bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of infection and antibiotics in chronic rhinosinusitis.
Authors: Barshak Miriam Baron , Durand Marlene L.
Published: January 2017

Objective

To review the current understanding of the role of infection and antibiotics in chronic rhinosinusitis.

Review methods

PubMed literature search

Results

Chronic rhinosinusitis (CRS) in adults is an inflammatory condition and the role of infection is unclear. Biofilms are present in both CRS and normal patients so their role in CRS is unknown. Sinus cultures in CRS demonstrate a mixture of aerobic and anaerobic bacteria but may be hard to interpret due to contaminating nasal flora. Staphylococcus aureus is common in CRS patients but also present in 20‐30% of nasal cultures in the normal population; eradicating this organism did not lead to symptom improvement versus placebo in a randomized controlled trial (RCT). In CRS patients who develop an episode of acute rhinosinusitis (ARS), bacteria typical of ARS can generally be cultured and require short‐course treatment. For CRS, topical antibacterial or antifungal agents have shown no benefit over placebo in RCTs, although RCTs of topical antibacterial agents have been small. Oral macrolides and doxycycline, antibiotics with anti‐inflammatory properties, are the only systemic antibiotics that have been evaluated in RCTs. One RCT found 3 weeks of doxycycline beneficial in patients with polyps but follow up was short (<3 months); RCTs of prolonged macrolide therapy have produced mixed results, and most show no benefit after cessation of therapy. Long‐term antibiotic therapy may produce side effects and select increasingly resistant flora. The American Academy of Otolaryngology—Head and Neck Surgery guidelines recommend against treatment of CRS with antifungal agents but do not comment on the role of antibacterial treatment.

Conclusion

The role of infection in CRS is unknown, and the only well‐defined role for antibiotics is for treatment of ARS episodes or their infectious complications.

Level of Evidence

N/A.
Understanding pathways of dissimilatory and assimilatory dissolved inorganic nitrogen uptake in streams
Authors: Ribot M. , von Schiller D. , Martí E.
Published: January 2017

Dissolved inorganic nitrogen (DIN) in streams is mostly available as two different species: nitrate (
) and ammonium (
). These two DIN species undergo specific dissimilatory uptake pathways and show distinct preference during biological assimilation. These differences ultimately dictate how DIN is cycled within streams and its further export to downstream ecosystems. Here, we provide a synthesis analysis of the uptake of
and
at the reach scale and on the contribution of dissimilatory and assimilatory uptake pathways. We combined 15N‐tracer experiments in a single stream with compiled results of
and
uptake from the literature. As expected, streams were more efficient in processing
than
at the reach scale. These results were partially explained by the fact that, on average, dissimilatory
uptake (i.e., denitrification and DNRA) had a low incidence on total
uptake, whereas dissimilatory
uptake (i.e., nitrification) contributed to a high proportion of total
uptake thereby increasing in‐stream
concentration. Furthermore, assimilatory uptake by in‐stream biotic compartments dominated the total uptake of the two DIN species and was generaly higher for
than for
. Overall, results from this study indicate that assimilatory uptake by biotic compartments rather than permanent removal dominates total
uptake in streams. In contrast, both assimilatory and dissimilatory uptake can contribute similarly to total
uptake. Our findings have strong implications for a better understanding of N cycling within the context of widespread increases in DIN concentration and changes in the
 : 
ratio driven by human activities.
Effects of grain refinement on age hardening behavior and precipitation kinetics of Al–Si–Cu–Mg alloys
Authors: Lu T. , Tao S. , Chen Y. , Pan Y. , Pi J.
Published: January 2017

The influences of grain refinement on precipitation kinetics were investigated for an Al–11 wt% Si–1.5 wt% Cu–0.3 wt% Mg casting alloy doped with B and and with La–B respectively by microstructure observation, hardness test and Johnson–Mehl–Avrami (JMA) equation. Co‐alloying of La–B facilitates the faster hardening response with higher hardness value for the alloy. The calculated Avarmi exponent indicates that the nucleation of θ′‐Al2Cu precipitates occurs on grain boundaries for the refined alloys. The activation energies for the precipitation are of 42 kJ/mol and 30 kJ/mol for B‐doped and La–B co‐doped alloys, respectively.
Comparison of carbon‐based nanomaterials characteristics on H13 tool steel
Authors: Emamian S. , Hussain P. , Awang M. , Arumugam T. , Yusof F. , Saheed M. S. M. , Mohamed N. M.
Published: January 2017

As the demand to weld higher strength materials through friction stir welding (FSW) increases, the need for better non‐consumable rotating tool also increases as it has to be able to endure high frictional and thermal deformation while the work‐piece undergoes intense plastic deformation at high temperatures. Carbon‐based nanomaterials are good options to increase strength of steel. An attempt to improve the friction stir welding tool through carbon‐based coatings on H13 tool steel has been carried out. This paper highlights the characterization of the carbon‐based coatings in regard to selected coating parameters through Field emission scanning electron microscope, energy dispersive spectroscopy, Raman Spectra, and X‐Ray photoelectron spectroscopy techniques. The analysis shows presence of graphite like structures whereas Carbon Nanotubes (CNT) was observed to be grown uniformly on the surface.
Pedicled chimeric sensitive fasciocutaneous anterolateral thigh (ALT) and vastus lateralis muscle (VLM) flap for groin defect reconstruction: A case report
Authors: Scaglioni Mario F. , Franchi Alberto , Giovanoli Pietro
Published: January 2017

