bluuebunny/crossref_metadata_2025 huggingface dataset:
CUBIC pathology: three-dimensional imaging for pathological diagnosis
Authors: Nojima Satoshi , Susaki Etsuo A. , Yoshida Kyotaro , Takemoto Hiroyoshi , Tsujimura Naoto , Iijima Shohei , Takachi Ko , Nakahara Yujiro , Tahara Shinichiro , Ohshima Kenji , Kurashige Masako , Hori Yumiko , Wada Naoki , Ikeda Jun-ichiro , Kumanogoh Atsushi , Morii Eiichi , Ueda Hiroki R.
Published: August 2017

The examination of hematoxylin and eosin (H&E)-stained tissues on glass slides by conventional light microscopy is the foundation for histopathological diagnosis. However, this conventional method has some limitations in x-y axes due to its relatively narrow range of observation area and in z-axis due to its two-dimensionality. In this study, we applied a CUBIC pipeline, which is the most powerful tissue-clearing and three-dimensional (3D)-imaging technique, to clinical pathology. CUBIC was applicable to 3D imaging of both normal and abnormal patient-derived, human lung and lymph node tissues. Notably, the combination of deparaffinization and CUBIC enabled 3D imaging of specimens derived from paraffin-embedded tissue blocks, allowing quantitative evaluation of nuclear and structural atypia of an archival malignant lymphoma tissue. Furthermore, to examine whether CUBIC can be applied to practical use in pathological diagnosis, we performed a histopathological screening of a lymph node metastasis based on CUBIC, which successfully improved the sensitivity in detecting minor metastatic carcinoma nodules in lymph nodes. Collectively, our results indicate that CUBIC significantly contributes to retrospective and prospective clinicopathological diagnosis, which might lead to the establishment of a novel field of medical science based on 3D histopathology.
Drug Loaded Gingival Mesenchymal Stromal Cells (GinPa-MSCs) Inhibit In Vitro Proliferation of Oral Squamous Cell Carcinoma
Authors: Coccè Valentina , Farronato Davide , Brini Anna Teresa , Masia Carla , Giannì Aldo Bruno , Piovani Giovanna , Sisto Francesca , Alessandri Giulio , Angiero Francesca , Pessina Augusto
Published: August 2017

Human mesenchymal stromal cells (MSCs) have been widely investigated both for regenerative medicine and their antinflammatory/immunomodulatory capacity. However, their ability to home pathological tissues suggested the development of strategies for using MSCs as carrier to deliver drug into tumor microenvironment. MSCs obtained from different tissues can be loaded in vitro with anti-cancer drugs by a simple procedures. In this report, we studied MSCs isolated and expanded from gingival papilla (GinPa-MSCs), by testing their ability to uptake and release three important anti-neoplastic drugs: Paclitaxel (PTX), Doxorubicin (DXR) and Gemcitabine (GCB). The efficacy of drugs releasing GinPa-MSCs was studied on a pancreatic cancer cell line and confirmed in vitro against a line of tongue squamous cell carcinoma (SCC154). Our results demonstrated that GinPa-MSCs efficiently incorporate the drugs and then released them in active form and in sufficient amount to produce a dramatic inhibition of squamous cell carcinoma growth in vitro. If compared with other MSCs sources, the collection of GinPa-MSCs is poorly invasive and cells can be easily expanded and efficiently loaded with anti cancer drugs. In particular, gemcitabine loaded GinPa-MSCs provide a good “cell-mediated drug delivery system” for a future potential application in the context of the oral oncology.
Simple MD-based model for oxidative folding of peptides and proteins
Authors: Izmailov Sergei A. , Podkorytov Ivan S. , Skrynnikov Nikolai R.
Published: August 2017

Significant strides have been recently made to fold peptides and small proteins in silico using MD simulations. However, facilities are currently lacking to include disulfide bonding in the MD models of protein folding. To address this problem, we have developed a simple empirical protocol to model formation of disulfides, which is perturbation-free, retains the same speed as conventional MD simulations and allows one to control the reaction rate. The new protocol has been tested on 15-aminoacid peptide guanylin containing four cysteine residues; the net simulation time using Amber ff14SB force field was 61 μs. The resulting isomer distribution is in qualitative agreement with experiment, suggesting that oxidative folding of guanylin in vitro occurs under kinetic control. The highly stable conformation of the so-called isomer 2(B) has been obtained for full-length guanylin, which is significantly different from the poorly ordered structure of the truncated peptide PDB ID 1GNB. In addition, we have simulated oxidative folding of guanylin within the 94-aminoacid prohormone proguanylin. The obtained structure is in good agreement with the NMR coordinates 1O8R. The proposed modeling strategy can help to explore certain fundamental aspects of protein folding and is potentially relevant for manufacturing of synthetic peptides and recombinant proteins.
A first-in-human study of the novel HIV-fusion inhibitor C34-PEG4-Chol
Authors: Quinn Killian , Traboni Cinzia , Penchala Sujan Dily , Bouliotis Georgios , Doyle Nicki , Libri Vincenzo , Khoo Saye , Ashby Deborah , Weber Jonathan , Nicosia Alfredo , Cortese Riccardo , Pessi Antonello , Winston Alan
Published: August 2017

