bluuebunny/crossref_metadata_2025 huggingface dataset:
The Crisis of Party Democracy, Cognitive Mobilization, and the Case for Making Parties More Deliberative
Authors: INVERNIZZI-ACCETTI CARLO , WOLKENSTEIN FABIO
Published: February 2017

The much-discussed crisis of political parties poses a challenge to democratic theorists as institutional designers: how can the capacity of parties to mediate between society and state be resuscitated? In this article, we suggest that parties need to become more internally deliberative, allowing partisans to debate policy and more general visions for the polity. We outline a prescriptive model of deliberative intraparty democracy, drawing on the empirical literature on the changing structure of civic and political engagement. We argue that deliberative reforms are the most appropriate response to the demands of an increasingly more cognitively mobilized citizenry which seeks self-expression and nonhierarchical forms of political engagement. We highlight the model's distinctive strengths and defend it against several objections.
The Architecture of Political Spaces: Trolls, Digital Media, and Deweyan Democracy
Authors: FORESTAL JENNIFER
Published: February 2017

The problem of trolls exemplifies the challenges of building democratic communities in the digital environment of social media. Distinguishing trolls from activists can be difficult; democratic theorists have yet to adequately address how to prevent the former while remaining open to the latter. In this article, I outline a theory of democratic politics that takes space as a central element in shaping democratic interactions. Using the work of John Dewey, I draw out two key characteristics of democratic space: boundedness and flexibility. Using these criteria, I then evaluate Kinja, Gawker Media's commenting platform, both before and after trolls attacked the site in 2014. I find that in altering its boundaries to successfully protect against trolls, Kinja introduced a new problem: a lack of flexibility that continues to affect the possibility for democratic discourse on the platform. I conclude by suggesting how this theory of democratic space might shape future research.
Irish adventurers and godly militants in the 1640s
Authors: Lindley Keith
Published: February 2017

This paper will attempt to shed some additional light on the background and motives of those who were to play a leading part in the scheme for the Irish adventurers. The focus will be upon those Englishmen, and Londoners in particular, who invested from 1642 onwards in the reconquest of Ireland in return for grants of Irish land once the island had been secured again. It will be argued that militants who regarded themselves as belonging to the chosen ranks of the godly — that is the minority of mankind singled out for salvation by God, and thus constituting his elect or saints — played a leading part in the scheme and were among its most committed participants, and that they later helped to shape English policy towards Ireland. These militants were also ardent advocates of reformation in church and state in England in the 1640s, and they viewed Ireland and the successful Catholic rising in 1641 from a perspective highly coloured by antipopery. They tended to see the struggle taking place in the mid-seventeenth century in Britain, Ireland and Europe generally in black-and-white terms, as a struggle between true religion (by which was meant a thoroughly reformed Protestant church) and the Antichrist as represented by the pope and the forces believed to be ranged under him in the Catholic church.
Early Literacy Development and School Entry
Authors: Pratt Chris , Garton Alison F.
Published: February 2017

In this paper we wish to put forward the argument that when one is considering the development of literacy in children, it is essential to consider both spoken and written language within the same integrated perspective. We also intend to argue that examining literacy from this perspective implies educators must meet the challenge of avoiding major discontinuities of experience for children. Further, given the large individual differences in children's development, we argue that the actual age of school entry is of little inportance. Of far greater importance is the provision of educational programmes that take account of the different experiences of individual children.
Mainstreaming and Labelling: An Assumption Challenged?
Authors: McDonald Narelle , Hayes Alan
Published: February 2017

A key assumption of the mainstreaming movement is that exposure of young children to their disabled peers provides opportunities for the formation of accurate views of the characteristics and attributes of children with disabilities. Essentially, it is argued that experience enables children to transcend labelling, stereotyping and stigmatization. Prospective data are reported on the mainstreaming of two preschool aged children with spina bifida, based on the content analysis of records of speech, collected over a school year, on 22% of the times when children had opportunities to interact socially. The data indicate that the children seemed to generate their own labels, disability terms and developmental mythologies, which endured across the year. The study highlights the limited attention that has been paid to the collection of data on the social-cognitive processes of children and their disabled peers in mainstreamed settings and emphasizes the scant consideration of evidence from psychology in the mainstreaming debate.
Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
Authors: Chavan S S , He J , Tytarenko R , Deshpande S , Patel P , Bailey M , Stein C K , Stephens O , Weinhold N , Petty N , Steward D , Rasche L , Bauer M , Ashby C , Peterson E , Ali S , Ross J , Miller V A , Stephens P , Thanendrarajan S , Schinke C , Zangari M , van Rhee F , Barlogie B , Mughal T I , Davies F E , Morgan G J , Walker B A
Published: February 2017

The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.
A generalized quantitative antibody homeostasis model: antigen saturation, natural antibodies and a quantitative antibody network
Authors: Prechl József
Published: February 2017

