bluuebunny/crossref_metadata_2025 huggingface dataset:
COHERENCE AND CORRESPONDENCE IN THE NETWORK DYNAMICS OF BELIEF SUITES
Authors: Grim Patrick , Modell Andrew , Breslin Nicholas , Mcnenny Jasmine , Mondescu Irina , Finnegan Kyle , Olsen Robert , An Chanyu , Fedder Alexander
Published: May 2016

Coherence and correspondence are classical contenders as theories of truth. In this paper we examine them instead as interacting factors in the dynamics of belief across epistemic networks. We construct an agent-based model of network contact in which agents are characterized not in terms of single beliefs but in terms of internal beliefsuites. Individuals update elements of their belief suites on input from other agents in order both to maximize internal belief coherence and to incorporate ‘trickled in’ elements of truth as correspondence. Results, though often intuitive, prove more complex than in simpler models (Hegselmann and Krause 2002, 2006; Grimet al. 2015). The optimistic finding is that pressures toward internal coherence can exploit and expand on small elements of truth as correspondence is introduced into epistemic networks. Less optimistic results show that pressures for coherence can also work directly against the incorporation of truth, particularly when coherence is established first and new data are introduced later.
Frequency selection by feedback control in a turbulent shear flow
Authors: Parezanović Vladimir , Cordier Laurent , Spohn Andreas , Duriez Thomas , Noack Bernd R. , Bonnet Jean-Paul , Segond Marc , Abel Markus , Brunton Steven L.
Published: May 2016

Many previous studies have shown that the turbulent mixing layer under periodic forcing tends to adopt a lock-on state, where the major portion of the fluctuations in the flow are synchronized at the forcing frequency. The goal of this experimental study is to apply closed-loop control in order to provoke the lock-on state, using information from the flow itself. We aim to determine the range of frequencies for which the closed-loop control can establish the lock-on, and what mechanisms are contributing to the selection of a feedback frequency. In order to expand the solution space for optimal closed-loop control laws, we use the genetic programming control (GPC) framework. The best closed-loop control laws obtained by GPC are analysed along with the associated physical mechanisms in the mixing layer flow. The resulting closed-loop control significantly outperforms open-loop forcing in terms of robustness to changes in the free-stream velocities. In addition, the selection of feedback frequencies is not locked to the most amplified local mode, but rather a range of frequencies around it.
Party System Institutionalization, Accountability and Governmental Corruption
Authors: Schleiter Petra , Voznaya Alisa
Published: May 2016

Why do repeated elections often fail to curb governmental corruption, even in full democracies? While much of the comparative literature on corruption focuses on the institutional features of democracies, this article argues that party system institutionalization is an additional and neglected factor in explaining why corruption may persist in the context of democratic elections. Under-institutionalized party systems impede accountability. They compromise the capacity of voters to attribute responsibility and undermine electoral co-ordination to punish incumbents for corruption. These expectations are tested by combining a controlled comparative study of eighty democracies around the world with an examination of the causal process in a case study of Panama. The findings suggest that party system institutionalization powerfully shapes the scope for governmental corruption.
Globalization in the Early Modern Era: New Evidence from the Dutch-Asiatic Trade, c. 1600–1800
Authors: de Zwart Pim
Published: May 2016

This article contributes to the ongoing debate on the origins of globalization. It examines the process of commodity price convergence, an indicator of globalization, between Europe and Asia on the basis of newly obtained price data from the Dutch East India Company (VOC) archives. Prices for many commodities in the Dutch-Asiatic trade converged already in the seventeenth and eighteenth centuries as a result of the growth of trade and competition among traders and companies. The extent of convergence, however, was determined, in part, by the ability of the VOC to control commodity markets.
Obama, Katrina, and the Persistence of Racial Inequality
Authors: Margo Robert A.
Published: May 2016

New benchmark estimates of Black-White income ratios for 1870, 1900, and 1940 are combined with standard post-World War census data. The resulting time series reveals that the pace of racial income convergence has generally been steady but slow, quickening only during the 1940s and the modern Civil Rights era. I explore the interpretation of the time series with a model of intergenerational transmission of inequality in which racial differences in causal factors that determine income are very large just after the Civil War and which erode slowly across subsequent generations.

“The problem of the twentieth century is the problem of the color line.”