The anterolateral thigh (ALT) flap is one of the most commonly used flap worldwide, as both free flap and pedicled local flap. Here, we report the use of a pedicled chimeric sensitive ALT and vastus lateralis muscle (VLM) flap in a patient with a 12 cm × 8 cm contaminated soft tissue defect of the right inguinal region with exposed femoral vessels. The flap was harvested based on two perforators, one musculocutaneous and one pure muscular, each nourished separately a sensitive fasciocutaneous component and a vastus lateralis muscle component, respectively. The muscle part was tailored to wrap around the exposed vascular structures, while the innervated skin and fascia component of the flap provided a tension‐free closure of the wound. The post‐operative course was uneventful and the patient was discharged at 1 week post‐operative. Even though it requires technical skills and experience in perforator dissection, we believe that the pedicled chimeric sensitive ALT and VLM flap may be one of the best solutions in case of exposed femoral vessels in contaminated wounds.
Delay‐dependent criteria on the global attractivity of Nicholson's blowflies model with patch structure
Authors: Jia Renwei , Long Zhiwen , Yang Mingquan
Published: January 2017

In this paper, we investigate the effect of delay on the asymptotic behavior of Nicholson's blowflies model with patch structure and multiple time‐varying delays. By using the fluctuation lemma and some differential inequality technique, delay‐dependent criteria are obtained for the global attractivity of the addressed system. Meanwhile, some numerical examples are given to illustrate the feasibility of the theoretical results. Copyright © 2017 John Wiley & Sons, Ltd.
New method to characterize and correct with sub‐µs precision gradient delays in bipolar multispoke RF pulses
Authors: Gras Vincent , Vignaud Alexandre , Amadon Alexis , Mauconduit Franck , Le Bihan Denis , Boulant Nicolas
Published: January 2017

Purpose

Small gradient delays with respect to radiofrequency (RF) events can have disastrous effects on the performance of bipolar spokes RF pulses used in parallel transmission (pTx). In this work, we propose a new method to characterize and correct this delay with sub‐µs precision.

Methods

By determining experimentally the phase
producing a 0 ° flip angle excitation in a
bipolar two‐spoke pulse configuration at multiple slice locations, we demonstrate the possibility of deducing the underlying gradient delay with precision. The technique also suggests prospectively compensating for the same delay by altering the phase of the second pulse. The approach was tested with a multislice gradient echo sequence on a phantom and on one healthy volunteer at 7 Tesla.

Results

Application of the method returned an accuracy of approximately 50 ns on the gradient delay measurement, a performance shown in fact to be desirable for high‐performance pTx 2D applications. Phase corrections of up to 180 ° on the second spoke RF pulse in the bipolar configuration allowed us to obtain similar performance as for unipolar designs, yet with significantly shorter excitations.

Conclusions

A simple and accurate gradient‐delay calibration method was proposed that offers the possibility of using bipolar multispoke pulses in multislice protocols. Magn Reson Med 78:2194–2202, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Permeability of the plasma membrane to water and cryoprotectants in mammalian oocytes and embryos: Its relevance to vitrification
Authors: Edashige Keisuke
Published: January 2017

The permeability of the plasma membrane to water and cryoprotectants is one of the important factors for determining the suitable condition for the vitrification of mammalian oocytes and embryos. Water and cryoprotectants move slowly through oocytes and early embryos, principally by simple diffusion, in the mouse, bovine, pig, and human. In contrast, water, glycerol, and ethylene glycerol move rapidly through morulae and blastocysts, principally by facilitated diffusion via aquaporin 3, in the mouse and bovine; whereas, in the pig, the permeability to water and these cryoprotectants increases not at the morula stage but at the blastocyst stage and further increases at the expanded blastocyst stage. Dimethyl sulfoxide also moves rapidly via channels other than aquaporin 3 in the mouse. In contrast, propylene glycol moves through morulae and blastocysts principally by simple diffusion in the mouse, bovine, and pig, as through oocytes. Therefore, the permeability of mammalian oocytes and embryos at early stages to water and cryoprotectants is low, but that of embryos at later stages to water and some cryoprotectants is markedly high by channel processes, although species specificity exists in some cases.
Economics
Authors: Ormerod Paul
Published: January 2017