Long-acting injectable antiretroviral (LA-ARV) drugs with low toxicity profiles and propensity for drug-drug interactions are a goal for future ARV regimens. C34-PEG4-Chol is a novel cholesterol tagged LA HIV-fusion-inhibitor (FI). We assessed pre-clinical toxicology and first-in-human administration of C34-PEG4-Chol. Pre-clinical toxicology was conducted in 2 species. HIV-positive men were randomised to a single subcutaneous dose of C34-PEG4-Chol at incrementing doses or placebo. Detailed clinical (including injection site reaction (ISR) grading), plasma pharmacokinetic (time-to-minimum-effective-concentration (MEC, 25 ng/mL) and pharmacodynamic (plasma HIV RNA) parameters were assessed. In both mice and dogs, no-observed-adverse effect level (NOAEL) was observed at a 12 mg/kg/dose after two weeks. Of 5 men enrolled, 3 received active drug (10 mg, 10 mg and 20 mg). In 2 individuals grade 3 ISR occurred and the study was halted. Both ISR emerged within 12 hours of active drug dosing. No systemic toxicities were observed. The time-to-MEC was >72 and >96 hours after 10 and 20 mg dose, respectively, and mean change in HIV RNA was −0.9 log10 copies/mL. These human pharmacodynamic and pharmacokinetic data, although limited to 3 subjects, of C34-PEG-4-Chol suggest continuing evaluation of this agent as a LA-ARV. However, alternative administration routes must be explored.
Three-dimensional Graphene with MoS
2
Nanohybrid as Potential Energy Storage/Transfer Device
Authors: Singh Kulvinder , Kumar Sushil , Agarwal Kushagra , Soni Khushboo , Ramana Gedela Venkata , Ghosh Kaushik
Published: August 2017

Portable and matured energy storage devices are in high demand for future flexible electronics. Flowery shaped MoS2 nanostructures with porous and flake like morphology was used to study the supercapacitive nature with specific capacitance (C
sp
) of 169.37F/g, the energy density of 28.43 Wh/Kg and power density of 10.18 W/Kg. This nanoflower like architecture was decorated on 3D-graphene on Graphite electrode to design the solid-state-supercapacitor prototype device of dimensions of 23.6 × 22.4 × 0.6 mm3 having considerable high Csp of 58.0F/g and energy density of 24.59 Wh/Kg, and power density of 8.8 W/Kg. Four fabricated supercapacitors were connected in series for real state practical demonstration using the light emitting diode that remains enlightened for 40 s by charging it only for 25 s. This study demonstrates the 3D-graphene/MoS2 nanohybrid has a quite high overall potential window nearly about 2.7 V (−1.5 to +1.2 V) in KOH-PVA medium which can be used for the development of solid-state supercapacitors thereby completely eliminating the need for any expensive ionic liquid mediums thus building an exciting potential for high-performance energy storage/transfer devices.
Deep Western Boundary Current in the South China Sea
Authors: Zhou Chun , Zhao Wei , Tian Jiwei , Zhao Xiaolong , Zhu Yuchao , Yang Qingxuan , Qu Tangdong
Published: August 2017

Deep western boundary current (DWBC) was observed for the first time by an array of 6 current meter moorings southeast of the Zhongsha Islands in the South China Sea (SCS) deep basin during the period from August 2012 to January 2014. In the mean, the DWBC in the SCS flows southwestward with core velocity of 2.0 cm/s and a volume transport of 1.65 Sv (1 Sv = 1 × 106 m3/s). Its temporal variability is dominated by intraseasonal fluctuations with period around 90 days. The main axis of the DWBC, characterized by a low temperature core, tends not to shift with the 90-day fluctuation.
The epigenetic modifier Fam208a is required to maintain epiblast cell fitness
Authors: Bhargava Shohag , Cox Brian , Polydorou Christiana , Gresakova Veronika , Korinek Vladimir , Strnad Hynek , Sedlacek Radislav , Epp Trevor Allan , Chawengsaksophak Kallayanee
Published: August 2017

Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epithelial-to-mesenchymal transition. Fam208a mutant epiblasts had increased expression of p53 pathway genes as well as several pluripotency-associated long non-coding RNAs. Fam208a mutants exhibited an increase in p53-driven apoptosis and complete removal of p53 could partially rescue their gastrulation block. This data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness, establishing it as an important factor at the onset of gastrulation when cells are exiting pluripotency.
Loss of Tmem30a leads to photoreceptor degeneration
Authors: Zhang Lin , Yang Yeming , Li Shujin , Zhang Shanshan , Zhu Xiong , Tai Zhengfu , Yang Mu , Liu Yuqing , Guo Xinzheng , Chen Bo , Jiang Zhilin , Lu Fang , Zhu Xianjun
Published: August 2017

