bluuebunny/crossref_metadata_2025 huggingface dataset:
Aromatic versus Aliphatic: Hydrogen Bonding Pattern in Chain‐Extended High‐Performance Polyurea
Authors: Iqbal Nahid , Tripathi Manorama , Parthasarathy Surekha , Kumar Devendra , Roy Prasun K.
Published: February 2018

Polyurea, a reaction product of functional isocyanates and amines, is finding increasing application in the field of protective coatings, especially for retrofitting purposes. The properties of polyurea can be tuned by the prudent choice of reactants, specifically chain extenders. In this work, an experimental study into the consequences of chain extension of a representative polyurea formulation with different type of chain extenders (aromatic and aliphatic) has been undertaken, with an aim to gain an insight into their role in improving properties. Rheological studies were performed to understand the effect of their inclusion on the processing conditions and quantification of the gelation time. Aromatic chain extenders are far more reactive than their aliphatic counterparts, which lead to significantly short ‘gel‐time’ as quantified by rheometry. The degree of H‐bonding was qualitatively established by the red‐shift associated with N−H and >C=O bands in the FTIR spectra of the polymer. Introduction of either type of chain extender lead to remarked processability of polyurea formulations through spray coating technique. An optimal aromatic: aliphatic chain extender ratio was found to result in optimal H‐bonding, which in turn reflected in terms of mechanical properties. Dynamic studies were performed and all formulations were found to exhibit sub‐ambient Tg which is appreciably affected by the type of chain extender used. Higher aromatic: aliphatic chain extender ratio was found to result in higher storage modulus and lower dissipation potential.
Literature review of flexibility attributes: A flexibility framework for software developing organization
Authors: Nurdiani Indira , Börstler Jürgen , Fricker Samuel A.
Published: February 2018

Software developing organizations strive to achieve flexibility to maintain a competitive advantage. There is no common understanding of what characterize flexibility for a software organization beyond the scope of the software product. Without a common understanding, it is difficult to evaluate the degrees of flexibility of software development approaches. The aim of this literature review is to collect attributes that characterize flexibility. The collected attributes are consolidated into a flexibility framework with 3 main attributes: properties of change, flexibility perspectives, and flexibility enablers. The resulting flexibility framework is then used to evaluate Agile and Lean practices. The evaluation shows that Agile and Lean practices address many flexibility attributes. However, some attributes are not addressed, such as infrastructure flexibility and strategic flexibility. On the basis of our evaluation, the classifications of flexibility attributes that we present in this paper could be used to aid software organization flexibility evaluation.
Influence of Ionic Liquids on the Morphology of Corn Flour/Polyester Mixtures
Authors: Polaskova Martina , Cermak Roman , Polasek Zdenek , Commereuc Sophie , Verney Vincent , Costa Gomes Margarida F. , Padua Agilio A. H.
Published: February 2018

Polymer mixtures based on native corn flour and synthetic biodegradable polyester are prepared in one processing step. Melt mixing is performed in a laboratory micro‐compounder. Starch contained in native corn flour is plasticized either by commonly used glycerol/water mixture or by two types of ionic liquids, 1‐allyl‐3‐methylimidazolium chloride, and 1‐butyl‐3‐methylimidazolium chloride. Efficiency of plasticizers on the compatibility of native corn flour with polyester and starch plasticizing ability is evaluated and compared. The structure of mixtures is examined using scanning electron microscopy and wide‐angle X‐ray scattering. It is found that the plasticizer applied has a crucial effect on the resulting morphology. Both ionic liquids show a better plasticizing effect on starch compared to the traditional glycerol/water plasticizer.
An experimental study on shear capacity of interfaces in recycled aggregate concrete
Authors: Waseem Shakeel Ahmad , Singh Bhupinder
Published: February 2018

Forty‐eight initially uncracked push‐off specimens were used for the investigation of the interface shear strength of natural and recycled coarse aggregate concrete. The parameters varied in the push‐off tests were the recycled aggregate replacement level (0, 50, and 100%), the clamping force across the shear‐transfer plane and the concrete grade (normal‐ and medium‐strength). The inclined cracks crossing the shear plane, noted before the development of shear cracks, were indicative of the truss like action for resisting shear in push‐off specimens. An analytical approach based on the truss modeling of the force system within the push‐off specimens using the method initially proposed by Mattock and Hawkins has been used for prediction of interface cracking stress of both the concrete types. Calibration of the proposed analytical procedure has been done with the help of the experimental results of the tested push‐off specimens. Using the experimental results as well as comparable results from the literature, a shear‐friction regression equation accounting for the effect of concrete grade, normal force on the shear plane and the recycled coarse aggregate replacement level has been proposed for shear strength.
From Aqueous Dispersions to Functional Materials: Capillarity and Electrostatic Adhesion
Authors: Galembeck Fernando
Published: February 2018