Economics is by no means an empty box. For example, it offers what is possibly the only general law of behaviour in the social sciences, namely that agents react to incentives. Over the past two decades or so, at the micro level, the level of individual agent decision making, the discipline has made progress. Developments in the econometric theory of the analysis of large longitudinal data bases and the rise of behavioural and experimental economics have made the discipline much more empirical. However, at the macro level, economics has, if anything, gone backwards. The main intellectual effort since the 1980s has been to import the concept of equilibrium into macroeconomics. It is no surprise that policymakers during the financial crisis of the late 2000s found the mainstream economic models to be of little or no help at all. In the 1950s, there was an active debate about the computational limits which agents faced when making decisions. The polymath Nobel Laureate Herbert Simon was prominent in arguing that the rational model of choice, the core model of economic theory, was not realistic in many situations because of these limits. Even after the event, it may not be possible to determine what the optimal decision would have been at any given time. The world is in general too complex. Mainstream economics gradually lost sight of this fundamental challenge to one of its key assumptions. The rise of cyber society and Big Data mean that Simon’s challenge is more relevant than ever. Looking to the future, new models of ‘rational’ agent behaviour are required which are better suited to the cyber society of the twenty-first century. Key areas of research include: agent decision making rules; heuristics to identify decision types in any given context; network percolation of imitation, incentives, ideas, beliefs, influence and sentiments; networks evolution; the policy implications of different modes of behaviour; fundamental theory and tools to operationalise narrative dynamics; computational theories of narratives, including Big Data; tools for processing narratives and sentiment; and predicting the emergence of narratives.
Social Psychology and the Narrative Economy
Authors: Nowak Andrzej , Kacprzyk-Murawska Marta , Serwotka Ewa
Published: January 2017

Economics can benefit through adopting various ideas from social psychology. Social and economic processes can be analysed at different levels: the microlevel (individuals), mesolevel (system structures), and macrolevel (whole socioeconomic system). Contrary to classic economic models, when making decisions, people do not consider all available information at the microlevel—this is not possible. Decisions may have many competing dimensions and there may be no single optimum. Whereas in traditional economy the main difference between the levels is the degree of aggregation,social constructionismstudies how individuals cooperatively create, change and maintain their understanding of the world. Meanings arise as a result of coordinated action of humans who interpret their world by building models of it and how it functions. A natural way of acquiring meanings and conveying them to others is throughnarratives—stories that have a beginning, a body, and an end. Narratives exist at all levels of social reality. They provide the structure by which an individual can understand the world, with their roles in narratives individuals suggesting how to behave. Interacting individuals socially construct narratives bottom-up. Group narratives emerge from integration of stories describing individual experiences of actors. Shared narratives allow actors to find commonality in their experiences, find coherence in the flow of events and allow them to coordinate in common actions. At the macrolevel narratives define the system and its common culture. Sometimes narration may have more impact on an economy than hard data. Even the choice of which facts we refer to and those we do not may determine the leading narrative and hence the behaviour of people. Socio-economic processes can and should be analysed in line with narratives linking individuals, organisations and societies to better understand what is happening in the whole economic system.
Global Political Dynamics and the Science of Complex Systems
Authors: Root Hilton L.
Published: January 2017

Do the complex dynamics of international relations resemble the long-term evolution observed in living systems? This chapter will try to identify the mechanisms associated with those dynamics, and to determine if the science of complex adaptive systems can aid in the understanding of international development.It tries to address the weaknesses of current theories of international political economy to adequately explain global diversity and queries its empirical and theoretical limitations. Providing insight on the mechanisms by which divergence is a response to heightened interconnectivity, complexity theory offers a way to overcome the limitations of conventional political economy analysis.We find that at a qualitative level the dynamics of the international system resemble known aspects of biological behaviour, speciation and intermittent behaviour. The next frontier for the study of social development is to find quantitative measures that define these processes.
Corporate distress and turnaround: integrating the literature and directing future research
Authors: Schweizer Lars , Nienhaus Andreas
Published: January 2017

The topic of corporate distress and turnaround has been of interest to organizational change theory for many decades. This article considers existing reviews in discussing the current body of turnaround literature across multiple research fields and structures its work along a holistic framework. The numerous facets of corporate turnaround, resorting to general corporate restructuring research classifications, are clustered in a more detailed manner than those that merely rely on two commonly employed turnaround dimensions: “retrenchment” and “recovery.” The authors develop an agenda for future research based on this cross-disciplinary literature aggregation by highlighting current gaps and offering potential research questions. The review contributes to the understanding of corporate distress and turnaround by integrating different research streams. Additionally, the work emphasizes the need for further harmonization and operationalization in turnaround success metrics.
Serum IL‐8 is a marker of white‐matter hyperintensities in patients with Alzheimer's disease
Authors: Zhu Yanan , Chai Yuek Ling , Hilal Saima , Ikram M. Kamran , Venketasubramanian Narayanaswamy , Wong Boon‐Seng , Chen Christopher P. , Lai Mitchell K.P.
Published: January 2017

Introduction

Neuroinflammation and cerebrovascular disease (CeVD) have been implicated in cognitive impairment and Alzheimer's disease (AD). The present study aimed to examine serum inflammatory markers in preclinical stages of dementia and in AD, as well as to investigate their associations with concomitant CeVD.

Methods

We performed a cross‐sectional case–control study including 96 AD, 140 cognitively impaired no dementia (CIND), and 79 noncognitively impaired participants. All subjects underwent neuropsychological and neuroimaging assessments, as well as collection of blood samples for measurements of serum samples interleukin (IL)‐6, IL‐8, and tumor necrosis factor α levels. Subjects were classified as CIND or dementia based on clinical criteria. Significant CeVD, including white‐matter hyperintensities (WMHs), lacunes, and cortical infarcts, was assessed by magnetic resonance imaging.