—W. E. B. Du Bois,The Souls of Black Folk
Contribution to the knowledge of the deep brachyuran fauna (Crustacea: Decapoda) in waters off Mauritania (NW Africa)
Authors: De Matos-Pita Susana S. , Castillo Sara , Ramil Fran
Published: May 2016

Four multidisciplinary oceanographic surveys were conducted in November and December from 2007 to 2010, along the Mauritanian coast (NW Africa). A total of 10,514 brachyuran crabs belonging to 33 species were captured in 316 hauls at depths between 79 and 1867 m. The most specious family was Inachidae represented by nine species; the remaining 24 species belonged to 16 other brachyuran families.Monodaeus cristulatusis reported for the first time since its original description. Seven other species,Ethusa rugulosa, Pseudomyra mbizi, Inachus grallator, Macropodia gilsoni, Macropodia hesperiae, Solenolambrus noordendeiandSpinolambrus notialisextend their range of distribution northwards and, together withGoneplax barnardi, are reported here for the first time in Mauritanian waters. New data about depth ranges are reported forAcanthocarpus brevispinis, Ethusa rugulosa, Inachus aguiarii, Inachus grallator, Inachus nanus, Macropodia macrocheles, Solenolambrus noordendei, Spinolambrus notialis, Liocarcinus corrugatusandMonodaeus cristulatus. New data relating to the spawning period for most of the species are also included, as are some biogeographic and bathymetric considerations about brachyurans studied in the area.
Successful intestinal Echinococcus multilocularis oncosphere invasion and subsequent hepatic metacestode establishment in resistant RccHan™:WIST rats after pharmacological immunosuppression
Authors: ARMUA-FERNANDEZ MARIA TERESA , JOEKEL DEBORAH , SCHWEIGER ALEXANDER , EICHENBERGER RAMON MARC , MATSUMOTO JUN , DEPLAZES PETER
Published: May 2016

Susceptibility/resistance to larval Echinococcus multilocularis infection varies greatly depending on host species and strains. Whereas several mice strains and non-human primates are highly susceptible to alveolar echinococcosis, rats and most of humans are considered as more resistant. In this study, we aimed to elucidate factors responsible for host resistance in rats (Experiments A–D). (A) The parasite establishment was not observed in immunocompetent Wistar rats orally inoculated with sodium hypochlorite resistant eggs with/without pig bile, or activated/non-activated oncospheres (NAO). Peritoneal inoculation with NAO or metacestode tissue allowed the parasite establishment in rats. (B) T-cell-deficient athymic nude rats showed complete resistance against the metacestode establishment after oral inoculation with parasite eggs. This finding suggests that T-cell-independent parasite clearance occurred in the animals during early phase of the parasite invasion. Finally, Wistar rats that received pharmacological immunosuppression using either dexamethasone (DMS) alone or methotrexate (MTX) i.p. alone or a combination of these compounds were orally inoculated with the parasite's eggs. As a result (D), successful establishment of metacestode with protoscoleces was observed in all 3 rats treated with DMS (s.c.) alone or in all 6 rats treated with DMS (s.c.) plus MTX but not in 8 rats with MTX alone, suggesting that factors affected by DMS treatment are responsible to regulate the parasite invasion and establishment.
Enhanced neural response to anticipation, effort and consummation of reward and aversion during bupropion treatment
Authors: Dean Z. , Horndasch S. , Giannopoulos P. , McCabe C.
Published: May 2016

Background

We have previously shown that the selective serotonergic reuptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear.

Method

Seventeen healthy volunteers (9 female, 8 male) received 7 days bupropion (150 mg/day) and 7 days placebo treatment, in a double-blind crossover design. Our functional magnetic resonance imaging task consisted of three phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes.

Results

Relative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase.

Conclusions

Our results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect.
FAST NON-NEGATIVE LEAST-SQUARES LEARNING IN THE RANDOM NEURAL NETWORK
Authors: Timotheou Stelios
Published: May 2016

The random neural network is a biologically inspired neural model where neurons interact by probabilistically exchanging positive and negative unit-amplitude signals that has superior learning capabilities compared to other artificial neural networks. This paper considers non-negative least squares supervised learning in this context, and develops an approach that achieves fast execution and excellent learning capacity. This speedup is a result of significant enhancements in the solution of the non-negative least-squares problem which regard (a) the development of analytical expressions for the evaluation of the gradient and objective functions and (b) a novel limited-memory quasi-Newton solution algorithm. Simulation results in the context of optimizing the performance of a disaster management problem using supervised learning verify the efficiency of the approach, achieving two orders of magnitude execution speedup and improved solution quality compared to state-of-the-art algorithms.
Wordbank: an open repository for developmental vocabulary data
Authors: FRANK MICHAEL C. , BRAGINSKY MIKA , YUROVSKY DANIEL , MARCHMAN VIRGINIA A.
Published: May 2016

The MacArthur-Bates Communicative Development Inventories (CDIs) are a widely used family of parent-report instruments for easy and inexpensive data-gathering about early language acquisition. CDI data have been used to explore a variety of theoretically important topics, but, with few exceptions, researchers have had to rely on data collected in their own lab. In this paper, we remedy this issue by presenting Wordbank, a structured database of CDI data combined with a browsable web interface. Wordbank archives CDI data across languages and labs, providing a resource for researchers interested in early language, as well as a platform for novel analyses. The site allows interactive exploration of patterns of vocabulary growth at the level of both individual children and particular words. We also introduce wordbankr, a software package for connecting to the database directly. Together, these tools extend the abilities of students and researchers to explore quantitative trends in vocabulary development.
Assemblage Theory and Town Foundation in Medieval England
Authors: Jervis Ben
Published: May 2016