Phosphatidylserine (PS) is asymmetrically distributed between the outer and inner leaflets of the plasma membrane in eukaryotic cells. PS asymmetry on the plasma membrane depends on the activities of P4-ATPases, and disruption of PS distribution can lead to various disease conditions. Folding and transporting of P4-ATPases to their cellular destination requires the β subunit TMEM30A proteins. However, the in vivo functions of Tmem30a remain unknown. To this end, we generated retinal-specific Tmem30a-knockout mice to investigate its roles in vivo for the first time. Our data demonstrated that loss of Tmem30a in mouse cone cells leads to mislocalization of cone opsin, loss of photopic electroretinogram (ERG) responses and loss of cone cells. Mechanistically, Tmem30a-mutant mouse embryonic fibroblasts (MEFs) exhibited diminished PS flippase activity and increased exposure of PS on the cell surface. The broad loss of Tmem30a in adult mice led to a reduced scotopic photoresponse, mislocalization of ATP8A2 to the inner segment and cell body, and increased apoptosis in the retina. Our data demonstrated novel essential roles of Tmem30a in the retina.
Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs
Authors: Lee Karla Chui Luan , Baker Luisa , Mallett Susan , Riddell Anne , Chowdary Pratima , Alibhai Hatim , Chang Yu-Mei , Priestnall Simon , Stanzani Giacomo , Davies Nathan , Mookerjee Rajeshwar , Jalan Rajiv , Agarwal Banwari
Published: August 2017

Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability.
DrwH, a novel WHy domain-containing hydrophobic LEA5C protein from Deinococcus radiodurans, protects enzymatic activity under oxidative stress
Authors: Jiang Shijie , Wang Jin , Liu Xiaoli , Liu Yingying , Guo Cui , Zhang Liwen , Han Jiahui , Wu Xiaoli , Xue Dong , Gomaa Ahmed E. , Feng Shuai , Zhang Heng , Chen Yun , Ping Shuzhen , Chen Ming , Zhang Wei , Li Liang , Zhou Zhengfu , Zuo Kaijing , Li Xufeng , Yang Yi , Lin Min
Published: August 2017

Water stress and hypersensitive response (WHy) domain is typically found as a component of atypical late embryogenesis abundant (LEA) proteins closely associated with resistance to multiple stresses in numerous organisms. Several putative LEA proteins have been identified in Deinococcus bacteria; however their precise function remains unclear. This work reports the characterization of a Deinococcus-specific gene encoding a novel WHy domain-containing hydrophobic LEA5C protein (named DrwH) in D. radiodurans R1. The expression of the drwH gene was induced by oxidative and salinity stresses. Inactivation of this gene resulted in increased sensitivity to oxidative and salinity stresses as well as reduced activities of antioxidant enzymes. The WHy domain of the DrwH protein differs structurally from that of a previously studied bacterial LEA5C protein, dWHy1, identified as a gene product from an Antarctic desert soil metagenome library. Further analysis indicated that in E. coli, the function of DrwH is related to oxidative stress tolerance, whereas dWHy1 is associated with freezing-thawing stress tolerance. Under oxidative stress induced by H2O2, DrwH protected the enzymatic activities of malate dehydrogenase (MDH) and lactate dehydrogenase (LDH). These findings provide new insight into the evolutionary and survival strategies of Deinococcus bacteria under extreme environmental conditions.
Neglected role of hydrogen sulfide in sulfur mustard poisoning: Keap1 S-sulfhydration and subsequent Nrf2 pathway activation
Authors: Meng Wenqi , Pei Zhipeng , Feng Yongwei , Zhao Jie , Chen Yongchun , Shi Wenwen , Xu Qingqiang , Lin Fengwu , Sun Mingxue , Xiao Kai
Published: August 2017

Sulfur mustard (SM) is a chemical warfare agent and a terrorism choice that targets various organs and tissues, especially lung tissues. Its toxic effects are tightly associated with oxidative stress. The signaling molecule hydrogen sulfide (H2S) protects the lungs against oxidative stress and activates the NF-E2 p45-related factor 2 (Nrf2) pathway. Here, we sought to establish whether endogenous H2S plays a role in SM induced lesion in mouse lungs and lung cells and whether endogenous H2S plays the role through Nrf2 pathway to protect against SM-induced oxidative damage. Furthermore, we also explored whether activation of Nrf2 by H2S involves sulfhydration of Kelch-like ECH-associated protein-1 (Keap1). Using a mouse model of SM-induced lung injury, we demonstrated that SM-induced attenuation of the sulfide concentration was prevented by NaHS. Concomitantly, NaHS attenuates SM-induced oxidative stress. We also found that H2S enhanced Nrf2 nuclear translocation, and stimulated expression of Nrf2-targeted downstream protein and mRNA levels. Incubation of the lung cells with NaHS decreased SM-induced ROS production. Furthermore, we also found that H2S S-sulfhydrated Keap1, which induced Nrf2 dissociation from Keap1, and enhanced Nrf2 nuclear translocation. Our data indicate that H2S is a critical, however, being long neglected signal molecule in SM-induced lung injury.
Tuning Metamaterials by using Amorphous Magnetic Microwires
Authors: Lopez-Dominguez V. , Garcia M. A. , Marin P. , Hernando A.
Published: August 2017

In this work, we demonstrate theoretically and experimentally the possibility of tuning the electromagnetic properties of metamaterials with magnetic fields by incorporating amorphous magnetic microwires. The large permeability of these wires at microwave frequencies allows tuning the resonance of the metamaterial by using magnetic fields of the order of tens of Oe. We describe here the physical basis of the interaction between a prototypical magnetic metamaterial with magnetic microwires and electromagnetic waves plus providing detailed calculations and experimental results for the case of an array of Split Ring Resonators with Co-based microwires.
RETRACTED ARTICLE: Norcantharidin combined with Coix seed oil synergistically induces apoptosis and inhibits hepatocellular carcinoma growth by downregulating regulatory T cells accumulation
Authors: Wang Dan , Yang Chendong , Wang Zhuien , Yang Yi , Li Defang , Ding Xiaojie , Xu Wenjuan , Zheng Qiusheng
Published: August 2017