The author was first acquainted with polymer lattices as model particles for studying sedimentation phenomena, evolving towards the elucidation of synthetic and natural latex heterogeneity and microchemistry. This brought new elements to understand the remarkable mechanical properties of natural rubber, leading to the latex route for making nanocomposites. These materials show exceptional properties that are largely due to electrostatic adhesion, a concept that had been previously presented by Deryagin but was later abandoned. Electrostatic adhesion is the outcome of ion partition and self‐assembly within drying aqueous dispersions, producing co‐existing domains with opposite charges. Their examination allowed several experimental observations leading to the proposal of mechanisms to explain hitherto challenging electrostatic phenomena shown by solids and liquids. Water plays a decisive role in all the different phenomena described in this account.
Radical Empathy in Teaching
Authors: Jordan Judith V. , Schwartz Harriet L.
Published: February 2018

Radical empathy positions us to engage and connect with our students while also staying grounded in our role and responsibilities as educators.
Cover Image, Volume 8, Issue 2
Authors: Hu Xixi , Zhou Linsen , Xie Daiqian
Published: February 2018

The cover image, by Xixi Hu et al., is based on the Advanced Review State‐to‐state photodissociation dynamics of the water molecule, DOI: 10.1002/wcms.1350.

image
The Long-Term Effects of the Deepwater Horizon Oil Spill on Women’s Depression and Mental Distress
Authors: Rung Ariane Lisann , Oral Evrim , Fontham Elizabeth , Harrington Daniel J. , Trapido Edward J. , Peters Edward S.
Published: February 2018

Objective

The purpose of the study is to describe changes in mental health among women following an oil spill and to examine their association with the Deepwater Horizon oil spill (DHOS).

Methods

The Women and Their Children’s Health study followed 2038 women in Louisiana after the DHOS. Subjects were interviewed in 2012-2014 and 2014-2016. Oil spill exposure was characterized using survey items about economic and physical exposures. Outcomes were depressive symptoms and mental distress.

Results

After adjustment for relevant demographics, depressive symptoms increased over 2 time points following the DHOS, whereas symptoms of mental distress decreased. For every year increase in time since the DHOS, the rate ratio for depressive symptoms increased by a factor of 1.08. In contrast, the rate ratio for mental distress decreased by a factor of 0.97. In addition, initial associations between economic and physical exposure to the DHOS persisted up to 6 years after the spill; women who were more highly exposed experienced higher levels of depressive symptoms (rate ratios ranged from 1.08 to 1.11) and mental distress (rate ratios from 1.05 to 1.11) at each time point than women who were less exposed.

Conclusion

A better understanding of recovery patterns following an oil spill can help direct critical mental health response efforts. (Disaster Med Public Health Preparedness. 2019;13:183–190)
Diversity of cnidarians and cycloneuralians in the Fortunian (early Cambrian) Kuanchuanpu Formation at Zhangjiagou, South China
Authors: Shao Tiequan , Tang Hanhua , Liu Yunhuan , Waloszek Dieter , Maas Andreas , Zhang Huaqiao
Published: February 2018

The latest discovery of microfossils from the lower Cambrian (Fortunian Stage) Zhangjiagou Lagerstätte in South China are presented. This lagerstätte is rich in exceptionally preserved microfossils, including embryos ofOlivooides multisulcatus,Olivooides mirabilis, andPseudooides prima; hatched stages ofO.multisulcatus,O.mirabilis,Hexaconularia sichuanensis, andQuadrapyrgites quadratacris; and cycloneuralians represented byEopriapulites sphinx. The largest known fragment ofO.mirabilisimplies that its adult length can be more than 9.0 mm with at least 50 annuli, and the longest known specimen ofQ.quadratacrishas at least 18 annuli. These unusually large specimens refute the non-feeding larvae hypothesis forOlivooidesandQuadrapyrgites.

Based on the current material, it is inferred that (1) early cnidarians have a high diversity in the Fortunian Stage; (2)P.primamight represent the embryonic stages ofH.sichuanensis; (3) adults ofOlivooidesandQuadrapyrgitesmay have reached centimeter-scale dimensions with more than 50 annuli; (4)OlivooidesandQuadrapyrgitesmay be better interpreted as coronate scyphozoans; (5) cycloneuralians also had a high diversity in the Zhangjiagou Lagerstätte; and (6) cycloneuralians might have originally been part of the early Cambrian meiofauna rather than belonging to the macrobenthos. Such ancestral cycloneuralians might have beenEopriapulites-like, possessing pentaradially symmetric, backward pointing, and internally hollow introvert scalids used as locomotory devices.
The Age of the ‘Anosovka-Tel’manskaya Culture’ and the Issue of a Late Streletskian at Kostёnki 11, SW Russia
Authors: Dinnis Rob , Bessudnov Alexander A. , Reynolds Natasha , Douka Katerina , Dudin Alexander E. , Khlopachev Gennady A. , Sablin Mikhail V. , Sinitsyn Andrei A. , Higham Thomas F.G.
Published: February 2018

Triangular, concave-base ‘Streletskian points’ are documented in several assemblages from the Kostёnki complex of Upper Palaeolithic sites in south-western Russia. Some of these assemblages have been argued to evidence very early modern human occupation of Eastern Europe. However, Streletskian points are also recorded from younger contexts, notably at Kostёnki 11, where examples are attributed both to Layer V and the stratigraphically higher Layer III. The apparent relatively young age of Layer III has led some to view it as the latest manifestation of the Streletskian, although its assemblage has also been compared to the non-Streletskian Layer I of Kostёnki 8, with the two described together as the Anosovka-Tel’manskaya Culture.