In a pair of articles, we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this second paper, we describe how antibody production controls the saturation of antigens and the network of antibody interactions that emerges in the epitome space with the establishment of the immune system. Efficient control of antigens, be it self or foreign, requires the maintenance of antibody concentrations that saturate antigen to relevant levels. Simple calculations suggest that the observed diverse recognition of antigens by natural antibodies is only possible by cross‐reactivity whereby particular clones of antibodies bind to diverse targets and shared recognition of particular antigens by multiple antibody clones contribute to the maintenance of antigen control. We also argue that natural antibodies are none else than the result of thymus‐independent responses against immunological self. We interpret and explain antibody production and function in a virtual molecular interaction space and as a network of interactions. Indeed, the general quantitative (GQM) model we propose is in agreement with earlier models, confirms some assumptions and presumably provides the theoretical basis for the construction of a real antibody network using the sequence and interaction database data.
Mixed transmission modes and dynamic genome evolution in an obligate animal–bacterial symbiosis
Authors: Russell Shelbi L , Corbett-Detig Russell B , Cavanaugh Colleen M
Published: February 2017

Reliable transmission of symbionts between host generations facilitates the evolution of beneficial and pathogenic associations. Although transmission mode is typically characterized as either vertical or horizontal, the prevalence of intermediate transmission modes, and their impact on symbiont genome evolution, are understudied. Here, we use population genomics to explore mixed transmission modes of chemosynthetic bacterial symbionts in the bivalve Solemya velum. Despite strong evidence for symbiont inheritance through host oocytes, whole-genome analyses revealed signatures of frequent horizontal transmission, including discordant mitochondrial-symbiont genealogies, widespread recombination and a dynamic symbiont genome structure consistent with evolutionary patterns of horizontally transmitted associations. Population-level analyses thus provide a tractable means of ascertaining the fidelity of vertical versus horizontal transmission. Our data support the strong influence horizontal transmission can have on symbiont genome evolution, and shed light on the dynamic evolutionary pressures shaping symbiotic bacterial genomes.
Feasibility and coexistence of large ecological communities
Authors: Grilli Jacopo , Adorisio Matteo , Suweis Samir , Barabás György , Banavar Jayanth R. , Allesina Stefano , Maritan Amos
Published: February 2017

The role of species interactions in controlling the interplay between the stability of ecosystems and their biodiversity is still not well understood. The ability of ecological communities to recover after small perturbations of the species abundances (local asymptotic stability) has been well studied, whereas the likelihood of a community to persist when the conditions change (structural stability) has received much less attention. Our goal is to understand the effects of diversity, interaction strengths and ecological network structure on the volume of parameter space leading to feasible equilibria. We develop a geometrical framework to study the range of conditions necessary for feasible coexistence. We show that feasibility is determined by few quantities describing the interactions, yielding a nontrivial complexity–feasibility relationship. Analysing more than 100 empirical networks, we show that the range of coexistence conditions in mutualistic systems can be analytically predicted. Finally, we characterize the geometric shape of the feasibility domain, thereby identifying the direction of perturbations that are more likely to cause extinctions.
Erratum: Measurement of transverse emittance and coherence of double-gate field emitter array cathodes
Authors: Tsujino Soichiro , Das Kanungo Prat , Monshipouri Mahta , Lee Chiwon , Dwayne Miller R. J.
Published: February 2017

Nature Communications 7: Article number: 13976 (2016); Published 23 December 2016; Updated 24 February 2017 An incorrect version of the Supplementary Information was inadvertently published with this Article where wrong vector notation was used for equation (4), wrong font for ‘phi’ on page 10 and the wrong unit ‘(m)’ was used instead of ‘(mm)’ for the x-axis of Supplementary Fig.
Rosin-enabled ultraclean and damage-free transfer of graphene for large-area flexible organic light-emitting diodes
Authors: Zhang Zhikun , Du Jinhong , Zhang Dingdong , Sun Hengda , Yin Lichang , Ma Laipeng , Chen Jiangshan , Ma Dongge , Cheng Hui-Ming , Ren Wencai
Published: February 2017

The large polymer particle residue generated during the transfer process of graphene grown by chemical vapour deposition is a critical issue that limits its use in large-area thin-film devices such as organic light-emitting diodes. The available lighting areas of the graphene-based organic light-emitting diodes reported so far are usually <1 cm2. Here we report a transfer method using rosin as a support layer, whose weak interaction with graphene, good solubility and sufficient strength enable ultraclean and damage-free transfer. The transferred graphene has a low surface roughness with an occasional maximum residue height of about 15 nm and a uniform sheet resistance of 560 Ω per square with about 1% deviation over a large area. Such clean, damage-free graphene has produced the four-inch monolithic flexible graphene-based organic light-emitting diode with a high brightness of about 10,000 cd m−2 that can already satisfy the requirements for lighting sources and displays.
An intelligent artificial throat with sound-sensing ability based on laser induced graphene
Authors: Tao Lu-Qi , Tian He , Liu Ying , Ju Zhen-Yi , Pang Yu , Chen Yuan-Quan , Wang Dan-Yang , Tian Xiang-Guang , Yan Jun-Chao , Deng Ning-Qin , Yang Yi , Ren Tian-Ling
Published: February 2017