Results

After controlling for covariates, higher concentrations of IL‐8, but not the other measured cytokines, were associated with both CIND and AD only in the presence of significant CeVD (CIND with CeVD: odds ratios [ORs] 4.53; 95% confidence interval [CI] 1.5–13.4 and AD with CeVD: OR 7.26; 95% CI 1.2–43.3). Subsequent multivariate analyses showed that among the types of CeVD assessed, only WMH was associated with higher IL‐8 levels in CIND and AD (WMH: OR 2.81; 95% CI 1.4–5.6).

Discussion

Serum IL‐8 may have clinical utility as a biomarker for WMH in AD. Longitudinal follow‐up studies would help validate these findings.
Creating Community Resilience Through Elder-Led Physical and Social Infrastructure
Authors: Aldrich Daniel P. , Kyota Emi
Published: January 2017

Objective

Natural disasters and rapidly aging populations are chronic problems for societies worldwide. We investigated the effects of an intervention in Japan known asIbasho, which embeds elderly residents in vulnerable areas within larger social networks and encourages them to participate in leadership activities. This project sought to deepen the connections of these elderly residents to society and to build elderly leadership and community capacity for future crises.

Methods

We carried out surveys of participants and nonparticipant residents across the city of Ofunato in Tohoku, Japan, 1 year after the intervention began. Our surveys included questions assessing participation levels inIbasho, demographic characteristics, efficacy, social networks, and a sense of belonging.

Results

Regression analysis and propensity score matching of more than 1100 respondents showed that regular participation in theIbashoproject had a statistically significant and positive connection with various measures of social capital.

Conclusions

Given its relatively low cost and focus on deepening cohesion, we suggest that this community-based project could be replicated and scaled up in other countries to deepen resilience, elder health, and social capital. Moving away from an emphasis on investing in physical infrastructure, we believe that disaster risk reduction strategies should center on social infrastructure. (Disaster Med Public Health Preparedness. 2017;11:120–126)
The Problem of Habitual Body and Memory in Hegel and Merleau-Ponty
Authors: Magrì Elisa
Published: January 2017

In this paper, I shall focus on the relation between habitual body and memory in Hegel’sPhilosophy of Subjective Spiritand Merleau-Ponty’sPhenomenology of Perception. Both Hegel and Merleau-Ponty defend a view of the self that is centred on the role of habituality as embodied activity situated in a context. However, both philosophers avoid committing to what Edward Casey has defined habitual body memory, i.e., an active immanence of the past in the body that informs present bodily actions in an efficacious, orienting and regular manner. I shall explore the reasons why neither Hegel nor Merleau-Ponty develops an explicit account of habitual body memory. This will shed light not only on Hegel’s account of lived experience, but also on Hegel and Merleau-Ponty’s common concern with the habitual body.
Last Glacial climate reconstruction by exploring glacier sensitivity to climate on the southeastern slope of the western Nyaiqentanglha Shan, Tibetan Plateau
Authors: XU XIANGKE , PAN BAOLIN , DONG GUOCHENG , YI CHAOLU , GLASSER NEIL F.
Published: January 2017

Improvements in understanding glacial extents and chronologies for the southeastern slope of the western Nyaiqentanglha Shan on the Tibetan Plateau are required to understand regional climate changes during the Last Glacial cycle. A two-dimensional numerical model of mass balance, based on snow–ice melting factors, and of ice flow for mountain glaciers is used to assess the glacier sensitivity to climatic change in a catchment of the region. The model can reproduce valley glaciers, wide-tongued glaciers and a coalescing glacier within step temperature lowering and precipitation increasing experiments. The model sensitivity experiments also indicate that the dependence of glacier growth on temperature and/or precipitation is nonlinear. The model results suggest that the valley glaciers respond more sensitively to an imposed climate change than wide-tongued and coalescing glaciers. Guided by field geological evidence of former glacier extent and other independent paleoclimate reconstructions, the model is also used to constrain the most realistic multi-year mean temperatures to be 2.9–4.6°C and 1.8–2.5°C lower than present in the glacial stages of the Last Glacial Maximum and middle marine oxygen isotope stage 3, respectively.
Inflammation and depression: a causal or coincidental link to the pathophysiology?
Authors: Leonard Brian E.
Published: January 2017

This review summarises the evidence that chronic low grade inflammation triggers changes that contribute to the mental and physical ill health of patients with major depression. Inflammation, and the activation of the hypothalamic pituitary axis by stress, are normal components of the stress response but when stress is prolonged and the endocrine and immune system become chronic resulting in the activation of the peripheral macrophages, the central microglia and hypercortisolemia, the neuronal networks are damaged and become dysfunctional. The proinflammatory cytokines, in addition to activating the hypothalamic–pituitary–adrenal axis and thereby increasing cortisol synthesis, also activate the tryptophan–kynurenine pathway. This results in the synthesis of the neurotoxicN-methyl-d-aspartate (NMDA) glutamate agonist quinolinic acid and 3-hydroxykynurenine thereby enhancing oxidative stress and contributes to neurodegeneration which characterise major depression particularly in late life.While antidepressants attenuate some of the endocrine and immune changes caused by inflammation, not all therapeutically effective antidepressants do so. This suggests that drugs which specifically target the immune, endocrine and neurotransmitter systems may be more effective antidepressants.The preliminary clinical evidence that some non-steroidal anti-inflammatory drugs, such as the cyclooxygenase 2 inhibitor celecoxib, can enhance the response to standard antidepressant treatment is therefore considered and a critical assessment made of the possible limitations of such an approach to novel antidepressant development.
Defects in quantum ring to control high-harmonic spectrum
Authors: Fiordilino E. , Frusteri B.
Published: January 2017