Radiocarbon dates of 24–23,000 bp (c. 28,500–27,000 cal bp) for a wolf burial associated with Layer III of Kostёnki 11 confirm the layer as younger than other Streletskian assemblages at Kostёnki. New radiocarbon dates for Kostёnki 8 Layer I show that the two layers are broadly contemporary, and that both are close in age to assemblages of Kostёnki’s (Late Gravettian) Kostёnki-Avdeevo Culture. In the light of these new radiocarbon dates the context of the Streletskian point from Kostёnki 11 Layer III is considered. Although firm conclusions are not possible, unresolved stratigraphic problems and the lack of technological context for this single artefact at the very least leave a question mark over its association with other material from the layer.
Identification of vitamin B12 deficiency in vegetarian Indians
Authors: Naik Sadanand , Mahalle Namita , Bhide Vijayshri
Published: February 2018

The prevalence of a sub-clinical vitamin B12 deficiency in the vegetarians is high. Total serum vitamin B12 concentration alone does not reliably reflect vitamin B12 status. Holotranscobalamin (holo-TC) II is a bioactive B12 fraction promoting specific uptake of B12 by cells and the circulating concentration reflects the intake of B12, whereas total homocysteine (tHcy) indicates the metabolic ability. In this study, we investigated the diagnostic value of circulating holo-TC, B12, folate and homocysteine in vegetarians who were at risk of B12 deficiency. B12-related biomarkers were measured in 119 young, healthy graduate vegetarians. None was folate deficient. As per reported definition, half were B12 deficient; 70 % of males and 50 % of females had low plasma holo-TC concentrations; and 92 % of males and half of females had hyperhomocysteinaemia. None had any clinical signs of B12 deficiency. Receiver operating characteristic curve analysis demonstrated similar AUC at the B12 concentration of 100 and 150 pmol/l when holo-TC (0·777 and 0·784) and homocysteine (0·924 and 0·928) were used as variables. Cut-off value of 100 pmol/l resulted in the highest sensitivity of 77·78 % and specificity of 71·05 % with a predictive value of 19·6 pmol/l for holo-TC and a sensitivity of 82·72 % and specificity of 89·7 % with a predictive value of 21·7 µmol/l for homocysteine. The combination of B12, holo-TC and tHcy improves the diagnostic accuracy at these cut-offs, and we suggest that for the young Indian vegetarians the cut-off for plasma B12 and holotrancobalamin is 100 pmol/l and 19·6 pmol/l, respectively, and for homocysteine it is 17·6 (females) and 27 µmol/l (males) for identifying B12 deficiency.
Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms
Authors: Ferri J. , Ford J. M. , Roach B. J. , Turner J. A. , van Erp T. G. , Voyvodic J. , Preda A. , Belger A. , Bustillo J. , O'Leary D. , Mueller B. A. , Lim K. O. , McEwen S. C. , Calhoun V. D. , Diaz M. , Glover G. , Greve D. , Wible C. G. , Vaidya J. G. , Potkin S. G. , Mathalon D. H.
Published: February 2018

Background

Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.

Method

Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.

Results

HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.

Conclusions

Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Cost-utility analysis of antiviral use under pandemic influenza using a novel approach – linking pharmacology, epidemiology and heath economics
Authors: Wu D. B. C. , Chaiyakunapruk N. , Pratoomsoot C. , Lee K. K. C. , Chong H. Y. , Nelson R. E. , Smith P. F. , Kirkpatrick C.M. , Kamal M. A. , Nieforth K. , Dall G. , Toovey S. , Kong D. C. M. , Kamauu A. , Rayner C. R.
Published: February 2018

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
Hydrocarbons in soil and meltwater stream sediments near Artigas Antarctic Research Station: origin, sources and levels
Authors: Rodríguez Carolina , Iglesias Karen , Bícego Márcia C. , Taniguchi Satie , Sasaki Silvio Tarou , Kandratavicius Noelia , Bueno Carolina , Brugnoli Ernesto , Venturini Natalia
Published: February 2018

