bluuebunny/crossref_metadata_2025 huggingface dataset:
A new electro-optical approach for conductance measurement: an assay for the study of drugs acting on ligand-gated ion channels
Authors: Menegon A. , Pitassi S. , Mazzocchi N. , Redaelli L. , Rizzetto R. , Rolland J. F. , Poli C. , Imberti M. , Lanati A. , Grohovaz F.
Published: March 2017

Ligand gated ion channels are involved in many pathophysiological processes and represent a relevant, although challenging, target for drug discovery. We propose an innovative electro-optical approach to their analysis able to derive membrane conductance values from the local membrane potential changes imposed by test current pulses and measured by fast voltage-sensitive fluorescent dyes. We exploited the potential of this proprietary method by developing a drug testing system called “ionChannel Optical High-content Microscope” (ionChannelΩ). This automated platform was validated by testing the responses of reference drugs on cells expressing different ligand-gated ion channels. Furthermore, a double-blind comparison with FLIPR and automated patch-clamp was performed on molecules designed to act as antagonists of the P2RX7 receptor. ionChannelΩ proved highly reliable in all tests, resulting faster and more cost-effective than electrophysiological techniques. Overall, ionChannelΩ is amenable to the study of ligand gated ion channels that are receiving less attention due to limitations in current assays.
Investigation on the corrosive effect of NH3 during InGaN/GaN multi-quantum well growth in light emitting diodes
Authors: Yang J. , Zhao D. G. , Jiang D. S. , Chen P. , Zhu J. J. , Liu Z. S. , Liu W. , Li X. , Liang F. , Liu S. T. , Zhang L. Q. , Yang H.
Published: March 2017

Three series of samples with different NH3 flow rate are grown and the optical and structural properties are investigated. It is found that apart from a positive effect on keeping a high partial pressure of nitrogen to enhance indium incorporation, NH3 may also play a negative effect on indium incorporation during InGaN growth. Especially, when temperature is relatively high, the hydrogen generated from the dissociation of NH3 may suppress the chemical reaction which produces InN, leading to a reduced indium incorporation efficiency during the InGaN layer growth.
Orogen-scale uplift in the central Italian Apennines drives episodic behaviour of earthquake faults
Authors: Cowie P. A. , Phillips R. J. , Roberts G. P. , McCaffrey K. , Zijerveld L. J. J. , Gregory L. C. , Faure Walker J. , Wedmore L. N. J. , Dunai T. J. , Binnie S. A. , Freeman S. P. H. T. , Wilcken K. , Shanks R. P. , Huismans R. S. , Papanikolaou I. , Michetti A. M. , Wilkinson M.
Published: March 2017

Many areas of the Earth’s crust deform by distributed extensional faulting and complex fault interactions are often observed. Geodetic data generally indicate a simpler picture of continuum deformation over decades but relating this behaviour to earthquake occurrence over centuries, given numerous potentially active faults, remains a global problem in hazard assessment. We address this challenge for an array of seismogenic faults in the central Italian Apennines, where crustal extension and devastating earthquakes occur in response to regional surface uplift. We constrain fault slip-rates since ~18 ka using variations in cosmogenic36Cl measured on bedrock scarps, mapped using LiDAR and ground penetrating radar, and compare these rates to those inferred from geodesy. The36Cl data reveal that individual faults typically accumulate meters of displacement relatively rapidly over several thousand years, separated by similar length time intervals when slip-rates are much lower, and activity shifts between faults across strike. Our rates agree with continuum deformation rates when averaged over long spatial or temporal scales (104 yr; 102 km) but over shorter timescales most of the deformation may be accommodated by <30% of the across-strike fault array. We attribute the shifts in activity to temporal variations in the mechanical work of faulting.
Optimum soil frost depth to alleviate climate change effects in cold region agriculture
Authors: Yanai Yosuke , Iwata Yukiyoshi , Hirota Tomoyoshi
Published: March 2017

On-farm soil frost control has been used for the management of volunteer potatoes (Solanum tuberosum L.), a serious weed problem caused by climate change, in northern Japan. Deep soil frost penetration is necessary for the effective eradication of unharvested small potato tubers; however, this process can delay soil thaw and increase soil wetting in spring, thereby delaying agricultural activity initiation and increasing nitrous oxide emissions from soil. Conversely, shallow soil frost development helps over-wintering of unharvested potato tubers and nitrate leaching from surface soil owing to the periodic infiltration of snowmelt water. In this study, we synthesised on-farm snow cover manipulation experiments to determine the optimum soil frost depth that can eradicate unharvested potato tubers without affecting agricultural activity initiation while minimising N pollution from agricultural soil. The optimum soil frost depth was estimated to be 0.28–0.33 m on the basis of the annual maximum soil frost depth. Soil frost control is a promising practice to alleviate climate change effects on agriculture in cold regions, which was initiated by local farmers and further promoted by national and local research institutes.
Effects of dipeptidyl peptidase-4 inhibitors on beta-cell function and insulin resistance in type 2 diabetes: meta-analysis of randomized controlled trials
Authors: Lyu Xiafei , Zhu Xiaolin , Zhao Bin , Du Liang , Chen Dawei , Wang Chun , Liu Guanjian , Ran Xingwu
Published: March 2017