The high-harmonic generation from a structured quantum ring (SQR) driven by an intense laser field is presented within the single active electron approximation. The spectrum is studied by varying the symmetry of the physical system. The standard SQR (six identical and equidistant dots in a ring) presents a 60° rotational symmetry, that in this work is broken, moving or changing only one potential hole. We find that careful designed breaking of the geometrical symmetry of the SQR opens the possibility of controlling the characteristics of the harmonic lines such as intensity and polarization. HHG analysis of the emission spectrum performed through a Morlet wavelet, shows that the high-frequency emission occurs during short time intervals.
Whither Rural China? A Case Study of Gao Village
Authors: Gao Mobo
Published: January 2017

This case study of Gao Village has two aims: to provide an update on Gao Village since 1997, when Gao Village (Gao 1999, 2014) leaves off, and to ponder the future direction of rural China. The article begins with an update on the development of Gao Village from the late 1990s up to 2015, dealing with several major thematic topics such as demography, family and marriage, living standards, education and health care. Using empirical evidence gathered during several years of fieldwork as background, the paper then moves on to discuss the future direction of rural China. This second part covers the current intellectual and policy debate on two crucial issues: land ownership and urbanization. The paper concludes that the Chinese state is still undecided on a grand narrative: whether to travel further in the direction of full-scale capitalism or whether to retain some kind of socialist collectivism.
Economics of zoonoses surveillance in a ‘One Health’ context: an assessment of Campylobacter surveillance in Switzerland
Authors: BABO MARTINS S. , RUSHTON J. , STÄRK K. D. C.
Published: January 2017

Cross-sectorial surveillance and general collaboration between the animal and the public health sectors are increasingly recognized as needed to better manage the impacts of zoonoses. From 2009, the Swiss established a Campylobacter mitigation system that includes human and poultry surveillance data-sharing within a multi-sectorial platform, in a ‘One Health’ approach. The objective of this study was to explore the economics of this cross-sectorial approach, including surveillance and triggered interventions. Costs and benefits of the One Health and of the uni-sectorial approach to Campylobacter surveillance were identified using an economic assessment framework developed earlier. Cost information of surveillance activities and interventions was gathered and disability-adjusted life years (DALYs) associated with the disease estimated for 2008 and 2013. In the first 5 years of this One Health approach to Campylobacter mitigation, surveillance contributed with information mainly used to perform risk assessments, monitor trends and shape research efforts on Campylobacter. There was an increase in costs associated with the mitigation activities following integration, due mainly to the allocation of additional resources to research and implementation of poultry surveillance. The overall burden of campylobacteriosis increased by 3·4–8·8% to 1751–2852 DALYs in 2013. In the timing of the analysis, added value associated with this cross-sectorial approach to surveillance of Campylobacter in the country was likely generated through non-measurable benefits such as intellectual capital and social capital.
Matrine induces RIP3-dependent necroptosis in cholangiocarcinoma cells
Authors: Xu Beibei , Xu Minying , Tian Yuan , Yu Qiang , Zhao Yujie , Chen Xiong , Mi Panying , Cao Hanwei , Zhang Bing , Song Gang , Zhan Yan-yan , Hu Tianhui
Published: January 2017

The development of acquired resistance to pro-apoptotic antitumor agents is a major impediment to the cure of cholangiocarcinoma (CCA). Antitumor drugs inducing non-apoptotic cell death are considered as a new approach to overcome such drug resistance. Here, we reported for the first time that matrine-induced necroptosis in CCA cell lines, differing from its classical role to induce apoptosis in many other kinds of cancer cells. CCA cells under matrine treatment exhibited typical necrosis-like but not apoptotic morphologic change. These matrine-induced morphologic change and cell death in CCA cells were greatly attenuated by necroptosis inhibitor necrostatin-1, but not apoptosis inhibitor z-VAD-fmk. Unlike many cancer cells with negative receptor-interacting protein 3 (RIP3) expression, moderate expression of RIP3 in CCA cells was observed and was required for matrine to induce necroptosis, which was switched to apoptosis after knocking down endogenous RIP3. Moreover, matrine could increase RIP3 expression level, which may facilitate the necroptosis process. Translocation of mixed lineage kinase-domain like (MLKL) from cytoplasm to plasma membrane as a downstream event of RIP3, as well as the increased production of reactive oxygen species (ROS) by RIP3/MLKL, was critical for matrine to induce necroptosis. In clinical study, we found RIP3 was lower but still moderately expressed in most CCA tissue samples compared with adjacent normal tissues. Taken together, we identified matrine as a necroptosis inducer in CCA by enhancing RIP3 expression and the following RIP3/MLKL/ROS signaling pathway, which provided new individualized strategies based on RIP3 expression to overcome chemoresistance in CCA therapy.
A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation
Authors: Delile Julien , Herrmann Matthieu , Peyriéras Nadine , Doursat René
Published: January 2017