Aliphatic and polycyclic aromatic hydrocarbons (AHs and PAHs) were investigated in soil and meltwater stream sediments near the Uruguayan Artigas Research Station (BCAA). Gas chromatography with flame ionization detection and gas chromatography mass spectrometry were used to determine the composition of AHs and PAHs, respectively. Total AH concentrations were in the range 0.57–2333 µg g-1, while total PAH concentrations were in the range 1.36–51 650 ng g-1. Based on AH and PAH concentrations, sites in the service area and next to the boat storeroom are highly contaminated, while the other sites sampled have moderate to low contamination levels or are not impacted. High unresolved complex mixture concentrations indicate the occurrence of previous petrogenic contamination, but the dominance of low molecular weight and alkyl PAHs indicate recent oil introductions. Anthropogenic hydrocarbons dominate and are related to diesel fuel and organic residue combustion, fuel storage and boat traffic. Petrogenic contamination is relatively high, as at other Antarctic stations, but is restricted to the boat storeroom and the service area where the incinerator, the generator room and fuel tanks are located. Improvements made in fuel management procedures and the dismantling of the old fuel tanks will reduce the risk of diesel leaks and their impact on the environment near the BCAA. This study provides reference information for future environmental monitoring.
Non-linear electrical modeling of MASMOS structure to design power amplifiers for 4G applications
Authors: Simbélie Frédérique , Laurent Sylvain , Medrel Pierre , Prigent Michel , Regis Myrianne , Creveuil Yann , Quéré Raymond
Published: February 2018

This paper presents the characterization and modeling process of MASMOS structures by means of a classical compact three-port electrical non-linear model approach. From DC andS-parameters measurements, a large signal model (LSM) has been developed for two different MASMOS structures. The proposed LSM and associated modeling approach have been validated through load pull measurements with different harmonic load conditions. Then, generic multi-tone measurements have been carried out making use of an innovative test bench to quantify linearity performances of MASMOS structures. The model is used in a power amplifiers design flow for LTE applications and is expected to allow a significant reduction of simulation time, compared with technological-oriented model as BSIM3.
Offspring birth weight and cardiovascular mortality among parents: the role of cardiovascular risk factors
Authors: Shaikh F. , Kjøllesdal M. K. , Naess Ø.
Published: February 2018

An inverse association between offspring birth weight (BW) and higher risk of parental cardiovascular disease (CVD) mortality and morbidity has been reported. Shared environmental, genetic and intrauterine factors may be responsible for explaining these associations. We studied the role of parental CVD risk factors in the association between offspring BW and CVD mortality among mothers and fathers. All births registered in Medical Birth Registry Norway (1967–2012) were linked to three health surveys, National Educational Registry and Cause of Death Registry. Number of births with information of parental CVD risk factors available for the analyses was 1,006,557 (520,670 for mothers and 485,887 for fathers). Cox proportional hazards regression models were used, following CVD deaths in parents from 1974 to 2012. An inverse association between offspring BW and CVD mortality was observed among both parents: hazard ratio 1.60 (1.44–1.75) for mothers and 1.16 (1.10–1.23) for fathers. Among mothers, adjustment for smoking, triglycerides and diabetes reduced the risk to 1.36 (1.25–1.52), 1.57 (1.43–1.73) and 1.58 (1.43–1.79), respectively. Adjustment for diastolic blood pressure (DBP) and systolic blood pressure (SBP) both reduced the risk to 1.53 (1.37–1.66). Among fathers, adjustments for smoking, DBP, SBP reduced the risk to 1.08 (1.02–1.15), 1.13 (1.06–1.19) and 1.14 (1.08–1.22), respectively. Triglycerides and diabetes both reduced the risk to 1.15 (1.09–1.12). Our results indicate that shared environmental factors might be important in the association. A stronger association in mothers suggest that intrauterine factors also are at play.
CRISPR whole-genome screening identifies new necroptosis regulators and RIPK1 alternative splicing
Authors: Callow Marinella G. , Watanabe Colin , Wickliffe Katherine E. , Bainer Russell , Kummerfield Sarah , Weng Julie , Cuellar Trinna , Janakiraman Vasantharajan , Chen Honglin , Chih Ben , Liang Yuxin , Haley Benjamin , Newton Kim , Costa Michael R.
Published: February 2018

The necroptotic cell death pathway is a key component of human pathogen defense that can become aberrantly derepressed during tissue homeostasis to contribute to multiple types of tissue damage and disease. While formation of the necrosome kinase signaling complex containing RIPK1, RIPK3, and MLKL has been extensively characterized, additional mechanisms of its regulation and effector functions likely remain to be discovered. We screened 19,883 mouse protein-coding genes by CRISPR/Cas9-mediated gene knockout for resistance to cytokine-induced necroptosis and identified 112 regulators and mediators of necroptosis, including 59 new candidate pathway components with minimal or no effect on cell growth in the absence of necroptosis induction. Among these, we further characterized the function of PTBP1, an RNA binding protein whose activity is required to maintain RIPK1 protein abundance by regulating alternative splice-site selection.
EGFR-PI3K-PDK1 pathway regulates YAP signaling in hepatocellular carcinoma: the mechanism and its implications in targeted therapy
Authors: Xia Hongwei , Dai Xinyu , Yu Huangfei , Zhou Sheng , Fan Zhenghai , Wei Guoqing , Tang Qiulin , Gong Qiyong , Bi Feng
Published: February 2018