The immune system plays a critical role in exerts effects in the growth and progression of hepatocellular carcinoma (HCC), which needs interacting approaches for effective therapy. In this study, we have found that the Norcantharidin (NCTD) + Coix lacryma-jobi seed oil (CLSO) combination exhibited more potent antitumor effects in an terms of cytotoxicity and apoptotic induction in human HepG2 and HepG2/ADM cells than NCTD or CLSO alone. In vivo, administration of NCTD+CLSO combinations significantly suppressed the formation of tumor in Hepal-1 hepatoma-bearing mice. Furthermore, we found that the in vitro co-cultures of HepG2 or HepG2/ADM cells with PBMCs from healthy donors led to an increase in the number of CD4+CD25+ T cells. This increase was down-regulated by the combination effectively. Down-regulation of FoxP3 mRNA and protein expression occurred during the combination in the co-cultures. The amount of Tregs of Hepal-1 hepatoma-bearing mice was significantly decreased in the combination treated group. The combination down-regulated the expression of FoxP3, CTLA-4 and Tregs related cytokine (TGF-β and IL-10) in the serum of tumor bearing mice. Taken together, these results suggest that the most valuable aspect of the NCTD+CLSO combined use improves the anti-tumor activity and regulates tumor infiltrating Tregs.
MiR-34c represses muscle development by forming a regulatory loop with Notch1
Authors: Hou Lianjie , Xu Jian , Li Huaqin , Ou Jinxin , Jiao Yiren , Hu Chingyuan , Wang Chong
Published: August 2017

Since pork accounts for about 40% of global meat consumption, the pig is an important economic animal for meat production. Pig is also a useful medical model for humans due to its similarity in size and physiology. Understanding the mechanism of muscle development has great implication for animal breeding and human health. Previous studies showed porcine muscle satellite cells (PSCs) are important for postnatal skeletal muscle growth, and Notch1 signaling pathway and miRNAs regulate the skeletal muscle development. Notch1 signal pathway regulates the transcription of certain types of miRNAs which further affects target gene expression. However, the specific relationship between Notch1 and miRNAs during muscle development has not been established. We found miR-34c is decreased in PSCs overexpressed N1ICD. Through the overexpression and inhibition of mi-34c, we demonstrated that miR-34c inhibits PSCs proliferation and promotes PSCs differentiation. Using dual-luciferase reporter assay and Chromatin immunoprecipitation, we demonstrate there is a reciprocal regulatory loop between Notch1 and miR-34c. Furthermore, injection of miR-34c lentivirus into mice caused repression of gastrocnemius muscle development. In summary, our data revealed that miR-34c can form a regulatory loop with Notch1 to repress muscle development, and this result expands our understanding of muscle development mechanism.
Physical determinants of asymmetric cell divisions in the early development of Caenorhabditis elegans
Authors: Fickentscher Rolf , Weiss Matthias
Published: August 2017

Asymmetric cell divisions are of fundamental importance for the development of multicellular organisms, e.g. for the generation of founder cells. Prime examples are asymmetric cell divisions in germline precursors during the early embryogenesis of the transparent roundworm Caenorhabditis elegans, one of the major developmental model organisms. However, due to a lack of quantitative data it has remained unclear how frequent unequal daughter cell sizes emerge in the worm’s early embryogenesis, and whether these originate from sterical or biochemical cues. Using quantitative light-sheet microscopy, we have found that about 40% of all cell divisions in C. elegans until gastrulation generate daughter cells with significantly different volumes. Removing the embryo’s rigid eggshell revealed asymmetric divisions in somatic cells to be primarily induced by steric effects. Division asymmetries in the germline remained unaltered and were correctly reproduced by a model based on a cell-size independent, eccentric displacement of the metaphase plate. Our data suggest that asymmetric cell divisions, imposed by physical determinants, are essential for establishing important cell-cell interactions that eventually fuel a successful embryogenesis.
Fitness consequences of peak reproductive effort in a resource pulse system
Authors: Hämäläinen Anni , McAdam Andrew G. , Dantzer Ben , Lane Jeffrey E. , Haines Jessica A. , Humphries Murray M. , Boutin Stan
Published: August 2017

The age trajectory of reproductive performance of many iteroparous species features an early - life increase in performance followed by a late - life senescent decline. The largest contribution of lifetime reproductive success is therefore gained at the age at which reproductive performance peaks. Using long term data on North American red squirrels we show that the environmental conditions individuals encountered could cause variation among individuals in the “height” and timing of this peak, contributing to life history variation and fitness in this population that experiences irregular resource pulses. As expected, high peak effort was positively associated with lifetime reproductive output up to a high level of annual effort. Furthermore, individuals that matched their peak reproductive effort to an anticipated resource pulse gained substantial fitness benefits through recruiting more offspring over their lifetime. Individual variation in peak reproductive effort thus has strong potential to shape life history evolution by facilitating adaptation to fluctuating environments.
Effects of scale of movement, detection probability, and true population density on common methods of estimating population density
Authors: Keiter David A. , Davis Amy J. , Rhodes Olin E. , Cunningham Fred L. , Kilgo John C. , Pepin Kim M. , Beasley James C.
Published: August 2017