The study of multicellular development is grounded in two complementary domains: cell biomechanics, which examines how physical forces shape the embryo, and genetic regulation and molecular signalling, which concern how cells determine their states and behaviours. Integrating both sides into a unified framework is crucial to fully understand the self-organized dynamics of morphogenesis. Here we introduce MecaGen, an integrative modelling platform enabling the hypothesis-driven simulation of these dual processes via the coupling between mechanical and chemical variables. Our approach relies upon a minimal ‘cell behaviour ontology’ comprising mesenchymal and epithelial cells and their associated behaviours. MecaGen enables the specification and control of complex collective movements in 3D space through a biologically relevant gene regulatory network and parameter space exploration. Three case studies investigating pattern formation, epithelial differentiation and tissue tectonics in zebrafish early embryogenesis, the latter with quantitative comparison to live imaging data, demonstrate the validity and usefulness of our framework.
mTORC1 inhibition in cancer cells protects from glutaminolysis-mediated apoptosis during nutrient limitation
Authors: Villar Victor H. , Nguyen Tra Ly , Delcroix Vanessa , Terés Silvia , Bouchecareilh Marion , Salin Bénédicte , Bodineau Clément , Vacher Pierre , Priault Muriel , Soubeyran Pierre , Durán Raúl V.
Published: January 2017

A master coordinator of cell growth, mTORC1 is activated by different metabolic inputs, particularly the metabolism of glutamine (glutaminolysis), to control a vast range of cellular processes, including autophagy. As a well-recognized tumour promoter, inhibitors of mTORC1 such as rapamycin have been approved as anti-cancer agents, but their overall outcome in patients is rather poor. Here we show that mTORC1 also presents tumour suppressor features in conditions of nutrient restrictions. Thus, the activation of mTORC1 by glutaminolysis during nutritional imbalance inhibits autophagy and induces apoptosis in cancer cells. Importantly, rapamycin treatment reactivates autophagy and prevents the mTORC1-mediated apoptosis. We also observe that the ability of mTORC1 to activate apoptosis is mediated by the adaptor protein p62. Thus, the mTORC1-mediated upregulation of p62 during nutrient imbalance induces the binding of p62 to caspase 8 and the subsequent activation of the caspase pathway. Our data highlight the role of autophagy as a survival mechanism upon rapamycin treatment.
Sec3 promotes the initial binary t-SNARE complex assembly and membrane fusion
Authors: Yue Peng , Zhang Yubo , Mei Kunrong , Wang Shaoxiao , Lesigang Johannes , Zhu Yueyao , Dong Gang , Guo Wei
Published: January 2017

The soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (SNAREs) constitute the core machinery for membrane fusion during eukaryotic cell vesicular trafficking. However, how the assembly of the SNARE complex is initiated is unknown. Here we report that Sec3, a component of the exocyst complex that mediates vesicle tethering during exocytosis, directly interacts with the t-SNARE protein Sso2. This interaction promotes the formation of an Sso2-Sec9 ‘binary’ t-SNARE complex, the early rate-limiting step in SNARE complex assembly, and stimulates membrane fusion. The crystal structure of the Sec3-Sso2 complex suggests that Sec3 binding induces conformational changes of Sso2 that are crucial for the relief of its auto-inhibition. Interestingly, specific disruption of the Sec3–Sso2 interaction in cells blocks exocytosis without affecting the function of Sec3 in vesicle tethering. Our study reveals an activation mechanism for SNARE complex assembly, and uncovers a role of the exocyst in promoting membrane fusion in addition to vesicle tethering.
Property database for single-element doping in ZnO obtained by automated first-principles calculations
Authors: Yim Kanghoon , Lee Joohee , Lee Dongheon , Lee Miso , Cho Eunae , Lee Hyo Sug , Nahm Ho-Hyun , Han Seungwu
Published: January 2017

Throughout the past decades, doped-ZnO has been widely used in various optical, electrical, magnetic, and energy devices. While almost every element in the Periodic Table was doped in ZnO, the systematic computational study is still limited to a small number of dopants, which may hinder a firm understanding of experimental observations. In this report, we systematically calculate the single-element doping property of ZnO using first-principles calculations. We develop an automation code that enables efficient and reliable high-throughput calculations on thousands of possible dopant configurations. As a result, we obtain formation-energy diagrams for total 61 dopants, ranging from Li to Bi. Furthermore, we evaluate each dopant in terms of n-type/p-type behaviors by identifying the major dopant configurations and calculating carrier concentrations at a specific dopant density. The existence of localized magnetic moment is also examined for spintronic applications. The property database obtained here for doped ZnO will serve as a useful reference in engineering the material property of ZnO through doping.
Up-regulation of syncytin-1 contributes to TNF-α-enhanced fusion between OSCC and HUVECs partly via Wnt/β-catenin-dependent pathway
Authors: Yan Ting-Lin , Wang Meng , Xu Zhi , Huang Chun-Ming , Zhou Xiao-Cheng , Jiang Er-Hui , Zhao Xiao-Ping , Song Yong , Song Kai , Shao Zhe , Liu Ke , Shang Zheng-Jun
Published: January 2017