The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways. While YAP knockdown hardly affected the EGFR signaling. In addition, EGF could promote the proliferation of HCC cells in a YAP-independent manner. Combined targeting of YAP and EGFR signaling by simvastatin and the EGFR signaling inhibitors, including the EGFR tyrosine kinase inhibitor (TKI) gefitinib, the RAF inhibitor sorafenib and the MEK inhibitor trametinib, presented strong synergistic cytotoxicities in HCC cells. Therefore, the EGFR-PI3K-PDK1 pathway could activate the YAP signaling, and the activated EGFR signaling could promote the HCC cell growth in a YAP-independent manner. Combined use of FDA-approved inhibitors to simultaneously target YAP and EGFR signaling presented several promising therapeutic approaches for HCC treatment.
Long noncoding RNA MEG3 suppresses liver cancer cells growth through inhibiting β-catenin by activating PKM2 and inactivating PTEN
Authors: Zheng Qidi , Lin Zhuojia , Xu Jie , Lu Yanan , Meng Qiuyu , Wang Chen , Yang Yuxin , Xin Xiaoru , Li Xiaonan , Pu Hu , Gui Xin , Li Tianming , Xiong Wujun , Lu Dongdong
Published: February 2018

Maternally expressed gene 3 (MEG3) encodes an lncRNA which is suggested to function as a tumor suppressor and has been showed to involve in a variety of cancers. Herein, our findings demonstrate that MEG3 inhibits the malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, MEG3 promotes the expression and maturition of miR122 which targets PKM2. Therefore, MEG3 decreases the expression and nuclear location of PKM2 dependent on miR122. Furthermore, MEG3 also inhibits CyclinD1 and C-Myc via PKM2 in liver cancer cells. On the other hand, MEG3 promotes β-catenin degradation through ubiquitin–proteasome system dependent on PTEN. Strikingly, MEG3 inhibits β-catenin activity through PKM2 reduction and PTEN increase. Significantly, we also found that excessive β-catenin abrogated the effect of MEG3 in liver cancer. In conclusion, our study for the first time demonstrates that MEG3 acts as a tumor suppressor by negatively regulating the activity of the PKM2 and β-catenin signaling pathway in hepatocarcinogenesis and could provide potential therapeutic targets for the treatment of liver cancer.
Rhinovirus 3C protease suppresses apoptosis and triggers caspase-independent cell death
Authors: Lötzerich Mark , Roulin Pascal S. , Boucke Karin , Witte Robert , Georgiev Oleg , Greber Urs F.
Published: February 2018

Apoptosis and programmed necrosis (necroptosis) determine cell fate, and antagonize infection. Execution of these complementary death pathways involves the formation of receptor-interacting protein kinase 1 (RIPK1) containing complexes. RIPK1 binds to adaptor proteins, such as TRIF (Toll-IL-1 receptor-domain-containing-adaptor-inducing interferon-beta factor), FADD (Fas-associated-protein with death domain), NEMO (NF-κB regulatory subunit IKKγ), SQSTM1 (sequestosome 1/p62), or RIPK3 (receptor-interacting protein kinase 3), which are involved in RNA sensing, NF-κB signaling, autophagosome formation, apoptosis, and necroptosis. We report that a range of rhinoviruses impair apoptosis and necroptosis in epithelial cells late in infection. Unlike the double-strand (ds) RNA mimetic poly I:C (polyinosinic:polycytidylic acid), the exposure of dsRNA to toll-like receptor 3 (TLR3) in rhinovirus-infected cells did not lead to apoptosis execution. Accordingly, necroptosis and the production of ROS (reactive oxygen species) were not observed late in infection, when RIPK3 was absent. Instead, a virus-induced alternative necrotic cell death pathway proceeded, which led to membrane rupture, indicated by propidium iodide staining. The impairment of dsRNA-induced apoptosis late in infection was controlled by the viral 3C-protease (3Cpro), which disrupted RIPK1-TRIF/FADD /SQSTM1 immune-complexes. 3Cpro and 3C precursors were found to coimmuno-precipitate with RIPK1, cleaving the RIPK1 death-domain, and generating N-terminal RIPK1 fragments. The depletion of RIPK1 or chemical inhibition of its kinase at the N-terminus did not interfere with virus progeny formation or cell fate. The data show that rhinoviruses suppress apoptosis and necroptosis, and release progeny by an alternative cell death pathway, which is controlled by viral proteases modifying innate immune complexes.
Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer
Authors: Wen Yang-An , Xiong Xiaopeng , Zaytseva Yekaterina Y. , Napier Dana L. , Vallee Emma , Li Austin T. , Wang Chi , Weiss Heidi L. , Evers B. Mark , Gao Tianyan
Published: February 2018

Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2 decreased levels of fatty acids as a result of decreased expression of SREBP target genes required for lipid biosynthesis in colon cancer cells. Bioenergetic analysis revealed that silencing SREBP1 or SREBP2 expression reduced the mitochondrial respiration, glycolysis, as well as fatty acid oxidation indicating an alteration in cellular metabolism. Consequently, the rate of cell proliferation and the ability of cancer cells to form tumor spheroids in suspension culture were significantly decreased. Similar results were obtained in colon cancer cells in which the proteolytic activation of SREBP was blocked. Importantly, knockdown of either SREBP1 or SREBP2 inhibited xenograft tumor growth in vivo and decreased the expression of genes associated with cancer stem cells. Taken together, our findings establish the molecular basis of SREBP-dependent metabolic regulation and provide a rationale for targeting lipid biosynthesis as a promising approach in colon cancer treatment.
Knockout of zebrafish interleukin 7 receptor (IL7R) by the CRISPR/Cas9 system delays retinal neurodevelopment
Authors: Cai Shijiao , Chen Yang , Shang Yue , Cui Jianlin , Li Zongjin , Li Yuhao
Published: February 2018

Interleukin 7 receptor (il7r), a transmembrane receptor, belongs to the type I cytokine receptor family. Il7r is involved in the pathogenesis of neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown of il7r leads to delayed myelination, highlighting the potential role of il7r in the development of the nervous system. Zebrafish is an ideal model for the study of neurogenesis; moreover, the il7r gene is highly conserved between zebrafish and human. The aim of the present study was to investigate the novel function of il7r in neurogenesis. First, an il7r−/− homozygous mutant line was generated by clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. Second, the gross development of il7r−/− mutants revealed remarkably smaller eyes and delayed retinal neurodifferentiation. Third, microarray analysis revealed that genes associated with the phototransduction signalling pathway were strongly down-regulated in il7r−/− mutants. Finally, the results from behavioural tests indicated that visual function was impaired in il7r−/− mutant larvae. Overall, our data demonstrate that a lack of il7r retards the development of the retina. Thus, il7r is an essential molecule for maintaining normal retinal development in zebrafish.
High-performance graphdiyne-based electrochemical actuators
Authors: Lu Chao , Yang Ying , Wang Jian , Fu Ruoping , Zhao Xinxin , Zhao Lei , Ming Yue , Hu Ying , Lin Hongzhen , Tao Xiaoming , Li Yuliang , Chen Wei
Published: February 2018

Electrochemical actuators directly converting electrical energy to mechanical energy are critically important for artificial intelligence. However, their energy transduction efficiency is always lower than 1.0% because electrode materials lack active units in microstructure, and their assembly systems can hardly express the intrinsic properties. Here, we report a molecular-scale active graphdiyne-based electrochemical actuator with a high electro-mechanical transduction efficiency of up to 6.03%, exceeding that of the best-known piezoelectric ceramic, shape memory alloy and electroactive polymer reported before, and its energy density (11.5 kJ m−3) is comparable to that of mammalian skeletal muscle (~8 kJ m−3). Meanwhile, the actuator remains responsive at frequencies from 0.1 to 30 Hz with excellent cycling stability over 100,000 cycles. Furthermore, we verify the alkene–alkyne complex transition effect responsible for the high performance through in situ sum frequency generation spectroscopy. This discovery sheds light on our understanding of actuation mechanisms and will accelerate development of smart actuators.
Dynamic air/liquid pockets for guiding microscale flow
Authors: Hou Xu , Li Jianyu , Tesler Alexander B. , Yao Yuxing , Wang Miao , Min Lingli , Sheng Zhizhi , Aizenberg Joanna
Published: February 2018

Microscale flows of fluids are mainly guided either by solid matrices or by liquid–liquid interfaces. However, the solid matrices are plagued with persistent fouling problems, while liquid–liquid interfaces are limited to low-pressure applications. Here we report a dynamic liquid/solid/gas material containing both air and liquid pockets, which are formed by partially infiltrating a porous matrix with a functional liquid. Using detailed theoretical and experimental data, we show that the distribution of the air- and liquid-filled pores is responsive to pressure and enables the formation and instantaneous recovery of stable liquid–liquid interfaces that sustain a wide range of pressures and prevent channel contamination. This adaptive design is demonstrated for polymeric materials and extended to metal-based systems that can achieve unmatched mechanical and thermal stability. Our platform with its unique adaptive pressure and antifouling capabilities may offer potential solutions to flow control in microfluidics, medical devices, microscale synthesis, and biological assays.
Clove Bud Oil Modulates Pathogenicity Phenotypes of the Opportunistic Human Pathogen Pseudomonas aeruginosa
Authors: Haripriyan Jayalekshmi , Omanakuttan Athira , Menon Nitasha D. , Vanuopadath Muralidharan , Nair Sudarslal Sadasivan , Corriden Ross , Nair Bipin G. , Nizet Victor , Kumar Geetha B.
Published: February 2018