Knowledge of population density is necessary for effective management and conservation of wildlife, yet rarely are estimators compared in their robustness to effects of ecological and observational processes, which can greatly influence accuracy and precision of density estimates. In this study, we simulate biological and observational processes using empirical data to assess effects of animal scale of movement, true population density, and probability of detection on common density estimators. We also apply common data collection and analytical techniques in the field and evaluate their ability to estimate density of a globally widespread species. We find that animal scale of movement had the greatest impact on accuracy of estimators, although all estimators suffered reduced performance when detection probability was low, and we provide recommendations as to when each field and analytical technique is most appropriately employed. The large influence of scale of movement on estimator accuracy emphasizes the importance of effective post-hoc calculation of area sampled or use of methods that implicitly account for spatial variation. In particular, scale of movement impacted estimators substantially, such that area covered and spacing of detectors (e.g. cameras, traps, etc.) must reflect movement characteristics of the focal species to reduce bias in estimates of movement and thus density.
Deficient Insulin-mediated Upregulation of the Equilibrative Nucleoside Transporter 2 Contributes to Chronically Increased Adenosine in Diabetic Glomerulopathy
Authors: Alarcón Sebastián , Garrido Wallys , Vega Génesis , Cappelli Claudio , Suárez Raibel , Oyarzún Carlos , Quezada Claudia , San Martín Rody
Published: August 2017

Deficient insulin signaling is a key event mediating diabetic glomerulopathy. Additionally, diabetic kidney disease has been related to increased levels of adenosine. Therefore, we tested a link between insulin deficiency and dysregulated activity of the equilibrative nucleoside transporters (ENTs) responsible for controlling extracellular levels of adenosine. In ex vivo glomeruli, high D-glucose decreased nucleoside uptake mediated by ENT1 and ENT2 transporters, resulting in augmented extracellular levels of adenosine. This condition was reversed by exposure to insulin. Particularly, insulin through insulin receptor/PI3K pathway markedly upregulated ENT2 uptake activity to restores the extracellular basal level of adenosine. Using primary cultured rat podocytes as a cellular model, we found insulin was able to increase ENT2 maximal velocity of transport. Also, PI3K activity was necessary to maintain ENT2 protein levels in the long term. In glomeruli of streptozotocin-induced diabetic rats, insulin deficiency leads to decreased activity of ENT2 and chronically increased extracellular levels of adenosine. Treatment of diabetic rats with adenosine deaminase attenuated both the glomerular loss of nephrin and proteinuria. In conclusion, we evidenced ENT2 as a target of insulin signaling and sensitive to dysregulation in diabetes, leading to chronically increased extracellular adenosine levels and thereby setting conditions conducive to kidney injury.
Highly hard yet toughened bcc-W coating by doping unexpectedly low B content
Authors: Yang Lina , Zhang Kan , Wen Mao , Hou Zhipeng , Gong Chen , Liu Xucheng , Hu Chaoquan , Cui Xiaoqiang , Zheng Weitao
Published: August 2017

Either hardness or toughness has been the core interest in scientific exploration and technological pursuit for a long time. However, it is still a big challenge to enhance the hardness and toughness at the same time, since the improvement of one side is always at the expense of the other one. Here, we have succeeded in dealing with this pair of conflict based on tungsten (W) coating by doping boron (B) via magnetron co-sputtering. The results reveal that the introduction of low concentrations of B (6.3 at. %), in the doping regime, leads to the formation of W(B) supersaturated solid solution with refined grains. Meanwhile, the doping-induced higher compressive stress, higher H/E* and denser microstructure result in a surprising combination of improved hardness (2 × larger than pure W) and superior toughness (higher crack formation threshold compared to pure W). We believe this is an innovative sight to design new generation of transition-metal-based multifunctional coatings. Besides, our results are applicable for industrial application because it can be realized by simple manufacturing approaches, e.g. magnetron sputtering technology.
A Biomimetic Microfluidic Tumor Microenvironment Platform Mimicking the EPR Effect for Rapid Screening of Drug Delivery Systems
Authors: Tang Yuan , Soroush Fariborz , Sheffield Joel B. , Wang Bin , Prabhakarpandian Balabhaskar , Kiani Mohammad F.
Published: August 2017

Real-time monitoring of tumor drug delivery in vivo is a daunting challenge due to the heterogeneity and complexity of the tumor microenvironment. In this study, we developed a biomimetic microfluidic tumor microenvironment (bMTM) comprising co-culture of tumor and endothelial cells in a 3D environment. The platform consists of a vascular compartment featuring a network of vessels cultured with endothelial cells forming a complete lumen under shear flow in communication with 3D solid tumors cultured in a tumor compartment. Endothelial cell permeability to both small dye molecules and large liposomal drug carriers were quantified using fluorescence microscopy. Endothelial cell intercellular junction formation was characterized by immunostaining. Endothelial cell permeability significantly increased in the presence of either tumor cell conditioned media (TCM) or tumor cells. The magnitude of this increase in permeability was significantly higher in the presence of metastatic breast tumor cells as compared to non-metastatic ones. Immunostaining revealed impaired endothelial cell-cell junctions in the presence of either metastatic TCM or metastatic tumor cells. Our findings indicate that the bMTM platform mimics the tumor microenvironment including the EPR effect. This platform has a significant potential in applications such as cell-cell/cell-drug carrier interaction studies and rapid screening of cancer drug therapeutics/carriers.
Effects of surface defects on the mechanical properties of ZnO nanowires
Authors: Roy Aditi , Mead James , Wang Shiliang , Huang Han
Published: August 2017