Accumulating evidence implies that cell fusion is one of the driving forces of cancer invasion and metastasis. However, considerably less is still known about the triggering factors and underlying mechanisms associated with cancer-host cell fusion, particularly in inflammatory tumor microenvironment. In this study, we confirmed that inflammatory factor TNF-α could enhance fusion between squamous cell carcinoma cells 9 (SCC-9) and human umbilical vein endothelial cells (HUVEC). Further study revealed that TNF-α could promote up-regulation of syncytin-1 in SCC-9 and its receptor neutral amino acid transporter type 2 (ASCT-2) in HUVEC. Syncytin-1 acted as an important downstream effector in TNF-α-enhanced cancer-endothelial cell fusion. TNF-α treatment also led to the activation of Wnt/β-catenin signal pathway in SCC-9. The activation of Wnt/β-catenin signal pathway was closely associated with the up-regulation of syncytin-1 in SCC-9 and increased fusion between SCC-9 and HUVEC while blocking of Wnt/β-catenin signal pathway resulted in the corresponding down-regulation of syncytin-1 accompanied by sharp decrease of cancer-endothelial cell fusion. Taking together, our results suggest that Wnt/β-catenin signal pathway activation-dependent up-regulation of syncytin-1 contributes to the pro-inflammatory factor TNF-α-enhanced fusion between oral squamous cell carcinoma cells and endothelial cells.
Serum levels of galectin-1, galectin-3, and galectin-9 are associated with large artery atherosclerotic stroke
Authors: He Xin-Wei , Li Wei-Ling , Li Cai , Liu Peng , Shen Yu-Guang , Zhu Min , Jin Xiao-Ping
Published: January 2017

The aim of this study was to assess the expression patterns of serum galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-3 binding protein (Gal-3BP) and their associations with stroke outcome in large artery atherosclerotic (LAA) stroke. The serum levels of Gal-1, Gal-3, Gal-9, and Gal-3BP were measured by ELISA in 130 patients with LAA stroke and 130 age- and sex-matched controls. Serum samples were collected from the patients on day 1, day 6, and in the 4th week after ischaemic stroke (IS). An unfavourable outcome was defined as a modified Rankin Scale score of >2 on day 90 after IS. Our results indicated that the Gal-3 and Gal-9 levels were higher in patients with LAA stroke than in controls. A higher Gal-3 level was independently associated with an unfavourable outcome both on day 1 and day 6 after IS. In addition, Gal-9 and Gal-1 levels were upregulated on day 6 and in the 4th week after IS, respectively. For Gal-3BP, no difference was detected between patients and controls and no predictive value was found in patients. In conclusion, these findings suggest that the serum levels of Gal-1, Gal-3, and Gal-9 may be associated with LAA stroke.
Potentially high-risk medication categories and unplanned hospitalizations: a case–time–control study
Authors: Lin Chih-Wan , Wen Yu-Wen , Chen Liang-Kung , Hsiao Fei-Yuan
Published: January 2017

Empirical data of medication-related hospitalization are very limited. We aimed to investigate the associations between 12 high risk medication categories (diabetic agents, diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, antiplatelets, antihypertensives, antiarrhythmics, anticonvulsants, antipsychotics, antidepressants, benzodiazepine (BZD)/Z-hypnotics, and narcotics) and unplanned hospitalizations. A population-based case–time–control study was performed using Taiwan’s National Health Insurance Research Database. Patients who experienced an unplanned hospitalization (index visit) were identified as index subjects and matched to a randomly selected reference visit within users of a specific category of high-risk medication. An unplanned hospitalization was defined as a hospital admission immediately after an emergency department visit. Discordant exposures to the high-risk medication during the case period (1–14 days before the visit) and the control period (366–379 days before the visit) were examined in both index and reference visits. Antipsychotics was associated with the highest risk of unplanned hospitalizations (adjusted OR: 1.54, 95% CI [1.37–1.73]), followed by NSAIDs (1.50, [1.44–1.56]), anticonvulsants (1.34, [1.10–1.64]), diuretics (1.24, [1.15–1.33]), BZD/Z-hypnotics (1.23, [1.16–1.31]), antidepressants (1.17, [1.05–1.31]) and antiplatelets (1.16, [1.07–1.26]). NSAIDs and narcotics were associated with the highest risks of unplanned hospitalizations with a length of stay ≥10 days. These medication categories should be targeted for clinical and policy interventions.
Quantitative 3D investigation of Neuronal network in mouse spinal cord model
Authors: Bukreeva I. , Campi G. , Fratini M. , Spanò R. , Bucci D. , Battaglia G. , Giove F. , Bravin A. , Uccelli A. , Venturi C. , Mastrogiacomo M. , Cedola A.
Published: January 2017