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a novel family of glucose-lowering agents. Accumulating evidence suggests that DPP-4 inhibitors preserve pancreatic beta-cell function, but results in previous studies have been inconsistent. We assessed the effects of DPP-4 inhibitors on the homoeostasis model assessment beta-cell function (HOMA-B) or insulin resistance (HOMA-IR) index in patients with type 2 diabetes through a systematic review and meta-analysis of randomized controlled trials (RCTs). Relevant articles were identified from PubMed, Embase, and Cochrane Library databases up to December 27, 2016. We calculated weighted mean differences (WMDs) and 95% confidence intervals (CIs) in each included trial and pooled the data using a random-effects model. Fifty-two trials were included in the present analysis. Compared with placebo control, DPP-4 inhibitors as monotherapy significantly improved HOMA-B (WMD 9.15; 95% CI 7.48, 10.81). Similarly, DPP-4 inhibitors as add-on therapy in combination with other drugs showed significant improvement in HOMA-B (WMD 9.04; 95% CI 5.72, 12.37). However, we found no significant improvement in HOMA-IR following treatment with DPP-4 inhibitors as mono-therapy or as add-on therapy. In conclusion, DPP-4 inhibitors as monotherapy or as add-on therapy significantly improved beta-cell function but had no significant effect on insulin resistance in type 2 diabetes.
Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate Cells
Authors: Chen Jennifer Y. , Newcomb Benjamin , Zhou Chan , Pondick Joshua V. , Ghoshal Sarani , York Samuel R. , Motola Daniel L. , Coant Nicolas , Yi Jae Kyo , Mao Cungui , Tanabe Kenneth K. , Bronova Irina , Berdyshev Evgeny V. , Fuchs Bryan C. , Hannun Yusuf , Chung Raymond T. , Mullen Alan C.
Published: March 2017

Activation of hepatic stellate cells (HSCs) in response to injury is a key step in hepatic fibrosis, and is characterized by trans-differentiation of quiescent HSCs to HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies to directly inhibit hepatic fibrosis. We developed a small molecule screen to identify compounds that inactivate human HSC myofibroblasts through the quantification of lipid droplets. We screened 1600 compounds and identified 21 small molecules that induce HSC inactivation. Four hits were tricyclic antidepressants (TCAs), and they repressed expression of pro-fibrotic factors Alpha-Actin-2 (ACTA2) and Alpha-1 Type I Collagen (COL1A1) in HSCs. RNA sequencing implicated the sphingolipid pathway as a target of the TCAs. Indeed, TCA treatment of HSCs promoted accumulation of ceramide through inhibition of acid ceramidase (aCDase). Depletion of aCDase also promoted accumulation of ceramide and was associated with reduced COL1A1 expression. Treatment with B13, an inhibitor of aCDase, reproduced the antifibrotic phenotype as did the addition of exogenous ceramide. Our results show that detection of lipid droplets provides a robust readout to screen for regulators of hepatic fibrosis and have identified a novel antifibrotic role for ceramide.
A novel procedure for the identification of chaos in complex biological systems
Authors: Bazeia D. , Pereira M. B. P. N. , Brito A. V. , Oliveira B.F. de , Ramos J. G. G. S.
Published: March 2017

We demonstrate the presence of chaos in stochastic simulations that are widely used to study biodiversity in nature. The investigation deals with a set of three distinct species that evolve according to the standard rules of mobility, reproduction and predation, with predation following the cyclic rules of the popular rock, paper and scissors game. The study uncovers the possibility to distinguish between time evolutions that start from slightly different initial states, guided by the Hamming distance which heuristically unveils the chaotic behavior. The finding opens up a quantitative approach that relates the correlation length to the average density of maxima of a typical species, and an ensemble of stochastic simulations is implemented to support the procedure. The main result of the work shows how a single and simple experimental realization that counts the density of maxima associated with the chaotic evolution of the species serves to infer its correlation length. We use the result to investigate others distinct complex systems, one dealing with a set of differential equations that can be used to model a diversity of natural and artificial chaotic systems, and another one, focusing on the ocean water level.
Quantitative Proteomic analysis on Activated Hepatic Stellate Cells reversion Reveal STAT1 as a key regulator between Liver Fibrosis and recovery
Authors: Zhang Hongyu , Chen Fangyan , Fan Xu , Lin Cong , Hao Yunwei , Wei Handong , Lin Weiran , Jiang Ying , He Fuchu
Published: March 2017

Understanding the changes of activated HSCs reversion is an essential step toward clarifying the potential roles of HSCs in the treatment of liver fibrosis. In this study, we chose adipocyte differentiation mixture to induce LX-2 cells for 2 days in vitro as reversion phase, comparing with normal cultured LX-2 cells as activation phase. Mass spectrometric-based SILAC technology was adopted to study differentially expressed proteome of LX-2 cells between reversion and activation. Compared with activated HSCs, 273 proteins showed significant differences in reverted HSCs. The main pathway of up-regulated proteins associated with reversion of HSCs mainly related to oxidation-reduction and lipid metabolism, while the top pathway of down-regulated proteins was found in regulated cytoskeleton formation. Changes in the expression levels of selected proteins were verified by Western blotting analysis, especially STAT1, FLNA, LASP1, and NAMPT proteins. The distinct roles of STAT1 were further analyzed between activated and reverted of HSCs, it was found that STAT1 could affect cell proliferation of HSCs and could be viewed as a key regulator in the reversion of HSCs. Thus, the proteomic analysis could accelerate our understanding of the mechanisms of HSC reversion on cessation of fibrogenic stimuli and provide new targets for antifibrotic liver therapy.
Unprecedented simultaneous enhancement in damage tolerance and fatigue resistance of zirconia/Ta composites
Authors: Smirnov A. , Beltrán J. I. , Rodriguez-Suarez T. , Pecharromán C. , Muñoz M. C. , Moya J. S. , Bartolomé J. F.
Published: March 2017

Dense (>98 th%) and homogeneous ceramic/metal composites were obtained by spark plasma sintering (SPS) using ZrO2and lamellar metallic powders of tantalum or niobium (20 vol.%) as starting materials. The present study has demonstrated the unique and unpredicted simultaneous enhancement in toughness and strength with very high flaw tolerance of zirconia/Ta composites. In addition to their excellent static mechanical properties, these composites also have exceptional resistance to fatigue loading. It has been shown that the major contributions to toughening are the resulting crack bridging and plastic deformation of the metallic particles, together with crack deflection and interfacial debonding, which is compatible with the coexistence in the composite of both, strong and weak ceramic/metal interfaces, in agreement with predictions of ab-initio calculations. Therefore, these materials are promising candidates for designing damage tolerance components for aerospace industry, cutting and drilling tools, biomedical implants, among many others.
Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus
Authors: Park Joo Youn , Moon Bo Youn , Park Juw Won , Thornton Justin A. , Park Yong Ho , Seo Keun Seok
Published: March 2017

Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of virulence genes by generalized transduction. In this study, we demonstrate genetic engineering strategies to overcome these shortcomings by integrating CRISPR/Cas9 system into a temperate phage genome, removing major virulence genes from the host chromosome, and expanding host specificity of the phage by complementing tail fiber protein. This significantly improved the efficacy and safety of CRISPR/Cas9 antimicrobials to therapeutic levels in both in vitro and in vivo assays. The genetic engineering tools and resources established in this study are expected to provide an efficacious and safe CRISPR/Cas9 antimicrobial, broadly applicable to Staphylococcus aureus.
Tumor Wide Horizontal Invasion Predicts Local Recurrence for Scrotal Extramammary Paget’s Disease
Authors: Wang Lujia , Feng Chenchen , Zhou Minwei , Zhou Zhongwen , Ding Guanxiong , Gao Peng , Ding Qiang , Wu Zhong
Published: March 2017

Extramammary Paget’s disease (EMPD) is a rare malignancy, and little was known about its prognostic factors and optimal treatment. In the current study, we aimed to discuss clinical and pathological features of scrotal EMPD and determine the prognostic factors for cancer-specific survival and local recurrence. A total of 206 patients with scrotal EMPD lesions surgically treated at our institute were studied. All clinical and pathological data were reviewed. Immunohistochemical staining of TP53 and Ki67 was examined as well. At the last follow-up, 175 patients (84.95%) were alive. Twelve patients (5.83%) had died of the disease due to distant metastases. Fifteen patients (7.28%) developed local recurrences of scrotal EMPD. Ki67 expression was significantly elevated in patients with wide horizontal invasion (P = 0.003). In univariate analysis, high invasion level, presence of nodule, presence of lymphovascular invasion, adnexa invasion, lymph node metastasis and high p53 expression were significant factors for poor cancer-specific survival. In multivariate analysis, high p53 expression was significantly correlated with poor cancer-specific survival. Wide horizontal invasion was independently correlated with local recurrence-free survival of scrotal EMPD. In conclusion, wide horizontal invasion is an independent risk factor for local recurrence-free survival in the patients with scrotal EMPD.
Imaging tissue-mimic with light sheet microscopy: A comparative guideline
Authors: Andilla Jordi , Jorand Raphael , Olarte Omar E. , Dufour Alexandre C. , Cazales Martine , Montagner Yoann L. E. , Ceolato Romain , Riviere Nicolas , Olivo-Marin Jean-Christophe , Loza-Alvarez Pablo , Lorenzo Corinne
Published: March 2017

Tissue mimics (TMs) on the scale of several hundred microns provide a beneficial cell culture configuration for in vitro engineered tissue and are currently under the spotlight in tissue engineering and regenerative medicine. Due to the cell density and size, TMs are fairly inaccessible to optical observation and imaging within these samples remains challenging. Light Sheet Fluorescence Microscopy (LSFM)- an emerging and attractive technique for 3D optical sectioning of large samples- appears to be a particularly well-suited approach to deal with them. In this work, we compared the effectiveness of different light sheet illumination modalities reported in the literature to improve resolution and/or light exposure for complex 3D samples. In order to provide an acute and fair comparative assessment, we also developed a systematic, computerized benchmarking method. The outcomes of our experiment provide meaningful information for valid comparisons and arises the main differences between the modalities when imaging different types of TMs.
Sweet taste in apple: the role of sorbitol, individual sugars, organic acids and volatile compounds
Authors: Aprea Eugenio , Charles Mathilde , Endrizzi Isabella , Laura Corollaro Maria , Betta Emanuela , Biasioli Franco , Gasperi Flavia
Published: March 2017

Sweetness is one of the main drivers of consumer preference, and thus is given high priority in apple breeding programmes. Due to the complexity of sweetness evaluation, soluble solid content (SSC) is commonly used as an estimation of this trait. Nevertheless, it has been demonstrated that SSC and sweet taste are poorly correlated. Though individual sugar content may vary greatly between and within apple cultivars, no previous study has tried to investigate the relationship between the amount of individual sugars, or ratios of these, and apple sweetness. In this work, we quantified the major sugars (sucrose, glucose, fructose, xylose) and sorbitol and explored their influence on perceived sweetness in apple; we also related this to malic acid content, SSC and volatile compounds. Our data confirmed that the correlation between sweetness and SSC is weak. We found that sorbitol content correlates (similarly to SSC) with perceived sweetness better than any other single sugar or total sugar content. The single sugars show no differentiable importance in determining apple sweetness. Our predictive model based on partial least squares regression shows that after sorbitol and SSC, the most important contribution to apple sweetness is provided by several volatile compounds, mainly esters and farnesene.
Optimising reliability of mouse performance in behavioural testing: the major role of non-aversive handling
Authors: Gouveia Kelly , Hurst Jane L.
Published: March 2017

Handling laboratory animals during test procedures is an important source of stress that may impair reliability of test responses. Picking up mice by the tail is aversive, stimulating stress and anxiety. Responses among anxious animals can be confounded further by neophobia towards novel test environments and avoidance of test stimuli in open areas. However, handling stress can be reduced substantially by using a handling tunnel, or cupping mice without restraint on the open hand. Here we establish whether non-aversive handling, brief prior familiarisation with the test arena and alternative stimulus placement could significantly improve performance of mice in behavioural tests. We use a simple habituation-dishabituation paradigm in which animals must discriminate between two urine stimuli in successive trials, a task that mice can easily perform. Tail handled mice showed little willingness to explore and investigate test stimuli, leading to poor test performance that was only slightly improved by prior familiarisation. By contrast, those handled by tunnel explored readily and showed robust responses to test stimuli regardless of prior familiarisation or stimulus location, though responses were more variable for cup handling. Our study shows that non-aversive tunnel handling can substantially improve mouse performance in behavioural tests compared to traditional tail handling.
An Expanded Multi-scale Monte Carlo Simulation Method for Personalized Radiobiological Effect Estimation in Radiotherapy: a feasibility study
Authors: Zhang Ying , Feng Yuanming , Wang Wei , Yang Chengwen , Wang Ping
Published: March 2017

A novel and versatile “bottom-up” approach is developed to estimate the radiobiological effect of clinic radiotherapy. The model consists of multi-scale Monte Carlo simulations from organ to cell levels. At cellular level, accumulated damages are computed using a spectrum-based accumulation algorithm and predefined cellular damage database. The damage repair mechanism is modeled by an expanded reaction-rate two-lesion kinetic model, which were calibrated through replicating a radiobiological experiment. Multi-scale modeling is then performed on a lung cancer patient under conventional fractionated irradiation. The cell killing effects of two representative voxels (isocenter and peripheral voxel of the tumor) are computed and compared. At microscopic level, the nucleus dose and damage yields vary among all nucleuses within the voxels. Slightly larger percentage of cDSB yield is observed for the peripheral voxel (55.0%) compared to the isocenter one (52.5%). For isocenter voxel, survival fraction increase monotonically at reduced oxygen environment. Under an extreme anoxic condition (0.001%), survival fraction is calculated to be 80% and the hypoxia reduction factor reaches a maximum value of 2.24. In conclusion, with biological-related variations, the proposed multi-scale approach is more versatile than the existing approaches for evaluating personalized radiobiological effects in radiotherapy.
Distribution of Bathyarchaeota Communities Across Different Terrestrial Settings and Their Potential Ecological Functions
Authors: Xiang Xing , Wang Ruicheng , Wang Hongmei , Gong Linfeng , Man Baiying , Xu Ying
Published: March 2017

High abundance and widespread distribution of the archaeal phylum Bathyarchaeota in marine environment have been recognized recently, but knowledge about Bathyarchaeota in terrestrial settings and their correlation with environmental parameters is fairly limited. Here we reported the abundance of Bathyarchaeota members across different ecosystems and their correlation with environmental factors by constructing 16S rRNA clone libraries of peat from the Dajiuhu Peatland, coupling with bioinformatics analysis of 16S rRNA data available to date in NCBI database. In total, 1456 Bathyarchaeota sequences from 28 sites were subjected to UniFrac analysis based on phylogenetic distance and multivariate regression tree analysis of taxonomy. Both phylogenetic and taxon-based approaches showed that salinity, total organic carbon and temperature significantly influenced the distribution of Bathyarchaeota across different terrestrial habitats. By applying the ecological concept of ‘indicator species’, we identify 9 indicator groups among the 6 habitats with the most in the estuary sediments. Network analysis showed that members of Bathyarchaeota formed the “backbone” of archaeal community and often co-occurred with Methanomicrobia. These results suggest that Bathyarchaeota may play an important ecological role within archaeal communities via a potential symbiotic association with Methanomicrobia. Our results shed light on understanding of the biogeography, potential functions of Bathyarchaeota and environment conditions that influence Bathyarchaea distribution in terrestrial settings.
Signalling mechanisms mediating Zn2+-induced TRPM2 channel activation and cell death in microglial cells
Authors: Mortadza Sharifah Syed , Sim Joan A. , Stacey Martin , Jiang Lin-Hua
Published: March 2017

Excessive Zn2+ causes brain damage via promoting ROS generation. Here we investigated the role of ROS-sensitive TRPM2 channel in H2O2/Zn2+-induced Ca2+ signalling and cell death in microglial cells. H2O2/Zn2+ induced concentration-dependent increases in cytosolic Ca2+ concentration ([Ca2+]c), which was inhibited by PJ34, a PARP inhibitor, and abolished by TRPM2 knockout (TRPM2-KO). Pathological concentrations of H2O2/Zn2+ induced substantial cell death that was inhibited by PJ34 and DPQ, PARP inhibitors, 2-APB, a TRPM2 channel inhibitor, and prevented by TRPM2-KO. Further analysis indicate that Zn2+ induced ROS production, PARP-1 stimulation, increase in the [Ca2+]c and cell death, all of which were suppressed by chelerythrine, a protein kinase C inhibitor, DPI, a NADPH-dependent oxidase (NOX) inhibitor, GKT137831, a NOX1/4 inhibitor, and Phox-I2, a NOX2 inhibitor. Furthermore, Zn2+-induced PARP-1 stimulation, increase in the [Ca2+]c and cell death were inhibited by PF431396, a Ca2+-sensitive PYK2 inhibitor, and U0126, a MEK/ERK inhibitor. Taken together, our study shows PKC/NOX-mediated ROS generation and PARP-1 activation as an important mechanism in Zn2+-induced TRPM2 channel activation and, TRPM2-mediated increase in the [Ca2+]c to trigger the PYK2/MEK/ERK signalling pathway as a positive feedback mechanism that amplifies the TRPM2 channel activation. Activation of these TRPM2-depenent signalling mechanisms ultimately drives Zn2+-induced Ca2+ overloading and cell death.
Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer
Authors: Yoo Byunghee , Kavishwar Amol , Wang Ping , Ross Alana , Pantazopoulos Pamela , Dudley Michael , Moore Anna , Medarova Zdravka
Published: March 2017

Treatment of stage IV metastatic breast cancer patients is limited to palliative options and represents an unmet clinical need. Here, we demonstrate that pharmacological inhibition of miRNA-10b - a master regulator of metastatic cell viability – leads to elimination of distant metastases in a mouse model of metastatic breast cancer. This was achieved using the miRNA-10b inhibitory nanodrug, MN-anti-miR10b, which consists of magnetic nanoparticles, conjugated to LNA-based miR-10b antagomirs. Intravenous injection of MN-anti-miR10b into mice bearing lung, bone, and brain metastases from breast cancer resulted in selective accumulation of the nanodrug in metastatic tumor cells. Weekly treatments of mice with MN-anti-miR-10b and low-dose doxorubicin resulted in complete regression of pre-existing distant metastases in 65% of the animals and a significant reduction in cancer mortality. These observations were supported by dramatic reduction in proliferation and increase in apoptosis in metastatic sites. On a molecular level, we observed a significant increase in the expression of HOXD10, which is a known target of miRNA-10b. These results represent first steps into the uncharted territory of therapy targeted to the metastatic niche.
Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa
Authors: Phyu Win Kyaw , Ong Kien Chai , Kong Chee Kwan , Alizan Abdul Khalil , Ramanujam Tindivanam Muthurangam , Wong Kum Thong
Published: March 2017

Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion.
The evolutionary origin of jaw yaw in mammals
Authors: Grossnickle David M.
Published: March 2017

Theria comprises all but three living mammalian genera and is one of the most ecologically pervasive clades on Earth. Yet, the origin and early history of therians and their close relatives (i.e., cladotherians) remains surprisingly enigmatic. A critical biological function that can be compared among early mammal groups is mastication. Morphometrics and modeling analyses of the jaws of Mesozoic mammals indicate that cladotherians evolved musculoskeletal anatomies that increase mechanical advantage during jaw rotation around a dorsoventrally-oriented axis (i.e., yaw) while decreasing the mechanical advantage of jaw rotation around a mediolaterally-oriented axis (i.e., pitch). These changes parallel molar transformations in early cladotherians that indicate their chewing cycles included significant transverse movement, likely produced via yaw rotation. Thus, I hypothesize that cladotherian molar morphologies and musculoskeletal jaw anatomies evolved concurrently with increased yaw rotation of the jaw during chewing cycles. The increased transverse movement resulting from yaw rotation may have been a crucial evolutionary prerequisite for the functionally versatile tribosphenic molar morphology, which underlies the molars of all therians and is retained by many extant clades.
Flexible frequency selective metamaterials for microwave applications
Authors: Gao Bo , Yuen Matthew M. F , Ye Terry Tao
Published: March 2017

Metamaterials have attracted more and more research attentions recently. Metamaterials for electromagnetic applications consist of sub-wavelength structures designed to exhibit particular responses to an incident EM (electromagnetic) wave. Traditional EM (electromagnetic) metamaterial is constructed from thick and rigid structures, with the form-factor suitable for applications only in higher frequencies (above GHz) in microwave band. In this paper, we developed a thin and flexible metamaterial structure with small-scale unit cell that gives EM metamaterials far greater flexibility in numerous applications. By incorporating ferrite materials, the thickness and size of the unit cell of metamaterials have been effectively scaled down. The design, mechanism and development of flexible ferrite loaded metamaterials for microwave applications is described, with simulation as well as measurements. Experiments show that the ferrite film with permeability of 10 could reduce the resonant frequency. The thickness of the final metamaterials is only 0.3mm. This type of ferrite loaded metamaterials offers opportunities for various sub-GHz microwave applications, such as cloaks, absorbers, and frequency selective surfaces.
Erythrocyte glutathione levels as long-term predictor of transition to psychosis
Authors: Lavoie S , Berger M , Schlögelhofer M , Schäfer M R , Rice S , Kim S-W , Hesse J , McGorry P D , Smesny S , Amminger G P
Published: March 2017

A high proportion of individuals deemed at elevated risk for psychosis will actually never progress to develop the illness. Pharmaceutical intervention may not be necessary in these cases, and may in fact be damaging depending on the invasiveness of the treatment strategy. This highlights the need for biomarkers that are better able to reliably differentiate between at-risk individuals who will subsequently transition to psychosis and those who will not. Low glutathione (GSH) levels have been observed in schizophrenia and in patients with first-episode psychosis. The aim of this study was to determine the predictive value of erythrocyte GSH levels on the transition to psychosis in individuals at risk of developing the illness. Erythrocyte GSH levels were measured in 36 at-risk individuals, 15 of whom had transitioned to psychosis at the 7-year follow-up. Univariate Cox regression analysis showed that transition to psychosis at the 7-year time point was significantly associated with low GSH levels at baseline. The area under the receiving operating characteristic curve was 0.819, indicating that GSH can be considered a good predictor of outcome. Although these results need to be replicated, adding the criterion ‘low erythrocyte GSH’ to the set of criteria used to identify individuals at risk of psychosis may be indicated.
Experimental medication treatment approaches for depression
Authors: Ionescu D F , Papakostas G I
Published: March 2017

Depression is one of the most common psychiatric conditions. Symptoms can lead to significant disability, which result in impairments in overall quality of life. Though there are many approved antidepressant treatments for depression—including selective serotonin reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors—about a third of patients do not respond to these medications. Therefore, it is imperative for drug discovery to continue towards the development of novel and rapidly acting compounds, especially for patients with treatment-resistant depression. After a brief review of the efficacy of approved antidepressant therapies, we will discuss experimental medication treatments for depression. Specifically, we examine novel medications that are thought to primarily modulate the glutamatergic, cholinergic and opioid systems to achieve antidepressant efficacy. We also give examples of anti-inflammatories, neurokinin-1 modulators, vasopressin antagonists and neurogenesis enhancers that may have a therapeutic role in treatment-resistant depression. The current pipeline of antidepressant treatments is shifting towards medications with novel mechanisms, which may lead to important, life-changing discoveries for patients with severe disease.
Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study
Authors: Chiarotti F , Viglione A , Giuliani A , Branchi I
Published: March 2017

Selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressant drugs, have a variable and incomplete efficacy. In order to better understand SSRI action, we explored the hypothesis that SSRIs do not affect mood per se but amplify the influence of the living conditions on mood. To this aim, we exploited the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set, selected a subpopulation of 591 patients with an overlapping clinical history and analyzed treatment outcome according to dosage −20 or 40 mg per day of citalopram. We found that sociodemographic characteristics affected treatment response in the same direction in the two dose groups, but these effects reached statistical significance only in the 40 mg per day dose group. In the latter, higher improvement rate was associated with having a working employment status (P=0.0219), longer education (P=0.0053), high income (P=0.01) or a private insurance (P=0.0031), and the higher remission rate was associated with having a working employment status (P=0.0326) or longer education (P=0.0484). Moreover, the magnitude of the effect of the sociodemographic characteristics on mood, measured as the percent of patients showing a positive outcome when exposed to favorable living conditions, was much greater—up to 37-fold—in the 40 compared to the 20 mg per day dose group. Overall, our results indicate that citalopram amplifies the influence of the living conditions on mood in a dose-dependent manner. These findings provide a potential explanation for the variable efficacy of SSRIs and might lead to the development of personalized strategies aimed at enhancing their efficacy.
Determination of 43 prohibited glucocorticoids in cosmetic products using a simultaneous LC-MS/MS method
Authors: Kim Nam Sook , Yoo Geum Joo , Lee Ji Hyun , Park Hyoung-Joon , Cho Sooyeul , Shin Dong Woo , Kim Younglim , Baek Sun Young
Published: March 2017

Forty-three glucocorticoids in deceptively advertised cosmetic products from the online or offline market are detected and determined through a validated simultaneous detection method based on LC-MS/MS.
Development of analytical methods for the determination of copper and manganese in infant formula using high resolution continuum source graphite furnace atomic absorption spectrometry and direct solid sample analysis
Authors: Gamela Raimundo R. , Duarte Álvaro T. , Barrera Eliana G. , Welz Bernhard , Dessuy Morgana B. , Messias da Silva Márcia , Vale Maria Goreti R.
Published: March 2017

Two fast, simple and reliable methods for the determination of Cu and Mn in infant formula were developed by HR-CS GF AAS.
Regulation of RAW 264.7 cell-mediated immunity by polysaccharides from Agaricus blazei Murill via the MAPK signal transduction pathway
Authors: Cheng Feier , Yan Xiaoyan , Zhang Miaoqing , Chang Mingchang , Yun Shaojun , Meng Junlong , Liu Jingyu , Feng Cui-ping
Published: March 2017

Agaricus blazei Murill (ABM) is a common anticancer folk remedy.
High-efficiency photoelectrochemical hydrogen generation enabled by p-type semiconductor nanoparticle-decorated n-type nanotube arrays
Authors: Sun Lan , Wu Zhi , Xiang Siwan , Yu Jiangdong , Wang Yingying , Lin Changjian , Lin Zhiqun
Published: March 2017

A photoelectrocatalytic hydrogen production rate of 37.8 μmol h−1 cm−2 was obtained by a newly designed NiO nanoparticle modified TiO2 nanotube array photoanode.
A stronger reversal effect of the combination of dasatinib and menadione on P-gp-mediated multidrug resistance in human leukemia K562/Adr cell line
Authors: Wang Changyuan , Liu Zhihao , Sun Yaoting , Chen Ting , Huo Xiaokui , Meng Qiang , Liu Qi , Sun Huijun , Sun Pengyuan , Peng Jinyong , Ma Xiaodong , Liu Kexin
Published: March 2017

Multidrug resistance (MDR) leads to poor efficiency of chemotherapy.
Numerical simulation of natural convection in an inclined porous cavity under time-periodic boundary conditions with a partially active thermal side wall
Authors: Wu Feng , Wang Gang
Published: March 2017

Natural convection in an inclined porous cavity with positively or negatively inclined angles is studied numerically for time-periodic boundary conditions on the left side wall and partially active thermal boundary conditions on the right wall.
Improved compatibility of DDAB-functionalized graphene oxide with a conjugated polymer by isocyanate treatment
Authors: Zheng Fei , Yang Xiao-Yu , Bi Peng-Qing , Niu Meng-Si , Lv Cheng-Kun , Feng Lin , Hao Xiao-Tao , Ghiggino Kenneth P.
Published: March 2017

2-Chlorophenyl isocyanate (CI) treatment significantly improves the compatibility of DDAB functionalized GO (DDAB-GO) with a conjugated polymer, P3HT.
Insights into Cr/SiO2catalysts during dehydrogenation of propane: an operando XAS investigation
Authors: Botavina M. , Barzan C. , Piovano A. , Braglia L. , Agostini G. , Martra G. , Groppo E.
Published: March 2017

In situandoperandoXAS spectroscopic methods were applied to monitor the variations in the oxidation state and in the local structure of the chromium sites in a 2.0Cr/SiO2-DHScatalyst during propane dehydrogenation under non-oxidative and different oxidative conditions.
Hydroisomerization of n-hexadecane: remarkable selectivity of mesoporous silica post-synthetically modified with aluminum
Authors: Sabyrov Kairat , Musselwhite Nathan , Melaet Gérôme , Somorjai Gabor A.
Published: March 2017

Post-synthetic aluminum grafting is employed to synthesize highly selective hydroisomerization catalyst and to demonstrate the effect of acid strength and density, catalyst microstructure, and platinum nanoparticle size on reaction rate and selectivity.
High power densities created from salinity differences by combining electrode and Donnan potentials in a concentration flow cell
Authors: Kim Taeyoung , Logan Bruce E. , Gorski Christopher A.
Published: March 2017

A concentration flow cell combines electrode and Donnan potentials, enabling high power densities from salinity differences.
Effective compounds in the fruit of Muntingia calabura Linn. cultivated in Taiwan evaluated with scavenging free radicals and suppressing LDL oxidation
Authors: Lin Jau-Tien , Chen Yi-Chen , Chang Yan-Zin , Chen Ting-Yu , Yang Deng-Jye
Published: March 2017

The effective antioxidant compounds ofM. calaburaLinn. fruit.
Hypolipidemic effect of Youcha in hyperlipidemia rats induced by high-fat diet
Authors: Zhu Zhenjun , Lin Zhongyi , Jiang Hongrui , Jiang Yi , Zhao Mouming , Liu Xiaoling
Published: March 2017

Youcha is a novel tea drink from the northeast of Guangxi.
Characterizing serum metabolic alterations of Alzheimer's disease and intervention of Shengmai-San by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry
Authors: Lu Shengwen , Han Ying , Chu Hang , Kong Ling , Zhang Aihua , Yan Guangli , Sun Hui , Wang Ping , Wang Xijun
Published: March 2017

Metabolomics approach describing the nervous protective mechanism of Shengmai-San (SMS) in Alzheimer's disease (AD).
Bioinspired peptosomes with programmed stimuli-responses for sequential drug release and high-performance anticancer therapy
Authors: Li Yuan , Li Wei , Bao Weier , Liu Bin , Li Dan , Jiang Yumeng , Wei Wei , Ren Fazheng
Published: March 2017

Bioinspired peptosomes based on natural α-lactalbumin were developed with triple-responses for sequential drug release and high anticancer efficacy.
Effect of polymer topology on non-covalent polymer–protein complexation: miktoarm versus linear mPEG-poly(glutamic acid) copolymers
Authors: Nieto-Orellana Alejandro , Di Antonio Marco , Conte Claudia , Falcone Franco H. , Bosquillon Cynthia , Childerhouse Nick , Mantovani Giuseppe , Stolnik Snow
Published: March 2017

We report the design of mPEG-(poly(glutamic acid)) with different macromolecular topology – linear and miktoarm – for reversible non-covalent protein complexation.
Quantitatively monitoring polymer chain growth and topology formation based on monodisperse polymers
Authors: Wang Zimu , Huang Zhihao , Zhou Nianchen , Dong Xue-Hui , Zhu Xiulin , Zhang Zhengbiao
Published: March 2017

In this work, a novel technique for monitoring polymer chain growth and topology formation was demonstrated by precision synthesis of monodisperse polymers, which opened a novel avenue for obtaining real-time polymer structure information.
Functionalization of pentacene-5,7,12,14-tetraone with geminal enediyne and 1,3-dithiole groups
Authors: Younes Eyad A. , Zhao Yuming
Published: March 2017

Pentacene-5,7,12,14-tetraone was subjected to selective olefination and cross-coupling reactions to yield a new class of pentacene-based π-conjugated systems with intriguing structural, electronic, and redox properties.
Copper-catalyzed highly selective approach to 2-boroallylic silanes from allenylsilanes
Authors: Song Liu , Yuan Weiming , Ma Shengming
Published: March 2017

A highly selective copper-catalyzed borylcupration of 1,2-allenylsilanes affords 2-borylallylsilanes with many synthetically attractive functional groups by applying BIPHEP as the ligand has been developed.
Growth of two-dimensional silicalite-1 on graphene oxide with controllable electrical conductivity
Authors: Ding He , Zhang Yixiao , Ni Xiuxiu , Zhang Jingshuang , Zeng Zhouliangzi , Bai Peng , Guo Xianghai
Published: March 2017

Two-dimensional (2D) silicalite-1 zeolites are fabricated by introducing graphene oxide (GO) into a multilamellar MFI synthesis system. These composite materials exhibit high and controllable electrical conductivity with different amounts of GO.
Epitaxial crystallization of precisely bromine-substituted polyethylene induced by carbon nanotubes and graphene
Authors: Miao Weijun , Wang Bingjie , Li Yiguo , Zheng Wenge , Chen Hongbing , Zhang Li , Wang Zongbao
Published: March 2017

Epitaxial crystallization of precisely bromine-substituted polyethylene induced by carbon nanotubes and graphene.
Graphene quantum dots: effect of size, composition and curvature on their assembly
Authors: Elvati Paolo , Baumeister Elizabeth , Violi Angela
Published: March 2017

The enhanced configurational stability of graphene quantum dots in clusters.
Synthesis and water sorption properties of a series of exfoliated graphene/MIL-100(Fe) composites
Authors: Said S. A. M. , Qadir N. U. , Mansour R. B. , Mezghani K. , Irshad H. M.
Published: March 2017

Graphene oxide/MIL-100(Fe) composites synthesized using covalent chemistry present an attractive strategy to develop adsorbents with high uptakes as well as heat transfer rates.
Synthesis, structure and gas adsorption properties of a stable microporous Cu-based metal–organic framework assembled from a T-shaped pyridyl dicarboxylate ligand
Authors: Wang Di , Sun Libo , Liu Yuchuan , Du Jianfeng , Wang Shun , Song Xiaowei , Liang Zhiqiang
Published: March 2017

A three-dimensional microporous metal–organic framework assembled from a T-shaped pyridyl dicarboxylate ligand has been synthesized. It possesses high stability and adsorption capacities for CO2 (114 cm3 g−1, 273 K) under ambient pressure.
Microtubular solid oxide fuel cells fabricated by gel-casting: the role of supporting microstructure on the mechanical properties
Authors: Morales M. , Laguna-Bercero M. A.
Published: March 2017

Different cell configurations of anode-supported microtubular solid oxide fuel cells (mT-SOFCs) using samaria-doped ceria (SDC) as the electrolyte were fabricated.
Protein-directed synthesis of Bi2S3 nanoparticles as an efficient contrast agent for visualizing the gastrointestinal tract
Authors: Zu Yan , Yong Yuan , Zhang Xiao , Yu Jie , Dong Xinghua , Yin Wenyan , Yan Liang , Zhao Feng , Gu Zhanjun , Zhao Yuliang
Published: March 2017

BSA@Bi2S3 nanoparticles can be applied for CT imaging of the gastrointestinal tract, realizing the visualization of gastrointestinal structures.
Mn2+ doped CdAl2O4 phosphors with new structure and special fluorescence properties: experimental and theoretical analysis
Authors: Ran Weiguang , Wang Lili , Liu Qingzhi , Liu Guangzeng , Qu Dan , Pan Xiaohua , Shi Jinsheng
Published: March 2017

Mn2+-activated CdAl2O4 phosphors with the new structure of space group R3̄ (no. 148) have been prepared by a high-temperature solid-state reaction and their luminescence properties have been investigated in detail.
Kx(C2H8N2)yFe2−zS2: synthesis, phase structure and correlation between K+ intercalation and Fe depletion
Authors: Guo Zhongnan , Zhou Liang , Jin Shifeng , Han Bingling , Sun Fan , Yuan Wenxia
Published: March 2017

Co-intercalated FeS Kx(C2H8N2)yFe2−zS2 has been synthesized by a sonochemical method. It has been found that the charged K+ intercalation depleted the Fe from [FeS] layers, resulting in disordered Fe vacancies and weak ferrimagnetic semiconducting behavior.
Dopamine-modified TiO2 monolith-assisted LDI MS imaging for simultaneous localization of small metabolites and lipids in mouse brain tissue with enhanced detection selectivity and sensitivity
Authors: Wu Qian , Chu James L. , Rubakhin Stanislav S. , Gillette Martha U. , Sweedler Jonathan V.
Published: March 2017

A dopamine-modified TiO2 monolith was developed to assist LDI MS imaging for small metabolites and lipids simultaneously with enhanced sensitivity.