunized MV-susceptible IFNAR−/−-CD46Ge mice. These immune responses significantly inhibited metastasis formation or increased therapeutic efficacy compared to control MV in respective novel in vivo tumor models using syngeneic B16-hCD46/mCLDN6 murine melanoma cells. These data indicate the potential of MV to trigger selected tumor antigen-specific immune responses on top of direct tumor lysis for enhanced efficacy.
CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages
Authors: Zhang Yang , Li Xiang-Xiang , Ma Yuan , Xu Jie , Zhao Li-Na , Qian Xue-Feng , Zhang Xian-Feng , Shi Jin-Fang , Han Qing-Zhen
Published: November 2017

Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.
Construction of a system using a deep learning algorithm to count cell numbers in nanoliter wells for viable single-cell experiments
Authors: Kamatani Takashi , Fukunaga Koichi , Miyata Kaede , Shirasaki Yoshitaka , Tanaka Junji , Baba Rie , Matsusaka Masako , Kamatani Naoyuki , Moro Kazuyo , Betsuyaku Tomoko , Uemura Sotaro
Published: November 2017

For single-cell experiments, it is important to accurately count the number of viable cells in a nanoliter well. We used a deep learning-based convolutional neural network (CNN) on a large amount of digital data obtained as microscopic images. The training set consisted of 103 019 samples, each representing a microscopic grayscale image. After extensive training, the CNN was able to classify the samples into four categories, i.e., 0, 1, 2, and more than 2 cells per well, with an accuracy of 98.3% when compared to determination by two trained technicians. By analyzing the samples for which judgments were discordant, we found that the judgment by technicians was relatively correct although cell counting was often difficult by the images of discordant samples. Based on the results, the system was further enhanced by introducing a new algorithm in which the highest outputs from CNN were used, increasing the accuracy to higher than 99%. Our system was able to classify the data even from wells with a different shape. No other tested machine learning algorithm showed a performance higher than that of our system. The presented CNN system is expected to be useful for various single-cell experiments, and for high-throughput and high-content screening.