The investigation of the neuronal network in mouse spinal cord models represents the basis for the research on neurodegenerative diseases. In this framework, the quantitative analysis of the single elements in different districts is a crucial task. However, conventional 3D imaging techniques do not have enough spatial resolution and contrast to allow for a quantitative investigation of the neuronal network. Exploiting the high coherence and the high flux of synchrotron sources, X-ray Phase-Contrast multiscale-Tomography allows for the 3D investigation of the neuronal microanatomy without any aggressive sample preparation or sectioning. We investigated healthy-mouse neuronal architecture by imaging the 3D distribution of the neuronal-network with a spatial resolution of 640 nm. The high quality of the obtained images enables a quantitative study of the neuronal structure on a subject-by-subject basis. We developed and applied a spatial statistical analysis on the motor neurons to obtain quantitative information on their 3D arrangement in the healthy-mice spinal cord. Then, we compared the obtained results with a mouse model of multiple sclerosis. Our approach paves the way to the creation of a “database” for the characterization of the neuronal network main features for a comparative investigation of neurodegenerative diseases and therapies.
The kinetochore-dependent and -independent formation of the CDC20-MAD2 complex and its functions in HeLa cells
Authors: Li Jianquan , Dang Nanmao , Wood Daniel James , Huang Jun-Yong
Published: January 2017

The mitotic checkpoint complex (MCC) is formed from two sub-complexes of CDC20-MAD2 and BUBR1-BUB3, and current models suggest that it is generated exclusively by the kinetochores after nuclear envelope breakdown (NEBD). However, neither sub-complex has been visualised in vivo, and when and where they are formed during the cell cycle and their response to different SAC conditions remains elusive. Using single cell analysis in HeLa cells, we show that the CDC20-MAD2 complex is cell cycle regulated with a “Bell” shaped profile and peaks at prometaphase. Its formation begins in early prophase before NEBD when the SAC has not been activated. The complex prevents the premature degradation of cyclin B1. Tpr, a component of the NPCs (nuclear pore complexes), facilitates the formation of this prophase form of the CDC20-MAD2 complex but is inactive later in mitosis. Thus, we demonstrate that the CDC20-MAD2 complex could also be formed independently of the SAC. Moreover, in prolonged arrest caused by nocodazole treatment, the overall levels of the CDC20-MAD2 complex are gradually, but significantly, reduced and this is associated with lower levels of cyclin B1, which brings a new insight into the mechanism of mitotic “slippage” of the arrested cells.
Facile synthesis of high strength hot-water wood extract films with oxygen-barrier performance
Authors: Chen Ge-Gu , Fu Gen-Que , Wang Xiao-Jun , Gong Xiao-Dong , Niu Ya-Shuai , Peng Feng , Yao Chun-Li , Sun Run-Cang
Published: January 2017

Biobased nanocomposite films for food packaging with high mechanical strength and good oxygen-barrier performance were developed using a hot-water wood extract (HWE). In this work, a facile approach to produce HWE/montmorillonite (MMT) based nanocomposite films with excellent physical properties is described. The focus of this study was to determine the effects of the MMT content on the structure and mechanical properties of nanocomposites and the effects of carboxymethyl cellulose (CMC) on the physical properties of the HWE-MMT films. The experimental results suggested that the intercalation of HWE and CMC in montmorillonite could produce compact, robust films with a nacre-like structure and multifunctional characteristics. This results of this study showed that the mechanical properties of the film designated FCMC0.05(91.5 MPa) were dramatically enhanced because the proportion of HWE, MMT and CMC was 1:1.5:0.05. In addition, the optimized films exhibited an oxygen permeability below 2.0 cm3μm/day·m2·kPa, as well as good thermal stability due to the small amount of CMC. These results provide a comprehensive understanding for further development of high-performance nanocomposites which are based on natural polymers (HWE) and assembled layered clays (MMT). These films offer great potential in the field of sustainable packaging.
Cortical mechanisms for afterimage formation: evidence from interocular grouping
Authors: Dong Bo , Holm Linus , Bao Min
Published: January 2017

Whether the retinal process alone or retinal and cortical processes jointly determine afterimage (AI) formation has long been debated. Based on the retinal rebound responses, recent work proposes that afterimage signals are exclusively generated in the retina, although later modified by cortical mechanisms. We tested this notion with the method of “indirect proof”. Each eye was presented with a 2-by-2 checkerboard of horizontal and vertical grating patches. Each corresponding patch of the two checkerboards was perpendicular to each other, which produces binocular rivalry, and can generate percepts ranging from complete interocular grouping to either monocular pattern. The monocular percepts became more frequent with higher contrast. Due to adaptation, the visual system is less sensitive during the AIs than during the inductions with AI-similar contrast. If the retina is the only origin of AIs, comparable contrast appearance would require stronger retinal signals in the AIs than in the inductions, thus leading to more frequent monocular percepts in the AIs than in the inductions. Surprisingly, subjects saw the fully coherent stripes significantly more often in AIs. Our results thus contradict the retinal generation notion, and suggest that in addition to the retina, cortex is directly involved in the generation of AI signals.
Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella
Authors: Xie Shuyu , Yang Fei , Tao Yanfei , Chen Dongmei , Qu Wei , Huang Lingli , Liu Zhenli , Pan Yuanhu , Yuan Zonghui
Published: January 2017

Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06–37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from −8.1 to −24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment.