bluuebunny/crossref_metadata_2025 huggingface dataset:
Eukaryotic association module in phage WO genomes from Wolbachia
Authors: Bordenstein Sarah R. , Bordenstein Seth R.
Published: October 2016

Viruses are trifurcated into eukaryotic, archaeal and bacterial categories. This domain-specific ecology underscores why eukaryotic viruses typically co-opt eukaryotic genes and bacteriophages commonly harbour bacterial genes. However, the presence of bacteriophages in obligate intracellular bacteria of eukaryotes may promote DNA transfers between eukaryotes and bacteriophages. Here we report a metagenomic analysis of purified bacteriophage WO particles of Wolbachia and uncover a eukaryotic association module in the complete WO genome. It harbours predicted domains, such as the black widow latrotoxin C-terminal domain, that are uninterrupted in bacteriophage genomes, enriched with eukaryotic protease cleavage sites and combined with additional domains to forge one of the largest bacteriophage genes to date (14,256 bp). To the best of our knowledge, these eukaryotic-like domains have never before been reported in packaged bacteriophages and their phylogeny, distribution and sequence diversity imply lateral transfers between bacteriophage/prophage and animal genomes. Finally, the WO genome sequences and identification of attachment sites will potentially advance genetic manipulation of Wolbachia.
Effect of Mild Heating on Human Lens Epithelial Cells: A Possible Model of Lens Aging
Authors: Zhang Keke , Zhu Xiangjia , Lu Yi
Published: October 2016

This study aims to investigate the effect of mild heating on lens epithelial cells and to explore its possibility as an in vitro model for lens aging. Human lens epithelial cells (LECs) were heated at 50 °C for a cellular lens aging study. Analysis of the head group order of lens membranes was performed using Laurdan labeling. Immunofluorescence was performed to detect changes in α-crystallin expression and its cellular distribution. The chaperone-like activity of α-crystallin was also assessed. After mild heating, α-crystallin in LECs showed a tendency towards accumulation around the nucleus. The membrane head group environment of lens epithelial cells became more fluid with increasing time of exposure to mild heating, as indicated by increased water penetration. Furthermore, the chaperone activity of α-crystallin decreased, and suggests a relatively lower protective effect on other functional proteins in LECs. Thus, compared to the mild heating model based on lens tissue, this cellular model could provide a more convenient and accurate method for studying lens aging in vitro, including changes in membrane head group order in each cell, the real-time observation of crystallin distribution, and the monitoring of functional changes in the chaperone activity of crystallins as a result of aging.
Glycosylation site occupancy in health, congenital disorder of glycosylation and fatty liver disease
Authors: Hülsmeier Andreas J. , Tobler Micha , Burda Patricie , Hennet Thierry
Published: October 2016

Glycosylation is an integral part in health and disease, as emphasized by the growing number of identified glycosylation defects. In humans, proteins are modified with a diverse range of glycoforms synthesized in complex biosynthetic pathways. Glycosylation disorders have been described in congenital disorders of glycosylation (CDG) as well as in acquired disease conditions such and non-alcoholic fatty liver disease (NAFLD). A hallmark in a subset of CDG cases is the reduced glycosylation site occupancy of asparagine-linked glycans. Using an optimized method protocol, we determined the glycosylation site occupancy from four proteins of hepatic and lymphatic origin from CDG and NAFLD patients. We found variable degrees of site occupancy, depending on the tissue of origin and the disease condition. In CDG glycosylation sites of IgG2 and IgA1 were occupied to normal levels. In NAFLD haptoglobin and transferrin glycosylation sites were hyper-glycosylated, a property qualifying for its use as a potential biomarker. Furthermore, we observed, that glycosylation sites of liver-originating transferrin and haptoglobin are differentially occupied under physiological conditions, a further instance not noticed in serum proteins to date. Our findings suggest the use of serum protein hyperglycosylation as a biomarker for early stages of NAFLD.
Cyr61 participates in the pathogenesis of acute lymphoblastic leukemia by enhancing cellular survival via the AKT/NF-κB signaling pathway
Authors: Zhu Xianjin , Song Yanfang , Wu Conglian , Pan Chuxi , Lu Pingxia , Wang Meihua , Zheng Peizheng , Huo Rongfen , Zhang Chenqing , Li Wanting , Lin Yulin , Cao Yingping , Li Ningli
Published: October 2016

Cyr61 (CCN1) is the product of a growth factor–inducible immediate early gene and is involved in cell adhesion, survival, proliferation and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients. Furthermore, we observed that Cyr61 could effectively stimulate Jurkat (T ALL cell lines), Nalm-6 (B ALL cell lines) and primary ALL cell survival. Mechanistically, we showed that Cyr61 stimulated ALL cell survival via the AKT/NF-κB signaling pathways and the consequent up-regulation of Bcl-2. Taken together, our study is the first to reveal that Cyr61 is elevated in ALL and promotes cell survival through the AKT/NF-κB pathway by up-regulating Bcl-2. Our findings suggest that Cyr61 plays an important role in the pathogenesis of ALL.
Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy
Authors: Murugan Chandran , Rayappan Kathirvel , Thangam Ramar , Bhanumathi Ramasamy , Shanthi Krishnamurthy , Vivek Raju , Thirumurugan Ramasamy , Bhattacharyya Atanu , Sivasubramanian Srinivasan , Gunasekaran Palani , Kannan Soundarapandian
Published: October 2016

Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms asin vitroandin vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium.
Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA
Authors: Hsu Min-Yen , Hung Yu-Chien , Hwang De-Kuang , Lin Shang-Chi , Lin Keng-Hung , Wang Chun-Yuan , Choi Hin-Yeung , Wang Yu-Ping , Cheng Chao-Min
Published: October 2016

Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies.
ADHD-associated risk taking is linked to exaggerated views of the benefits of positive outcomes
Authors: Shoham Rachel , Sonuga-Barke Edmund J. S. , Aloni Hamutal , Yaniv Ilan , Pollak Yehuda
Published: October 2016

Attention deficit and hyperactivity disorder (ADHD) is often assumed to be associated with increased engagement in risk-taking behaviors. The current study sought to understand the mental processes underlying this association using a theory-driven behavioral economics perspective. Psychological risk-return models suggest that risk and benefit are inherently subjective, and risk taking is best understood as the interplay between cognitions and motivations regarding the benefits and risks of alternatives. A sample of 244 adults was assessed for ADHD symptoms. The likelihood of engagement in a range of risky behaviors (e.g., driving without wearing a seat belt), the magnitude of perceived benefit and risk ascribed to these behaviors, and benefit and risk attitudes of each participant were extracted from the Domain Specific Risk Taking (DOSPERT) scales. ADHD symptoms were correlated with more risky behaviors and perception of greater benefits from engaging in these behaviors, but were not correlated with risk perception. Mediation analysis revealed that the association between ADHD symptoms and engagement in risk taking was mediated by perceived benefits. These findings highlight the idea that people with high level ADHD symptoms tend to engage in risky behaviors because they find such behavior particularly appealing, rather than because they seek risk per se.
Graph distance for complex networks
Authors: Shimada Yutaka , Hirata Yoshito , Ikeguchi Tohru , Aihara Kazuyuki
Published: October 2016

Networks are widely used as a tool for describing diverse real complex systems and have been successfully applied to many fields. The distance between networks is one of the most fundamental concepts for properly classifying real networks, detecting temporal changes in network structures, and effectively predicting their temporal evolution. However, this distance has rarely been discussed in the theory of complex networks. Here, we propose a graph distance between networks based on a Laplacian matrix that reflects the structural and dynamical properties of networked dynamical systems. Our results indicate that the Laplacian-based graph distance effectively quantifies the structural difference between complex networks. We further show that our approach successfully elucidates the temporal properties underlying temporal networks observed in the context of face-to-face human interactions.
Highly stable, extremely high-temperature, nonvolatile memory based on resistance switching in polycrystalline Pt nanogaps
Authors: Suga Hiroshi , Suzuki Hiroya , Shinomura Yuma , Kashiwabara Shota , Tsukagoshi Kazuhito , Shimizu Tetsuo , Naitoh Yasuhisa
Published: October 2016

Highly stable, nonvolatile, high-temperature memory based on resistance switching was realized using a polycrystalline platinum (Pt) nanogap. The operating temperature of the memory can be drastically increased by the presence of a sharp-edged Pt crystal facet in the nanogap. A short distance between the facet edges maintains the nanogap shape at high temperature, and the sharp shape of the nanogap densifies the electric field to maintain a stable current flow due to field migration. Even at 873 K, which is a significantly higher temperature than feasible for conventional semiconductor memory, the nonvolatility of the proposed memory allows stable ON and OFF currents, with fluctuations of less than or equal to 10%, to be maintained for longer than eight hours. An advantage of this nanogap scheme for high-temperature memory is its secure operation achieved through the assembly and disassembly of a Pt needle in a high electric field.
Swiss identity smells like chocolate: Social identity shapes olfactory judgments
Authors: Coppin Géraldine , Pool Eva , Delplanque Sylvain , Oud Bastiaan , Margot Christian , Sander David , Van Bavel Jay J.
Published: October 2016

There is extensive evidence that social identities can shape people’s attitudes and behavior, but what about sensory judgments? We examined the possibility that social identity concerns may also shape the judgment of non-social properties—namely, olfactory judgment. In two experiments, we presented Swiss and non-Swiss participants with the odor of chocolate, for which Switzerland is world-famous, and a control odor (popcorn). Swiss participants primed with Swiss identity reported the odor of chocolate (but not popcorn) as more intense than non-Swiss participants (Experiments 1 and 2) and than Swiss participants primed with individual identity or not primed (Experiment 2). The self-reported intensity of chocolate smell tended to increase as identity accessibility increased—but only among Swiss participants (Experiment 1). These results suggest that identity priming can counter-act classic sensory habituation effects, allowing identity-relevant smells to maintain their intensity after repeated presentations. This suggests that social identity dynamically influences sensory judgment. We discuss the potential implications for models of social identity and chemosensory perception.
Quantitative analysis of hydrogen sites and occupancy in deep mantle hydrous wadsleyite using single crystal neutron diffraction
Authors: Purevjav Narangoo , Okuchi Takuo , Tomioka Naotaka , Wang Xiaoping , Hoffmann Christina
Published: October 2016

Evidence from seismological and mineralogical studies increasingly indicates that water from the oceans has been transported to the deep earth to form water-bearing dense mantle minerals. Wadsleyite [(Mg, Fe2+)2SiO4] has been identified as one of the most important host minerals incorporating this type of water, which is capable of storing the entire mass of the oceans as a hidden reservoir. To understand the effects of such water on the physical properties and chemical evolution of Earth’s interior, it is essential to determine where in the crystal structure the hydration occurs and which chemical bonds are altered and weakened after hydration. Here, we conduct a neutron time-of-flight single-crystal Laue diffraction study on hydrous wadsleyite. Single crystals were grown under pressure to a size suitable for the experiment and with physical qualities representative of wet, deep mantle conditions. The results of this neutron single crystal diffraction study unambiguously demonstrate the method of hydrogen incorporation into the wadsleyite, which is qualitatively different from that of its denser polymorph, ringwoodite, in the wet mantle. The difference is a vital clue towards understanding why these dense mantle minerals show distinctly different softening behaviours after hydration.
The unravelling of the complex pattern of tyrosinase inhibition
Authors: Deri Batel , Kanteev Margarita , Goldfeder Mor , Lecina Daniel , Guallar Victor , Adir Noam , Fishman Ayelet
Published: October 2016

Tyrosinases are responsible for melanin formation in all life domains. Tyrosinase inhibitors are used for the prevention of severe skin diseases, in skin-whitening creams and to avoid fruit browning, however continued use of many such inhibitors is considered unsafe. In this study we provide conclusive evidence of the inhibition mechanism of two well studied tyrosinase inhibitors, KA (kojic acid) and HQ (hydroquinone), which are extensively used in hyperpigmentation treatment. KA is reported in the literature with contradicting inhibition mechanisms, while HQ is described as both a tyrosinase inhibitor and a substrate. By visualization of KA and HQ in the active site of TyrBm crystals, together with molecular modeling, binding constant analysis and kinetic experiments, we have elucidated their mechanisms of inhibition, which was ambiguous for both inhibitors. We confirm that while KA acts as a mixed inhibitor, HQ can act both as a TyrBm substrate and as an inhibitor.
Crystal structure of a DNA aptamer bound to PvLDH elucidates novel single-stranded DNA structural elements for folding and recognition
Authors: Choi Sung-Jin , Ban Changill
Published: October 2016

Structural elements are key elements for understanding single-stranded nucleic acid folding. Although various RNA structural elements have been documented, structural elements of single-stranded DNA (ssDNA) have rarely been reported. Herein, we determined a crystal structure of PvLDH in complex with a DNA aptamer called pL1. This aptamer folds into a hairpin-bulge contact by adopting three novel structural elements, viz, DNA T-loop-like motif, base–phosphate zipper, and DNA G·G metal ion zipper. Moreover, the pL1:PvLDH complex shows unique properties compared with other protein:nucleic acid complexes. Generally, extensive intermolecular hydrogen bonds occur between unpaired nucleotides and proteins for specific recognitions. Although most protein-interacting nucleotides of pL1 are unpaired nucleotides, pL1 recognizes PvLDH by predominant shape complementarity with many bridging water molecules owing to the combination of three novel structural elements making protein-binding unpaired nucleotides stable. Moreover, the additional set of Plasmodium LDH residues which were shown to form extensive hydrogen bonds with unpaired nucleotides of 2008s does not participate in the recognition of pL1. Superimposition of the pL1:PvLDH complex with hLDH reveals steric clashes between pL1 and hLDH in contrast with no steric clashes between 2008s and hLDH. Therefore, specific protein recognition mode of pL1 is totally different from that of 2008s.
Cleaning patch-clamp pipettes for immediate reuse
Authors: Kolb I. , Stoy W. A. , Rousseau E. B. , Moody O. A. , Jenkins A. , Forest C. R.
Published: October 2016

Patch-clamp recording has enabled single-cell electrical, morphological and genetic studies at unparalleled resolution. Yet it remains a laborious and low-throughput technique, making it largely impractical for large-scale measurements such as cell type and connectivity characterization of neurons in the brain. Specifically, the technique is critically limited by the ubiquitous practice of manually replacing patch-clamp pipettes after each recording. To circumvent this limitation, we developed a simple, fast, and automated method for cleaning glass pipette electrodes that enables their reuse within one minute. By immersing pipette tips into Alconox, a commercially-available detergent, followed by rinsing, we were able to reuse pipettes 10 times with no degradation in signal fidelity, in experimental preparations ranging from human embryonic kidney cells to neurons in culture, slices, and in vivo. Undetectable trace amounts of Alconox remaining in the pipette after cleaning did not affect ion channel pharmacology. We demonstrate the utility of pipette cleaning by developing the first robot to perform sequential patch-clamp recordings in cell culture and in vivo without a human operator.
Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging
Authors: Xu Jing , Chen Yanhua , Zhang Ruiping , He Jiuming , Song Yongmei , Wang Jingbo , Wang Huiqing , Wang Luhua , Zhan Qimin , Abliz Zeper
Published: October 2016

We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.
Good Biocompatibility and Sintering Properties of Zirconia Nanoparticles Synthesized via Vapor-phase Hydrolysis
Authors: Wang Jigang , Yin Wenyan , He Xiao , Wang Qiang , Guo Ming , Chen Shaowei
Published: October 2016

ZrO2 nanoparticles were synthesized by a vapor-phase hydrolysis process, and characterized in terms of crystalline structures, hardness and microstructures by X-ray diffraction, Vickers hardness test method, and atomic force microscopy (AFM) measurements. Moreover, in vitro cytotoxicity evaluation and hemolysis assay showed that the nanoparticles possessed good biocompatibility. Hardness investigations and AFM measurements indicated that both the sintering temperature and compression force played an important role in determining the physical behaviors (hardness, roughness and density) of flakes of the ZrO2 nanoparticles. When ZrO2 nanoparticles synthesized at 500 °C were pressed into flakes under 6 MPa and sintered at 1400 °C, the resulting flakes exhibited an optimal combination of hardness (534.58 gf·mm−2), roughness (0.07 μm) and density (4.41 g·cm−3). As the Vickers hardness value of human bones is of 315~535 gf·mm−2 and the density of adult femuris about 1.3~1.7 g·cm−3, the experimental results showed that the ZrO2 flakes were comparable to human bones with a higher density. As a result, the synthesized ZrO2 NPs may be useful for biomedical applications, especially for bone repair and replacement in future.
Microstructural characterization of random packings of cubic particles
Authors: Malmir Hessam , Sahimi Muhammad , Tabar M. Reza Rahimi
Published: October 2016

Understanding the properties of random packings of solid objects is of critical importance to a wide variety of fundamental scientific and practical problems. The great majority of the previous works focused, however, on packings of spherical and sphere-like particles. We report the first detailed simulation and characterization of packings of non-overlapping cubic particles. Such packings arise in a variety of problems, ranging from biological materials, to colloids and fabrication of porous scaffolds using salt powders. In addition, packing of cubic salt crystals arise in various problems involving preservation of pavements, paintings, and historical monuments, mineral-fluid interactions, CO2 sequestration in rock, and intrusion of groundwater aquifers by saline water. Not much is known, however, about the structure and statistical descriptors of such packings. We have developed a version of the random sequential addition algorithm to generate such packings, and have computed a variety of microstructural descriptors, including the radial distribution function, two-point probability function, orientational correlation function, specific surface, and mean chord length, and have studied the effect of finite system size and porosity on such characteristics. The results indicate the existence of both spatial and orientational long-range order in the packing, which is more distinctive for higher packing densities. The maximum packing fraction is about 0.57.
Consistent responses of the microbial community structure to organic farming along the middle and lower reaches of the Yangtze River
Authors: Wang Wenhui , Wang Hui , Feng Youzhi , Wang Lei , Xiao Xingji , Xi Yunguan , Luo Xue , Sun Ruibo , Ye Xianfeng , Huang Yan , Zhang Zhengguang , Cui Zhongli
Published: October 2016

Soil microorganisms play a crucial role in the biogeochemical cycling of nutrient elements and maintaining soil health. We aimed to investigate the response of bacteria communities to organic farming over different crops (rice, tea and vegetable) along the middle and lower reaches of the Yangtze River of China. Compared with conventional farming, organic farming significantly increased soil nutrients, soil enzyme activities, and bacterial richness and diversity. A Venn diagram and principal component analysis revealed that the soils with 3 different crops under organic farming have more number and percent of shared OTUs (operational taxonomic units), and shared a highly similar microbial community structure. Under organic farming, several predominant guilds and major bacterial lineages (Rhizobiales, Thiotrichaceae, Micromonosporaceae, Desulfurellaceae and Myxococcales) contributing to nutrient (C, N, S and P) cycling were enriched, whereas the relative abundances of acid and alkali resistant microorganisms (Acidobacteriaceae and Sporolactobacillaceae) were increased under conventional farming practices. Our results indicated that, for all three crops, organic farming have a more stable microflora and the uniformity of the bacterial community structure. Organic agriculture significantly increased the abundance of some nutrition-related bacteria, while reducing some of the abundance of acid and alkali resistant bacteria.
Safety Evaluation and Imaging Properties of Gadolinium-Based Nanoparticles in nonhuman primates
Authors: Kotb Shady , Piraquive Joao , Lamberton Franck , Lux François , Verset Michael , Di Cataldo Vanessa , Contamin Hugues , Tillement Olivier , Canet-Soulas Emmanuelle , Sancey Lucie
Published: October 2016