Traditional sound sources and sound detectors are usually independent and discrete in the human hearing range. To minimize the device size and integrate it with wearable electronics, there is an urgent requirement of realizing the functional integration of generating and detecting sound in a single device. Here we show an intelligent laser-induced graphene artificial throat, which can not only generate sound but also detect sound in a single device. More importantly, the intelligent artificial throat will significantly assist for the disabled, because the simple throat vibrations such as hum, cough and scream with different intensity or frequency from a mute person can be detected and converted into controllable sounds. Furthermore, the laser-induced graphene artificial throat has the advantage of one-step fabrication, high efficiency, excellent flexibility and low cost, and it will open practical applications in voice control, wearable electronics and many other areas.
Ensemble forecast of human West Nile virus cases and mosquito infection rates
Authors: DeFelice Nicholas B. , Little Eliza , Campbell Scott R. , Shaman Jeffrey
Published: February 2017

West Nile virus (WNV) is now endemic in the continental United States; however, our ability to predict spillover transmission risk and human WNV cases remains limited. Here we develop a model depicting WNV transmission dynamics, which we optimize using a data assimilation method and two observed data streams, mosquito infection rates and reported human WNV cases. The coupled model-inference framework is then used to generate retrospective ensemble forecasts of historical WNV outbreaks in Long Island, New York for 2001–2014. Accurate forecasts of mosquito infection rates are generated before peak infection, and >65% of forecasts accurately predict seasonal total human WNV cases up to 9 weeks before the past reported case. This work provides the foundation for implementation of a statistically rigorous system for real-time forecast of seasonal outbreaks of WNV.
ASAP3 regulates microvilli structure in parietal cells and presents intervention target for gastric acidity
Authors: Qian Jin , Li Yueyuan , Yao Han , Tian Haiying , Wang Huanbin , Ai Luoyan , Xie Yuanhong , Bao Yujie , Liang Lunxi , Hu Ye , Zhang Yao , Wang Jilin , Li Chushu , Tang Jiayin , Chen Yingxuan , Xu Jie , Fang Jing-Yuan
Published: February 2017

Gastric acidity-associated disorders such as peptic ulcer and reflux diseases are widespread, and the reported resistance and side effects of currently used medicines suggest an urgent requirement for alternative therapeutic approaches. Here we demonstrate a critical role of ASAP3 in regulating the microvilli structure of parietal cells in vivo, and reveal the feasibility of controlling gastric acidity by targeting ASAP3. Conditional knockout of ASAP3 in mice caused elongation and stacking of microvilli in parietal cells, and substantially decreased gastric acid secretion. These were associated with active assembly of F-actin caused by a higher level of GTP-bound Arf6 GTPase. Consistently, a small molecular compound QS11 inhibited ASAP3 function and significantly reduced gastric acidity in vivo. Of note, the expression of ASAP3 was positively correlated with gastric acid secretion in 90 human cases, and high expression of ASAP3 was associated with reflux disease and peptic ulcer. These results reveal for the first time that ASAP3 regulates the microvilli structures in parietal cells. Our data also suggest ASAP3 as a feasible and drugable therapeutic target for gastric acidity-associated diseases.
Feature-based attentional weighting and spreading in visual working memory
Authors: Niklaus Marcel , Nobre Anna C. , van Ede Freek
Published: February 2017

Attention can be directed at features and feature dimensions to facilitate perception. Here, we investigated whether feature-based-attention (FBA) can also dynamically weight feature-specific representations within multi-feature objects held in visual working memory (VWM). Across three experiments, participants retained coloured arrows in working memory and, during the delay, were cued to either the colour or the orientation dimension. We show that directing attention towards a feature dimension (1) improves the performance in the cued feature dimension at the expense of the uncued dimension, (2) is more efficient if directed to the same rather than to different dimensions for different objects, and (3) at least for colour, automatically spreads to the colour representation of non-attended objects in VWM. We conclude that FBA also continues to operate on VWM representations (with similar principles that govern FBA in the perceptual domain) and challenge the classical view that VWM representations are stored solely as integrated objects.
Prediction of Mortality and Postoperative Complications using the Hip-Multidimensional Frailty Score in Elderly Patients with Hip Fracture
Authors: Choi Jung-Yeon , Cho Kwan-Jae , Kim Sun-wook , Yoon Sol-Ji , Kang Min-gu , Kim Kwang-il , Lee Young-Kyun , Koo Kyung-Hoi , Kim Cheol-Ho
Published: February 2017