It is proposed that our understanding of medieval town foundation is limited by a failure to appreciate that ‘town’ is a relational category. It is argued that urban character emerges from social relations, with some sets of social relationship revealing urbanity and others not, as places develop along distinctive, but related, trajectories. This argument is developed through the application of assemblage theory to the development of towns in thirteenth-century southern England. The outcome is a proposal that, by focusing on the social relations through which towns are revealed as a distinctive category of place, we can better comprehend why and how towns mattered in medieval society and develop a greater understanding of the relationship of urbanization to other social processes such as commercialization and associated changes in the countryside.
Videoconferencing and telementoring about dementia care: evaluation of a pilot model for sharing scarce old age psychiatry resources
Authors: Doyle Colleen , Jackson David , Loi Samantha , Malta Sue , Moore Kirsten
Published: May 2016

Background:

While videoconferencing, telementoring, and peer support have been shown to enhance services in some instances, there has been no research investigating the use of these technologies in supporting professionals managing clients with dementia. The objective of this research was to evaluate expansion of an old age psychiatry consultation service and pilot test a model to improve medical supervision and clinical governance for staff within regional and remote areas using remote information technology.

Methods:

The design was a mixed methods (qualitative and quantitative) evaluation using before, mid-point and post-implementation semi-structured interviews and questionnaires to examine orientation, acceptance, and impact underpinned by theoretical approaches to evaluation. Education evaluations used a Likert style response template. Participants were 18 dementia service staff, including staff from linked services and old age psychiatrists. Qualitative interviews addressed the pilot implementation including: expectations, experiences, strategies for improving the pilot, and perceived impact on work practice and professional development opportunities.

Results:

There was high satisfaction with the program. The case conference process contributed to perceived improved outcomes for clients, family, and staff. Clinicians perceived improvement in family carer and staff carer stress and their confidence in managing clients with behavioral and psychological symptoms of dementia (BPSD). Thematic analysis indicated that the pilot enhanced professional development, decreased travel time, and improved team cohesion.

Conclusions:

Given the increasing aging population in regional, rural, and remote areas, initiatives using videoconferencing and telementoring will help to develop a confident and skilled workforce. This pilot program was found to be acceptable and feasible. Potential benefits for clients and family carers should be examined in future resesarch.
Mixed cultural context brings out bilingual advantage on executive function
Authors: YE YANYAN , MO LEI , WU QIHAN
Published: May 2016

The issue of whether bilinguals have advantages over monolinguals in cognitive functions has received ongoing research attention. Most researchers have agreed that continuously shifting between two languages enhances bilinguals' executive function, but several recent studies failed to find any evidence of bilingual advantage. In addition, the mechanism of bilingual advantage in executive function is not fully understood. Here, we hypothesized that a bilingual advantage should appear on tasks requiring an enhanced level of executive function, and tested this hypothesis in a non-language-based mixed culture context and single culture context. Proficient bilinguals and non-proficient bilinguals completed an Eriksen Flanker Task in these two contexts. The results showed that proficient bilinguals’ performance on incongruent trials was better than that of non-proficient bilinguals in the mixed cultural context, but not in the single cultural context. These findings cast important light on understanding the nature of bilingual advantage.
Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials
Authors: Isomura T , Suzuki S , Origasa H , Hosono A , Suzuki M , Sawada T , Terao S , Muto Y , Koga T
Published: May 2016

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5–9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare.
Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies
Authors: Veiga M. Isabel , Dhingra Satish K. , Henrich Philipp P. , Straimer Judith , Gnädig Nina , Uhlemann Anne-Catrin , Martin Rowena E. , Lehane Adele M. , Fidock David A.
Published: May 2016

Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance inPlasmodium falciparumparasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaquine and the former first-line agent chloroquine. In contrast, N86Y increases parasite susceptibility to the partner drugs lumefantrine and mefloquine, and the active artemisinin metabolite dihydroartemisinin. The PfMDR1 N86 plus Y184F isoform moderately reduces piperaquine potency in strains expressing an Asian/African variant of the chloroquine resistance transporter PfCRT. Mutations in both digestive vacuole-resident transporters are thought to differentially regulate ACT drug interactions with host haem, a product of parasite-mediated haemoglobin degradation. Global mapping of these mutations illustrates where the different ACTs could be selectively deployed to optimize treatment based on regional differences in PfMDR1 haplotypes.
Direct imaging of molecular symmetry by coherent anti-stokes Raman scattering
Authors: Cleff Carsten , Gasecka Alicja , Ferrand Patrick , Rigneault Hervé , Brasselet Sophie , Duboisset Julien
Published: May 2016