Earlier studies from our laboratory have demonstrated that clove bud oil (CBO) attenuates expression of certain virulence factors of Pseudomonas aeruginosa PAO1. Here, we probe more deeply into the effect of CBO on four pseudomonal proteases - elastase A, elastase B, protease IV and alkaline protease - each known to play key roles in disease pathogenesis. CBO inhibited the activity of these proteases present in the bacterial culture supernatant. Zymography studies indicated that these proteases can activate host matrix metalloproteases (MMPs) to establish infection, through conversion of pro-MMP-2 to active MMP-2. PAO1 is a predominant pathogen in burn wound infections and we show the modulatory effect of CBO on MMPs in an in vitro model of burn injury. Furthermore, CBO induced dose-dependent neutrophil extracellular trap formation in human neutrophils. CBO also increased the survival of C. elegans infected with PAO1, establishing an anti-infective role in a whole animal model of pathogenesis. LC-MS/MS analysis indicated that CBO treatment elicited a significant reduction of signalling molecules (Acyl-Homoserine-Lactone) involved in quorum sensing regulation. Our observations demonstrate that CBO attenuates key virulence mechanisms of this important human pathogen, while concomitantly enhancing host innate immunomodulatory functions, with potential implications for topical therapy against antibiotic-resistant infections.
Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets
Authors: Lempiäinen Harri , Brænne Ingrid , Michoel Tom , Tragante Vinicius , Vilne Baiba , Webb Tom R. , Kyriakou Theodosios , Eichner Johannes , Zeng Lingyao , Willenborg Christina , Franzen Oscar , Ruusalepp Arno , Goel Anuj , van der Laan Sander W. , Biegert Claudia , Hamby Stephen , Talukdar Husain A. , Foroughi Asl Hassan ,   CVgenes@target consortium, Dichgans Martin , Dreker Tobias , Graettinger Mira , Gribbon Philip , Kessler Thorsten , Malik Rainer , Prestel Matthias , Stiller Barbara , Schofield Christine , Pasterkamp Gerard , Watkins Hugh , Samani Nilesh J. , Wittenberger Timo , Erdmann Jeanette , Schunkert Heribert , Asselbergs Folkert W. , Björkegren Johan L. M.
Published: February 2018

Genome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these loci are largely unknown and an untapped resource to improve our understanding of CAD pathophysiology and identify potential therapeutic targets. Here, we prioritized 68 genes as the most likely causal genes at genome-wide significant loci identified by GWAS of CAD and examined their regulatory roles in 286 metabolic and vascular tissue gene-protein sub-networks (“modules”). The modules and genes within were scored for CAD druggability potential. The scoring enriched for targets of cardiometabolic drugs currently in clinical use and in-depth analysis of the top-scoring modules validated established and revealed novel target tissues, biological processes, and druggable targets. This study provides an unprecedented resource of tissue-defined gene–protein interactions directly affected by genetic variance in CAD risk loci.
Exogenous nitric oxide stimulates the odontogenic differentiation of rat dental pulp stem cells
Authors: Sonoda Soichiro , Mei Yu-feng , Atsuta Ikiru , Danjo Atsushi , Yamaza Haruyoshi , Hama Shion , Nishida Kento , Tang Ronghao , Kyumoto-Nakamura Yukari , Uehara Norihisa , Kukita Toshio , Nishimura Fusanori , Yamaza Takayoshi
Published: February 2018

Nitric oxide (NO) is thought to play a pivotal regulatory role in dental pulp tissues under both physiological and pathological conditions. However, little is known about the NO functions in dental pulp stem cells (DPSCs). We examined the direct actions of a spontaneous NO gas-releasing donor, NOC-18, on the odontogenic capacity of rat DPSCs (rDPSCs). In the presence of NOC-18, rDPSCs were transformed into odontoblast-like cells with long cytoplasmic processes and a polarized nucleus. NOC-18 treatment increased alkaline phosphatase activity and enhanced dentin-like mineralized tissue formation and the expression levels of several odontoblast-specific genes, such as runt related factor 2, dentin matrix protein 1 and dentin sialophosphoprotein, in rDPSCs. In contrast, carboxy-PTIO, a NO scavenger, completely suppressed the odontogenic capacity of rDPSCs. This NO-promoted odontogenic differentiation was activated by tumor necrosis factor-NF-κB axis in rDPSCs. Further in vivo study demonstrated that NOC-18-application in a tooth cavity accelerated tertiary dentin formation, which was associated with early nitrotyrosine expression in the dental pulp tissues beneath the cavity. Taken together, the present findings indicate that exogenous NO directly induces the odontogenic capacity of rDPSCs, suggesting that NO donors might offer a novel host DPSC-targeting alternative to current pulp capping agents in endodontics.
Alcohol Impairs N100 Response to Dorsolateral Prefrontal Cortex Stimulation
Authors: Loheswaran Genane , Barr Mera S. , Zomorrodi Reza , Rajji Tarek K. , Blumberger Daniel M. , Le Foll Bernard , Daskalakis Zafiris J.
Published: February 2018