High mortality and dependent living after hip fracture pose a significant public health concern. Retrospective study was conducted with 481 hip fracture patients (≥65 years of age) undergoing surgery from March 2009 to May 2014. The Hip-MFS was calculated by Comprehensive Geriatric Assessment (CGA). The primary outcome was the 6-month all-cause mortality rate. The secondary outcomes were 1-year all-cause mortality, postoperative complications and prolonged hospital stay, and institutionalization. Thirty-five patients (7.3%) died within 6 months after surgery (median [interquartile range], 2.9 [1.4–3.9] months). The fully adjusted hazard ratio per 1 point increase in Hip-MFS was 1.458 (95% confidence interval [CI]: 1.210–1.758) for 6-months mortality and odds ratio were 1.239 (95% CI: 1.115–1.377), 1.156 (95% CI: 1.031–1.296) for postoperative complications and prolonged total hospital stay, respectively. High-risk patients (Hip-MFS > 8) showed higher risk of 6-month mortality (hazard ratio: 3.545, 95% CI: 1.466–8.572) than low-risk patients after adjustment. Hip-MFS successfully predict 6-month mortality, postoperative complications and prolonged hospital stay in elderly hip fracture patients after surgery. Hip-MFS more precisely predict 6-month mortality than age or existing tools (P values of comparison of ROC curve: 0.002, 0.004, and 0.044 for the ASA classification, age and NHFS, respectively).
Changes in biomass allocation buffer low CO2 effects on tree growth during the last glaciation
Authors: Li Guangqi , Gerhart Laci M. , Harrison Sandy P. , Ward Joy K. , Harris John M. , Prentice I. Colin
Published: February 2017

Isotopic measurements on junipers growing in southern California during the last glacial, when the ambient atmospheric [CO2] (ca) was ~180 ppm, show the leaf-internal [CO2] (ci) was approaching the modern CO2compensation point for C3plants. Despite this, stem growth rates were similar to today. Using a coupled light-use efficiency and tree growth model, we show that it is possible to maintain a stable ci/caratio because both vapour pressure deficit and temperature were decreased under glacial conditions at La Brea, and these have compensating effects on the ci/caratio. Reduced photorespiration at lower temperatures would partly mitigate the effect of low cion gross primary production, but maintenance of present-day radial growth also requires a ~27% reduction in the ratio of fine root mass to leaf area. Such a shift was possible due to reduced drought stress under glacial conditions at La Brea. The necessity for changes in allocation in response to changes in [CO2] is consistent with increased below-ground allocation, and the apparent homoeostasis of radial growth, as caincreases today.
Development of an ex vivo human-porcine respiratory model for preclinical studies
Authors: Perinel Sophie , Pourchez Jérémie , Leclerc Lara , Avet John , Durand Marc , Prévôt Nathalie , Cottier Michèle , Vergnon Jean M.
Published: February 2017

Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures “pleural” depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with 81mKrypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies.
Mechanical diagnosis of human erythrocytes by ultra-high speed manipulation unraveled critical time window for global cytoskeletal remodeling
Authors: Ito Hiroaki , Murakami Ryo , Sakuma Shinya , Tsai Chia-Hung Dylan , Gutsmann Thomas , Brandenburg Klaus , Pöschl Johannes M. B. , Arai Fumihito , Kaneko Makoto , Tanaka Motomu
Published: February 2017

Large deformability of erythrocytes in microvasculature is a prerequisite to realize smooth circulation. We develop a novel tool for the three-step “Catch-Load-Launch” manipulation of a human erythrocyte based on an ultra-high speed position control by a microfluidic “robotic pump”. Quantification of the erythrocyte shape recovery as a function of loading time uncovered the critical time window for the transition between fast and slow recoveries. The comparison with erythrocytes under depletion of adenosine triphosphate revealed that the cytoskeletal remodeling over a whole cell occurs in 3 orders of magnitude longer timescale than the local dissociation-reassociation of a single spectrin node. Finally, we modeled septic conditions by incubating erythrocytes with endotoxin, and found that the exposure to endotoxin results in a significant delay in the characteristic transition time for cytoskeletal remodeling. The high speed manipulation of erythrocytes with a robotic pump technique allows for high throughput mechanical diagnosis of blood-related diseases.
LHCSR3 affects de-coupling and re-coupling of LHCII to PSII during state transitions in Chlamydomonas reinhardtii
Authors: Roach Thomas , Na Chae Sun
Published: February 2017

Photosynthetic organisms have to tolerate rapid changes in light intensity, which is facilitated by non-photochemical quenching (NPQ) and involves modification of energy transfer from light-harvesting complexes (LHC) to the photosystem reaction centres. NPQ includes dissipating excess light energy to heat (qE) and the reversible coupling of LHCII to photosystems (state transitions/qT), which are considered separate NPQ mechanisms. In the model alga Chlamydomonas reinhardtii the LHCSR3 protein has a well characterised role in qE. Here, it is shown in the npq4 mutant, deficient in LHCSR3, that energy coupling to photosystem II (PSII) more akin to qT is also disrupted, but no major differences in LHC phosphorylation or LHC compositions were found in comparison to wild-type cells. The qT of wild-type cells possessed two kinetically distinguishable phases, with LHCSR3 participating in the more rapid (<2 min) phase. This LHCSR3-mediated qT was sensitive to physiological levels of H2O2, which accelerated qE induction, revealing a way that may help C. reinhardtii tolerate a sudden increase in light intensity. Overall, a clear mechanistic overlap between qE and qT is shown.
Integrated Organotypic Slice Cultures and RT-QuIC (OSCAR) Assay: Implications for Translational Discovery in Protein Misfolding Diseases
Authors: Kondru Naveen , Manne Sireesha , Greenlee Justin , West Greenlee Heather , Anantharam Vellareddy , Halbur Patrick , Kanthasamy Arthi , Kanthasamy Anumantha
Published: February 2017

Protein misfolding is a key pathological event in neurodegenerative diseases like prion diseases, synucleinopathies, and tauopathies that are collectively termed protein misfolding disorders. Prions are a prototypic model to study protein aggregation biology and therapeutic development. Attempts to develop anti-prion therapeutics have been impeded by the lack of screening models that faithfully replicate prion diseases and the lack of rapid, sensitive biological screening systems. Therefore, a sensitive model encompassing prion replication and neurotoxicity would be indispensable to the pursuit of intervention strategies. We present an ultra-sensitive screening system coupled to an ex vivo prion organotypic slice culture model to rapidly advance rationale-based high-throughput therapeutic strategies. This hybrid Organotypic Slice Culture Assay coupled with RT-QuIC (OSCAR) permits sensitive, specific and quantitative detection of prions from an infectious slice culture model on a reduced time scale. We demonstrate that the anti-prion activity of test compounds can be readily resolved based on the power and kinetics of seeding activity in the OSCAR screening platform and that the prions generated in slice cultures are biologically active. Collectively, our results imply that OSCAR is a robust model of prion diseases that offers a promising platform for understanding prion proteinopathies and advancing anti-prion therapeutics.
Targeting Thioredoxin-1 by dimethyl fumarate induces ripoptosome-mediated cell death
Authors: Schroeder Anne , Warnken Uwe , Röth Daniel , Klika Karel D. , Vobis Diana , Barnert Andrea , Bujupi Fatmire , Oberacker Tina , Schnölzer Martina , Nicolay Jan P. , Krammer Peter H. , Gülow Karsten
Published: February 2017

Constitutively active NFκB promotes survival of many cancers, especially T-cell lymphomas and leukemias by upregulating antiapoptotic proteins such as inhibitors of apoptosis (IAPs) and FLICE-like inhibitory proteins (cFLIPs). IAPs and cFLIPs negatively regulate the ripoptosome, which mediates cell death in an apoptotic or necroptotic manner. Here, we demonstrate for the first time, that DMF antagonizes NFκB by suppressing Thioredoxin-1 (Trx1), a major regulator of NFκB transcriptional activity. DMF-mediated inhibition of NFκB causes ripoptosome formation via downregulation of IAPs and cFLIPs. In addition, DMF promotes mitochondrial Smac release and subsequent degradation of IAPs, further enhancing cell death in tumor cells displaying constitutive NFκB activity. Significantly, CTCL patients treated with DMF display substantial ripoptosome formation and caspase-3 cleavage in T-cells. DMF induces cell death predominantly in malignant or activated T-cells. Further, we show that malignant T-cells can die by both apoptosis and necroptosis, in contrast to resting T-cells, which are restricted to apoptosis upon DMF administration. In summary, our data provide new mechanistic insight in the regulation of cell death by targeting NFκB via Trx1 in cancer. Thus, interference with Trx1 activity is a novel approach for treatment of NFκB-dependent tumors.
A record of igneous evolution in Elysium, a major martian volcanic province
Authors: Susko David , Karunatillake Suniti , Kodikara Gayantha , Skok J. R. , Wray James , Heldmann Jennifer , Cousin Agnes , Judice Taylor
Published: February 2017

A major knowledge gap exists on how eruptive compositions of a single martian volcanic province change over time. Here we seek to fill that gap by assessing the compositional evolution of Elysium, a major martian volcanic province. A unique geochemical signature overlaps with the southeastern flows of this volcano, which provides the context for this study of variability of martian magmatism. The southeastern lava fields of Elysium Planitia show distinct chemistry in the shallow subsurface (down to several decimeters) relative to the rest of the martian mid-to-low latitudes (average crust) and flows in northwest Elysium. By impact crater counting chronology we estimated the age of the southeastern province to be 0.85 ± 0.08 Ga younger than the northwestern fields. This study of the geochemical and temporal differences between the NW and SE Elysium lava fields is the first to demonstrate compositional variation within a single volcanic province on Mars. We interpret the geochemical and temporal differences between the SE and NW lava fields to be consistent with primary magmatic processes, such as mantle heterogeneity or change in depth of melt formation within the martian mantle due to crustal loading.
Thyroid nodule sizes influence the diagnostic performance of TIRADS and ultrasound patterns of 2015 ATA guidelines: a multicenter retrospective study
Authors: Xu Ting , Gu Jing-yu , Ye Xin-hua , Xu Shu-hang , Wu Yang , Shao Xin-yu , Liu De-zhen , Lu Wei-ping , Hua Fei , Shi Bi-min , Liang Jun , Xu Lan , Tang Wei , Liu Chao , Wu Xiao-hong
Published: February 2017

To evaluate the impact of thyroid nodule sizes on the diagnostic performance of thyroid imaging reporting and data system (TIRADS) and ultrasound patterns of 2015 American Thyroid Association (ATA) guidelines. Total 734 patients with 962 thyroid nodules were recruited in this retrospective study. All nodules were divided into three groups according to the maximal diameter (d < 10 mm, d = 10–20 mm and d > 20 mm). The ultrasound images were categorized based on TIRADS and ATA ultrasound patterns, respectively. A total of 931 (96.8%) and 906 (94.2%) patterns met the criteria for TIRADS and ATA ultrasound patterns. The AUC (0.849) and sensitivity (85.3%) of TIRADS were highest in d = 10–20 mm group. However, ATA had highest AUC (0.839) and specificity (89.8%) in d > 20 mm group. ATA ultrasound patterns had higher specificity (P = 0.04), while TI-RADS had higher sensitivity (P = 0.02). In nodules d > 20 mm, the specificity of ATA patterns was higher than TIRADS (P = 0.003). Our results indicated that nodule sizes may influence the diagnostic performance of TIRADS and ATA ultrasound patterns. The ATA patterns may yield higher specificity than TIRADS, especially in nodules larger than 20 mm.
Protective effects on liver, kidney and pancreas of enzymatic- and acidic-hydrolysis of polysaccharides by spent mushroom compost (Hypsizigus marmoreus)
Authors: Liu Min , Song Xinling , Zhang Jianjun , Zhang Chen , Gao Zheng , Li Shangshang , Jing Huijuan , Ren Zhenzhen , Wang Shouxian , Jia Le
Published: February 2017

The present work investigated the protective effects on liver, kidneys and pancreas of spent mushroom compost polysaccharide (SCP) and its hydrolysates (enzymatic- (ESCP) and acid-hydrolyzed SCP (ASCP)) fromHypsizigus marmoreus, in streptozotocin (STZ)-induced diabetic mice. The results showed that enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) and non-enzymatic activities (total antioxidant capacity (T-AOC)) were significantly increased, the lipid peroxide contents (lipid peroxide (LPO) and malonaldehyde (MDA)) were remarkably reduced, and the clinical parameters were observably mitigated in diabetic mice treated with these three polysaccharides. Furthermore, histological observations also indicated recovery. These conclusions demonstrated that both SCP and its hydrolysates ESCP and ASCP possessed potent antioxidant activities and can be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ.
Comparative transcriptomic analysis reveals the roles of overlapping heat-/drought-responsive genes in poplars exposed to high temperature and drought
Authors: Jia Jingbo , Zhou Jing , Shi Wenguang , Cao Xu , Luo Jie , Polle Andrea , Luo Zhi-Bin
Published: February 2017

High temperature (HT) and drought are both critical factors that constrain tree growth and survival under global climate change, but it is surprising that the transcriptomic reprogramming and physiological relays involved in the response to HT and/or drought remain unknown in woody plants. Thus,Populus simoniisaplings were exposed to either ambient temperature or HT combined with sufficient watering or drought. RNA-sequencing analysis showed that a large number of genes were differentially expressed in poplar roots and leaves in response to HT and/or desiccation, but only a small number of these genes were identified as overlapping heat-/drought-responsive genes that are mainly involved in RNA regulation, transport, hormone metabolism, and stress. Furthermore, the overlapping heat-/drought-responsive genes were co-expressed and formed hierarchical genetic regulatory networks under each condition compared. HT-/drought-induced transcriptomic reprogramming is linked to physiological relays in poplar roots and leaves. For instance, HT- and/or drought-induced abscisic acid accumulation and decreases in auxin and other phytohormones corresponded well with the differential expression of a few genes involved in hormone metabolism. These results suggest that overlapping heat-/drought-responsive genes will play key roles in the transcriptional and physiological reconfiguration of poplars to HT and/or drought under future climatic scenarios.
Cerebral Edema in Chronic Mountain Sickness: a New Finding
Authors: Bao Haihua , Wang Duoyao , Zhao Xipeng , Wu Youshen , Yin Guixiu , Meng Li , Wang Fangfang , Ma Lan , Hackett Peter , Ge Ri-Li
Published: February 2017

We observed patients with chronic mountain sickness (CMS) in our clinic who developed progressive neurological deterioration (encephalopathy) and we wished to investigate this. We studied nine such CMS patients, and compared them to 21 CMS patients without encephalopathy, and to 15 healthy control subjects without CMS. All 45 subjects lived permanently at 3200–4000 m. Measurements at 2260 m included CMS symptom score, multi-slice CT, perfusion CT, pulse oximetry (SpO2%), and hemoglobin concentration (Hb). One patient had MRI imaging but not CT; 5 had CSF pressure measurements. CMS subjects had lower SpO2, higher Hb, higher brain blood density, lower mean cerebral blood flow (CBF), and significant cerebral circulatory delay compared to controls. The nine CMS subjects with neurological deterioration showed diffuse cerebral edema on imaging and more deranged cerebral hemodynamics. CSF pressure was elevated in those with edema. We conclude that cerebral edema, a previously unrecognized complication, may develop in CMS patients and cause encephalopathy. Contributing factors appear to be exaggerated polycythemia and hypoxemia, and lower and sluggish CBF compared to CMS patients without cerebral edema; but what triggers this complication is unknown. Recognition and treatment of this serious complication will help reduce morbidity and mortality from CMS.
In silico serine β-lactamases analysis reveals a huge potential resistome in environmental and pathogenic species
Authors: Brandt Christian , Braun Sascha D. , Stein Claudia , Slickers Peter , Ehricht Ralf , Pletz Mathias W. , Makarewicz Oliwia
Published: February 2017