Nonlinear optical methods, such as coherent anti-Stokes Raman scattering and stimulated Raman scattering, are able to perform label-free imaging, with chemical bonds specificity. Here we demonstrate that the use of circularly polarized light allows to retrieve not only the chemical nature but also the symmetry of the probed sample, in a single measurement. Our symmetry-resolved scheme offers simple access to the local organization of vibrational bonds and as a result provides enhanced image contrast for anisotropic samples, as well as an improved chemical selectivity. We quantify the local organization of vibrational bonds on crystalline and biological samples, thus providing information not accessible by spontaneous Raman and stimulated Raman scattering techniques. This work stands for a symmetry-resolved contrast in vibrational microscopy, with potential application in biological diagnostic.
Flow cytometry combined with viSNE for the analysis of microbial biofilms and detection of microplastics
Authors: Sgier Linn , Freimann Remo , Zupanic Anze , Kroll Alexandra
Published: May 2016

Biofilms serve essential ecosystem functions and are used in different technical applications. Studies from stream ecology and waste-water treatment have shown that biofilm functionality depends to a great extent on community structure. Here we present a fast and easy-to-use method for individual cell-based analysis of stream biofilms, based on stain-free flow cytometry and visualization of the high-dimensional data by viSNE. The method allows the combined assessment of community structure, decay of phototrophic organisms and presence of abiotic particles. In laboratory experiments, it allows quantification of cellular decay and detection of survival of larger cells after temperature stress, while in the field it enables detection of community structure changes that correlate with known environmental drivers (flow conditions, dissolved organic carbon, calcium) and detection of microplastic contamination. The method can potentially be applied to other biofilm types, for example, for inferring community structure for environmental and industrial research and monitoring.
Fitness consequences of artificial selection on relative male genital size
Authors: Booksmythe Isobel , Head Megan L. , Keogh J. Scott , Jennions Michael D.
Published: May 2016

Male genitalia often show remarkable differences among related species in size, shape and complexity. Across poeciliid fishes, the elongated fin (gonopodium) that males use to inseminate females ranges from 18 to 53% of body length. Relative genital size therefore varies greatly among species. In contrast, there is often tight within-species allometric scaling, which suggests strong selection against genital–body size combinations that deviate from a species’ natural line of allometry. We tested this constraint by artificially selecting on the allometric intercept, creating lines of males with relatively longer or shorter gonopodia than occur naturally for a given body size in mosquitofish, Gambusia holbrooki. We show that relative genital length is heritable and diverged 7.6–8.9% between our up-selected and down-selected lines, with correlated changes in body shape. However, deviation from the natural line of allometry does not affect male success in assays of attractiveness, swimming performance and, crucially, reproductive success (paternity).
Alanine aminotransferase controls seed dormancy in barley
Authors: Sato Kazuhiro , Yamane Miki , Yamaji Nami , Kanamori Hiroyuki , Tagiri Akemi , Schwerdt Julian G. , Fincher Geoffrey B. , Matsumoto Takashi , Takeda Kazuyoshi , Komatsuda Takao
Published: May 2016

Dormancy allows wild barley grains to survive dry summers in the Near East. After domestication, barley was selected for shorter dormancy periods. Here we isolate the major seed dormancy geneqsd1from wild barley, which encodes an alanine aminotransferase (AlaAT). The seed dormancy gene is expressed specifically in the embryo. The AlaAT isoenzymes encoded by the long and short dormancy alleles differ in a single amino acid residue. The reduced dormancy alleleQsd1evolved from barleys that were first domesticated in the southern Levant and had the long dormancyqsd1allele that can be traced back to wild barleys. The reduced dormancy mutation likely contributed to the enhanced performance of barley in industrial applications such as beer and whisky production, which involve controlled germination. In contrast, the long dormancy allele might be used to control pre-harvest sprouting in higher rainfall areas to enhance global adaptation of barley.
Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells
Authors: Göbel Kerstin , Pankratz Susann , Asaridou Chloi-Magdalini , Herrmann Alexander M. , Bittner Stefan , Merker Monika , Ruck Tobias , Glumm Sarah , Langhauser Friederike , Kraft Peter , Krug Thorsten F. , Breuer Johanna , Herold Martin , Gross Catharina C. , Beckmann Denise , Korb-Pap Adelheid , Schuhmann Michael K. , Kuerten Stefanie , Mitroulis Ioannis , Ruppert Clemens , Nolte Marc W. , Panousis Con , Klotz Luisa , Kehrel Beate , Korn Thomas , Langer Harald F. , Pap Thomas , Nieswandt Bernhard , Wiendl Heinz , Chavakis Triantafyllos , Kleinschnitz Christoph , Meuth Sven G.
Published: May 2016

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders.
Context-dependent switch in chemo/mechanotransduction via multilevel crosstalk among cytoskeleton-regulated MRTF and TAZ and TGFβ-regulated Smad3
Authors: Speight Pam , Kofler Michael , Szászi Katalin , Kapus András
Published: May 2016

Myocardin-related transcription factor (MRTF) and TAZ are major mechanosensitive transcriptional co-activators that link cytoskeleton organization to gene expression. Despite many similarities in their regulation, their physical and/or functional interactions are unknown. Here we show that MRTF and TAZ associate partly through a WW domain-dependent mechanism, and exhibit multilevel crosstalk affecting each other’s expression, transport and transcriptional activity. Specifically, MRTF is essential for TAZ expression; TAZ and MRTF inhibit each other’s cytosolic mobility and stimulus-induced nuclear accumulation; they antagonize each other’s stimulatory effect on the α-smooth muscle actin (SMA) promoter, which harbours nearby cis-elements for both, but synergize on isolated TEAD-elements. Importantly, TAZ confers Smad3 sensitivity to the SMA promoter. Thus, TAZ is a context-dependent switch during mechanical versus mechano/chemical signalling, which inhibits stretch-induced but is indispensable for stretch+TGFβ-induced SMA expression. Crosstalk between these cytoskeleton-regulated factors seems critical for fine-tuning mechanical and mechanochemical transcriptional programmes underlying myofibroblast transition, wound healing and fibrogenesis.
Correction: Corrigendum: Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies
Authors: Fish Maryam , Shaboodien Gasnat , Kraus Sarah , Sliwa Karen , Seidman Christine E. , Burke Michael A. , Crotti Lia , Schwartz Peter J. , Mayosi Bongani M.
Published: May 2016

Scientific Reports 6: Article number: 22235; published online: 26 February 2016; updated: 18 May 2016 In this Article, Lia Crotti is incorrectly affiliated with ‘Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy’. Furthermore, an additional affiliation was omitted.
In vivo Real-Time Mass Spectrometry for Guided Surgery Application
Authors: Fatou Benoit , Saudemont Philippe , Leblanc Eric , Vinatier Denis , Mesdag Violette , Wisztorski Maxence , Focsa Cristian , Salzet Michel , Ziskind Michael , Fournier Isabelle
Published: May 2016

Here we describe a new instrument (SpiderMass) designed for in vivo and real-time analysis. In this instrument ion production is performed remotely from the MS instrument and the generated ions are transported in real-time to the MS analyzer. Ion production is promoted by Resonant Infrared Laser Ablation (RIR-LA) based on the highly effective excitation of O-H bonds in water molecules naturally present in most biological samples. The retrieved molecular patterns are specific to the cell phenotypes and benign versus cancer regions of patient biopsies can be easily differentiated. We also demonstrate by analysis of human skin that SpiderMass can be used under in vivo conditions with minimal damage and pain. Furthermore SpiderMass can also be used for real-time drug metabolism and pharmacokinetic (DMPK) analysis or food safety topics. SpiderMass is thus the first MS based system designed for in vivo real-time analysis under minimally invasive conditions.
IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa
Authors: Lorè Nicola Ivan , Cigana Cristina , Riva Camilla , De Fino Ida , Nonis Alessandro , Spagnuolo Lorenza , Sipione Barbara , Cariani Lisa , Girelli Daniela , Rossi Giacomo , Basso Veronica , Colombo Carla , Mondino Anna , Bragonzi Alessandra
Published: May 2016

Resistance and tolerance mechanisms participate to the interplay between host and pathogens. IL-17-mediated response has been shown to be crucial for host resistance to respiratory infections, whereas its role in host tolerance during chronic airway colonization is still unclear. Here, we investigated whether IL-17-mediated response modulates mechanisms of host tolerance during airways chronic infection by P. aeruginosa. First, we found that IL-17A levels were sustained in mice at both early and advanced stages of P. aeruginosa chronic infection and confirmed these observations in human respiratory samples from cystic fibrosis patients infected by P. aeruginosa. Using IL-17a−/− or IL-17ra−/− mice, we found that the deficiency of IL-17A/IL-17RA axis was associated with: i) increased incidence of chronic infection and bacterial burden, indicating its role in the host resistance to P. aeruginosa; ii) reduced cytokine levels (KC), tissue innate immune cells and markers of tissue damage (pro-MMP-9, elastin degradation, TGF-β1), proving alteration of host tolerance. Blockade of IL-17A activity by a monoclonal antibody, started when chronic infection is established, did not alter host resistance but increased tolerance. In conclusion, this study identifies IL-17-mediated response as a negative regulator of host tolerance during P. aeruginosa chronic airway infection.
Morc3 mutant mice exhibit reduced cortical area and thickness, accompanied by altered haematopoietic stem cells niche and bone cell differentiation
Authors: Jadhav Gaurav , Teguh Dian , Kenny Jacob , Tickner Jennifer , Xu Jiake
Published: May 2016

Morc3, a member of a highly conserved nuclear matrix protein super-family plays an important part in chromatin remodeling, DNA repair, epigenetic regulation and cellular senescence. However, its role in bone homeostasis is not known. In the present study, a phenotype-driven ENU mouse mutagenesis screen revealed that Morc3mut +/− mice exhibit reduced cortical area and thickness with increased cortical porosity. Morc3mut +/− mice displayed reduced osteoclast numbers and surface per bone surface as well as osteocyte numbers, concomitant with altered gene expressions such as Rankl/Opg and Sost in ex vivo long bones. In vitro experiments revealed a significant increase in the number of Sca-1+/c-kit+ haematopoietic stem cells (HSCs) and a significant reduction in senescence associated β-galactosidase activity in bone marrow macrophages (BMMs). In addition, we observed a decrease in osteoclastogenesis and bone resorption accompanied by upregulation of STAT1 expression in osteoclast lineage cells. Strikingly, Morc3 protein localization within the nuclear membrane was shifted to the cytoplasm in Morc3mut +/− osteoclasts. Further, Morc3mut +/− mice displayed increased osteoblast differentiation and altered gene expression. Collectively, our data show that Morc3 is a previously unreported regulator of cortical bone homeostasis and haematopoietic stem cells niche, accompanied by altered bone cell differentiation.
Analogue simulation of pharyngeal airflow response to Twin Block treatment in growing patients with Class II1 and mandibular retrognathia
Authors: Li Liang , Wu Wei , Yan Guijun , Liu Li , Liu Hong , Li Guojv , Li Jing , Liu Dongxu
Published: May 2016

The flow dynamics of respiratory airflow is the basic factor that influences the ventilation function of the upper airway. This research aimed to investigate the pharyngeal flow field characteristics after Twin Block (TB) treatment in growing patients with Class II1 and mandibular retrognathia by computation fluid dynamics (CFD) simulation. Cone beam computed tomography (CBCT) scans of patients who have completed TB treatment (n = 30) and about to accept TB treatment (n = 30) were reconstructed. After CFD simulation, correlations between the pharyngeal pressure drop and morphological parameters were further analyzed. During inspiration, we found that the pressure minimum occurred in the hypopharynx, while the maximum pressure drop and velocity was located in the oropharynx. After TB treatment, the oropharynx and hypopharynx showed significant differences in airflow features and the most obvious change was observed in the oropharynx. A significant correlation was discovered between the change amount of oropharyngeal pressure drop and volume (r = 0.694, p = 0.001), mean cross-sectional area (r = 0.859, p = 0.000) and ratio of the minimum and mean cross-sectional area (r = 0.898, p = 0.000) of the oropharynx. Our research suggested that the pharyngeal airflow characteristics response positively to mandibular advancement with the enlargement in volume, cross-sectional area and more uniform oropharyngeal area distribution.
A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone
Authors: Raina Deepak Bushan , Isaksson Hanna , Hettwer Werner , Kumar Ashok , Lidgren Lars , Tägil Magnus
Published: May 2016

In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone.
Contrasting Linguistic and Genetic Origins of the Asian Source Populations of Malagasy
Authors: Kusuma Pradiptajati , Brucato Nicolas , Cox Murray P. , Pierron Denis , Razafindrazaka Harilanto , Adelaar Alexander , Sudoyo Herawati , Letellier Thierry , Ricaut François-Xavier
Published: May 2016

The Austronesian expansion, one of the last major human migrations, influenced regions as distant as tropical Asia, Remote Oceania and Madagascar, off the east coast of Africa. The identity of the Asian groups that settled Madagascar is particularly mysterious. While language connects Madagascar to the Ma’anyan of southern Borneo, haploid genetic data are more ambiguous. Here, we screened genome-wide diversity in 211 individuals from the Ma’anyan and surrounding groups in southern Borneo. Surprisingly, the Ma’anyan are characterized by a distinct, high frequency genomic component that is not found in Malagasy. This novel genetic layer occurs at low levels across Island Southeast Asia and hints at a more complex model for the Austronesian expansion in this region. In contrast, Malagasy show genomic links to a range of Island Southeast Asian groups, particularly from southern Borneo, but do not have a clear genetic connection with the Ma’anyan despite the obvious linguistic association.
Sustainable, Rapid Synthesis of Bright-Luminescent CuInS2-ZnS Alloyed Nanocrystals: Multistage Nano-xenotoxicity Assessment and Intravital Fluorescence Bioimaging in Zebrafish-Embryos
Authors: Chetty S. Shashank , Praneetha S. , Basu Sandeep , Sachidanandan Chetana , Murugan A. Vadivel
Published: May 2016

Near-infrared (NIR) luminescent CuInS2-ZnS alloyed nanocrystals (CIZS-NCs) for highly fluorescence bioimaging have received considerable interest in recent years. Owing, they became a desirable alternative to heavy-metal based-NCs and organic dyes with unique optical properties and low-toxicity for bioimaging and optoelectronic applications. In the present study, bright and robust CIZS-NCs have been synthesized within 5 min, as-high-as 230 °C without requiring any inert-gas atmosphere via microwave-solvothermal (MW-ST) method. Subsequently, the in vitro and in vivo nano-xenotoxicity and cellular uptake of the MUA-functionalized CIZS-NCs were investigated in L929, Vero, MCF7 cell lines and zebrafish-embryos. We observed minimal toxicity and acute teratogenic consequences upto 62.5 μg/ml of the CIZS-NCs in zebrafish-embryos. We also observed spontaneous uptake of the MUA-functionalized CIZS-NCs by 3 dpf older zebrafish-embryos that are evident through bright red fluorescence-emission at a low concentration of 7.8 μg/mL. Hence, we propose that the rapid, low-cost, large-scale “sustainable” MW-ST synthesis of CIZS-NCs, is an ideal bio-nanoprobe with good temporal and spatial resolution for rapid labeling, long-term in vivo tracking and intravital-fluorescence-bioimaging (IVBI).
Evolution of Moiré Profiles from van der Waals Superstructures of Boron Nitride Nanosheets
Authors: Liao Yunlong , Cao Wei , Connell John W. , Chen Zhongfang , Lin Yi
Published: May 2016

Two-dimensional (2D) van der Waals (vdW) superstructures, or vdW solids, are formed by the precise restacking of 2D nanosheet lattices, which can lead to unique physical and electronic properties that are not available in the parent nanosheets. Moiré patterns formed by the crystalline mismatch between adjacent nanosheets are the most direct features for vdW superstructures under microscopic imaging. In this article, transmission electron microscopy (TEM) observation of hexagonal Moiré patterns with unusually large micrometer-sized lateral areas (up to ~1 μm2) and periodicities (up to ~50 nm) from restacking of liquid exfoliated hexagonal boron nitride nanosheets (BNNSs) is reported. This observation was attributed to the long range crystallinity and the contaminant-free surfaces of these chemically inert nanosheets. Parallel-line-like Moiré fringes with similarly large periodicities were also observed. The simulations and experiments unambiguously revealed that the hexagonal patterns and the parallel fringes originated from the same rotationally mismatched vdW stacking of BNNSs and can be inter-converted by simply tilting the TEM specimen following designated directions. This finding may pave the way for further structural decoding of other 2D vdW superstructure systems with more complex Moiré images.
Whole genome nucleosome sequencing identifies novel types of forensic markers in degraded DNA samples
Authors: Dong Chun-nan , Yang Ya-dong , Li Shu-jin , Yang Ya-ran , Zhang Xiao-jing , Fang Xiang-dong , Yan Jiang-wei , Cong Bin
Published: May 2016

In the case of mass disasters, missing persons and forensic caseworks, highly degraded biological samples are often encountered. It can be a challenge to analyze and interpret the DNA profiles from these samples. Here we provide a new strategy to solve the problem by taking advantage of the intrinsic structural properties of DNA. We have assessed the in vivo positions of more than 35 million putative nucleosome cores in human leukocytes using high-throughput whole genome sequencing, and identified 2,462 single nucleotide variations (SNVs), 128 insertion-deletion polymorphisms (indels). After comparing the sequence reads with 44 STR loci commonly used in forensics, five STRs (TH01, TPOX, D18S51, DYS391, and D10S1248)were matched. We compared these “nucleosome protected STRs” (NPSTRs) with five other non-NPSTRs using mini-STR primer design, real-time PCR, and capillary gel electrophoresis on artificially degraded DNA. Moreover, genotyping performance of the five NPSTRs and five non-NPSTRs was also tested with real casework samples. All results show that loci located in nucleosomes are more likely to be successfully genotyped in degraded samples. In conclusion, after further strict validation, these markers could be incorporated into future forensic and paleontology identification kits, resulting in higher discriminatory power for certain degraded sample types.
High Resolution X-ray-Induced Acoustic Tomography
Authors: Xiang Liangzhong , Tang Shanshan , Ahmad Moiz , Xing Lei
Published: May 2016

Absorption based CT imaging has been an invaluable tool in medical diagnosis, biology and materials science. However, CT requires a large set of projection data and high radiation dose to achieve superior image quality. In this letter, we report a new imaging modality, X-ray Induced Acoustic Tomography (XACT), which takes advantages of high sensitivity to X-ray absorption and high ultrasonic resolution in a single modality. A single projection X-ray exposure is sufficient to generate acoustic signals in 3D space because the X-ray generated acoustic waves are of a spherical nature and propagate in all directions from their point of generation. We demonstrate the successful reconstruction of gold fiducial markers with a spatial resolution of about 350 μm. XACT reveals a new imaging mechanism and provides uncharted opportunities for structural determination with X-ray.
SOX7 co-regulates Wnt/β-catenin signaling with Axin-2: both expressed at low levels in breast cancer
Authors: Liu Huidi , Mastriani Emilio , Yan Zi-Qiao , Yin Si-Yuan , Zeng Zheng , Wang Hong , Li Qing-Hai , Liu Hong-Yu , Wang Xiaoyu , Bao Hong-Xia , Zhou Yu-Jie , Kou Jun-Jie , Li Dongsheng , Li Ting , Liu Jianrui , Liu Yongfang , Yin Lin , Qiu Li , Gong Liling , Liu Shu-Lin
Published: May 2016

SOX7 as a tumor suppressor belongs to the SOX F gene subfamily and is associated with a variety of human cancers, including breast cancer, but the mechanisms involved are largely unclear. In the current study, we investigated the interactions between SOX7 and AXIN2 in their co-regulation on the Wnt/β-catenin signal pathway, using clinical specimens and microarray gene expression data from the GEO database, for their roles in breast cancer. We compared the expression levels of SOX7 and other co-expressed genes in the Wnt/β-catenin pathway and found that the expression of SOX7, SOX17 and SOX18 was all reduced significantly in the breast cancer tissues compared to normal controls. AXIN2 had the highest co-relativity with SOX7 in the Wnt/β-catenin signaling pathway. Clinicopathological analysis demonstrated that the down-regulated SOX7 was significantly correlated with advanced stages and poorly differentiated breast cancers. Consistent with bioinformatics predictions, SOX7 was correlated positively with AXIN2 and negatively with β-catenin, suggesting that SOX7 and AXIN2 might play important roles as co-regulators through the Wnt-β-catenin pathway in the breast tissue to affect the carcinogenesis process. Our results also showed Smad7 as the target of SOX7 and AXIN2 in controlling breast cancer progression through the Wnt/β-catenin signaling pathway.
Identification of biomarkers for development of end-stage kidney disease in chronic kidney disease by metabolomic profiling
Authors: Kimura Tomonori , Yasuda Keiko , Yamamoto Ryohei , Soga Tomoyoshi , Rakugi Hiromi , Hayashi Terumasa , Isaka Yoshitaka
Published: May 2016

A critical issue in the management of chronic kidney disease (CKD) is to prevent patients from the progression to end-stage kidney disease (ESKD), however, there is only limited number of biomarkers for the discrimination of the high-risk CKD patients. We aimed to identify the metabolites which possess the ability to predict the earlier kidney deterioration. We performed capillary electrophoresis and liquid chromatography mass spectrometry (CE-MS)-based metabolic profiling in a prospective cohort, which consisted of referred 112 CKD patients with median follow-up period of 4.4 years. The association between the levels of candidate metabolites and the outcomes (progression to ESKD alone or in combination with death before ESKD) were assessed by multivariate Cox proportional hazard models after adjusting for the baseline covariates. A total of 218 metabolites were detected in the plasma of CKD patients. We identified 16 metabolites which have predictive values for the composite outcome: The risk for composite outcome was elevated from 2.0- to 8.0-fold in those with higher levels of 16 plasma metabolites. Our results suggest that the measurement of these metabolites may facilitate CKD management by predicting the risk of progression to ESKD.
Polar flagella rotation in Vibrio parahaemolyticus confers resistance to bacteriophage infection
Authors: Zhang Hui , Li Lu , Zhao Zhe , Peng Daxin , Zhou Xiaohui
Published: May 2016

Bacteriophage has been recognized as a novel approach to treat bacterial infectious diseases. However, phage resistance may reduce the efficacy of phage therapy. Here, we described a mechanism of bacterial resistance to phage infections. In Gram-negative enteric pathogen Vibrio parahaemolyticus, we found that polar flagella can reduce the phage infectivity. Deletion of polar flagella, but not the lateral flagella, can dramatically promote the adsorption of phage to the bacteria and enhances the phage infectivity to V. parahaemolyticus, indicating that polar flagella play an inhibitory role in the phage infection. Notably, it is the rotation, not the physical presence, of polar flagella that inhibits the phage infection of V. parahaemolyticus. Strikingly, phage dramatically reduces the virulence of V. parahaemolyticus only when polar flagella were absent both in vitro and in vivo. These results indicated that polar flagella rotation is a previously unidentified mechanism that confers bacteriophage resistance.