Alcohol is thought to exert its effect by acting on gamma-aminobutyric (GABA) inhibitory neurotransmission. The N100, the negative peak on electroencephalography (EEG) that occurs approximately 100 ms following the transcranial magnetic stimulation (TMS) pulse, is believed to represent GABAB receptor mediated neurotransmission. However, no studies have examined the effect of alcohol on the N100 response to TMS stimulation of the dorsolateral prefrontal cortex (DLPFC). In the present study, we aimed to explore the effect of alcohol on the DLPFC TMS-evoked N100 response. The study was a within-subject cross-over design study. Fifteen healthy alcohol drinkers were administered TMS to the DLPFC before (PreBev) and after consumption (PostBev) of an alcohol or placebo beverage. The amplitude of the N100 before and after beverage was compared for both the alcohol and placebo beverage. Alcohol produced a significant decrease in N100 amplitude (t = 4.316, df = 14, p = 0.001). The placebo beverage had no effect on the N100 amplitude (t = −1.856, df = 14, p = 0.085). Acute alcohol consumption produces a decrease in N100 amplitude to TMS stimulation of the DLPFC, suggesting a decrease in GABAB receptor mediated neurotransmission. Findings suggest that the N100 may represent a marker of alcohol’s effects on inhibitory neurotransmission.
Predatory flying squids are detritivores during their early planktonic life
Authors: Fernández-Álvarez Fernando Á. , Machordom Annie , García-Jiménez Ricardo , Salinas-Zavala César A. , Villanueva Roger
Published: February 2018

Cephalopods are primarily active predators throughout life. Flying squids (family Ommastrephidae) represents the most widely distributed and ecologically important family of cephalopods. While the diets of adult flying squids have been extensively studied, the first feeding diet of early paralarvae remains a mystery. The morphology of this ontogenetic stage notably differs from other cephalopod paralarvae, suggesting a different feeding strategy. Here, a combination of Laser Capture Microdissection (LCM) and DNA metabarcoding of wild-collected paralarvae gut contents for eukaryotic 18S v9 and prokaryotic 16S rRNA was applied, covering almost every life domain. The gut contents were mainly composed by fungus, plants, algae and animals of marine and terrestrial origin, as well as eukaryotic and prokaryotic microorganisms commonly found in fecal pellets and particulate organic matter. This assemblage of gut contents is consistent with a diet based on detritus. The ontogenetic shift of diet from detritivore suspension feeding to active predation represents a unique life strategy among cephalopods and allows ommastrephid squids to take advantage of an almost ubiquitous and accessible food resource during their early stages. LCM was successfully applied for the first time to tiny, wild-collected marine organisms, proving its utility in combination with DNA metabarcoding for dietary studies.
Phosphorus addition changes belowground biomass and C:N:P stoichiometry of two desert steppe plants under simulated N deposition
Authors: Huang Juying , Yu Hailong , Liu Jili , Luo Chengke , Sun Zhaojun , Ma Kaibo , Kang Yangmei , Du Yaxian
Published: February 2018

Many studies have reported that increasing atmospheric nitrogen (N) deposition broadens N:phosphorus (P) in both soils and plant leaves and potentially intensifies P limitation for plants. However, few studies have tested whether P addition alleviates N-induced P limitation for plant belowground growth. It is also less known how changed N:P in soils and leaves affect plant belowground stoichiometry, which is significant for maintaining key belowground ecological processes. We conducted a multi-level N:P supply experiment (varied P levels combined with constant N amount) for Glycyrrhiza uralensis (a N fixing species) and Pennisetum centrasiaticum (a grass) from a desert steppe in Northwest China during 2011–2013. Results showed that increasing P addition increased the belowground biomass and P concentrations of both species, resulting in the decreases in belowground carbon (C):P and N:P. These results indicate that P inputs alleviated N-induced P limitation and hence stimulated belowground growth. Belowground C:N:P stoichiometry of both species, especially P. centrasiaticum, tightly linked to soil and green leaf C:N:P stoichiometry. Thus, the decoupling of C:N:P ratios in both soils and leaves under a changing climate could directly alter plant belowground stoichiometry, which will in turn have important feedbacks to primary productivity and C sequestration.
Lifetime of racetrack skyrmions
Authors: Bessarab Pavel F. , Müller Gideon P. , Lobanov Igor S. , Rybakov Filipp N. , Kiselev Nikolai S. , Jónsson Hannes , Uzdin Valery M. , Blügel Stefan , Bergqvist Lars , Delin Anna
Published: February 2018

The skyrmion racetrack is a promising concept for future information technology. There, binary bits are carried by nanoscale spin swirls–skyrmions–driven along magnetic strips. Stability of the skyrmions is a critical issue for realising this technology. Here we demonstrate that the racetrack skyrmion lifetime can be calculated from first principles as a function of temperature, magnetic field and track width. Our method combines harmonic transition state theory extended to include Goldstone modes, with an atomistic spin Hamiltonian parametrized from density functional theory calculations. We demonstrate that two annihilation mechanisms contribute to the skyrmion stability: At low external magnetic field, escape through the track boundary prevails, but a crossover field exists, above which the collapse in the interior becomes dominant. Considering a Pd/Fe bilayer on an Ir(111) substrate as a well-established model system, the calculated skyrmion lifetime is found to be consistent with reported experimental measurements. Our simulations also show that the Arrhenius pre-exponential factor of escape depends only weakly on the external magnetic field, whereas the pre-exponential factor for collapse is strongly field dependent. Our results open the door for predictive simulations, free from empirical parameters, to aid the design of skyrmion-based information technology.