The elastic modulus of ZnO nanowires was measured using a resonance method based on laser Doppler effect and their fracture strains were determined via two-point bending with the aid of optical nanomanipulation. The elastic moduli of ZnO nanowires with diameters of 78 to 310 nm vary from 123 to 154 GPa, which are close to the bulk value of 140 GPa and independent of the diameters and surface defects. However, the fracture strains of the ZnO nanowires depend significantly on their diameters, increasing from 2.1% to 6.0% with the decrease in diameter from 316 to 114 nm. Post-mortem TEM analysis of the ends of the fractured nanowires revealed that fracture initiated at surface defects. The Weibull statistical analysis demonstrated that a greater defect depth led to a smaller fracture strain. The surface-defect dominated fracture should be an important consideration for the design and application of nanowire-based nanoelectromechanical systems.
Multipole Modes Excitation of uncoupled dark Plasmons Resonators based on Frequency Selective Surface at X-band Frequency Regime
Authors: Lan Yu , Xu Yuehang , Jia Yonghao , Mei Tengda , Qu Shiwei , Yan Bo , Yang Deqiang , Chen Bo , Xu Ruimin , Li Yanrong
Published: August 2017

In this report, we theoretically and experimentally demonstrates that multipole modes could be excited effectively in dark plasmonic resonators without introducing any other bright resonators at microwave range based on a two-dimensional frequency selective surface (FSS) structure. These excited multipole resonances are closely related to the coupling strength between adjacent S-LSPs resonators (the periodicity of the FSS). The modes splitting effects and resonance frequencies of the excited multipole modes are regulated by changing the numbers of grooves and inner disk radius, both of which play significant roles in the excitation of the dark S-LSPs disk resonator at normal incidence. Moreover, the multipole resonances characteristics of dark S-LSPs resonators in the case of oblique incidence are also presented. Observation of such multipole resonances in dark S-LSPs without introducing extra bright resonance at normal/oblique incidence would find more potential applications in microwave and terahertz based sensors, plasmonic resonance devices and metamaterial devices.
Response of ecosystem CO2 fluxes to grazing intensities – a five-year experiment in the Hulunber meadow steppe of China
Authors: Yan R. R. , Tang H. J. , Lv S. H. , Jin D. Y. , Xin X. P. , Chen B. R. , Zhang B. H. , Yan Y. C. , Wang X. , Murray Philip J. , Yang G. X. , Xu L. J. , Li L. H. , Zhao S.
Published: August 2017

Grazing is the primary land use in the Hulunber meadow steppe. However, the quantitative effects of grazing on ecosystem carbon dioxide (CO2) fluxes in this zone remain unclear. A controlled experiment was conducted from 2010 to 2014 to study the effects of six stocking rates on CO2 flux, and the results showed that there were significant differences in CO2 fluxes by year, treatment, and month. The effects of light and intermediate grazing remained relatively constant with grazing year, whereas the effects of heavy grazing increased substantially with grazing duration. CO2 flux significantly decreased with increasing grazing intensity and duration, and it was significantly positively correlated with rainfall, soil moisture (SM), the carbon to nitrogen ratio (C/N ratio), soil available phosphorus (SAP), soil NH4+-N, soil NO3−N, aboveground biomass (AGB), coverage, height, and litter and negatively correlated with air temperature, total soil N (TN) and microbial biomass N (MBN). A correspondence analysis showed that the main factors influencing changes in CO2 emissions under grazing were AGB, height, coverage, SM, NH4+-N and NO3−N. Increased rainfall and reduced grazing resulted in greater CO2 emissions. Our study provides important information to improve our understanding of the role of livestock grazing in GHG emissions.
Linoleic acid metabolite leads to steroid resistant asthma features partially through NF-κB
Authors: Panda Lipsa , Gheware Atish , Rehman Rakhshinda , Yadav Manish K. , Jayaraj B. S. , Madhunapantula SubbaRao V. , Mahesh Padukudru Anand , Ghosh Balaram , Agrawal Anurag , Mabalirajan Ulaganathan
Published: August 2017

Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15–lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI). HODE treatment to allergic mice further increased airway hyperresponsiveness and goblet metaplasia. Treatment with dexamethasone was associated with increased neutrophilic inflammation in HODE treated allergic mice; unlike control allergic mice that showed resolution of inflammation. HODE induced loss of steroid sensitivity was associated with increased p-NFkB in mice and reduced GR-α transcript levels in cultured human bronchial epithelia. In summary, HODE modifies typical AAI to recapitulate many of the phenotypic features seen in severe steroid unresponsive asthma. We speculate that since HODE is a natural metabolite, it may be relevant to the increased asthma severity and steroid insensitivity in patients who are obese or consume high fat diets. Further characterization of HODE induced steroid insensitivity may clarify the mechanisms.
Defect generation in Pd layers by ‘smart’ films with high H-affinity
Authors: Burlaka Vladimir , Roddatis Vladimir , Bongers Marian David , Pundt Astrid
Published: August 2017

In this paper, we demonstrate that the microstructure and the surface of a thin palladium (Pd) film can be intentionally altered by the presence of a subjacent niobium (Nb) film. Depending on the thickness of the Nb film and on the hydrogen gas pressure, defects in the Pd film can be healed or created. To demonstrate this effect, Pd/Nb/sapphire (Al2O3) stacks are studied during hydrogen gas exposure at room temperature by using scanning tunneling microscopy (STM), X-ray diffraction (XRD) and environmental transmission electron microscopy (ETEM). STM shows that hydrogen-induced topography changes in the Nb films depend on the film thickness which affects the height of the Nb surface corrugations, their lateral size and distribution. XRD measurements show that these changes in the Nb hydride film influence the microstructure of the overlaying Pd film. ETEM reveals that the modifications of the Pd film occur due to the precipitation and growth of the Nb hydride phase. The appearance of new defects, interface and surface roughening is observed in the Pd film above locally grown Nb hydride grains. These results can open a new route to design ‘smart’ catalysts or membranes, which may accommodate their microstructure depending on the gaseous environment.
Drastic Improvement in Adhesion Property of Polytetrafluoroethylene (PTFE) via Heat-Assisted Plasma Treatment Using a Heater
Authors: Ohkubo Yuji , Ishihara Kento , Shibahara Masafumi , Nagatani Asahiro , Honda Koji , Endo Katsuyoshi , Yamamura Kazuya
Published: August 2017

The heating effect on the adhesion property of plasma-treated polytetrafluoroethylene (PTFE) was examined. For this purpose, a PTFE sheet was plasma-treated at atmospheric pressure while heating using a halogen heater. When plasma-treated at 8.3 W/cm2 without using the heater (Low-P), the surface temperature of Low-P was about 95 °C. In contrast, when plasma-treated at 8.3 W/cm2 while using the heater (Low-P+Heater), the surface temperature of Low-P+Heater was controlled to about 260 °C. Thermal compression of the plasma-treated PTFE with or without heating and isobutylene−isoprene rubber (IIR) was performed, and the adhesion strength of the IIR/PTFE assembly was measured via the T-peel test. The adhesion strengths of Low-P and Low-P+Heater were 0.12 and 2.3 N/mm, respectively. Cohesion failure of IIR occurred during the T-peel test because of its extremely high adhesion property. The surfaces of the plasma-treated PTFE with or without heating were investigated by the measurements of electron spin resonance, X-ray photoelectron spectroscopy, nanoindentation, scanning electron microscopy, and scanning probe microscopy. These results indicated that heating during plasma treatment promotes the etching of the weak boundary layer (WBL) of PTFE, resulting in a sharp increase in the adhesion property of PTFE.
Optogenetic regulation of insulin secretion in pancreatic β-cells
Authors: Zhang Fan , Tzanakakis Emmanuel S.
Published: August 2017

Pancreatic β-cell insulin production is orchestrated by a complex circuitry involving intracellular elements including cyclic AMP (cAMP). Tackling aberrations in glucose-stimulated insulin release such as in diabetes with pharmacological agents, which boost the secretory capacity of β-cells, is linked to adverse side effects. We hypothesized that a photoactivatable adenylyl cyclase (PAC) can be employed to modulate cAMP in β-cells with light thereby enhancing insulin secretion. To that end, the PAC gene from Beggiatoa (bPAC) was delivered to β-cells. A cAMP increase was noted within 5 minutes of photostimulation and a significant drop at 12 minutes post-illumination. The concomitant augmented insulin secretion was comparable to that from β-cells treated with secretagogues. Greater insulin release was also observed over repeated cycles of photoinduction without adverse effects on viability and proliferation. Furthermore, the expression and activation of bPAC increased cAMP and insulin secretion in murine islets and in β-cell pseudoislets, which displayed a more pronounced light-triggered hormone secretion compared to that of β-cell monolayers. Calcium channel blocking curtailed the enhanced insulin response due to bPAC activity. This optogenetic system with modulation of cAMP and insulin release can be employed for the study of β-cell function and for enabling new therapeutic modalities for diabetes.
Solving the inverse problem for coarse-mode aerosol particle morphology with digital holography
Authors: Berg Matthew J. , Heinson Yuli W. , Kemppinen Osku , Holler Stephen
Published: August 2017

Coarse mode atmospheric aerosol particles are abundant in agricultural, desert, and urban environments. Accurate characterisation of these particles’ morphology is an important need in scientific and applied contexts, especially to advance our understanding for how such aerosols influence solar radiative forcing of the atmosphere. Elastic light scattering is a standard method to study aerosol particles in a contact-free manner, wherein measured scattering patterns are interpreted to infer particle morphology. Due in part to the absence of wave-phase information in these measurements, the inference is not unique, a difficulty generally known as the inverse problem. An alternative approach is digital holography where wave-phase information is encoded in the measurements. We show that digital holography and spatial filtering can solve the inverse problem for free-flowing aerosol particles in the sense that a measured scattering pattern can be uniquely associated with the particle size, shape, and orientation producing it.
Process performance and methane production optimizing of anaerobic co-digestion of swine manure and corn straw
Authors: Mao Chunlan , Zhang Tong , Wang Xiaojiao , Feng Yongzhong , Ren Guangxin , Yang Gaihe
Published: August 2017