The secretion of antimicrobial compounds is an ancient mechanism with clear survival benefits for microbes competing with other microorganisms. Consequently, mechanisms that confer resistance are also ancient and may represent an underestimated reservoir in environmental bacteria. In this context, β-lactamases (BLs) are of great interest due to their long-term presence and diversification in the hospital environment, leading to the emergence of Gram-negative pathogens that are resistant to cephalosporins (extended spectrum BLs = ESBLs) and carbapenems (carbapenemases). In the current study, protein sequence databases were used to analyze BLs, and the results revealed a substantial number of unknown and functionally uncharacterized BLs in a multitude of environmental and pathogenic species. Together, these BLs represent an uncharacterized reservoir of potentially transferable resistance genes. Considering all available data, in silico approaches appear to more adequately reflect a given resistome than analyses of limited datasets. This approach leads to a more precise definition of BL clades and conserved motifs. Moreover, it may support the prediction of new resistance determinants and improve the tailored development of robust molecular diagnostics.
Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study
Authors: Ibáñez-Sanz Gemma , Díez-Villanueva Anna , Alonso M. Henar , Rodríguez-Moranta Francisco , Pérez-Gómez Beatriz , Bustamante Mariona , Martin Vicente , Llorca Javier , Amiano Pilar , Ardanaz Eva , Tardón Adonina , Jiménez-Moleón Jose J. , Peiró Rosana , Alguacil Juan , Navarro Carmen , Guinó Elisabet , Binefa Gemma , Fernández-Navarro Pablo , Espinosa Anna , Dávila-Batista Verónica , Molina Antonio José , Palazuelos Camilo , Castaño-Vinyals Gemma , Aragonés Nuria , Kogevinas Manolis , Pollán Marina , Moreno Victor
Published: February 2017

Colorectal cancer (CRC) screening of the average risk population is only indicated according to age. We aim to elaborate a model to stratify the risk of CRC by incorporating environmental data and single nucleotide polymorphisms (SNP). The MCC-Spain case-control study included 1336 CRC cases and 2744 controls. Subjects were interviewed on lifestyle factors, family and medical history. Twenty-one CRC susceptibility SNPs were genotyped. The environmental risk model, which included alcohol consumption, obesity, physical activity, red meat and vegetable consumption, and nonsteroidal anti-inflammatory drug use, contributed to CRC with an average per factor OR of 1.36 (95% CI 1.27 to 1.45). Family history of CRC contributed an OR of 2.25 (95% CI 1.87 to 2.72), and each additional SNP contributed an OR of 1.07 (95% CI 1.04 to 1.10). The risk of subjects with more than 25 risk alleles (5th quintile) was 82% higher (OR 1.82, 95% CI 1.11 to 2.98) than subjects with less than 19 alleles (1st quintile). This risk model, with an AUROC curve of 0.63 (95% CI 0.60 to 0.66), could be useful to stratify individuals. Environmental factors had more weight than the genetic score, which should be considered to encourage patients to achieve a healthier lifestyle.
High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha
Authors: Ban Zsofia , Maurischat Paul , Benz Verena , Brix Sarah , Sonnenburg Anna , Schuler Gerhard , Klopfleisch Robert , Rothe Michael , Gustafsson Jan-Åke , Foryst-Ludwig Anna , Kintscher Ulrich
Published: February 2017

Estrogen receptor alpha (ERα) is a major regulator of metabolic processes in obesity. In this study we aimed to define the relevance of adipose tissue ERα during high-fat diet (HFD)-induced obesity using female aP2-Cre−/+/ERαfl/fl mice (atERαKO). HFD did not affect body weight or glucose metabolism in atERαKO- compared to control mice. Surprisingly, HFD feeding markedly increased mortality in atERαKO mice associated with a destructive bacterial infection of the uterus driven by commensal microbes, an alteration likely explaining the absence of a metabolic phenotype in HFD-fed atERαKO mice. In order to identify a mechanism of the exaggerated uterine infection in HFD-fed atERαKO mice, a marked reduction of uterine M2-macrophages was detected, a cell type relevant for anti-microbial defence. In parallel, atERαKO mice exhibited elevated circulating estradiol (E2) acting on E2-responsive tissue/cells such as macrophages. Accompanying cell culture experiments showed that despite E2 co-administration stearic acid (C18:0), a fatty acid elevated in plasma from HFD-fed atERαKO mice, blocks M2-polarization, a process known to be enhanced by E2. In this study we demonstrate an unexpected phenotype in HFD-fed atERαKO involving severe uterine bacterial infections likely resulting from a previously unknown negative interference between dietary FAs and ERα-signaling during anti-microbial defence.
Optical coherence tomography evaluation of pulmonary arterial vasculopathy in Systemic Sclerosis
Authors: Schwaiger Johannes P. , Loder Christopher D. , Dobarro David , Kaier Thomas , Reddecliffe Sally , Schreiber Benjamin E. , Handler Clive , Denton Christopher P. , Coghlan John G.
Published: February 2017