In this article, we report the safety evaluation of gadolinium-based nanoparticles in nonhuman primates (NHP) in the context of magnetic resonance imaging (MRI) studies in atherosclerosis bearing animals and healthy controls. In healthy NHP, the pharmacokinetics and toxicity profiles demonstrated the absence of dose, time, and sex-effects, as well as a suitable tolerance of intravenous administration of the nanoparticles. We investigated their imaging properties for arterial plaque imaging in a standard diet or a high cholesterol diet NHP, and compared their characteristics with clinically applied Gd-chelate. This preliminary investigation reports the efficient and safe imaging of atherosclerotic plaques.
Three-dimensional X-ray visualization of axonal tracts in mouse brain hemisphere
Authors: Mizutani Ryuta , Saiga Rino , Ohtsuka Masato , Miura Hiromi , Hoshino Masato , Takeuchi Akihisa , Uesugi Kentaro
Published: October 2016

Neurons transmit active potentials through axons, which are essential for the brain to function. In this study, the axonal networks of the murine brain were visualized with X-ray tomographic microscopy, also known as X-ray microtomography or micro-CT. Murine brain samples were freeze-dried to reconstitute the intrinsic contrast of tissue constituents and subjected to X-ray visualization. A whole brain hemisphere visualized by absorption contrast illustrated three-dimensional structures including those of the striatum, corpus callosum, and anterior commissure. Axonal tracts observed in the striatum start from the basal surface of the cerebral cortex and end at various positions in the basal ganglia. The distribution of X-ray attenuation coefficients indicated that differences in water and phospholipid content between the myelin sheath and surrounding tissue constituents account for the observed contrast. A rod-shaped cutout of brain tissue was also analyzed with a phase retrieval method, wherein tissue microstructures could be resolved with up to 2.7 μm resolution. Structures of axonal networks of the striatum were reconstructed by tracing axonal tracts. Such an analysis should be able to delineate the functional relationships of the brain regions involved in the observed network.
Three-dimensional electron microscopy reveals the evolution of glomerular barrier injury
Authors: Randles Michael J. , Collinson Sophie , Starborg Tobias , Mironov Aleksandr , Krendel Mira , Königshausen Eva , Sellin Lorenz , Roberts Ian S. D. , Kadler Karl E. , Miner Jeffrey H. , Lennon Rachel
Published: October 2016

Glomeruli are highly sophisticated filters and glomerular disease is the leading cause of kidney failure. Morphological change in glomerular podocytes and the underlying basement membrane are frequently observed in disease, irrespective of the underlying molecular etiology. Standard electron microscopy techniques have enabled the identification and classification of glomerular diseases based on two-dimensional information, however complex three-dimensional ultrastructural relationships between cells and their extracellular matrix cannot be easily resolved with this approach. We employed serial block face-scanning electron microscopy to investigate Alport syndrome, the commonest monogenic glomerular disease, and compared findings to other genetic mouse models of glomerular disease (Myo1e−/−, Ptpro−/−). These analyses revealed the evolution of basement membrane and cellular defects through the progression of glomerular injury. Specifically we identified sub-podocyte expansions of the basement membrane with both cellular and matrix gene defects and found a corresponding reduction in podocyte foot process number. Furthermore, we discovered novel podocyte protrusions invading into the glomerular basement membrane in disease and these occurred frequently in expanded regions of basement membrane. These findings provide new insights into mechanisms of glomerular barrier dysfunction and suggest that common cell-matrix-adhesion pathways are involved in the progression of disease regardless of the primary insult.
Microfluidics-based point-of-care test for serodiagnosis of Lyme Disease
Authors: Nayak Samiksha , Sridhara Archana , Melo Rita , Richer Luciana , Chee Natalie H. , Kim Jiyoon , Linder Vincent , Steinmiller David , Sia Samuel K. , Gomes-Solecki Maria
Published: October 2016

Currently, diagnostic testing for Lyme disease is done by determination of the serologic responses to Borrelia burgdorferi antigens, with the exception of the early localized phase of disease where diagnosis must be done clinically. Here, we describe the use of microfluidics technology to develop a multiplexed rapid lab-on-a-chip point of care (POC) assay for the serologic diagnosis of human Lyme disease. Following ELISA screening of 12 candidate antigens, we tested 8 on a microfluidic diagnostic system, called mChip-Ld, using a set of 60 serological samples. The mChip-Ld test, which can be performed in 15 minutes at the point of care, showed promising performance for detection of antibodies to B. burgdorferi using the PPO triplex test (rP100 + PepVF + rOspC-K, AUC of 0.844) compared to a gold-standard reference of culture confirmed clinical samples. The performance is comparable to the commonly used C6 peptide by lab-based ELISA. In addition, the mChip-Ld test showed promising performance for early-stage diagnosis of the disease using the antigen OspC-K (sensitivity and specificity of 84% and 92%, respectively; AUC of 0.877). Overall, this study underscores the potential of using microfluidics to aid the diagnosis of Lyme disease at the point of care.
RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma
Authors: Rau Julietta V. , Graziani Valerio , Fosca Marco , Taffon Chiara , Rocchia Massimiliano , Crucitti Pierfilippo , Pozzilli Paolo , Onetti Muda Andrea , Caricato Marco , Crescenzi Anna
Published: October 2016

Recent investigations strongly suggest that Raman spectroscopy (RS) can be used as a clinical tool in cancer diagnosis to improve diagnostic accuracy. In this study, we evaluated the efficiency of Raman imaging microscopy to discriminate between healthy and neoplastic thyroid tissue, by analyzing main variants of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. We performed Raman imaging of large tissue areas (from 100 × 100 μm2 up to 1 × 1 mm2), collecting 38 maps containing about 9000 Raman spectra. Multivariate statistical methods, including Linear Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Our study is the first demonstration of specific biochemical features of the PTC profile, characterized by significant presence of carotenoids with respect to the healthy tissue. Moreover, this is the first evidence of Raman spectra differentiation between classical and follicular variant of PTC, discriminated by LDA with high efficiency. The combined histological and Raman microscopy analyses allow clear-cut integration of morphological and biochemical observations, with dramatic improvement of efficiency and reliability in the differential diagnosis of neoplastic thyroid nodules, paving the way to integrative findings for tumorigenesis and novel therapeutic strategies.
PAI: Predicting adenosine to inosine editing sites by using pseudo nucleotide compositions
Authors: Chen Wei , Feng Pengmian , Ding Hui , Lin Hao
Published: October 2016

The adenosine to inosine (A-to-I) editing is the most prevalent kind of RNA editing and involves in many biological processes. Accurate identification of A-to-I editing site is invaluable for better understanding its biological functions. Due to the limitations of experimental methods, in the present study, a support vector machine based-model, called PAI, is proposed to identify A-to-I editing site in D. melanogaster. In this model, RNA sequences are encoded by “pseudo dinucleotide composition” into which six RNA physiochemical properties were incorporated. PAI achieves promising performances in jackknife test and independent dataset test, indicating that it holds very high potential to become a useful tool for identifying A-to-I editing site. For the convenience of experimental scientists, a web-server was constructed for PAI and it is freely accessible at http://lin.uestc.edu.cn/server/PAI.
Capturing coupled riparian and coastal disturbance from industrial mining using cloud-resilient satellite time series analysis
Authors: Alonzo Michael , Van Den Hoek Jamon , Ahmed Nabil
Published: October 2016

The socio-ecological impacts of large scale resource extraction are frequently underreported in underdeveloped regions. The open-pit Grasberg mine in Papua, Indonesia, is one of the world’s largest copper and gold extraction operations. Grasberg mine tailings are discharged into the lowland Ajkwa River deposition area (ADA) leading to forest inundation and degradation of water bodies critical to indigenous peoples. The extent of the changes and temporal linkages with mining activities are difficult to establish given restricted access to the region and persistent cloud cover. Here, we introduce remote sensing methods to “peer through” atmospheric contamination using a dense Landsat time series to simultaneously quantify forest loss and increases in estuarial suspended particulate matter (SPM) concentration. We identified 138 km2of forest loss between 1987 and 2014, an area >42 times larger than the mine itself. Between 1987 and 1998, the rate of disturbance was highly correlated (Pearson’sr = 0.96) with mining activity. Following mine expansion and levee construction along the ADA in the mid-1990s, we recorded significantly (p < 0.05) higher SPM in the Ajkwa Estuary compared to neighboring estuaries. This research provides a means to quantify multiple modes of ecological damage from mine waste disposal or other disturbance events.
Bone marrow-derived macrophages distinct from tissue-resident macrophages play a pivotal role in Concanavalin A-induced murine liver injury via CCR9 axis
Authors: Amiya Takeru , Nakamoto Nobuhiro , Chu Po-sung , Teratani Toshiaki , Nakajima Hideaki , Fukuchi Yumi , Taniki Nobuhito , Yamaguchi Akihiro , Shiba Shunsuke , Miyake Rei , Katayama Tadashi , Ebinuma Hirotoshi , Kanai Takanori
Published: October 2016

The fundamental mechanism how heterogeneous hepatic macrophage (Mφ) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9+ inflammatory Mφs play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9+Mφs, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident Mφs. First, irradiated mice developed less liver injury with less Mφs accumulation by Concanavalin A (Con A) regardless of liver shielding. In mice receiving further BM transplantation, CD11blowF4/80high hepatic-resident Mφs were not replaced by transplanted donors under steady state, while under inflammatory state by Con A, CCR9+Mφs were firmly replaced by donors, indicating that CCR9+Mφs originate from BM, but not from hepatic-resident cells. Regarding the mechanism of differentiation and proliferation, EdU+CCR9+Mφs with a proliferative potential were detected specifically in the inflamed liver, and in vitro study revealed that BM-derived CD11b+ cells co-cultured with hepatic stellate cells (HSCs) or stimulated with retinoic acids could acquire CCR9 with antigen-presenting ability. Collectively, our study demonstrates that inflammatory Mφs originate from BM and became locally differentiated and proliferated by interaction with HSCs via CCR9 axis during acute liver injury.
Magnetocaloric Properties of Fe-Ni-Cr Nanoparticles for Active Cooling
Authors: Chaudhary V. , Ramanujan R.V.
Published: October 2016

Low cost, earth abundant, rare earth free magnetocaloric nanoparticles have attracted an enormous amount of attention for green, energy efficient, active near room temperature thermal management. Hence, we investigated the magnetocaloric properties of transition metal based (Fe70Ni30)100−xCrx (x = 1, 3, 5, 6 and 7) nanoparticles. The influence of Cr additions on the Curie temperature (TC) was studied. Only 5% of Cr can reduce the TC from ~438 K to 258 K. These alloys exhibit broad entropy v/s temperature curves, which is useful to enhance relative cooling power (RCP). For a field change of 5 T, the RCP for (Fe70Ni30)99Cr1 nanoparticles was found to be 548 J-kg−1. Tunable TCin broad range, good RCP, low cost, high corrosion resistance and earth abundance make these nanoparticles suitable for low-grade waste heat recovery as well as near room temperature active cooling applications.
Engineered Human Ferritin Nanoparticles for Direct Delivery of Tumor Antigens to Lymph Node and Cancer Immunotherapy
Authors: Lee Bo-Ram , Ko Ho Kyung , Ryu Ju Hee , Ahn Keum Young , Lee Young-Ho , Oh Se Jin , Na Jin Hee , Kim Tae Woo , Byun Youngro , Kwon Ick Chan , Kim Kwangmeyung , Lee Jeewon
Published: October 2016

Efficient delivery of tumor-specific antigens (TSAs) to lymph nodes (LNs) is essential to eliciting robust immune response for cancer immunotherapy but still remains unsolved. Herein, we evaluated the direct LN-targeting performance of four different protein nanoparticles with different size, shape, and origin [Escherichia coliDNA binding protein (DPS),Thermoplasma acidophilumproteasome (PTS), hepatitis B virus capsid (HBVC), and human ferritin heavy chain (hFTN)] in live mice, using an optical fluorescence imaging system. Based on the imaging results, hFTN that shows rapid LN targeting and prolonged retention in LNs was chosen as a carrier of the model TSA [red fluorescence protein (RFP)], and the flexible surface architecture of hFTN was engineered to densely present RFPs on the hFTN surface through genetic modification of subunit protein of hFTN. The RFP-modified hFTN rapidly targeted LNs, sufficiently exposed RFPs to LN immune cells during prolonged period of retention in LNs, induced strong RFP-specific cytotoxic CD8+T cell response, and notably inhibited RFP-expressing melanoma tumor growth in live mice. This suggests that the strategy using protein nanoparticles as both TSA-carrying scaffold and anti-cancer vaccine holds promise for clinically effective immunotherapy of cancer.
One-step Maskless Fabrication and Optical Characterization of Silicon Surfaces with Antireflective Properties and a White Color Appearance
Authors: Schneider Ling , Feidenhans’l Nikolaj A. , Telecka Agnieszka , Taboryski Rafael J.
Published: October 2016

We report a simple one-step maskless fabrication of inverted pyramids on silicon wafers by reactive ion etching. The fabricated surface structures exhibit excellent anti-reflective properties: The total reflectance of the nano inverted pyramids fabricated by our method can be as low as 12% without any anti-reflective layers, and down to only 0.33% with a silicon nitride coating. The results from angle resolved scattering measurements indicate that the existence of triple reflections is responsible for the reduced reflectance. The surfaces with the nano inverted pyramids also exhibit a distinct milky white color.
Hydrophilic Graphene Preparation from Gallic Acid Modified Graphene Oxide in Magnesium Self-Propagating High Temperature Synthesis Process
Authors: Cao Lei , Li Zhenhuan , Su Kunmei , Cheng Bowen
Published: October 2016