During anaerobic digestion (AD) process, process parameters e.g., VFA, pH, COD removal … and kinetic parameters e.g., hydrolysis rate, lag phase and methane production potential… are the important indicator for illustrating AD process performance, however, the AD process performance based on these parameters remains poorly understood. To estimate process performance focusing on initial pH and substrate composition, the effects of initial pH and swine manure to corn straw ratio on biogas production and these parameters and linkages of these parameters were analyzed. Also, the methane production was optimized. The results revealed that the maximum methane yield and methane production rate were obtained with initial pH 7.5 and SM/CS ratio of 70:30. Kinetic parameters are coupled with process parameters, especially for COD removal rate, VS degradation rate, VFA and pH. Hydrolysis constant positively correlated with pH, COD removal rate and VS degradation rate, then impacted methane production and lag phase. Meanwhile, lag phase and the maximum methane production rate were directly determined by VFA and COD removal rate. The optimum initial pH and SM/CS ratio were 7.15 and 0.62, respectively, with a predicted maximum methane content of 55.12%. Thinking these findings together, they provide a scientific theory for estimating AD performance.
Changes of plasmalogen phospholipid levels during differentiation of induced pluripotent stem cells 409B2 to endothelial phenotype cells
Authors: Nakamura Yusuke , Shimizu Yasuo , Horibata Yasuhiro , Tei Rinna , Koike Ryosuke , Masawa Meitetsu , Watanabe Taiji , Shiobara Taichi , Arai Ryo , Chibana Kazuyuki , Takemasa Akihiro , Sugimoto Hiroyuki , Ishii Yoshiki
Published: August 2017

Endothelial cells (EC) are involved in regulating several aspects of lipid metabolism, with recent research revealing the clinicopathological significance of interactions between EC and lipids. Induced pluripotent stem cells (iPSC) have various possible medical uses, so understanding the metabolism of these cells is important. In this study, endothelial phenotype cells generated from human iPSC formed cell networks in co-culture with fibroblasts. Changes of plasmalogen lipids and sphingomyelins in endothelial phenotype cells generated from human iPSC were investigated by reverse-phase ultra-high-pressure liquid chromatography mass spectrometry (UHPLC-MS/MS) analysis. The levels of plasmalogen phosphatidylethanolamines (38:5) and (38:4) increased during differentiation of EC, while sphingomyelin levels decreased transiently. These changes of plasmalogen lipids and sphingomyelins may have physiological significance for EC and could be used as markers of differentiation.
Activation-tagging in indica rice identifies a novel transcription factor subunit, NF-YC13 associated with salt tolerance
Authors: Manimaran P. , Venkata Reddy S. , Moin Mazahar , Raghurami Reddy M. , Yugandhar Poli , Mohanraj S. S. , Balachandran S. M. , Kirti P. B.
Published: August 2017

Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor with three distinct NF-YA, NF-YB and NF-YC subunits. It plays important roles in plant growth, development and stress responses. We have reported earlier on development of gain-of-function mutants in an indica rice cultivar, BPT-5204. Now, we screened 927 seeds from 70 Ac/Ds plants for salinity tolerance and identified one activation-tagged salt tolerant DS plant (DS-16, T3 generation) that showed enhanced expression of a novel ‘histone-like transcription factor’ belonging to rice NF-Y subfamily C and was named as OsNF-YC13. Localization studies using GFP-fusion showed that the protein is localized to nucleus and cytoplasm. Real time expression analysis confirmed upregulation of transcript levels of OsNF-YC13 during salt treatment in a tissue specific manner. Biochemical and physiological characterization of the DS-16 revealed enhanced K+/Na+ ratio, proline content, chlorophyll content, enzymes with antioxidant activity etc. DS-16 also showed transcriptional up-regulation of genes that are involved in salinity tolerance. In-silico analysis of OsNF-YC13 promoter region evidenced the presence of various key stress-responsive cis-regulatory elements. OsNF-YC13 subunit alone does not appear to have the capacity for direct transcription activation, but appears to interact with the B- subunits in the process of transactivation.
Giardia’s primitive GPL biosynthesis pathways with parasitic adaptation ‘patches’: implications for Giardia’s evolutionary history and for finding targets against Giardiasis
Authors: Ye Qingqing , Tian Haifeng , Chen Bing , Shao Jingru , Qin Yan , Wen Jianfan
Published: August 2017

Giardia is a worldwide spread protozoan parasite colonizing in small intestines of vertebrates, causing Giardiasis. The controversy about whether it is an extremely primitive eukaryote or just a highly evolved parasite has become a fetter to its uses as a model for both evolutionary and parasitological studies for years. Glycerophospholipid (GPL) synthesis is a conserved essential cellular process, and thus may retain some original features reflecting its evolutionary position, and this process should also have undergone parasitic adaptation to suit Giardia’s dietary lipid-rich environment. Thus, GPL synthesis pathways may be a perfect object to examine the controversy over Giardia. Here, we first clarified Giardia’s previously confusing GPL synthesis by re-identifying a reliable set of GPL synthesis genes/enzymes. Then using phylogenetic and comparative genomic analyses, we revealed that these pathways turn out to be evolutionarily primitive ones, but with many secondary parasitic adaptation ‘patches’ including gene loss, rapid evolution, product relocation, and horizontal gene transfer. Therefore, modern Giardia should be a mosaic of ‘primary primitivity’ and ‘secondary parasitic adaptability’, and to make a distinction between the two categories of features would restart the studies of eukaryotic evolution and parasitic adaptation using Giardia as a model system.