Our current understanding of the pathophysiology of pulmonary vascular disease is incomplete, since information about alterations of the pulmonary vasculature in pulmonary arterial hypertension (PAH) is primarily provided by autopsy or tissue specimens. The aim of this study was to compare the distal pulmonary vasculature of <2 mm in diameter in Systemic Sclerosis (SSc) patients with (n = 17) and without (n = 5) associated PAH using Optical Coherence Tomography during Right Heart catheterization. SSc-PAH patients showed significant thickening of Intima Media Thickening Area compared to patients without PAH (27 +/− 5.8% vs. 21 +/− 1.4%, p = 0.024). A good haemodynamic response to previous targeted PAH treatment was associated with a significantly greater number of small pulmonary artery side branches <300 μm per cm vessel (3.8 +/− 1.1 vs. 1.8 +/− 1.1; p = 0.010) and not associated with Intima Media thickening Area (26 +/− 5.4% vs. 28 +/− 6.7%; p = 0.6). Unexpected evidence of pulmonary artery thrombus formation was found in 19% of SSc-PAH patients. This is the first in-vivo study demonstrating a direct link between a structural abnormality of pulmonary arteries and a response to targeted treatment in PAH. Intravascular imaging may identify subgroups that may benefit from anticoagulation.
Interplay between Penicillin-binding proteins and SEDS proteins promotes bacterial cell wall synthesis
Authors: Leclercq Sophie , Derouaux Adeline , Olatunji Samir , Fraipont Claudine , Egan Alexander J. F. , Vollmer Waldemar , Breukink Eefjan , Terrak Mohammed
Published: February 2017

Bacteria utilize specialized multi-protein machineries to synthesize the essential peptidoglycan (PG) cell wall during growth and division. The divisome controls septal PG synthesis and separation of daughter cells. In E. coli, the lipid II transporter candidate FtsW is thought to work in concert with the PG synthases penicillin-binding proteins PBP3 and PBP1b. Yet, the exact molecular mechanisms of their function in complexes are largely unknown. We show that FtsW interacts with PBP1b and lipid II and that PBP1b, FtsW and PBP3 co-purify suggesting that they form a trimeric complex. We also show that the large loop between transmembrane helices 7 and 8 of FtsW is important for the interaction with PBP3. Moreover, we found that FtsW, but not the other flippase candidate MurJ, impairs lipid II polymerization and peptide cross-linking activities of PBP1b, and that PBP3 relieves these inhibitory effects. All together the results suggest that FtsW interacts with lipid II preventing its polymerization by PBP1b unless PBP3 is also present, indicating that PBP3 facilitates lipid II release and/or its transfer to PBP1b after transport across the cytoplasmic membrane. This tight regulatory mechanism is consistent with the cell’s need to ensure appropriate use of the limited pool of lipid II.
A new method for identifying the cut ends in canalicular laceration
Authors: Peng Wenyan , Wang Yandong , Tan Bowei , Wang Haiying , Liu Xuehua , Liang Xuanwei
Published: February 2017

To locate the proximal and distal cut ends of the canaliculus following trauma is the most difficult part of canalicular repair, especially in patients with complex acute canalicular lacerations and late presenting canalicular lacerations. Previously, irrigation and air-injection technique are reported and widely used to locate the cut ends of lacerated canaliculus. However, we have developed a novel technique in which with a 23 Ga fiber optic light pipe is used to identify the cut ends of the canaliculus allowing silicone tube intubation of the lacrimal system. The mean time from initiation of the identification of the cut ends of the canaliculus to insertion of the silicone tube was 5 minutes. In this study, the cut ends were successfully identified by using this novel method in 33 cases of acute and late presenting canalicular laceration for canalicular reconstruction without any complications. This light-guided technique may represent an improvement in the surgical repair of canalicular lacerations.
Rainfall reduction amplifies the stimulatory effect of nitrogen addition on N2O emissions from a temperate forest soil
Authors: Geng Shicong , Chen Zhijie , Han Shijie , Wang Fang , Zhang Junhui
Published: February 2017

Soil is a significant source of atmospheric N2O, and soil N2O emissions at a global scale are greatly affected by environment changes that include continuous deposition of atmospheric nitrogen and changing precipitation distribution. However, to date, field simulations of multiple factors that control the interaction between nitrogen deposition and precipitation on forest soil N2O emissions are scarce. In this study, we conducted a 2-year continuous assessment of N2O emissions from November 2012 to October 2014 at a nitrogen addition and rainfall reduction manipulation platform in an old broad-leaved Korean pine mixed forest at Changbai Mountain in northeastern China. We found that N2O emissions from control plots were 1.25 ± 0.22 kg N2O-N ha−1 a−1. Nitrogen addition significantly increased N2O emissions, with the emission factor of 1.59%. A 30% reduction in rainfall decreased N2O emissions by 17–45%. However, in combination, nitrogen addition and rainfall reduction increased N2O emissions by 58–140%, with the emission factor of 3.19%, and had a larger promotional effect than the addition of nitrogen alone. Our results indicated that drought slightly decreases forest soil N2O emission; however, with increasing deposition of atmospheric N in temperate forest soils, the effect of drought might become altered to increase N2O emission.