Hydrophilic graphene sheets were synthesized from a mixture of magnesium and gallic acid (GA) modified graphene oxide (GO) in a self-propagating high-temperature synthesis (SHS) process, and hydrophilic graphene sheets displayed the higher C/O ratio (16.36), outstanding conductivity (~88900 S/m) and excellent water-solubility. GO sheets were connected together by GA, and GA was captured to darn GO structure defects through the formation of hydrogen bonds and ester bonds. In SHS process, the most oxygen ions of GO reacted with magnesium to prevent the escape of carbon dioxide and carbon monoxide to from the structure defects associated with vacancies, and GA could take place the high-temperature carbonization, during which a large-area graphene sheets formed with a part of the structure defects being repaired. When only GO was reduced by magnesium in SHS process, and the reduced GO (rGO) exhibited the smaller sheets, the lower C/O ratio (15.26), the weaker conductivity (4200 S/m) and the poor water-solubility because rGO inevitably left behind carbon vacancies and topological defects. Therefore, the larger sheet, less edge defects and free structure defects associated with vacancies play a key role for graphene sheets good dispersion in water.
Fabrication of an antibody-aptamer sandwich assay for electrochemical evaluation of levels of β-amyloid oligomers
Authors: Zhou Yanli , Zhang Huanqing , Liu Lantao , Li Congming , Chang Zhu , Zhu Xu , Ye Baoxian , Xu Maotian
Published: October 2016

Amyloid β-peptide (Aβ) in its oligomeric form is often considered as the most toxic species in Alzheimer’s disease (AD), and thus Aβ oligomer is a potentially promising candidate biomarker for AD diagnosis. The development of a sensitive and reliable method for monitoring the Aβ oligomer levels in body fluids is an urgent requirement in order to predict the severity and progression at early or preclinical stages of AD. Here, we show a proof of concept for a sensitive and specific detection of Aβ oligomers by an antibody-aptamer sandwich assay. The antibodies of Aβ oligomers and a nanocomposite of gold nanoparticles with aptamer and thionine (aptamer-Au-Th) were used as the recognition element and the detection probe for specifically binding to Aβ oligomers, respectively. The electrochemical signal of Th reduction could provide measurable electrochemical signals, and a low limit of detection (100 pM) was achieved due to the signal amplification by high loading of Th on the gold nanoparticles. The feasibility of the assay was verified by test of Aβ oligomers in artificial cerebrospinal fluid. The proposed strategy presents valuable information related to early diagnosis of AD process.
A global-wide search for sexual dimorphism of glomeruli in the antennal lobe of female and male Helicoverpa armigera
Authors: Zhao Xin-Cheng , Ma Bai-Wei , Berg Bente G. , Xie Gui-Ying , Tang Qing-Bo , Guo Xian-Ru
Published: October 2016

By using immunostaining and three-dimensional reconstruction, the anatomical organization of the antennal lobe glomeruli of the female cotton bollworm Helicoverpa armigera was investigated. Eighty-one glomeruli were identified, 15 of which were not previously discovered. The general anatomical organization of the AL of female is similar to that of male and all glomeruli were classified into four sub-groups, including the female-specific glomerular complex, posterior complex, labial-palp pit organ glomerulus, and ordinary glomeruli. A global-wide comparison on the complete glomerular map of female and male was performed and for the first time the quantitative difference in volume for each individual homologous glomerulus was analyzed. We found that the sexual dimorphism includes not only the sex-specific glomeruli but also some of the other glomeruli. The findings in the present study may provide a reference to examine the antennal-lobe organization more in detail and to identify new glomeruli in other moth species. In addition, the complete identification and global-wide comparison of the sexes provide an important basis for mapping the function of distinct glomeruli and for understanding neural mechanisms underlying sexually dimorphic olfactory behaviors.
Powerful linearly-polarized high-order random fiber laser pumped by broadband amplified spontaneous emission source
Authors: Xu Jiangming , Zhou Pu , Leng Jinyong , Wu Jian , Zhang Hanwei
Published: October 2016

A great deal of attention has been drawn to Random fiber lasers (RFLs) for their typical features of modeless, cavity-less and low coherence length. However, most previously reported high power RFLs employ narrowband fiber lasers as the pump source, thus inducing the self-pulsing transferring from pump source to output Stokes. In this contribution, linearly-polarized RFL pumped by broadband amplified-spontaneous-emission (ASE) is demonstrated and continuous-wave (CW) high order Stokes can be obtained.With 30.6 W pump injected into the half-opened cavity, 23.51 W the 2nd order Stokes centered at 1178 nm with a full width at half-maximum linewidth of 1.73 nm and polarization extinction ratio of about 25 dB can be obtained. The standard deviation and peak-vale value of the 2nd order Stokes light at maximal output power is just 0.47% and 4.10%, which indicates the good power stability. Significantly, the corresponding quantum efficiency of the 1st and 2nd order Stokes light is about 87% and 85%, and almost all pump photons are converted into Stokes photons. As far as we know, it is the highest power ever reported from linearly polarized RFL, and further power scaling is available in the case of more powerful pump source and optimization of system parameters.